WO2024168123A1 - Synthesis of core 2 o-sialyl lewis-x polysaccharides - Google Patents

Abstract

Provided herein are methods and compounds useful in the preparation of Core 2 O-sialyl Lewis^x polysaccharides including compounds of Formula (C).

Description

  SYNTHESIS OF CORE 2 O-SIALYL LEWIS-X POLYSACCHARIDES   RELATED APPLICATIONS [1] This application claims priority under 35 U.S.C. § 119(e) to U.S. provisional patent application, U.S.S.N.63/484,052, filed February 9, 2023, the entire contents of which is incorporated herein by reference. GOVERNMENT SUPPORT [2] This invention was made with government support under GM116196, DK107405, and HL128237, awarded by the National Institutes of Health. The government has certain rights in the invention. BACKGROUND [3] The high affinity interaction between P-selectin glycoprotein ligand-1 (PSGL-1) and P-selectin is mediated by a multi-motif recognition domain consisting of clustered tyrosine sulfates and a Core 2 O- glycan terminated with sialyl Lewis^X (C2-O-sLe^X). This interaction is representative of many cell-cell recognition processes that are dependent upon the presentation of unique glycans in the context of other aglycone components. The distinct glycosulfopeptide (GSP) motifs present in PSGL-1 are much more common than previously appreciated within a wide variety of functionally important domains involved in protein-protein interactions or ligand binding. Defining the structure-function relationships that underly these interactions could lead to new opportunities for drug discovery. However, despite the potential of GSPs to serve as tools for fundamental studies and prospects for drug development, their utility has been limited by the absence of chemical schemes for synthesis on production scale. SUMMARY [4] Provided herein are methods and compounds useful in the preparation of Core 2 O-sialyl Lewis^X polysaccharides including compounds of Formula (C):

and salts thereof. [5] For example, provided herein are methods and compounds useful in the preparation of a key Core 2 O-sialyl Lewis^X polysaccharides having the following structure:  

(C2-O-sLe^X-Thr-COOH). [6] Taken together, the methods and compounds provided herein represent a streamlined and efficient approach accessing Core 2 O-sialyl Lewis^X polyssacharides, for example, in fewer steps and in higher overall yield compared to previous strategies. Core 2 O-sialyl Lewis^X polyssacharides prepared by the methods and compounds described herein can be used in the preparation of O-glycan bearing glycopeptides including GSnP-6 (e.g., via solid phase peptide synthesis (SPPS)). DEFINITIONS [7] Definitions of specific functional groups and chemical terms are described in more detail below. The chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75^th Ed., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Thomas Sorrell, Organic Chemistry, University Science Books, Sausalito, 1999; Michael B. Smith, March’s Advanced Organic Chemistry, 7^th Edition, John Wiley & Sons, Inc., New York, 2013; Richard C. Larock, Comprehensive Organic Transformations, John Wiley & Sons, Inc., New York, 2018; and Carruthers, Some Modern Methods of Organic Synthesis, 3^rd Edition, Cambridge University Press, Cambridge, 1987. [8] Compounds described herein comprise one or more asymmetric centers, and thus can exist in various stereoisomeric forms, e.g., enantiomers and/or diastereomers. For example, the compounds described herein can be in the form of an individual enantiomer, diastereomer, or geometric isomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer. Isomers can be isolated from mixtures by methods known to those skilled in the art, including chiral high pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers can be prepared by asymmetric syntheses. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen et al., Tetrahedron 33:2725 (1977); Eliel, E.L. Stereochemistry of Carbon Compounds (McGraw–Hill, NY, 1962); and Wilen, S.H., Tables of Resolving Agents and Optical Resolutions p.268 (E.L. Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972). The present disclosure additionally encompasses   compounds as individual isomers substantially free of other isomers, and alternatively, as mixtures of various isomers. [9] Compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or the arrangement of their atoms in space are termed “isomers”. Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers”. [10] “Stereoisomers” that are not mirror images of one another are termed “diastereomers” and those that are non-superimposable mirror images of each other are termed “enantiomers”. When a compound has an asymmetric center, for example, it is bonded to four different groups, a pair of enantiomers is possible. An enantiomer can be characterized by the absolute configuration of its asymmetric center and is described by the R- and S-sequencing rules of Cahn and Prelog, or by the manner in which the molecule rotates the plane of polarized light and designated as dextrorotatory or levorotatory (i.e., as (+)- or (−)- isomers respectively). A chiral compound can exist as either individual enantiomer or as a mixture thereof. A mixture containing equal proportions of the enantiomers is called a “racemic mixture.” [11] Unless otherwise provided, formulae and structures depicted herein include compounds that do not include isotopically enriched atoms, and also include compounds that include isotopically enriched atoms (“isotopically labeled derivatives”). For example, compounds having the present structures except for the replacement of hydrogen by deuterium or tritium, replacement of ¹⁹F with ¹⁸F, or the replacement of a carbon by a ¹³C- or ¹⁴C-enriched carbon are within the scope of the disclosure. Such compounds are useful, for example, as analytical tools or probes in biological assays. The term “isotopes” refers to variants of a particular chemical element such that, while all isotopes of a given element share the same number of protons in each atom of the element, those isotopes differ in the number of neutrons. [12] When a range of values (“range”) is listed, it encompasses each value and sub-range within the range. A range is inclusive of the values at the two ends of the range unless otherwise provided. For example, “C_1-6 alkyl” encompasses, C₁, C₂, C₃, C₄, C₅, C₆, C_1–6, C_1–5, C_1–4, C_1–3, C_1–2, C_2–6, C_2–5, C_2–4, C_2–3, C_3–6, C_3–5, C_3–4, C_4–6, C_4–5, and C_5–6 alkyl. [13] Use of the phrase “at least one” or “at least one instance” refers to 1, 2, 3, 4, or more instances, but also encompasses a range, e.g., for example, from 1 to 4, from 1 to 3, from 1 to 2, from 2 to 4, from 2 to 3, or from 3 to 4 instances, inclusive. [14] The term “alkyl” refers to a radical of a straight-chain or branched saturated hydrocarbon group having from 1 to 20 carbon atoms (“C_1–20 alkyl”). In some embodiments, an alkyl group has 1 to 12 carbon atoms (“C_1–12 alkyl”). In some embodiments, an alkyl group has 1 to 10 carbon atoms (“C_1–10 alkyl”). In some embodiments, an alkyl group has 1 to 9 carbon atoms (“C_1–9 alkyl”). In some embodiments, an alkyl group has 1 to 8 carbon atoms (“C_1–8 alkyl”). In some embodiments, an alkyl group has 1 to 7 carbon atoms (“C_1–7 alkyl”). In some embodiments, an alkyl group has 1 to 6 carbon atoms (“C_1–6 alkyl”). In some embodiments, an alkyl group has 1 to 5 carbon atoms (“C_1–5 alkyl”). In some embodiments, an alkyl group has 1 to 4 carbon atoms (“C_1–4 alkyl”). In some embodiments, an alkyl group has 1 to 3 carbon atoms (“C_1–3 alkyl”). In some embodiments, an alkyl group has 1 to 2 carbon atoms (“C_1–2 alkyl”). In some embodiments, an alkyl group has 1 carbon atom (“C₁ alkyl”). In   some embodiments, an alkyl group has 2 to 6 carbon atoms (“C_2-6 alkyl”). Examples of C_1–6 alkyl groups include methyl (C₁), ethyl (C₂), propyl (C₃) (e.g., n-propyl, isopropyl), butyl (C₄) (e.g., n-butyl, tert-butyl, sec-butyl, isobutyl), pentyl (C₅) (e.g., n-pentyl, 3-pentanyl, amyl, neopentyl, 3-methyl-2-butanyl, tert- amyl), and hexyl (C₆) (e.g., n-hexyl). Additional examples of alkyl groups include n-heptyl (C₇), n-octyl (C₈), n-dodecyl (C₁₂), and the like. Unless otherwise specified, each instance of an alkyl group is independently unsubstituted (an “unsubstituted alkyl”) or substituted (a “substituted alkyl”) with one or more substituents (e.g., halogen, such as F). In certain embodiments, the alkyl group is an unsubstituted C_1–12 alkyl (such as unsubstituted C_1–6 alkyl, e.g., −CH₃ (Me), unsubstituted ethyl (Et), unsubstituted propyl (Pr, e.g., unsubstituted n-propyl (n-Pr), unsubstituted isopropyl (i-Pr)), unsubstituted butyl (Bu, e.g., unsubstituted n-butyl (n-Bu), unsubstituted tert-butyl (tert-Bu or t-Bu), unsubstituted sec-butyl (sec- Bu or s-Bu), unsubstituted isobutyl (i-Bu)). In certain embodiments, the alkyl group is a substituted C_1–12 alkyl (such as substituted C_1–6 alkyl, e.g., –CH₂F, –CHF₂, –CF₃, –CH₂CH₂F, –CH₂CHF₂, –CH₂CF₃, or benzyl (Bn)). [15] The term “haloalkyl” is a substituted alkyl group, wherein one or more of the hydrogen atoms are independently replaced by a halogen, e.g., fluoro, bromo, chloro, or iodo. “Perhaloalkyl” is a subset of haloalkyl and refers to an alkyl group wherein all of the hydrogen atoms are independently replaced by a halogen, e.g., fluoro, bromo, chloro, or iodo. In some embodiments, the haloalkyl moiety has 1 to 20 carbon atoms (“C_1–20 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 10 carbon atoms (“C_1–10 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 9 carbon atoms (“C_1–9 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 8 carbon atoms (“C_1–8 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 7 carbon atoms (“C_1–7 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 6 carbon atoms (“C_1–6 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 5 carbon atoms (“C_1–5 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 4 carbon atoms (“C_1–4 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 3 carbon atoms (“C_1–3 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 2 carbon atoms (“C_1–2 haloalkyl”). In some embodiments, all of the haloalkyl hydrogen atoms are independently replaced with fluoro to provide a “perfluoroalkyl” group. In some embodiments, all of the haloalkyl hydrogen atoms are independently replaced with chloro to provide a “perchloroalkyl” group. Examples of haloalkyl groups include –CHF₂, −CH₂F, −CF₃, −CH₂CF₃, −CF₂CF₃, −CF₂CF₂CF₃, −CCl₃, −CFCl₂, −CF₂Cl, and the like. [16] The term “heteroalkyl” refers to an alkyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, sulfur, silicon, boron, and phosphorous within (e.g., inserted between adjacent carbon atoms of) and/or placed at one or more terminal position(s) of the parent chain. In certain embodiments, the heteroalkyl group is an alkyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, and sulfur within (e.g., inserted between adjacent carbon atoms of) and/or placed at one or more terminal position(s) of the parent chain. In certain embodiments, a heteroalkyl group refers to a saturated group having from 1 to 20 carbon atoms and 1 or more heteroatoms within the parent chain (“C_1–20 heteroalkyl”). In certain   embodiments, a heteroalkyl group refers to a saturated group having from 1 to 12 carbon atoms and 1 or more heteroatoms within the parent chain (“C_1–12 heteroalkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 11 carbon atoms and 1 or more heteroatoms within the parent chain (“C_1–11 heteroalkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 10 carbon atoms and 1 or more heteroatoms within the parent chain (“C_1–10 heteroalkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 9 carbon atoms and 1 or more heteroatoms within the parent chain (“C_1–9 heteroalkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 8 carbon atoms and 1 or more heteroatoms within the parent chain (“C_1–8 heteroalkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 7 carbon atoms and 1 or more heteroatoms within the parent chain (“C_1–7 heteroalkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 6 carbon atoms and 1 or more heteroatoms within the parent chain (“C_1–6 heteroalkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 5 carbon atoms and 1 or 2 heteroatoms within the parent chain (“C_1–5 heteroalkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 4 carbon atoms and 1 or 2 heteroatoms within the parent chain (“C_1–4 heteroalkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 3 carbon atoms and 1 heteroatom within the parent chain (“C_1–3 heteroalkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 2 carbon atoms and 1 heteroatom within the parent chain (“C_1–2 heteroalkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 carbon atom and 1 heteroatom (“C₁ heteroalkyl”). In some embodiments, a heteroalkyl group is a saturated group having 2 to 6 carbon atoms and 1 or 2 heteroatoms within the parent chain (“C_2-6 heteroalkyl”). Unless otherwise specified, each instance of a heteroalkyl group is independently unsubstituted (an “unsubstituted heteroalkyl”) or substituted (a “substituted heteroalkyl”) with one or more substituents. [17] The term “alkenyl” refers to a radical of a straight-chain or branched hydrocarbon group having from 2 to 20 carbon atoms and one or more carbon-carbon double bonds (e.g., 1, 2, 3, or 4 double bonds). In some embodiments, an alkenyl group has 2 to 20 carbon atoms (“C_2-20 alkenyl”). In some embodiments, an alkenyl group has 2 to 12 carbon atoms (“C_2–12 alkenyl”). In some embodiments, an alkenyl group has 2 to 11 carbon atoms (“C_2–11 alkenyl”). In some embodiments, an alkenyl group has 2 to 10 carbon atoms (“C_2–10 alkenyl”). In some embodiments, an alkenyl group has 2 to 9 carbon atoms (“C_2–9 alkenyl”). In some embodiments, an alkenyl group has 2 to 8 carbon atoms (“C_2–8 alkenyl”). In some embodiments, an alkenyl group has 2 to 7 carbon atoms (“C_2–7 alkenyl”). In some embodiments, an alkenyl group has 2 to 6 carbon atoms (“C_2–6 alkenyl”). In some embodiments, an alkenyl group has 2 to 5 carbon atoms (“C_2–5 alkenyl”). In some embodiments, an alkenyl group has 2 to 4 carbon atoms (“C_2–4 alkenyl”). In some embodiments, an alkenyl group has 2 to 3 carbon atoms (“C_2–3 alkenyl”). In some embodiments, an alkenyl group has 2 carbon atom (“C₂ alkenyl”). The one or more carbon-carbon double bonds can be internal (such as in 2-butenyl) or terminal (such as in 1-butenyl). Examples of C_2–4 alkenyl groups include ethenyl (C₂), 1-propenyl (C₃), 2-propenyl (C₃), 1-butenyl (C₄), 2-butenyl (C₄), butadienyl (C₄), and the like. Examples of C_2–6 alkenyl groups include the aforementioned C_2-4 alkenyl groups as   well as pentenyl (C₅), pentadienyl (C₅), hexenyl (C₆), and the like. Additional examples of alkenyl include heptenyl (C₇), octenyl (C₈), octatrienyl (C₈), and the like. Unless otherwise specified, each instance of an alkenyl group is independently unsubstituted (an “unsubstituted alkenyl”) or substituted (a “substituted alkenyl”) with one or more substituents. In an alkenyl group, a C=C double bond for which the stereochemistry is not specified (e.g., −CH=CHCH₃ or

) may be in the (E)- or (Z)- configuration. [18] The term “heteroalkenyl” refers to an alkenyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, sulfur, silicon, boron, and phosphorous within (e.g., inserted between adjacent carbon atoms of) and/or placed at one or more terminal position(s) of the parent chain. In certain embodiments, the heteroalkenyl group is an alkenyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, and sulfur within (e.g., inserted between adjacent carbon atoms of) and/or placed at one or more terminal position(s) of the parent chain. In certain embodiments, a heteroalkenyl group refers to a group having from 2 to 20 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“C_2–20 heteroalkenyl”). In certain embodiments, a heteroalkenyl group refers to a group having from 2 to 12 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“C_2–12 heteroalkenyl”). In certain embodiments, a heteroalkenyl group refers to a group having from 2 to 11 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“C_2–11 heteroalkenyl”). In certain embodiments, a heteroalkenyl group refers to a group having from 2 to 10 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“C_2–10 heteroalkenyl”). In some embodiments, a heteroalkenyl group has 2 to 9 carbon atoms at least one double bond, and 1 or more heteroatoms within the parent chain (“C_2–9 heteroalkenyl”). In some embodiments, a heteroalkenyl group has 2 to 8 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“C_2–8 heteroalkenyl”). In some embodiments, a heteroalkenyl group has 2 to 7 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“C_2–7 heteroalkenyl”). In some embodiments, a heteroalkenyl group has 2 to 6 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“C_2–6 heteroalkenyl”). In some embodiments, a heteroalkenyl group has 2 to 5 carbon atoms, at least one double bond, and 1 or 2 heteroatoms within the parent chain (“C_2–5 heteroalkenyl”). In some embodiments, a heteroalkenyl group has 2 to 4 carbon atoms, at least one double bond, and 1 or 2 heteroatoms within the parent chain (“C_2–4 heteroalkenyl”). In some embodiments, a heteroalkenyl group has 2 to 3 carbon atoms, at least one double bond, and 1 heteroatom within the parent chain (“C_2–3 heteroalkenyl”). In some embodiments, a heteroalkenyl group has 2 carbon atoms, at least one double bond, and 1 heteroatom within the parent chain (“C₂ heteroalkenyl”). In some embodiments, a heteroalkenyl group has 2 to 6 carbon atoms, at least one double bond, and 1 or 2 heteroatoms within the parent chain (“C_2–6 heteroalkenyl”). Unless otherwise specified, each instance of a heteroalkenyl group is independently unsubstituted (an “unsubstituted heteroalkenyl”) or substituted (a “substituted heteroalkenyl”) with one or more substituents.   [19] The term “alkynyl” refers to a radical of a straight-chain or branched hydrocarbon group having from 2 to 20 carbon atoms and one or more carbon-carbon triple bonds (e.g., 1, 2, 3, or 4 triple bonds) (“C_2-20 alkynyl”). In some embodiments, an alkynyl group has 2 to 10 carbon atoms (“C_2-10 alkynyl”). In some embodiments, an alkynyl group has 2 to 9 carbon atoms (“C_2-9 alkynyl”). In some embodiments, an alkynyl group has 2 to 8 carbon atoms (“C_2-8 alkynyl”). In some embodiments, an alkynyl group has 2 to 7 carbon atoms (“C_2-7 alkynyl”). In some embodiments, an alkynyl group has 2 to 6 carbon atoms (“C_2-6 alkynyl”). In some embodiments, an alkynyl group has 2 to 5 carbon atoms (“C_2-5 alkynyl”). In some embodiments, an alkynyl group has 2 to 4 carbon atoms (“C_2-4 alkynyl”). In some embodiments, an alkynyl group has 2 to 3 carbon atoms (“C_2-3 alkynyl”). In some embodiments, an alkynyl group has 2 carbon atoms (“C₂ alkynyl”). The one or more carbon-carbon triple bonds can be internal (such as in 2- butynyl) or terminal (such as in 1-butynyl). Examples of C_2-4 alkynyl groups include, without limitation, ethynyl (C₂), 1-propynyl (C₃), 2-propynyl (C₃), 1-butynyl (C₄), 2-butynyl (C₄), and the like. Examples of C_2-6 alkenyl groups include the aforementioned C_2-4 alkynyl groups as well as pentynyl (C₅), hexynyl (C₆), and the like. Additional examples of alkynyl include heptynyl (C₇), octynyl (C₈), and the like. Unless otherwise specified, each instance of an alkynyl group is independently unsubstituted (an “unsubstituted alkynyl”) or substituted (a “substituted alkynyl”) with one or more substituents. [20] The term “heteroalkynyl” refers to an alkynyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, sulfur, silicon, boron, and phosphorous within (e.g., inserted between adjacent carbon atoms of) and/or placed at one or more terminal position(s) of the parent chain. In certain embodiments, the heteroalkynyl group is an alkynyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, and sulfur within (e.g., inserted between adjacent carbon atoms of) and/or placed at one or more terminal position(s) of the parent chain. In certain embodiments, a heteroalkynyl group refers to a group having from 2 to 20 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain (“C_2–20 heteroalkynyl”). In certain embodiments, a heteroalkynyl group refers to a group having from 2 to 10 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain (“C_2–10 heteroalkynyl”). In some embodiments, a heteroalkynyl group has 2 to 9 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain (“C_2–9 heteroalkynyl”). In some embodiments, a heteroalkynyl group has 2 to 8 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain (“C_2–8 heteroalkynyl”). In some embodiments, a heteroalkynyl group has 2 to 7 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain (“C_2–7 heteroalkynyl”). In some embodiments, a heteroalkynyl group has 2 to 6 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain (“C_2–6 heteroalkynyl”). In some embodiments, a heteroalkynyl group has 2 to 5 carbon atoms, at least one triple bond, and 1 or 2 heteroatoms within the parent chain (“C_2–5 heteroalkynyl”). In some embodiments, a heteroalkynyl group has 2 to 4 carbon atoms, at least one triple bond, and 1or 2 heteroatoms within the parent chain (“C_2–4 heteroalkynyl”). In some embodiments, a heteroalkynyl group has 2 to 3 carbon atoms, at least one triple bond, and 1 heteroatom within the parent chain (“C_2–3 heteroalkynyl”). In some embodiments, a heteroalkynyl group has 2 carbon atoms, at   least one triple bond, and 1 heteroatom within the parent chain (“C₂ heteroalkynyl”). In some embodiments, a heteroalkynyl group has 2 to 6 carbon atoms, at least one triple bond, and 1 or 2 heteroatoms within the parent chain (“C_1–6 heteroalkynyl”). Unless otherwise specified, each instance of a heteroalkynyl group is independently unsubstituted (an “unsubstituted heteroalkynyl”) or substituted (a “substituted heteroalkynyl”) with one or more substituents. [21] The term “carbocyclyl” or “carbocyclic” refers to a radical of a non-aromatic cyclic hydrocarbon group having from 3 to 14 ring carbon atoms (“C_3-14 carbocyclyl”) and zero heteroatoms in the non- aromatic ring system. In some embodiments, a carbocyclyl group has 3 to 14 ring carbon atoms (“C_3-14 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 13 ring carbon atoms (“C_3-13 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 12 ring carbon atoms (“C_3-12 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 11 ring carbon atoms (“C_3-11 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 10 ring carbon atoms (“C_3-10 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 8 ring carbon atoms (“C_3-8 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 7 ring carbon atoms (“C_3-7 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 6 ring carbon atoms (“C_3-6 carbocyclyl”). In some embodiments, a carbocyclyl group has 4 to 6 ring carbon atoms (“C_4-6 carbocyclyl”). In some embodiments, a carbocyclyl group has 5 to 6 ring carbon atoms (“C_5-6 carbocyclyl”). In some embodiments, a carbocyclyl group has 5 to 10 ring carbon atoms (“C_5-10 carbocyclyl”). Exemplary C_3-6 carbocyclyl groups include cyclopropyl (C₃), cyclopropenyl (C₃), cyclobutyl (C₄), cyclobutenyl (C₄), cyclopentyl (C₅), cyclopentenyl (C₅), cyclohexyl (C₆), cyclohexenyl (C₆), cyclohexadienyl (C₆), and the like. Exemplary C_3-8 carbocyclyl groups include the aforementioned C_3-6 carbocyclyl groups as well as cycloheptyl (C₇), cycloheptenyl (C₇), cycloheptadienyl (C₇), cycloheptatrienyl (C₇), cyclooctyl (C₈), cyclooctenyl (C₈), bicyclo[2.2.1]heptanyl (C₇), bicyclo[2.2.2]octanyl (C₈), and the like. Exemplary C_3-10 carbocyclyl groups include the aforementioned C_3-8 carbocyclyl groups as well as cyclononyl (C₉), cyclononenyl (C₉), cyclodecyl (C₁₀), cyclodecenyl (C₁₀), octahydro-1H-indenyl (C₉), decahydronaphthalenyl (C₁₀), spiro[4.5]decanyl (C₁₀), and the like. Exemplary C_3-8 carbocyclyl groups include the aforementioned C_3-10 carbocyclyl groups as well as cycloundecyl (C₁₁), spiro[5.5]undecanyl (C₁₁), cyclododecyl (C₁₂), cyclododecenyl (C₁₂), cyclotridecane (C₁₃), cyclotetradecane (C₁₄), and the like. As the foregoing examples illustrate, in certain embodiments, the carbocyclyl group is either monocyclic (“monocyclic carbocyclyl”) or polycyclic (e.g., containing a fused, bridged or spiro ring system such as a bicyclic system (“bicyclic carbocyclyl”) or tricyclic system (“tricyclic carbocyclyl”)) and can be saturated or can contain one or more carbon-carbon double or triple bonds. “Carbocyclyl” also includes ring systems wherein the carbocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups wherein the point of attachment is on the carbocyclyl ring, and in such instances, the number of carbons continue to designate the number of carbons in the carbocyclic ring system. Unless otherwise specified, each instance of a carbocyclyl group is independently unsubstituted (an “unsubstituted carbocyclyl”) or substituted (a “substituted carbocyclyl”) with one or more substituents.   [22] In some embodiments, “carbocyclyl” is a monocyclic, saturated carbocyclyl group having from 3 to 14 ring carbon atoms (“C_3-14 cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 10 ring carbon atoms (“C_3-10 cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 8 ring carbon atoms (“C_3-8 cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 6 ring carbon atoms (“C_3-6 cycloalkyl”). In some embodiments, a cycloalkyl group has 4 to 6 ring carbon atoms (“C_4-6 cycloalkyl”). In some embodiments, a cycloalkyl group has 5 to 6 ring carbon atoms (“C_5-6 cycloalkyl”). In some embodiments, a cycloalkyl group has 5 to 10 ring carbon atoms (“C_5-10 cycloalkyl”). Examples of C_5-6 cycloalkyl groups include cyclopentyl (C₅) and cyclohexyl (C₅). Examples of C_3-6 cycloalkyl groups include the aforementioned C_5-6 cycloalkyl groups as well as cyclopropyl (C₃) and cyclobutyl (C₄). Examples of C_3-8 cycloalkyl groups include the aforementioned C_3-6 cycloalkyl groups as well as cycloheptyl (C₇) and cyclooctyl (C₈). Unless otherwise specified, each instance of a cycloalkyl group is independently unsubstituted (an “unsubstituted cycloalkyl”) or substituted (a “substituted cycloalkyl”) with one or more substituents. In certain embodiments, the carbocyclyl includes 0, 1, or 2 C=C double bonds in the carbocyclic ring system, as valency permits. [23] The term “heterocyclyl” or “heterocyclic” refers to a radical of a 3- to 14-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, sulfur, silicon, boron, and phosphorous (“3–14 membered heterocyclyl”). In certain embodiments, the heterocyclyl group is a radical of a 3- to 14-membered non- aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur. The point of attachment can be either to a ring carbon atom or a ring heteroatom of the heterocyclyl group, as valency permits. For example, in heterocyclyl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. A heterocyclyl group can either be monocyclic (“monocyclic heterocyclyl”) or polycyclic (e.g., a fused, bridged or spiro ring system such as a bicyclic system (“bicyclic heterocyclyl”) or tricyclic system (“tricyclic heterocyclyl”)), and can be saturated or can contain one or more carbon-carbon double or triple bonds. Heterocyclyl polycyclic ring systems can include one or more heteroatoms in one or both rings. “Heterocyclyl” also includes ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more carbocyclyl groups wherein the point of attachment is either on the carbocyclyl or heterocyclyl ring, or ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups, wherein the point of attachment is on the heterocyclyl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heterocyclyl ring system. Unless otherwise specified, each instance of heterocyclyl is independently unsubstituted (an “unsubstituted heterocyclyl”) or substituted (a “substituted heterocyclyl”) with one or more substituents. In certain embodiments, the heterocyclyl is substituted or unsubstituted, 3- to 8-membered, monocyclic heterocyclyl, wherein 1, 2, or 3 atoms in the heterocyclic ring system are independently oxygen, nitrogen, or sulfur, as valency permits. [24] In some embodiments, a heterocyclyl group is a 5–10 membered non-aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms, wherein each heteroatom is independently selected from   nitrogen, oxygen, and sulfur (“5–10 membered heterocyclyl”). In some embodiments, a heterocyclyl group is a 5–8 membered non-aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–8 membered heterocyclyl”). In some embodiments, a heterocyclyl group is a 5–6 membered non-aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–6 membered heterocyclyl”). In some embodiments, the 5–6 membered heterocyclyl has 1–3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5–6 membered heterocyclyl has 1–2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5–6 membered heterocyclyl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur. [25] Exemplary 3-membered heterocyclyl groups containing 1 heteroatom include azirdinyl, oxiranyl, and thiiranyl. Exemplary 4-membered heterocyclyl groups containing 1 heteroatom include azetidinyl, oxetanyl, and thietanyl. Exemplary 5-membered heterocyclyl groups containing 1 heteroatom include tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, pyrrolidinyl, dihydropyrrolyl, and pyrrolyl-2,5-dione. Exemplary 5-membered heterocyclyl groups containing 2 heteroatoms include dioxolanyl, oxathiolanyl and dithiolanyl. Exemplary 5-membered heterocyclyl groups containing 3 heteroatoms include triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary 6- membered heterocyclyl groups containing 1 heteroatom include piperidinyl, tetrahydropyranyl, dihydropyridinyl, and thianyl. Exemplary 6-membered heterocyclyl groups containing 2 heteroatoms include piperazinyl, morpholinyl, dithianyl, and dioxanyl. Exemplary 6-membered heterocyclyl groups containing 3 heteroatoms include triazinyl. Exemplary 7-membered heterocyclyl groups containing 1 heteroatom include azepanyl, oxepanyl and thiepanyl. Exemplary 8-membered heterocyclyl groups containing 1 heteroatom include azocanyl, oxecanyl and thiocanyl. Exemplary bicyclic heterocyclyl groups include indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, tetrahydrobenzo- thienyl, tetrahydrobenzofuranyl, tetrahydroindolyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, decahydroisoquinolinyl, octahydrochromenyl, octahydroisochromenyl, decahydronaphthyridinyl, decahydro-1,8-naphthyridinyl, octahydropyrrolo[3,2-b]pyrrole, indolinyl, phthalimidyl, naphthalimidyl, chromanyl, chromenyl, 1H-benzo[e][1,4]diazepinyl, 1,4,5,7-tetrahydro- pyrano[3,4-b]pyrrolyl, 5,6-dihydro-4H-furo[3,2-b]pyrrolyl, 6,7-dihydro-5H-furo[3,2-b]pyranyl, 5,7- dihydro-4H-thieno[2,3-c]pyranyl, 2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl, 2,3-dihydrofuro[2,3- b]pyridinyl, 4,5,6,7-tetrahydro-1H-pyrrolo[2,3-b]pyridinyl, 4,5,6,7-tetrahydrofuro[3,2-c]pyridinyl, 4,5,6,7-tetrahydrothieno[3,2-b]pyridinyl, 1,2,3,4-tetrahydro-1,6-naphthyridinyl, and the like. [26] The term “aryl” refers to a radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 π electrons shared in a cyclic array) having 6–14 ring carbon atoms and zero heteroatoms provided in the aromatic ring system (“C_6-14 aryl”). In some embodiments, an aryl group has 6 ring carbon atoms (“C₆ aryl”; e.g., phenyl). In some embodiments, an aryl group has 10 ring carbon atoms (“C₁₀ aryl”; e.g., naphthyl such as 1–naphthyl and 2-naphthyl). In some embodiments, an aryl group has 14 ring carbon atoms (“C₁₄ aryl”; e.g., anthracyl). “Aryl” also   includes ring systems wherein the aryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the radical or point of attachment is on the aryl ring, and in such instances, the number of carbon atoms continue to designate the number of carbon atoms in the aryl ring system. Unless otherwise specified, each instance of an aryl group is independently unsubstituted (an “unsubstituted aryl”) or substituted (a “substituted aryl”) with one or more substituents. [27] The term “heteroaryl” refers to a radical of a 5-14 membered monocyclic or polycyclic (e.g., bicyclic, tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 π electrons shared in a cyclic array) having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, sulfur, silicon, boron, and phosphorous (“5-14 membered heteroaryl”). In certain embodiments, the heteroaryl group is a radical of a 5-14 membered monocyclic or polycyclic (e.g., bicyclic, tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 π electrons shared in a cyclic array) having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur. The point of attachment can be either to a ring carbon atom or a ring heteroatom of the heteroaryl group, as valency permits. For example, in heteroaryl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. Heteroaryl polycyclic ring systems can include one or more heteroatoms in one or both rings. “Heteroaryl” includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the point of attachment is on the heteroaryl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heteroaryl ring system. “Heteroaryl” also includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more aryl groups wherein the point of attachment is either on the aryl or heteroaryl ring, and in such instances, the number of ring members designates the number of ring members in the fused polycyclic (aryl/heteroaryl) ring system. Polycyclic heteroaryl groups wherein one ring does not contain a heteroatom (e.g., indolyl, quinolinyl, carbazolyl, and the like) the point of attachment can be on either ring, e.g., either the ring bearing a heteroatom (e.g., 2-indolyl) or the ring that does not contain a heteroatom (e.g., 5-indolyl). In certain embodiments, the heteroaryl is substituted or unsubstituted, 5- or 6-membered, monocyclic heteroaryl, wherein 1, 2, 3, or 4 atoms in the heteroaryl ring system are independently oxygen, nitrogen, or sulfur. In certain embodiments, the heteroaryl is substituted or unsubstituted, 9- or 10-membered, bicyclic heteroaryl, wherein 1, 2, 3, or 4 atoms in the heteroaryl ring system are independently oxygen, nitrogen, or sulfur. [28] In some embodiments, a heteroaryl group is a 5-10 membered aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-10 membered heteroaryl”). In some embodiments, a heteroaryl group is a 5-8 membered aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-8 membered heteroaryl”). In some embodiments, a heteroaryl group is a 5-6 membered aromatic ring system having ring carbon atoms and 1–4 ring   heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-6 membered heteroaryl”). In some embodiments, the 5-6 membered heteroaryl has 1–3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 membered heteroaryl has 1–2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 membered heteroaryl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur. Unless otherwise specified, each instance of a heteroaryl group is independently unsubstituted (an “unsubstituted heteroaryl”) or substituted (a “substituted heteroaryl”) with one or more substituents. [29] Exemplary 5-membered heteroaryl groups containing 1 heteroatom include pyrrolyl, furanyl, and thiophenyl. Exemplary 5-membered heteroaryl groups containing 2 heteroatoms include imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Exemplary 5-membered heteroaryl groups containing 3 heteroatoms include triazolyl, oxadiazolyl, and thiadiazolyl. Exemplary 5-membered heteroaryl groups containing 4 heteroatoms include tetrazolyl. Exemplary 6-membered heteroaryl groups containing 1 heteroatom include pyridinyl. Exemplary 6-membered heteroaryl groups containing 2 heteroatoms include pyridazinyl, pyrimidinyl, and pyrazinyl. Exemplary 6-membered heteroaryl groups containing 3 or 4 heteroatoms include triazinyl and tetrazinyl, respectively. Exemplary 7-membered heteroaryl groups containing 1 heteroatom include azepinyl, oxepinyl, and thiepinyl. Exemplary 5,6- bicyclic heteroaryl groups include indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzoisofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzthiazolyl, benzisothiazolyl, benzthiadiazolyl, indolizinyl, and purinyl. Exemplary 6,6-bicyclic heteroaryl groups include naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl. Exemplary tricyclic heteroaryl groups include phenanthridinyl, dibenzofuranyl, carbazolyl, acridinyl, phenothiazinyl, phenoxazinyl, and phenazinyl. [30] The term “acyl” refers to a group having the general formula −C(=O)R^aa, wherein R^aa is as defined herein. [31] The term “halo” or “halogen” refers to fluorine (fluoro, −F), chlorine (chloro, −Cl), bromine (bromo, −Br), or iodine (iodo, −I). [32] The term “silyl” refers to the group –Si(R^aa)₃, wherein R^aa is as defined herein. [33] A group is optionally substituted unless expressly provided otherwise. The term “optionally substituted” refers to being substituted or unsubstituted. In certain embodiments, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl groups are optionally substituted. “Optionally substituted” refers to a group which is substituted or unsubstituted (e.g., “substituted” or “unsubstituted” alkyl, “substituted” or “unsubstituted” alkenyl, “substituted” or “unsubstituted” alkynyl, “substituted” or “unsubstituted” heteroalkyl, “substituted” or “unsubstituted” heteroalkenyl, “substituted” or “unsubstituted” heteroalkynyl, “substituted” or “unsubstituted” carbocyclyl, “substituted” or “unsubstituted” heterocyclyl, “substituted” or “unsubstituted” aryl or “substituted” or “unsubstituted” heteroaryl group). In general, the term “substituted” means that at least one hydrogen present on a group is replaced with a permissible substituent, e.g., a substituent which upon   substitution results in a stable compound, e.g., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, or other reaction. Unless otherwise indicated, a “substituted” group has a substituent at one or more substitutable positions of the group, and when more than one position in any given structure is substituted, the substituent is either the same or different at each position. The term “substituted” is contemplated to include substitution with all permissible substituents of organic compounds and includes any of the substituents described herein that results in the formation of a stable compound. The present disclosure contemplates any and all such combinations in order to arrive at a stable compound. For purposes of this disclosure, heteroatoms such as nitrogen, oxygen, and sulfur may have hydrogen substituents and/or any suitable substituent as described herein which satisfy the valencies of the heteroatoms and results in the formation of a stable moiety. The embodiments described herein are not limited in any manner by the exemplary substituents described herein. [34] Exemplary substituents (e.g., carbon atom substituents) include halogen, −CN, −NO₂, −N₃, −SO₂H, −SO₃H, −OH, −OR^aa, −ON(R^bb)₂, −N(R^bb)₂, −N(R^bb)₃ ⁺X⁻, −N(OR^cc)R^bb, −SH, −SR^aa, −SSR^cc, −C(=O)R^aa, −CO₂H, −CHO, −C(OR^cc)₂, −CO₂R^aa, −OC(=O)R^aa, −OCO₂R^aa, −C(=O)N(R^bb)₂, −OC(=O)N(R^bb)₂, −NR^bbC(=O)R^aa, −NR^bbCO₂R^aa, −NR^bbC(=O)N(R^bb)₂, −C(=NR^bb)R^aa, −C(=NR^bb)OR^aa, −OC(=NR^bb)R^aa, −OC(=NR^bb)OR^aa, −C(=NR^bb)N(R^bb)₂, −OC(=NR^bb)N(R^bb)₂, −NR^bbC(=NR^bb)N(R^bb)₂, −C(=O)NR^bbSO₂R^aa, −NR^bbSO₂R^aa, −SO₂N(R^bb)₂, −SO₂R^aa, −SO₂OR^aa, −OSO₂R^aa, −S(=O)R^aa, −OS(=O)R^aa, −Si(R^aa)₃, −OSi(R^aa)₃ −C(=S)N(R^bb)₂, −C(=O)SR^aa, −C(=S)SR^aa, −SC(=S)SR^aa, −SC(=O)SR^aa, −OC(=O)SR^aa, −SC(=O)OR^aa, −SC(=O)R^aa, −P(=O)(R^aa)₂, −P(=O)(OR^cc)₂, −OP(=O)(R^aa)₂, −OP(=O)(OR^cc)₂, −P(=O)(N(R^bb)₂)₂, −OP(=O)(N(R^bb)₂)₂, −NR^bbP(=O)(R^aa)₂, −NR^bbP(=O)(OR^cc)₂, −NR^bbP(=O)(N(R^bb)₂)₂, −P(R^cc)₂, −P(OR^cc)₂, −P(R^cc)₃ ⁺X⁻, −P(OR^cc)₃ ⁺X⁻, −P(R^cc)₄, −P(OR^cc)₄, −OP(R^cc)₂, −OP(R^cc)₃ ⁺X⁻, −OP(OR^cc)₂, −OP(OR^cc)₃ ⁺X⁻, −OP(R^cc)₄, −OP(OR^cc)₄, −B(R^aa)₂, −B(OR^cc)₂, −BR^aa(OR^cc), C_1–20 alkyl, C_1–20 perhaloalkyl, C_2–20 alkenyl, C_2–20 alkynyl, C_1–20 heteroalkyl, C_2–20 heteroalkenyl, C_2–20 heteroalkynyl, C_3-10 carbocyclyl, 3-14 membered heterocyclyl, C_6-14 aryl, and 5- 14 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^dd groups; wherein X⁻ is a counterion; or two geminal hydrogens on a carbon atom are replaced with the group =O, =S, =NN(R^bb)₂, =NNR^bbC(=O)R^aa, =NNR^bbC(=O)OR^aa, =NNR^bbS(=O)₂R^aa, =NR^bb, or =NOR^cc; wherein: each instance of R^aa is, independently, selected from C_1–20 alkyl, C_1–20 perhaloalkyl, C_2–20 alkenyl, C_2–20 alkynyl, C_1–20 heteroalkyl, C_2–20 heteroalkenyl, C_2–20 heteroalkynyl, C_3-10 carbocyclyl, 3-14 membered heterocyclyl, C_6-14 aryl, and 5-14 membered heteroaryl, or two R^aa groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^dd groups; each instance of R^bb is, independently, selected from hydrogen, −OH, −OR^aa, −N(R^cc)₂, −CN, −C(=O)R^aa, −C(=O)N(R^cc)₂, −CO₂R^aa, −SO₂R^aa, −C(=NR^cc)OR^aa, −C(=NR^cc)N(R^cc)₂, −SO₂N(R^cc)₂, −SO₂R^cc, −SO₂OR^cc, −SOR^aa, −C(=S)N(R^cc)₂, −C(=O)SR^cc, −C(=S)SR^cc, −P(=O)(R^aa)₂, −P(=O)(OR^cc)₂, −P(=O)(N(R^cc)₂)₂, C_1–20 alkyl, C_1–20 perhaloalkyl, C_2–20 alkenyl, C_2–20 alkynyl, C_1–20 heteroalkyl, C_2–20 heteroalkenyl, C_2–20 heteroalkynyl, C_3-10 carbocyclyl, 3-14 membered heterocyclyl, C_6-14 aryl, and 5-14 membered heteroaryl, or two R^bb groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^dd groups; each instance of R^cc is, independently, selected from hydrogen, C_1–20 alkyl, C_1–20 perhaloalkyl, C_2–20 alkenyl, C_2–20 alkynyl, C_1–20 heteroalkyl, C_2–20 heteroalkenyl, C_2–20 heteroalkynyl, C_3-10 carbocyclyl, 3-14 membered heterocyclyl, C_6-14 aryl, and 5-14 membered heteroaryl, or two R^cc groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^dd groups; each instance of R^dd is, independently, selected from halogen, −CN, −NO₂, −N₃, −SO₂H, −SO₃H, −OH, −OR^ee, −ON(R^ff)₂, −N(R^ff)₂, −N(R^ff)₃ ⁺X⁻, −N(OR^ee)R^ff, −SH, −SR^ee, −SSR^ee, −C(=O)R^ee, −CO₂H, −CO₂R^ee, −OC(=O)R^ee, −OCO₂R^ee, −C(=O)N(R^ff)₂, −OC(=O)N(R^ff)₂, −NR^ffC(=O)R^ee, −NR^ffCO₂R^ee, −NR^ffC(=O)N(R^ff)₂, −C(=NR^ff)OR^ee, −OC(=NR^ff)R^ee, −OC(=NR^ff)OR^ee, −C(=NR^ff)N(R^ff)₂, −OC(=NR^ff)N(R^ff)₂, −NR^ffC(=NR^ff)N(R^ff)₂, −NR^ffSO₂R^ee, −SO₂N(R^ff)₂, −SO₂R^ee, −SO₂OR^ee, −OSO₂R^ee, −S(=O)R^ee, −Si(R^ee)₃, −OSi(R^ee)₃, −C(=S)N(R^ff)₂, −C(=O)SR^ee, −C(=S)SR^ee, −SC(=S)SR^ee, −P(=O)(OR^ee)₂, −P(=O)(R^ee)₂, −OP(=O)(R^ee)₂, −OP(=O)(OR^ee)₂, C_1–10 alkyl, C_1–10 perhaloalkyl, C_2–10 alkenyl, C_2–10 alkynyl, C_1–10 heteroalkyl, C_2–10 heteroalkenyl, C_2–10 heteroalkynyl, C_3-10 carbocyclyl, 3-10 membered heterocyclyl, C_6-10 aryl, and 5-10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^gg groups, or two geminal R^dd substituents are joined to form =O or =S; wherein X⁻ is a counterion; each instance of R^ee is, independently, selected from C_1–10 alkyl, C_1–10 perhaloalkyl, C_2–10 alkenyl, C_2–10 alkynyl, C_1–10 heteroalkyl, C_2–10 heteroalkenyl, C_2–10 heteroalkynyl, C_3-10 carbocyclyl, C_6-10 aryl, 3-10 membered heterocyclyl, and 3-10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^gg groups; each instance of R^ff is, independently, selected from hydrogen, C_1–10 alkyl, C_1–10 perhaloalkyl, C_2–10 alkenyl, C_2–10 alkynyl, C_1–10 heteroalkyl, C_2–10 heteroalkenyl, C_2–10 heteroalkynyl, C_3-10 carbocyclyl, 3-10 membered heterocyclyl, C_6-10 aryl, and 5-10 membered heteroaryl, or two R^ff groups are joined to form a 3-10 membered heterocyclyl or 5-10 membered   heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^gg groups; each instance of R^gg is, independently, halogen, −CN, −NO₂, −N₃, −SO₂H, −SO₃H, −OH, −OC_1–6 alkyl, −ON(C_1–6 alkyl)₂, −N(C_1–6 alkyl)₂, −N(C_1–6 alkyl)₃ ⁺X⁻, −NH(C_1–6 alkyl)₂ ⁺X⁻, −NH₂(C_1–6 alkyl) ⁺X⁻, −NH₃ ⁺X⁻, −N(OC_1–6 alkyl)(C_1–6 alkyl), −N(OH)(C_1–6 alkyl), −NH(OH), −SH, −SC_1–6 alkyl, −SS(C_1–6 alkyl), −C(=O)(C_1–6 alkyl), −CO₂H, −CO₂(C_1–6 alkyl), −OC(=O)(C_1–6 alkyl), −OCO₂(C_1–6 alkyl), −C(=O)NH₂, −C(=O)N(C_1–6 alkyl)₂, −OC(=O)NH(C_1–6 alkyl), −NHC(=O)( C_1–6 alkyl), −N(C_1–6 alkyl)C(=O)( C_1–6 alkyl), −NHCO₂(C_1–6 alkyl), −NHC(=O)N(C_1–6 alkyl)₂, −NHC(=O)NH(C_1–6 alkyl), −NHC(=O)NH₂, −C(=NH)O(C_1–6 alkyl), −OC(=NH)(C_1–6 alkyl), −OC(=NH)OC_1–6 alkyl, −C(=NH)N(C_1–6 alkyl)₂, −C(=NH)NH(C_1–6 alkyl), −C(=NH)NH₂, −OC(=NH)N(C_1–6 alkyl)₂, −OC(NH)NH(C_1–6 alkyl), −OC(NH)NH₂, −NHC(NH)N(C_1–6 alkyl)₂, −NHC(=NH)NH₂, −NHSO₂(C_1–6 alkyl), −SO₂N(C_1–6 alkyl)₂, −SO₂NH(C_1–6 alkyl), −SO₂NH₂, −SO₂C_1–6 alkyl, −SO₂OC_1–6 alkyl, −OSO₂C_1–6 alkyl, −SOC_1–6 alkyl, −Si(C_1–6 alkyl)₃, −OSi(C_1–6 alkyl)₃ −C(=S)N(C_1–6 alkyl)₂, C(=S)NH(C_1–6 alkyl), C(=S)NH₂, −C(=O)S(C_1–6 alkyl), −C(=S)SC_1–6 alkyl, −SC(=S)SC_1–6 alkyl, −P(=O)(OC_1–6 alkyl)₂, −P(=O)(C_1–6 alkyl)₂, −OP(=O)(C_1–6 alkyl)₂, −OP(=O)(OC_1–6 alkyl)₂, C_1–10 alkyl, C_1–10 perhaloalkyl, C_2–10 alkenyl, C_2–10 alkynyl, C_1–10 heteroalkyl, C_2–10 heteroalkenyl, C_2–10 heteroalkynyl, C_3-10 carbocyclyl, C_6-10 aryl, 3-10 membered heterocyclyl, or 5-10 membered heteroaryl; or two geminal R^gg substituents can be joined to form =O or =S; and each X⁻ is a counterion. [35] In certain embodiments, the molecular weight of a substituent (e.g., carbon atom substituent) is lower than 250, lower than 200, lower than 150, lower than 100, or lower than 50 g/mol. In certain embodiments, a substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, iodine, oxygen, sulfur, nitrogen, and/or silicon atoms. In certain embodiments, a substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, iodine, oxygen, sulfur, and/or nitrogen atoms. In certain embodiments, a substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, and/or iodine atoms. In certain embodiments, a substituent consists of carbon, hydrogen, fluorine, and/or chlorine atoms. [36] In certain embodiments, exemplary carbon atom substituents include halogen, −CN, −NO₂, −N₃, −SO₂H, −SO₃H, −OH, −OR^aa, −N(R^bb)₂, −N(R^bb)₃ ⁺X⁻, −SH, −SR^aa, −C(=O)R^aa, −CO₂H, −CHO, −CO₂R^aa, −OC(=O)R^aa, −OCO₂R^aa, −C(=O)N(R^bb)₂, −OC(=O)N(R^bb)₂, −NR^bbC(=O)R^aa, −NR^bbCO₂R^aa, −NR^bbC(=O)N(R^bb)₂, −NR^bbSO₂R^aa, −SO₂N(R^bb)₂, −SO₂R^aa, −SO₂OR^aa, −OSO₂R^aa, −S(=O)R^aa, −OS(=O)R^aa, −Si(R^aa)₃, −OSi(R^aa)₃, −P(=O)(R^aa)₂, −P(=O)(OR^cc)₂, −OP(=O)(R^aa)₂, −OP(=O)(OR^cc)₂, −P(=O)(N(R^bb)₂)₂, −OP(=O)(N(R^bb)₂)₂, −NR^bbP(=O)(R^aa)₂, −NR^bbP(=O)(OR^cc)₂, −NR^bbP(=O)(N(R^bb)₂)₂, −B(R^aa)₂, −B(OR^cc)₂, −BR^aa(OR^cc), C_1-10 alkyl, C_1-10 perhaloalkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_1-10 heteroalkyl, C_2-10 heteroalkenyl, C_2-10 heteroalkynyl, C_3-10 carbocyclyl, 3-14 membered heterocyclyl, C_6-14 aryl, and 5-14 membered heteroaryl; wherein X⁻ is a counterion;   or two geminal hydrogens on a carbon atom are replaced with the group =O, =S, =NN(R^bb)₂, =NNR^bbC(=O)R^aa, =NNR^bbC(=O)OR^aa, =NNR^bbS(=O)₂R^aa, =NR^bb, or =NOR^cc; each instance of R^aa is, independently, selected from C_1-10 alkyl, C_1-10 perhaloalkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_1-10 heteroalkyl, C_2-10 heteroalkenyl, C_2-10 heteroalkynyl, C_3-10 carbocyclyl, 3-14 membered heterocyclyl, C_6-14 aryl, and 5-14 membered heteroaryl, or two R^aa groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; each instance of R^bb is, independently, selected from hydrogen, −OH, −OR^aa, −N(R^cc)₂, −CN, −C(=O)R^aa, −C(=O)N(R^cc)₂, −CO₂R^aa, −SO₂R^aa, −C(=NR^cc)OR^aa, −C(=NR^cc)N(R^cc)₂, −SO₂N(R^cc)₂, −SO₂R^cc, −SO₂OR^cc, −SOR^aa, −P(=O)(R^aa)₂, −P(=O)(OR^cc)₂, −P(=O)(N(R^cc)₂)₂, C_1-10 alkyl, C_1-10 perhaloalkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_1-10 heteroalkyl, C_2-10 heteroalkenyl, C_2-10 heteroalkynyl, C_3-10 carbocyclyl, 3-14 membered heterocyclyl, C_6-14 aryl, and 5-14 membered heteroaryl, or two R^bb groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; and each instance of R^cc is, independently, selected from hydrogen, C_1-10 alkyl, C_1-10 perhaloalkyl, C_{2- 10} alkenyl, C_2-10 alkynyl, C_1-10 heteroalkyl, C_2-10 heteroalkenyl, C_2-10 heteroalkynyl, C_3-10 carbocyclyl, 3-14 membered heterocyclyl, C_6-14 aryl, and 5-14 membered heteroaryl, or two R^cc groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring. [37] In certain embodiments, each carbon atom substituent is independently halogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C_1-6 alkyl, −OR^aa, −SR^aa, −N(R^bb)₂, –CN, –NO₂, −C(=O)R^aa, −CO₂R^aa, −C(=O)N(R^bb)₂, −OC(=O)R^aa, −OCO₂R^aa, −OC(=O)N(R^bb)₂, −NR^bbC(=O)R^aa, −NR^bbCO₂R^aa, or −NR^bbC(=O)N(R^bb)₂. In certain embodiments, each carbon atom substituent is independently halogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C_1–10 alkyl, −OR^aa, −SR^aa, −N(R^bb)₂, –CN, –NO₂, −C(=O)R^aa, −CO₂R^aa, −C(=O)N(R^bb)₂, −OC(=O)R^aa, −OCO₂R^aa, −OC(=O)N(R^bb)₂, −NR^bbC(=O)R^aa, −NR^bbCO₂R^aa, or −NR^bbC(=O)N(R^bb)₂, wherein R^aa is hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C_1–6 alkyl, an oxygen protecting group (e.g., silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl) when attached to an oxygen atom, or a sulfur protecting group (e.g., acetamidomethyl, t-Bu, 3-nitro-2-pyridine sulfenyl, 2-pyridine-sulfenyl, or triphenylmethyl) when attached to a sulfur atom; and each R^bb is independently hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C_1–6 alkyl, or a nitrogen protecting group (e.g., Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts). In certain embodiments, each carbon atom substituent is independently halogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C_1-6 alkyl, −OR^aa, −SR^aa, −N(R^bb)₂, –CN, or –NO₂. In certain embodiments, each carbon atom substituent is independently halogen, substituted (e.g., substituted with one or more halogen moieties) or unsubstituted C_1–6 alkyl, −OR^aa, −SR^aa, −N(R^bb)₂, –CN, –SCN, or –NO₂, wherein R^aa is hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C_1–6 alkyl, an oxygen protecting group (e.g., silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl) when attached to an oxygen atom, or a sulfur protecting group (e.g., acetamidomethyl, t-Bu, 3-nitro-2-pyridine sulfenyl, 2-pyridine-sulfenyl, or triphenylmethyl) when attached to a sulfur atom; and each R^bb is   independently hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C_1–10 alkyl, or a nitrogen protecting group (e.g., Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts). [38] In certain embodiments, the substituent present on the nitrogen atom is a nitrogen protecting group (also referred to herein as an “amino protecting group”). Nitrogen protecting groups include −OH, −OR^aa, −N(R^cc)₂, −C(=O)R^aa, −C(=O)N(R^cc)₂, −CO₂R^aa, −SO₂R^aa, −C(=NR^cc)R^aa, −C(=NR^cc)OR^aa, −C(=NR^cc)N(R^cc)₂, −SO₂N(R^cc)₂, −SO₂R^cc, −SO₂OR^cc, −SOR^aa, −C(=S)N(R^cc)₂, −C(=O)SR^cc, −C(=S)SR^cc, C_1–10 alkyl (e.g., aralkyl, heteroaralkyl), C_1–20 alkenyl, C_1–20 alkynyl, hetero C_1–20 alkyl, hetero C_1–20 alkenyl, hetero C_1–20 alkynyl, C_3-10 carbocyclyl, 3-14 membered heterocyclyl, C_6-14 aryl, and 5-14 membered heteroaryl groups, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aralkyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^dd groups, and wherein R^aa, R^bb, R^cc and R^dd are as defined herein. Nitrogen protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3^rd edition, John Wiley & Sons, 1999, incorporated herein by reference. [39] For example, in certain embodiments, at least one nitrogen protecting group is an amide group (e.g., a moiety that includes the nitrogen atom to which the nitrogen protecting groups (e.g., −C(=O)R^aa) is directly attached). In certain such embodiments, each nitrogen protecting group, together with the nitrogen atom to which the nitrogen protecting group is attached, is independently selected from the group consisting of formamide, acetamide, chloroacetamide, trichloroacetamide, trifluoroacetamide, phenylacetamide, 3-phenylpropanamide, picolinamide, 3-pyridylcarboxamide, N-benzoylphenylalanyl derivatives, benzamide, p-phenylbenzamide, o-nitophenylacetamide, o-nitrophenoxyacetamide, acetoacetamide, (N’-dithiobenzyloxyacylamino)acetamide, 3-(p-hydroxyphenyl)propanamide, 3-(o- nitrophenyl)propanamide, 2-methyl-2-(o-nitrophenoxy)propanamide, 2-methyl-2-(o- phenylazophenoxy)propanamide, 4-chlorobutanamide, 3-methyl-3-nitrobutanamide, o-nitrocinnamide, N-acetylmethionine derivatives, o-nitrobenzamide, and o-(benzoyloxymethyl)benzamide. [40] In certain embodiments, at least one nitrogen protecting group is a carbamate group (e.g., a moiety that includes the nitrogen atom to which the nitrogen protecting groups (e.g., −C(=O)OR^aa) is directly attached). In certain such embodiments, each nitrogen protecting group, together with the nitrogen atom to which the nitrogen protecting group is attached, is independently selected from the group consisting of methyl carbamate, ethyl carbamate, 9-fluorenylmethyl carbamate (Fmoc), 9-(2-sulfo)fluorenylmethyl carbamate, 9-(2,7-dibromo)fluoroenylmethyl carbamate, 2,7-di-t-butyl-[9-(10,10-dioxo-10,10,10,10- tetrahydrothioxanthyl)]methyl carbamate (DBD-Tmoc), 4-methoxyphenacyl carbamate (Phenoc), 2,2,2- trichloroethyl carbamate (Troc), 2-trimethylsilylethyl carbamate (Teoc), 2-phenylethyl carbamate (hZ), 1–(1-adamantyl)-1-methylethyl carbamate (Adpoc), 1,1-dimethyl-2-haloethyl carbamate, 1,1-dimethyl- 2,2-dibromoethyl carbamate (DB-t-BOC), 1,1-dimethyl-2,2,2-trichloroethyl carbamate (TCBOC), 1- methyl-1-(4-biphenylyl)ethyl carbamate (Bpoc), 1-(3,5-di-t-butylphenyl)-1-methylethyl carbamate (t- Bumeoc), 2-(2¢- and 4¢-pyridyl)ethyl carbamate (Pyoc), 2-(N,N-dicyclohexylcarboxamido)ethyl   carbamate, t-butyl carbamate (BOC or Boc), 1-adamantyl carbamate (Adoc), vinyl carbamate (Voc), allyl carbamate (Alloc), 1-isopropylallyl carbamate (Ipaoc), cinnamyl carbamate (Coc), 4-nitrocinnamyl carbamate (Noc), 8-quinolyl carbamate, N-hydroxypiperidinyl carbamate, alkyldithio carbamate, benzyl carbamate (Cbz), p-methoxybenzyl carbamate (Moz), p-nitrobenzyl carbamate, p-bromobenzyl carbamate, p-chlorobenzyl carbamate, 2,4-dichlorobenzyl carbamate, 4-methylsulfinylbenzyl carbamate (Msz), 9-anthrylmethyl carbamate, diphenylmethyl carbamate, 2-methylthioethyl carbamate, 2- methylsulfonylethyl carbamate, 2-(p-toluenesulfonyl)ethyl carbamate, [2-(1,3-dithianyl)]methyl carbamate (Dmoc), 4-methylthiophenyl carbamate (Mtpc), 2,4-dimethylthiophenyl carbamate (Bmpc), 2- phosphonioethyl carbamate (Peoc), 2-triphenylphosphonioisopropyl carbamate (Ppoc), 1,1-dimethyl-2- cyanoethyl carbamate, m-chloro-p-acyloxybenzyl carbamate, p-(dihydroxyboryl)benzyl carbamate, 5- benzisoxazolylmethyl carbamate, 2-(trifluoromethyl)-6-chromonylmethyl carbamate (Tcroc), m- nitrophenyl carbamate, 3,5-dimethoxybenzyl carbamate, o-nitrobenzyl carbamate, 3,4-dimethoxy-6- nitrobenzyl carbamate, phenyl(o-nitrophenyl)methyl carbamate, t-amyl carbamate, S-benzyl thiocarbamate, p-cyanobenzyl carbamate, cyclobutyl carbamate, cyclohexyl carbamate, cyclopentyl carbamate, cyclopropylmethyl carbamate, p-decyloxybenzyl carbamate, 2,2-dimethoxyacylvinyl carbamate, o-(N,N-dimethylcarboxamido)benzyl carbamate, 1,1-dimethyl-3-(N,N- dimethylcarboxamido)propyl carbamate, 1,1-dimethylpropynyl carbamate, di(2-pyridyl)methyl carbamate, 2-furanylmethyl carbamate, 2-iodoethyl carbamate, isoborynl carbamate, isobutyl carbamate, isonicotinyl carbamate, p-(p’-methoxyphenylazo)benzyl carbamate, 1-methylcyclobutyl carbamate, 1- methylcyclohexyl carbamate, 1-methyl-1-cyclopropylmethyl carbamate, 1-methyl-1-(3,5- dimethoxyphenyl)ethyl carbamate, 1-methyl-1-(p-phenylazophenyl)ethyl carbamate, 1-methyl-1- phenylethyl carbamate, 1-methyl-1-(4-pyridyl)ethyl carbamate, phenyl carbamate, p-(phenylazo)benzyl carbamate, 2,4,6-tri-t-butylphenyl carbamate, 4-(trimethylammonium)benzyl carbamate, and 2,4,6- trimethylbenzyl carbamate. [41] In certain embodiments, at least one nitrogen protecting group is a sulfonamide group (e.g., a moiety that includes the nitrogen atom to which the nitrogen protecting groups (e.g., −S(=O)₂R^aa) is directly attached). In certain such embodiments, each nitrogen protecting group, together with the nitrogen atom to which the nitrogen protecting group is attached, is independently selected from the group consisting of p-toluenesulfonamide (Ts), benzenesulfonamide, 2,3,6-trimethyl-4- methoxybenzenesulfonamide (Mtr), 2,4,6-trimethoxybenzenesulfonamide (Mtb), 2,6-dimethyl-4- methoxybenzenesulfonamide (Pme), 2,3,5,6-tetramethyl-4-methoxybenzenesulfonamide (Mte), 4- methoxybenzenesulfonamide (Mbs), 2,4,6-trimethylbenzenesulfonamide (Mts), 2,6-dimethoxy-4- methylbenzenesulfonamide (iMds), 2,2,5,7,8-pentamethylchroman-6-sulfonamide (Pmc), methanesulfonamide (Ms), β-trimethylsilylethanesulfonamide (SES), 9-anthracenesulfonamide, 4-(4¢,8¢- dimethoxynaphthylmethyl)benzenesulfonamide (DNMBS), benzylsulfonamide, trifluoromethylsulfonamide, and phenacylsulfonamide. [42] In certain embodiments, each nitrogen protecting group, together with the nitrogen atom to which the nitrogen protecting group is attached, is independently selected from the group consisting of   phenothiazinyl-(10)-acyl derivatives, N’-p-toluenesulfonylaminoacyl derivatives, N’- phenylaminothioacyl derivatives, N-benzoylphenylalanyl derivatives, N-acetylmethionine derivatives, 4,5-diphenyl-3-oxazolin-2-one, N-phthalimide, N-dithiasuccinimide (Dts), N-2,3-diphenylmaleimide, N- 2,5-dimethylpyrrole, N-1,1,4,4-tetramethyldisilylazacyclopentane adduct (STABASE), 5-substituted 1,3- dimethyl-1,3,5-triazacyclohexan-2-one, 5-substituted 1,3-dibenzyl-1,3,5-triazacyclohexan-2-one, 1- substituted 3,5-dinitro-4-pyridone, N-methylamine, N-allylamine, N-[2- (trimethylsilyl)ethoxy]methylamine (SEM), N-3-acetoxypropylamine, N-(1-isopropyl-4-nitro-2-oxo-3- pyroolin-3-yl)amine, quaternary ammonium salts, N-benzylamine, N-di(4-methoxyphenyl)methylamine, N-5-dibenzosuberylamine, N-triphenylmethylamine (Tr), N-[(4-methoxyphenyl)diphenylmethyl]amine (MMTr), N-9-phenylfluorenylamine (PhF), N-2,7-dichloro-9-fluorenylmethyleneamine, N- ferrocenylmethylamino (Fcm), N-2-picolylamino N’-oxide, N-1,1-dimethylthiomethyleneamine, N- benzylideneamine, N-p-methoxybenzylideneamine, N-diphenylmethyleneamine, N-[(2- pyridyl)mesityl]methyleneamine, N-(N’,N’-dimethylaminomethylene)amine, N-p-nitrobenzylideneamine, N-salicylideneamine, N-5-chlorosalicylideneamine, N-(5-chloro-2- hydroxyphenyl)phenylmethyleneamine, N-cyclohexylideneamine, N-(5,5-dimethyl-3-oxo-1- cyclohexenyl)amine, N-borane derivatives, N-diphenylborinic acid derivatives, N- [phenyl(pentaacylchromium- or tungsten)acyl]amine, N-copper chelate, N-zinc chelate, N-nitroamine, N- nitrosoamine, amine N-oxide, diphenylphosphinamide (Dpp), dimethylthiophosphinamide (Mpt), diphenylthiophosphinamide (Ppt), dialkyl phosphoramidates, dibenzyl phosphoramidate, diphenyl phosphoramidate, benzenesulfenamide, o-nitrobenzenesulfenamide (Nps), 2,4- dinitrobenzenesulfenamide, pentachlorobenzenesulfenamide, 2-nitro-4-methoxybenzenesulfenamide, triphenylmethylsulfenamide, and 3-nitropyridinesulfenamide (Npys). In some embodiments, two instances of a nitrogen protecting group together with the nitrogen atoms to which the nitrogen protecting groups are attached are N,N’-isopropylidenediamine. [43] In certain embodiments, a nitrogen protecting group is benzyl (Bn), tert-butyloxycarbonyl (BOC), carbobenzyloxy (Cbz), 9-flurenylmethyloxycarbonyl (Fmoc), trifluoroacetyl, triphenylmethyl, acetyl (Ac), benzoyl (Bz), p-methoxybenzyl (PMB), 3,4-dimethoxybenzyl (DMPM), p-methoxyphenyl (PMP), 2,2,2-trichloroethyloxycarbonyl (Troc), triphenylmethyl (Tr), tosyl (Ts), brosyl (Bs), nosyl (Ns), mesyl (Ms), triflyl (Tf), or dansyl (Ds). In certain embodiments, at least one nitrogen protecting group is Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts. [44] In certain embodiments, the substituent present on an oxygen atom is an oxygen protecting group (also referred to herein as an “hydroxyl protecting group”). Oxygen protecting groups include −R^aa, −N(R^bb)₂, −C(=O)SR^aa, −C(=O)R^aa, −CO₂R^aa, −C(=O)N(R^bb)₂, −C(=NR^bb)R^aa, −C(=NR^bb)OR^aa, −C(=NR^bb)N(R^bb)₂, −S(=O)R^aa, −SO₂R^aa, −Si(R^aa)₃, −P(R^cc)₂, −P(R^cc)₃ ⁺X⁻, −P(OR^cc)₂, −P(OR^cc)₃ ⁺X⁻, −P(=O)(R^aa)₂, −P(=O)(OR^cc)₂, and −P(=O)(N(R^bb) ₂)₂, wherein X⁻, R^aa, R^bb, and R^cc are as defined herein. Oxygen protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3^rd edition, John Wiley & Sons, 1999, incorporated herein by reference.   [45] In certain embodiments, each oxygen protecting group, together with the oxygen atom to which the oxygen protecting group is attached, is selected from the group consisting of methoxy, methoxylmethyl (MOM), methylthiomethyl (MTM), t-butylthiomethyl, (phenyldimethylsilyl)methoxymethyl (SMOM), benzyloxymethyl (BOM), p-methoxybenzyloxymethyl (PMBM), (4-methoxyphenoxy)methyl (p-AOM), guaiacolmethyl (GUM), t-butoxymethyl, 4-pentenyloxymethyl (POM), siloxymethyl, 2- methoxyethoxymethyl (MEM), 2,2,2-trichloroethoxymethyl, bis(2-chloroethoxy)methyl, 2- (trimethylsilyl)ethoxymethyl (SEMOR), tetrahydropyranyl (THP), 3-bromotetrahydropyranyl, tetrahydrothiopyranyl, 1-methoxycyclohexyl, 4-methoxytetrahydropyranyl (MTHP), 4- methoxytetrahydrothiopyranyl, 4-methoxytetrahydrothiopyranyl S,S-dioxide, 1-[(2-chloro-4- methyl)phenyl]-4-methoxypiperidin-4-yl (CTMP), 1,4-dioxan-2-yl, tetrahydrofuranyl, tetrahydrothiofuranyl, 2,3,3a,4,5,6,7,7a-octahydro-7,8,8-trimethyl-4,7-methanobenzofuran-2-yl, 1- ethoxyethyl, 1-(2-chloroethoxy)ethyl, 1-methyl-1-methoxyethyl, 1-methyl-1-benzyloxyethyl, 1-methyl-1- benzyloxy-2-fluoroethyl, 2,2,2-trichloroethyl, 2-trimethylsilylethyl, 2-(phenylselenyl)ethyl, t-butyl, allyl, p-chlorophenyl, p-methoxyphenyl, 2,4-dinitrophenyl, benzyl (Bn), p-methoxybenzyl (PMB), 3,4- dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6-dichlorobenzyl, p-cyanobenzyl, p- phenylbenzyl, 2-picolyl, 4-picolyl, 3-methyl-2-picolyl N-oxido, diphenylmethyl, p,p’-dinitrobenzhydryl, 5-dibenzosuberyl, triphenylmethyl, α-naphthyldiphenylmethyl, p-methoxyphenyldiphenylmethyl, di(p- methoxyphenyl)phenylmethyl, tri(p-methoxyphenyl)methyl, 4-(4’- bromophenacyloxyphenyl)diphenylmethyl, 4,4′,4″-tris(4,5-dichlorophthalimidophenyl)methyl, 4,4′,4″- tris(levulinoyloxyphenyl)methyl, 4,4′,4″-tris(benzoyloxyphenyl)methyl, 4,4'-Dimethoxy-3"'-[N- (imidazolylmethyl) ]trityl Ether (IDTr-OR), 4,4'-Dimethoxy-3"'-[N-(imidazolylethyl)carbamoyl]trityl Ether (IETr-OR), 1,1-bis(4-methoxyphenyl)-1′-pyrenylmethyl, 9-anthryl, 9-(9-phenyl)xanthenyl, 9-(9- phenyl-10-oxo)anthryl, 1,3-benzodithiolan-2-yl, benzisothiazolyl S,S-dioxido, trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), dimethylisopropylsilyl (IPDMS), diethylisopropylsilyl (DEIPS), dimethylthexylsilyl, t-butyldimethylsilyl (TBDMS), t-butyldiphenylsilyl (TBDPS), tribenzylsilyl, tri-p-xylylsilyl, triphenylsilyl, diphenylmethylsilyl (DPMS), t-butylmethoxyphenylsilyl (TBMPS), formate, benzoylformate, acetate, chloroacetate, dichloroacetate, trichloroacetate, trifluoroacetate, methoxyacetate, triphenylmethoxyacetate, phenoxyacetate, p-chlorophenoxyacetate, 3- phenylpropionate, 4-oxopentanoate (levulinate), 4,4-(ethylenedithio)pentanoate (levulinoyldithioacetal), pivaloate, adamantoate, crotonate, 4-methoxycrotonate, benzoate, p-phenylbenzoate, 2,4,6- trimethylbenzoate (mesitoate), methyl carbonate, 9-fluorenylmethyl carbonate (Fmoc), ethyl carbonate, 2,2,2-trichloroethyl carbonate (Troc), 2-(trimethylsilyl)ethyl carbonate (TMSEC), 2-(phenylsulfonyl) ethyl carbonate (Psec), 2-(triphenylphosphonio) ethyl carbonate (Peoc), isobutyl carbonate, vinyl carbonate, allyl carbonate, t-butyl carbonate (BOC or Boc), p-nitrophenyl carbonate, benzyl carbonate, p- methoxybenzyl carbonate, 3,4-dimethoxybenzyl carbonate, o-nitrobenzyl carbonate, p-nitrobenzyl carbonate, S-benzyl thiocarbonate, 4-ethoxy-1-napththyl carbonate, methyl dithiocarbonate, 2- iodobenzoate, 4-azidobutyrate, 4-nitro-4-methylpentanoate, o-(dibromomethyl)benzoate, 2- formylbenzenesulfonate, 2-(methylthiomethoxy)ethyl carbonate (MTMEC-OR), 4-   (methylthiomethoxy)butyrate, 2-(methylthiomethoxymethyl)benzoate, 2,6-dichloro-4- methylphenoxyacetate, 2,6-dichloro-4-(1,1,3,3-tetramethylbutyl)phenoxyacetate, 2,4-bis(1,1- dimethylpropyl)phenoxyacetate, chlorodiphenylacetate, isobutyrate, monosuccinoate, (E)-2-methyl-2- butenoate, o-(methoxyacyl)benzoate, α-naphthoate, nitrate, alkyl N,N,N’,N’- tetramethylphosphorodiamidate, alkyl N-phenylcarbamate, borate, dimethylphosphinothioyl, alkyl 2,4- dinitrophenylsulfenate, sulfate, methanesulfonate (mesylate), benzylsulfonate, and tosylate (Ts). [46] In certain embodiments, an oxygen protecting group is silyl. In certain embodiments, an oxygen protecting group is t-butyldiphenylsilyl (TBDPS), t-butyldimethylsilyl (TBDMS), triisoproylsilyl (TIPS), triphenylsilyl (TPS), triethylsilyl (TES), trimethylsilyl (TMS), triisopropylsiloxymethyl (TOM), acetyl (Ac), benzoyl (Bz), allyl carbonate, 2,2,2-trichloroethyl carbonate (Troc), 2-trimethylsilylethyl carbonate, methoxymethyl (MOM), 1-ethoxyethyl (EE), 2-methyoxy-2-propyl (MOP), 2,2,2-trichloroethoxyethyl, 2-methoxyethoxymethyl (MEM), 2-trimethylsilylethoxymethyl (SEM), methylthiomethyl (MTM), tetrahydropyranyl (THP), tetrahydrofuranyl (THF), p-methoxyphenyl (PMP), triphenylmethyl (Tr), methoxytrityl (MMT), dimethoxytrityl (DMT), allyl, p-methoxybenzyl (PMB), t-butyl, benzyl (Bn), allyl, or pivaloyl (Piv). In certain embodiments, at least one oxygen protecting group is silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl. [47] In certain embodiments, the substituent present on a sulfur atom is a sulfur protecting group (also referred to as a “thiol protecting group”). In some embodiments, each sulfur protecting group is selected from the group consisting of −R^aa, −N(R^bb)₂, −C(=O)SR^aa, −C(=O)R^aa, −CO₂R^aa, −C(=O)N(R^bb)₂, −C(=NR^bb)R^aa, −C(=NR^bb)OR^aa, −C(=NR^bb)N(R^bb)₂, −S(=O)R^aa, −SO₂R^aa, −Si(R^aa)₃, −P(R^cc)₂, −P(R^cc)₃ ⁺X⁻, −P(OR^cc)₂, −P(OR^cc)₃ ⁺X⁻, −P(=O)(R^aa)₂, −P(=O)(OR^cc)₂, and −P(=O)(N(R^bb) ₂)₂, wherein R^aa, R^bb, and R^cc are as defined herein. Sulfur protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3^rd edition, John Wiley & Sons, 1999, incorporated herein by reference. [48] In certain embodiments, a sulfur protecting group is acetamidomethyl, t-Bu, 3-nitro-2-pyridine sulfenyl, 2-pyridine-sulfenyl, or triphenylmethyl. [49] A “counterion” or “anionic counterion” is a negatively charged group associated with a positively charged group in order to maintain electronic neutrality. An anionic counterion may be monovalent (e.g., including one formal negative charge). An anionic counterion may also be multivalent (e.g., including more than one formal negative charge), such as divalent or trivalent. Exemplary counterions include halide ions (e.g., F^–, Cl^–, Br^–, I^–), NO₃ ^–, ClO₄ ^–, OH^–, H₂PO₄ ^–, HCO₃ ⁻ , HSO₄ ^–, sulfonate ions (e.g., methansulfonate, trifluoromethanesulfonate, p–toluenesulfonate, benzenesulfonate, 10–camphor sulfonate, naphthalene–2–sulfonate, naphthalene–1–sulfonic acid–5–sulfonate, ethan–1–sulfonic acid–2– sulfonate, and the like), carboxylate ions (e.g., acetate, propanoate, benzoate, glycerate, lactate, tartrate, glycolate, gluconate, and the like), BF₄ ⁻, PF₄ ^–, PF₆ ^–, AsF₆ ^–, SbF₆ ^–, B[3,5-(CF₃)₂C₆H₃]₄]^–, B(C₆F₅)₄ ⁻, BPh₄ ^– , Al(OC(CF₃)₃)₄ ^–, and carborane anions (e.g., CB₁₁H₁₂ ^– or (HCB₁₁Me₅Br₆)^–). Exemplary counterions which may be multivalent include CO₃ ²⁻, HPO₄ ²⁻, PO₄ ³⁻ , B₄O₇ ²⁻, SO₄ ²⁻, S₂O₃ ²⁻, carboxylate anions (e.g.,   tartrate, citrate, fumarate, maleate, malate, malonate, gluconate, succinate, glutarate, adipate, pimelate, suberate, azelate, sebacate, salicylate, phthalates, aspartate, glutamate, and the like), and carboranes. [50] As used herein, the term “salt” refers to any and all salts and encompasses pharmaceutically acceptable salts. Salts include ionic compounds that result from the neutralization reaction of an acid and a base. A salt is composed of one or more cations (positively charged ions) and one or more anions (negative ions) so that the salt is electrically neutral (without a net charge). Salts of the compounds of the present disclosure include those derived from inorganic and organic acids and bases. Examples of acid addition salts are salts of an amino group formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or with organic acids, such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid or by using other methods known in the art such as ion exchange. Other salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2– hydroxy–ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2–naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3–phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, hippurate, and the like. Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N⁺(C_1–4 alkyl)₄ salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further salts include ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate. [51] The term “pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19, incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of the present disclosure include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid or with organic acids, such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid or by using other methods known in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate,   lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p- toluenesulfonate, undecanoate, valerate salts, and the like. Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium, and N⁺(C_1-4 alkyl)₄ ⁻ salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate. [52] A “leaving group” (LG) is an art-understood term referring to an atomic or molecular fragment that departs with a pair of electrons in heterolytic bond cleavage, wherein the molecular fragment is an anion or neutral molecule. As used herein, a leaving group can be an atom or a group capable of being displaced by a nucleophile. See e.g., Smith, March Advanced Organic Chemistry 6th ed. (501–502). Exemplary leaving groups include, but are not limited to, halo (e.g., fluoro, chloro, bromo, iodo) and activated substituted hydroxyl groups (e.g., –OC(=O)SR^aa, –OC(=O)R^aa, –OCO₂R^aa, –OC(=O)N(R^bb)₂, – OC(=NR^bb)R^aa, –OC(=NR^bb)OR^aa, –OC(=NR^bb)N(R^bb)₂, –OS(=O)R^aa, –OSO₂R^aa, –OP(R^cc)₂, –OP(R^cc)₃, – OP(=O)₂R^aa, –OP(=O)(R^aa)₂, –OP(=O)(OR^cc)₂, –OP(=O)₂N(R^bb)₂, and –OP(=O)(NR^bb)₂, wherein R^aa, R^bb, and R^cc are as defined herein). Additional examples of suitable leaving groups include, but are not limited to, halogen alkoxycarbonyloxy, aryloxycarbonyloxy, alkanesulfonyloxy, arenesulfonyloxy, alkyl- carbonyloxy (e.g., acetoxy), arylcarbonyloxy, aryloxy, methoxy, N,O-dimethylhydroxylamino, pixyl, and haloformates. In some embodiments, the leaving group is a sulfonic acid ester, such as toluenesulfonate (tosylate, –OTs), methanesulfonate (mesylate, –OMs), p-bromobenzenesulfonyloxy (brosylate, –OBs), – OS(=O)₂(CF₂)₃CF₃ (nonaflate, –ONf), or trifluoromethanesulfonate (triflate, –OTf). _{[53] In certain embodiments, a leaving group is of the formula:}

R^LG is R^bb, hydrogen, optionally substituted alkyl, optionally substituted acyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted heterocyclyl, or optionally substituted heteroaryl; and each X^LG is independently halogen. [54] In certain embodiments, R^LG is hydrogen. In certain embodiments, RLG is optionally substituted aryl. In certain embodiments, R^LG is optionally substituted phenyl. In certain embodiments, R^LG is phenyl (Ph). In certain embodiments, each X^LG is –Cl. In certain embodiments, each X^LG is –F. NH _{[55] In certain embodiments, a leaving group is of the formula:}

_{In certain embodiments, a leaving group is of the formula:}

  [56] In certain embodiments, a leaving group is –SR^S, wherein R^S is R^aa, hydrogen, optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted heterocyclyl, or optionally substituted heteroaryl. In certain embodiments, R^S is optionally substituted aryl. In certain embodiments, R^S is optionally substituted phenyl. In certain embodiments, R^S is mono-, di-, or tri- substituted phenyl. In certain embodiments, R^S is disubstituted phenyl. In certain embodiments, R^S is 2,6- S

disubstituted phenyl. In certain embodiments, R is of the formula: , wherein each instance of R'' is independently C_1-6 alkyl. In certain embodiments, R^S is:

dimethylphenyl; “DMP”). In certain embodiments, R^S is phenyl (Ph). In certain embodiments, R^S is p-toluene (Tol). [57] In certain embodiments, R^S is optionally substituted alkyl. In certain embodiments, R^S is optionally substituted C_1-6 alkyl. In certain embodiments, R^S is unsubstituted C_1-6 alkyl. In certain embodiments, R^S is optionally substituted C_1-4 alkyl. In certain embodiments, R^S is unsubstituted C_1-4 alkyl (e.g., methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl). In certain embodiments, R^S is methyl (Me). In certain embodiments, R^S is ethyl (Me). [58] In certain embodiments, a leaving group is:

[59] These and other embodiments (including exemplary substituents) are described in more detail in the Detailed Description, Examples, Drawings, and Claims. The embodiments provided herein are not limited in any manner by the above exemplary listing of substituents. BRIEF DESCRIPTION OF THE DRAWINGS [60] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments of the invention and together with the description, provide non-limiting examples of the invention. [61] Figure 1 shows a general retrosynthetic scheme for the synthesis of C2-O-sLe^X-Thr-COOH. [62] Figure 2 shows the synthesis of disaccharide building blocks. The reagents and conditions were: [a] i.19, NIS, TfOH, -30°C, 0.5 hours ii. Et₃SiH, TfOH, CH₂Cl₂, -78°C, 5 hours, 71%, for 21 over two steps or i.20, 0°C TMSOTf , 0.5 hours ii. Et₃SiH, TfOH, CH₂Cl₂, 5 hours, -78°C, 64% for 22 and 61% for 6 over two steps. [b] i.24, NIS, TfOH, 0°C, 1 hour, 81% ii. N₂H₄.H₂O, MeOH, rt, 3 hours, 91%. [c] i.26, TMSOTf, 0°C, 0.5 hours, 79% ii. TBAHF, THF, rt, 2 hours, 86%. [63] Figure 3 shows the multi-gram scale convergent synthesis of C2-O-sLe^X-Thr-COOH. The reagents and conditions were: [a] i.5 [1 equivalent], TMSOTf [0.15 mol%], 0°C, 0.5 hours, 68% with for 27 [1.5   equivalents], 52% for 28 [1.5 equivalents] and 77% for 29 [1.5 equivalents]. [b] DDQ, aq. CH₂Cl₂, 0°C to rt, 10 hours iii. Ac₂O, pyridine, DMAP, rt, 6 hours, 74% for 30 over two steps, 71% for 31 over two steps, 92% for 3 over two steps. [c] i.3 [1 equivalent] or 28 [1 equivalent], NIS [2 equivalents], TfOH [0.2 mol%], 0°C, 1 hour ii. Ac₂O, DMAP, pyridine, 69% from 31 over two steps and 88% from 3 over two steps. [d] i. Zn:AcOH:Ac₂O:THF, 0°C to rt, 4 hours, 73% ii. TFA:CH₂Cl₂, 5 hours, 75% for 2. [64] Figure 4 shows a schematic of orthogonal one-pot synthesis. The reagents and conditions were: [i] 5 [1.2 equivalents], 6 [1 equivalent], TMSOTf [30 mol%], 4Å MS activated, -5°C, 0.5 hours [ii] i.4 [1.5 equivalents], NIS [2 equivalents + 1 equivalent after 30 minutes], TfOH [10 mol%], 2 hours, -15 to -5°C, 66% for 33. [a] i. DDQ, CH₂Cl₂:H₂O (20:1), 12 hours. ii. Pyridine, Ac₂O, DMAP, 8 hours, 72% over two steps [b]. i. Zn:AcOH:Ac₂O:THF, 0°C to rt, 4 hours ii. TFA:CH₂Cl₂, 3 hours or TIPS:H₂O:TFA, 5 hours, 0°C to rt, 62% for 2 over two steps. [65] Figure 5 shows the solid phase peptide synthesis and global deprotection of GSnP-6. The reagents and conditions were: [a] Fmoc SPPS via fragment-condensation strategy, NovaSyn®TGA resin followed by 95% aq. TFA:Et₃SiH:EDT. [b] H₂/Pd-C. [c] 0.1 M NaOMe, aq. LiOH. [66] Figure 6 shows the total synthesis of GSnP-6. The structure depicts the practical, scalable, and hydrogenolysis-free convergent and one-pot assembly of sLe^X-O-Core-Thr. >1 g of Thr COOH hexasaccharide was synthesized in 10 steps with a 23% overall yield, and > 6 g of sLe^X was synthesized with a 48% overall yield and 6 steps from oxazolidinone thiosialoside donor. [67] Figure 7 shows the solid phase peptide synthesis of GSnP-6 (1) via fragment condensation. DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS [68] Provided herein are methods and compounds useful in the preparation of Core 2 O-sialyl Lewis^X polysaccharides including compounds of Formula (C):

and salts thereof. [69] For example, provided herein are methods and compounds useful in the preparation of a key Core 2 O-sialyl Lewis^X polysaccharides having the following structure:  

(C2-O-sLe^X-Thr-COOH). [70] Taken together, the methods and compounds provided herein represent a streamlined and efficient approach accessing Core 2 O-sialyl Lewis^X polyssacharides, for example, in fewer steps and in higher overall yield compared to previous strategies. In certain embodiments, methods described herein can be used to prepare 1 g or greater of a compounds of Formula (C). In certain embodiments, methods described herein can be used to prepare and isolate compounds of Formula (C) in 20% or greater overall yield (i.e., after multiple steps) starting from compounds of Formula (17). In certain embodiments, the overall yield of a compound of Formula (C) is from 20-30% starting from compounds of Formula (17). General Reaction Conditions [71] The following embodiments can apply to any method described herein. [72] The reactions provided and described herein may involve one or more reagents. In certain embodiments, a reagent may be present in a catalytic amount. In certain embodiments, a catalytic amount is from 0.1-1 mol%, 0.1-5 mol%, 0.1-10 mol%, 1-5 mol%, 1-10 mol%, 1-20 mol%, 1-30 mol%, 1-40 mol%, 1-50 mol%, 5-10 mol%, 10-20 mol%, 20-30 mol%, 30-40 mol%, 40-50 mol%, 50-60 mol%, 60- 70 mol%, 70-80 mol%, 80-90 mol%, or 90-99 mol%. In certain embodiments, a reagent may be present in a stoichiometric amount (i.e., about 1 equivalent). In certain embodiments, a reagent may be present in excess amount (i.e., greater than 1 equivalent). In certain embodiments, the excess amount is about 1.1, 1.2, 1.3, 1.4, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10, 15, or 20 equivalents. In certain embodiments, the excess amount is from about 1.1-2, 2-3, 3-4, 4-5, 1.1-5, 5-10, 10-15, 15-20, or 10-20 equivalents. In certain embodiments, the excess amount is greater than 20 equivalents. [73] A reaction described herein may be carried out at any temperature. In certain embodiments, a reaction is carried out at approximately room temperature (rt) (20 ºC or 68 ºF). In certain embodiments, a reaction is carried out at below room temperature (e.g., from -100 ºC to 20 ºC). In certain embodiments, a reaction is carried out at a temperature from -110 ºC to 0 ºC, -78 ºC to 0 ºC, -50 ºC to 0 ºC, -35 ºC to 0 ºC, or -10 ºC to 0 ºC. In certain embodiments, a reaction is carried out at a temperature from -110 ºC to rt, - 78 ºC to rt, -50 ºC to rt, -35 ºC to rt, -10 ºC to rt, or -0 ºC to rt. In certain embodiments, a reaction is carried out at a temperature from -30 ºC to 30 ºC, -10 ºC to 30 ºC, 0 ºC to 30 ºC, or rt to 30 ºC. In certain   embodiments, a reaction is carried out at approximately -110 ºC. In certain embodiments, a reaction is carried out at approximately -78 ºC. In certain embodiments, a reaction is carried out at approximately - 50 ºC. In certain embodiments, a reaction is carried out at approximately -35 ºC. In certain embodiments, a reaction is carried out at approximately -10 ºC. In certain embodiments, a reaction is carried out at 0 ºC. In certain embodiments, a reaction is carried out at approximately room temperature. In certain embodiments, a reaction is carried out at above room temperature. In certain embodiments, a reaction is carried out at a temperature from rt to 150 ºC, rt to 100 ºC, rt to 75 ºC, rt to 50 ºC, rt to 40 ºC, or rt to 30 ºC. In certain embodiment, a reaction is carried out at approximately 30, 40, 50, 60, 70, 80, 110, 120, 130, 140, or 150 ºC. [74] A reaction described herein may be carried out in a solvent, or a mixture of solvents (i.e., cosolvents). Solvents can be polar or non-polar, protic or aprotic. Any solvent may be used in the reactions described herein, and the reactions are not limited to particular solvents or combinations of solvents. Common organic solvents useful in the methods described herein include, but are not limited to, acetone, acetonitrile, benzene, benzonitrile, 1-butanol, 2-butanone, butyl acetate, tert-butyl methyl ether, carbon disulfide carbon tetrachloride, chlorobenzene, 1-chlorobutane, chloroform, cyclohexane, cyclopentane, 1,2-dichlorobenzene, 1,2-dichloroethane, dichloromethane (DCM), N,N- dimethylacetamide N,N-dimethylformamide (DMF), 1,3-dimethyl-3,4,5,6-tetrahydro-2-pyrimidinone (DMPU), 1,4-dioxane, 1,3-dioxane, diethylether, 2-ethoxyethyl ether, ethyl acetate, ethyl alcohol, ethylene glycol, dimethyl ether, heptane, n-hexane, hexanes, hexamethylphosphoramide (HMPA), 2- methoxyethanol, 2-methoxyethyl acetate, methyl alcohol, 2-methylbutane, 4-methyl-2-pentanone, 2- methyl-1-propanol, 2-methyl-2-propanol, 1-methyl-2-pyrrolidinone, dimethylsulfoxide (DMSO), nitromethane, 1-octanol, pentane, 3-pentanone, 1-propanol, 2-propanol, pyridine, tetrachloroethylene, tetrahyrdofuran (THF), 2-methyltetrahydrofuran, toluene, trichlorobenzene, 1,1,2- trichlorotrifluoroethane, 2,2,4-trimethylpentane, trimethylamine, triethylamine, N,N- diisopropylethylamine, diisopropylamine, water, o-xylene, p-xylene. [75] A reaction described herein may be carried out over any amount of time. In certain embodiments, a reaction is allowed to run for seconds, minutes, hours, or days. In certain embodiments, the reaction is allowed to run for from 0.5-1 hour, 0.5-2 hours 0.5-3 hours, 0.5-4 hours, 0.5-5 hours, 0.5-6 hours, 0.5-7 hours, 0.5-8 hours, 0.5-9 hours, 0.5-10 hours, 0.5-11 hours, 0.5-12 hours, 0.5-18 hours, or 0.5-24 hours. In certain embodiments, the reaciton is allowed to run for longer than 24 hours. In certain embodiments, the reaction is allowed to run for 1-2 hours, 1-3 hours, 1-4 hours, 1-5 hours, or 1-6 hours. In certain embodiments, the reaction is allowed to run for about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15,116, 17, 18, 19, 20, 21, 22, 23, or 24 hours. [76] Methods described herein can be used to prepare and isolate compounds in any chemical yield. In certain embodiments, a compound is isolated in from 1-10%, 10-20% 20-30%, 30-40%, 40-50%, 50- 60%, 60-70%, 70-80%, 80-90%, or 90-99% yield. In certain embodiments, a compound is isolated in from 50-99%, 60-99%, 70-99%, 80-99%, 90-99%, or 95-99% yield. In certain embodiments, the yield is the percent yield after one synthetic step. In certain embodiments, the yield is the percent yield after more   than one synthetic step (e.g., 2, 3, 4, or 5 synthetic steps). In certain embodiments, the yield is the yield of the compound after one or more purification steps. [77] Methods described herein may further comprise one or more purification steps. For example, in certain embodiments, a compound produced by a method described herein may be purified by chromatography, extraction, filtration, precipitation, crystallization, or any other method known in the art. In certain embodiments, a compound or mixture is carried forward to the next synthetic step without purification (i.e., crude). [78] The synthetic method provided herein can be carried out on any scale (i.e., to yield any amount of product). In certain embodiments, the methods are applicable to small-scale synthesis or larger-scale process manufacture. In certain embodiments, a reaction provided herein is carried out to yield less than 1 g of product. In certain embodiments, a reaction provided herein is carried out to yield greater than 1 g, 2 g, 5 g, 10 g, 15 g, 20 g, 25 g, 30 g, 40 g, 50 g, 100 g, 200 g, 500 g, or 1 kg of product. [79] Glycosylation reactions described herein can yield a product which is the α-anomer, the β-anomer, or a mixture of both. In certain embodiments, a glycosylation reaction described herein is selective for the α-anomer (“α-anomeric product”). In certain embodiments, a glycosylation reaction described herein yields a ratio of α:β anomers that is 2:1 or greater, 3:1 or greater, 4:1 or greater, 5:1 or greater, 6:1 or greater, 7:1 or greater, 8:1 or greater, 9:1 or greater, 10:1 or greater, 20:1 or greater, 30:1 or greater, 40:1 or greater, 50:1 or greater, 60:1 or greater, 70:1 or greater, 80:1 or greater, 90:1 or greater, 100:1 or greater, 200:1 or greater, 300:1 or greater, 400:1 or greater, 500:1 or greater, 600:1 or greater, 700:1 or greater, 800:1 or greater, 900:1 or greater, or 1000:1 or greater. In certain embodiments, a glycosylation product consists essentially of the α-anomer (i.e., essentially free of the β-anomer; “stereospecific for the α-anomer”). [80] In certain embodiments, a glycosylation reaction described herein is selective for the β-anomer (“β- anomeric product”). In certain embodiments, a glycosylation reaction described herein yields a ratio of β:α anomers that is 2:1 or greater, 3:1 or greater, 4:1 or greater, 5:1 or greater, 6:1 or greater, 7:1 or greater, 8:1 or greater, 9:1 or greater, 10:1 or greater, 20:1 or greater, 30:1 or greater, 40:1 or greater, 50:1 or greater, 60:1 or greater, 70:1 or greater, 80:1 or greater, 90:1 or greater, 100:1 or greater, 200:1 or greater, 300:1 or greater, 400:1 or greater, 500:1 or greater, 600:1 or greater, 700:1 or greater, 800:1 or greater, 900:1 or greater, or 1000:1 or greater. In certain embodiments, a glycosylation product consists essentially of the β-anomer (i.e., essentially free of the α-anomer; “stereospecific for the β-anomer”). Methods for Preparing Core 2 O-sialyl Lewis^X Polysaccharides [81] Core 2 O-sialyl Lewis^X polysaccharides intermediates such as compounds of Formula (1) can be prepared by [4+2] glycosylation of compounds of Formula (2) with compounds of Formula (3) as shown in Scheme 1. In certain embodiments, a compound of Formula (1) is formed in high yield (e.g., greater than 60%, greater than 70%, greater than 80%) and/or with high selectivity for the β-anomer (e.g., 10:1 or greater, 20:1 or greater, 100:1 or greater). In certain embodiments, the yield of a compound of Formula (1) is from 60-70%, 70-80%, 80-90%, or 90-99%. In certain embodiments, the reaction is   stereospecific for the β-anomer. In certain embodiments, greater than 1 g of the compound of Formula (1) is obtained. [82] As shown in Scheme 1, subsequent protection of the compound of Formula (1) (i.e., to install R^1A) yields compounds of Formula (A). In certain embodiments, a compound of Formula (A) is formed in high yield (e.g., greater than 60%, greater than 70%, greater than 80%). In certain embodiments, the yield of a compound of Formula (A) is from 60-70%, 70-80%, 80-90%, or 90-99%. In certain embodiments, greater than 1 g of the compound of Formula (A) is obtained. Subsequent reduction of the azide of the compound of Formula (A), protection of the resulting amine (i.e., to install R⁵), and hydrolysis of the – CO₂R⁵ ester yields a compound of (C) which can be used to prepare glycopeptides described herein (e.g., via solid phase peptide synthesis (SPPS)). In certain embodiments, a compound of Formula (C) is formed in greater than 50% yield (e.g., from 50-60% yield) from the compound of Formula (A). In certain embodiments, greater than 1 g of the compound of Formula (C) is obtained.

  Scheme 1

  [83] Provided herein are method of preparing a compound of Formula (1):

  or a salt thereof, comprising reacting a compound of Formula (2):

or a salt thereof, in the presence of a compound of Formula (3):

or a salt thereof, wherein: R^L1 is –SR^S1, wherein R^S1 is substituted phenyl; each R¹ is independently optionally substituted acyl or an oxygen protecting group; R² is optionally substituted acyl or a nitrogen protecting group; R³ is optionally substituted alkyl, optionally substituted acyl, or an oxygen protecting group; R⁴ is optionally substituted acyl or a nitrogen protecting group; R^N is optionally substituted acyl or a nitrogen protecting group; and R^O is optionally substituted alkyl, optionally substituted acyl, or an oxygen protecting group. [84] In certain embodiments, R^S1 is mono-, di-, or tri-substituted phenyl. In certain embodiments, R^S1 is disubstituted phenyl. In certain embodiments, R^S1 is 2,6-disubstituted phenyl. In certain embodiments, S¹

R is of the formula: , wherein each instance of R'' is independently C_1-6 alkyl. In certain

[85] In other embodiments of the method, R^L1 is a leaving group (e.g., any leaving group described herein).   [86] In certain embodiments, at least one R¹ is optionally substituted acyl. In certain embodiments, each R¹ is optionally substituted acyl. In certain embodiments, at least one R¹ is –C(O)C_1-6 alkyl. In certain embodiments, each R¹ is –C(O)C_1-6 alkyl. In certain embodiments, at least one R¹ is Ac (i.e., –C(O)Me). In certain embodiments, each R¹ is Ac. [87] In certain embodiments, R^S1 is mono-, di-, or tri-substituted phenyl; and each R¹ is optionally substituted acyl. In certain embodiments, R^S1 is disubstituted phenyl; and each R¹ is optionally substituted acyl. In certain embodiments, R^S1 is 2,6-disubstituted phenyl; and each R¹ is optionally

substituted acyl. In certain embodiments, R^S1 is of the formula: , wherein each instance of R'' is independently C_1-6 alkyl; and each R¹ is –C(O)C_1-6 alkyl. In certain embodiments, R^S1 is DMP; and each R¹ is Ac. In certain embodiments, R^L1 is SDMP; and each R¹ is Ac. [88] In certain embodiments, R² is a nitrogen protecting group. In certain embodiments, R² is a carbamate protecting group. In certain embodiments, R² is Troc (2,2,2-trichloroethoxycarbonyl). [89] In certain embodiments, R³ is optionally substituted alkyl. In certain embodiments, R³ is optionally substituted C_1-6 alkyl. In certain embodiments, R³ is unsubstituted C_1-3 alkyl. In certain embodiments, R³ is methyl (Me). [90] In certain embodiments, R⁴ is optionally substituted acyl. In certain embodiments, R⁴ is –C(O)C_1-6 alkyl. In certain embodiments, R⁴ is Ac (i.e., –C(O)Me). [91] In certain embodiments, R^N is a nitrogen protecting group. In certain embodiments, R^N is a carbamate protecting group. In certain embodiments, R^N is fluorenylmethyloxycarbonyl (Fmoc). [92] In certain embodiments, R^O is optionally substituted C_1-6 alkyl. In certain embodiments, R^O is unsubstituted C_1-6 alkyl. In certain embodiments, R^O is optionally substituted C_1-4 alkyl. In certain embodiments, R^O is unsubstituted C_1-4 alkyl (e.g., methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl). In certain embodiments, R^O is tert-butyl (t-Bu). [93] In certain embodiments, the compound of Formula (1) is:

, or a salt thereof; the compound of Formula (2) is:  

, or a salt thereof; and the compound of Formula (3) is:

, or a salt thereof. [94] In certain embodiments, the reaction is carried out in the presence of an acid. In certain embodiments, the acid is a Brønsted acid. In certain embodiments, the acid is an organic Brønsted acid. In certain embodiments, the acid is a sulfonic acid. In certain embodiments, the acid is trifluoromethanesulfonic acid (TfOH). Other non-limiting examples of acids include trimethylsilyl trifluoromethanesulfonate (TMSOTf), Boron trifluoride diethyl etherate (BF₃•Et₂O), silver triflate (AgOTf), methyl triflate (MeOTf), triflic anhydride (Tf₂O), and trimethylsilyl trifluoromethanesulfonate (TESOTf). [95] In certain embodiments, the reaction is carried out in the presence of a halogenating reagent. In certain embodiments, the reaction is carried out in the presence of an N-halosuccinimide. In certain embodiments, the N-halosuccinimide is N-chlorosuccinimide, N-bromosuccinimide, or N- iodosuccinimide. In certain embodiments, the N-halosuccinimide is N-iodosuccinimide (NIS). [96] The reaction may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the reaction is carried out in an aprotic solvent. In certain embodiments, the reaction is carried out in dichloromethane (DCM). [97] In certain embodiments, the reaction is carried out at a temperature below room temperature. In certain embodiments, the reaction is carried out at a temperature of from approximately -10 °C to approximately room temperature. In certain embodiments, the reaction is carried out at a temperature of approximately 0 °C. [98] In certain embodiments, the reaction is allowed to run for under 10 hours. In certain embodiments, the reaction is allowed to run for 0.5-2 hours. In certain embodiments, the reaction is allowed to run for approximately 1 hour.   [99] In certain embodiments, the method further comprises protecting the compound of Formula (1), or a salt thereof, to yield a compound of Formula (A):

or a salt thereof, wherein R^1A is optionally substituted acyl or a nitrogen protecting group. [100] In certain embodiments, R^1A is optionally substituted acyl. In certain embodiments, R^1A is – C(O)C_1-6 alkyl. In certain embodiments, R^1A is Ac. [101] In certain embodiments, the compound of Formula (1) is: ,

,   or a salt thereof. [102] In certain embodiments, R^1A is optionally substituted acyl; and the reaction is carried out in the presence of an acylating reagent (e.g., an acid anhydride). In certain embodiments, R^1A is –C(O)C_1-6 alkyl; and the reaction is carried out in the presence of (C_1-6 alkyl-C(O))₂O. In certain embodiments, R^1A is –Ac; and the reaction is carried out in the presence of Ac₂O. [103] In certain embodiments, the reaction is carried out in the presence of a nucleophile capable of activating the acylating reagent. In certain embodiments, the reaction is carried out in the presence of 4- dimethylaminopyridine (DMAP). In certain embodiments, the reaction is carried out in the presence of a base. In certain embodiments, the reaction is carried out in the presence of pyridine. In certain embodiments, the reaction is carried out in the presence of DMAP and pyridine. [104] The reaction may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the solvent is an aprotic solvent. In certain embodiments, the solvent is pyridine. [105] In certain embodiments, the reaction is carried out at a temperature from approximately 0 °C to approximately 30 °C. In certain embodiments, the reaction is carried out at approximately room temperature. [106] In certain embodiments, the reaction is allowed to run for under 10 hours. In certain embodiments, the reaction is allowed to run for 1-5 hours. In certain embodiments, the reaction is allowed to run for approximately 3 hours. [107] In certain embodiments, the method further comprises: (a) reducing and protecting the compound of Formula (A), or a salt thereof, to yield a compound of Formula (B):

or a salt thereof; and (b) hydrolyzing the compound of Formula (B), or a salt thereof, to yield a compound of Formula (C):  

or a salt or a group. [108] In certain embodiments, R⁵ is optionally substituted acyl. In certain embodiments, R⁵ is –C(O)C_1-6 alkyl. In certain embodiments, R⁵ is Ac. [109] In certain embodiments, the compound of Formula (A) is:

, or a salt thereof; the compound of Formula (B) is:

, or a salt thereof; and the compound of Formula (C) is:  

, or a salt thereof. [110] In certain embodiments, the reaction in step (a) is carried out in the presence of a reducing agent. Any reducing agent capable of reducing an azide to an amine may be suitable in the reaction. In certain embodiments, the reducing agent is zinc (Zn) metal or zinc-copper couple (ZnCu). In certain embodiments, the reducing agent is a phosphine reagent (e.g., a triarylphosphine such as triphenylphosphine or polymer-bound triphenylphosphine). Other non-limiting examples of reducing agents include 1,3-propanedithiol and other dithiol reagents (e.g., under basic conditions), sodium borohydride, dichloroindium hydride, hydrogenation reagents, thioacetic acid, NaCNBH₃, BH₃/THF, H₂/Pd(OH)₂, Zn-Pb, and Cd-Pb. [OTHER POSSIBLE REDUCING AGENTS?] [111] In certain embodiments, R⁵ is optionally substituted acyl; and the reaction in step (a) is carried out in the presence of an acylating reagent (e.g., an acid anhydride). In certain embodiments, R⁵ is –C(O)C_1-6 alkyl; and the reaction in step (a) is carried out in the presence of (C_1-6 alkyl-C(O))₂O. In certain embodiments, R⁵ is –Ac; and the reaction in step (a) is carried out in the presence of Ac₂O. [112] The reaction in step (a) may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the solvent is THF and/or AcOH. In certain embodiments, the solvent is a mixture of THF and AcOH. [113] In certain embodiments, the reaction in step (a) is carried out at a temperature below room temperature. In certain embodiments, the reaction is carried out at a temperature of from approximately - 10 °C to approximately room temperature. In certain embodiments, the reaction is carried out at a temperature of approximately 0 °C to approximately room temperature. [114] In certain embodiments, the reaction in step (a) is allowed to run for under 10 hours. In certain embodiments, the reaction in step (a) is allowed to run for 2-6 hours. In certain embodiments, the reaction in step (a) is allowed to run for approximately 4 hours. [115] In certain embodiments, the reaction in step (b) is carried out in the presence of an acid. In certain embodiments, the acid is a Brønsted acid. In certain embodiments, the acid is an organic Brønsted acid. In certain embodiments, the acid is a carboxylic acid. In certain embodiments, the acid is trifluoroacetic acid (TFA). Other possible acids include formic acid, acetic acid, etc.   [116] The reaction in step (b) may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the solvent is an aprotic solvent. In certain embodiments, the reaction in step (b) is carried out in dichloromethane (DCM). [117] In certain embodiments, the reaction in step (b) is carried out at a temperature from approximately 0 °C to approximately 30 °C. In certain embodiments, the reaction in step (b) is carried out at approximately room temperature. [118] In certain embodiments, the reaction in step (a) is allowed to run for under 12 hours. In certain embodiments, the reaction in step (a) is allowed to run for 4-8 hours. In certain embodiments, the reaction in step (a) is allowed to run for approximately 6 hours. Methods for Preparing Compounds of Formula (2) [119] Compounds of Formula (2) can be prepared via compounds of Formula (4) according to Scheme 2. [2 + 2] Glycosylation of compounds of Formula (5) with compounds of Formula (6) yield compounds of Formula (4). In certain embodiments, a compound of Formula (4) is obtained in high yield (e.g., greater than 70%, greater than 80%, greater than 90%) due to, for example, suppression of side reactions. In certain embodiments, a compound of Formula (4) is obtained in 70-90% yield, e.g., 70-80% yield. In certain embodiments, the reaction to form a compound of Formula (4) is stereoselective (e.g., stereospecific) for the β-anomer. [120] Subsequent deprotection of the compound of Formula (4) (i.e., to remove R^1B groups) yields compounds of Formula (D) with free hydroxyl groups. Protection of the free hydroxyl groups of the compound of Formula (D) (i.e., to install R¹ groups) yield a compound of Formula (2). In certain embodiments, compound of Formula (4) and (2) can be obtained on gram or multigram scale (e.g., 1 g or more, 2 g or more, 3 g or more, 4 g or more, 5 g or more, 6 g or more) using the provided methods.

  Scheme 2

  [121] Provided herein are methods of preparing a compound of Formula (4):

or a salt thereof, comprising reacting a compound of Formula (5):

or a salt thereof, with a compound of Formula (6):  

or a salt thereof, wherein: R^L1 is a leaving group; R^L2 is optionally substituted aryl or optionally substituted heteroaryl; each X is independently halogen; each R^1B is independently optionally substituted naphthylmethyl; each R¹ is independently optionally substituted acyl or an oxygen protecting group; R² is optionally substituted acyl or a nitrogen protecting group; R³ is optionally substituted alkyl, optionally substituted acyl, or an oxygen protecting group; and R⁴ is optionally substituted acyl or a nitrogen protecting group. [122] In certain embodiments, R^L1 is –SR^S1, wherein R^S1 is optionally substituted phenyl. In certain embodiments, R^L1 is –SR^S1, wherein R^S1 is substituted phenyl. In certain embodiments, R^S1 is mono-, di-, or tri-substituted phenyl. In certain embodiments, R^S1 is disubstituted phenyl. In certain embodiments, S

R ¹ is 2,6-disubstituted phenyl. In certain embodiments, R^S1 is of the formula: , wherein each instance of R'' is independently C_1-6 alkyl. In certain embodiments, R^S1 is:

dimethylphenyl; “DMP”). In certain embodiments, R^L1 is:

[123] In certain embodiments, at least one R¹ is optionally substituted acyl. In certain embodiments, each R¹ is optionally substituted acyl. In certain embodiments, at least one R¹ is –C(O)C_1-6 alkyl. In certain embodiments, each R¹ is –C(O)C_1-6 alkyl. In certain embodiments, at least one R¹ is Ac (i.e., –C(O)Me). In certain embodiments, each R¹ is Ac. [124] In certain embodiments, each R^1B is independently optionally substituted naphthylmethyl. In certain embodiments, each R^1B is independently unsubstituted naphthylmethyl. In certain embodiments, each R^1B is:

(2-naphthylmethyl; “Nap”). [125] In certain embodiments, R^L1 is –SR^S1, wherein R^S1 is mono-, di-, or tri-substituted phenyl; each R¹ is optionally substituted acyl; and each R^1B is independently optionally substituted naphthylmethyl. In   certain embodiments, R^L1 is –SR^S1, wherein R^S1 is disubstituted phenyl; each R¹ is optionally substituted acyl; and each R^1B is independently optionally substituted naphthylmethyl. In certain embodiments, R^L1 is –SR^S1, wherein R^S1 is 2,6-disubstituted phenyl; each R¹ is optionally substituted acyl; and each R^1B is independently optionally substituted naphthylmethyl. In certain embodiments, R^L1 is –SR^S1, wherein R^S1

is of the formula: , wherein each instance of R'' is independently C_1-6 alkyl; each R¹ is – C(O)C_1-6 alkyl; and each R^1B is independently unsubstituted naphthylmethyl. In certain embodiments, R^L1 is –SR^S1, wherein R^S1 is DMP; each R¹ is Ac; and each R^1B is Nap. In certain embodiments, R^L1 is SDMP; each R¹ is Ac; and each R^1B is Nap. [126] In certain embodiments, R² is a nitrogen protecting group. In certain embodiments, R² is a carbamate protecting group. In certain embodiments, R² is Troc (2,2,2-trichloroethoxycarbonyl). [127] In certain embodiments, R³ is optionally substituted alkyl. In certain embodiments, R³ is optionally substituted C_1-6 alkyl. In certain embodiments, R³ is unsubstituted C_1-3 alkyl. In certain embodiments, R³ is methyl (Me). [128] In certain embodiments, R⁴ is optionally substituted acyl. In certain embodiments, R⁴ is –C(O)C_1-6 alkyl. In certain embodiments, R⁴ is Ac (i.e., –C(O)Me). [129] In certain embodiments, R^L2 is optionally substituted aryl. In certain embodiments, R^L2 is optionally substituted phenyl. In certain embodiments, R^L2 is unsubstituted phenyl (Ph). In certain embodiments, each X is halogen. In certain embodiments, each X is –Cl. In certain embodiments, each X is –F. In certain embodiments, R^L2 is optionally substituted aryl; and each X is –F. In certain embodiments, R^L2 is optionally substituted phenyl; and each X is –F. In certain embodiments, R^L2 is Ph; and each X is –F. [130] In certain embodiments, R^L1 is –SR^S1, wherein R^S1 is mono-, di-, or tri-substituted phenyl; each R¹ is optionally substituted acyl; each R^1B is independently optionally substituted naphthylmethyl; and R^L2 is optionally substituted phenyl. In certain embodiments, R^L1 is –SR^S1, wherein R^S1 is disubstituted phenyl; each R¹ is optionally substituted acyl; each R^1B is independently optionally substituted naphthylmethyl; and R^L2 is optionally substituted phenyl. In certain embodiments, R^L1 is –SR^S1, wherein R^S1 is 2,6- disubstituted phenyl; each R¹ is optionally substituted acyl; each R^1B is independently optionally substituted naphthylmethyl; and R^L2 is optionally substituted phenyl. In certain embodiments, R^L1 is – S¹

SR , wherein R^S1 is of the formula: , wherein each instance of R'' is independently C_1-6 alkyl; each R¹ is –C(O)C_1-6 alkyl; each R^1B is independently unsubstituted naphthylmethyl; R^L2 is Ph; and each X is –F. In certain embodiments, R^L1 is –SR^S1, wherein R^S1 is DMP; each R¹ is Ac; each R^1B is Nap; R^L2 is Ph; and each X is –F. In certain embodiments, R^L1 is SDMP; each R¹ is Ac; each R^1B is Nap; and R^L2 is Ph; and each X is –F.   [131] In certain embodiments, the compound of Formula (4) is:

, or a salt thereof; the compound of Formula (5) is:

, or a salt thereof; and the compound of Formula (6) is:

, or a salt thereof. [132] In certain embodiments, the reaction is carried out in the presence of a Lewis acid. In certain embodiments, the reaction is carried out in the presence of a trialkyl silyl Lewis acid. In certain embodiments, the Lewis acid is trimethylsilyl trifluoromethanesulfonate (TMSOTf). Other non-limiting examples of acids include trifluoromethanesulfonic acid (TfOH), boron trifluoride diethyl etherate (BF₃•Et₂O), silver triflate (AgOTf), methyl triflate (MeOTf), triflic anhydride (Tf2O), and trimethylsilyl trifluoromethanesulfonate (TESOTf). [133] In other embodiments, the reaction is carried out in the presence of a Brønsted acid and an N- halosuccinimide. [134] The reaction may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the reaction is carried out in an aprotic solvent. In certain embodiments, the reaction is carried out in dichloromethane (DCM). [135] In certain embodiments, the reaction is carried out at a temperature below room temperature. In certain embodiments, the reaction is carried out at a temperature of from approximately -10 °C to approximately room temperature. In certain embodiments, the reaction is carried out at a temperature of approximately 0 °C. [136] In certain embodiments, the reaction is allowed to run for under 10 hours. In certain embodiments, the reaction is allowed to run for 0.5-2 hours. In certain embodiments, the reaction is allowed to run for approximately 1 hour.   [137] In certain embodiments, the method further comprises: (a) deprotecting the compound of Formula (4), or a salt thereof, to yield a compound of Formula (D):

or a salt thereof; and (b) protecting the compound of Formula (D), or a salt thereof, to yield a compound of Formula (2):

or a salt thereof. [138] In certain embodiments, the compound of Formula (4) is:

, or a salt thereof; the compound of Formula (D) is:

, or a salt thereof; and the compound of Formula (2) is:  

, or a salt thereof. [139] In certain embodiments, the reaction in step (a) is carried out in the presence of an oxidant. In certain embodiments, the oxidant is 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Other non- limiting examples of oxidants include lithium or sodium metal in the presence of liquid ammonia, hydrogenolysis reagents, etc. [140] The reaction in step (a) may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the solvent is an aprotic solvent. In certain embodiments, the reaction is carried out in dichloromethane (DCM). [141] In certain embodiments, the reaction in step (a) is carried out at a temperature below room temperature. In certain embodiments, the reaction in step (a) is carried out at a temperature of from approximately -10 °C to approximately room temperature. In certain embodiments, the reaction in step (a) is carried out at a temperature of approximately 0 °C to approximately room temperature. [142] In certain embodiments, the reaction in step (a) is allowed to run for under 24 hours. In certain embodiments, the reaction in step (a) is allowed to run for 8-12 hours. In certain embodiments, the reaction in step (a) is allowed to run for approximately 10 hours. [143] In certain embodiments, each R¹ is optionally substituted acyl; and the reaction in step (b) is carried out in the presence of an acylating reagent (e.g., an acid anhydride). In certain embodiments, each R¹ is –C(O)C_1-6 alkyl; and the reaction in step (b) is carried out in the presence of (C_1-6 alkyl-C(O))₂O. In certain embodiments, each R¹ is –Ac; and the reaction in step (b) is carried out in the presence of Ac₂O. [144] In certain embodiments, the reaction is step (b) is carried out in the presence of a nucleophile capable of activating the acylating reagent. In certain embodiments, the reaction in step (b) is carried out in the presence of 4-dimethylaminopyridine (DMAP). In certain embodiments, the reaction in step (b) is carried out in the presence of a base. In certain embodiments, the reaction in step (b) is carried out in the presence of pyridine. In certain embodiments, the reaction in step (b) is carried out in the presence of DMAP and pyridine. [145] The reaction in step (b) may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the solvent is pyridine. [146] In certain embodiments, the reaction in step (b) is carried out at a temperature from approximately 0 °C to approximately 30 °C. In certain embodiments, the reaction is carried out at approximately room temperature.   [147] In certain embodiments, the reaction in step (b) is allowed to run for under 12 hours. In certain embodiments, the reaction in step (b) is allowed to run for 4-8 hours. In certain embodiments, the reaction in step (b) is allowed to run for approximately 6 hours. Methods for Preparing Compounds of Formula (3) [148] Compounds of Formula (3) can be prepared via compounds of Formula (7) as shown in Scheme 3. Glycosylation of a compound of Formula (9) with a compound of Formula (8) yield a Compound of Formula (7). In certain embodiments, a compound of Formula (7) is formed in high yield (e.g., greater than 70%, greater than 80%). In certain embodiments, a compound of Formula (7) is formed in 70-90% yield, e.g., 75-85% yield. Subsequent deprotection of the compound of Formula (7) (i.e., to remove the silylene protecting group) yields a compound of Formula (3). In certain embodiments, the compound of Formula (3) can be purified by column chromatography (e.g., one step of column chromatography purification). In certain embodiments, the two step reaction sequence represented in Scheme 3 can be carried out at a scale of 50 g or more. Scheme 3

    [149] Provided herein are methods of preparing a compound of Formula (7):

or a salt thereof, comprising reacting a compound of Formula (8):

or a salt thereof, with a compound of Formula (9):

or a salt thereof, wherein: R^L3 is a leaving group; each R¹ is independently optionally substituted acyl or an oxygen protecting group; each R^1C is independently optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; R^N is optionally substituted acyl or a nitrogen protecting group; and R^O is optionally substituted alkyl, optionally substituted acyl, or an oxygen protecting group. [150] In certain embodiments, R^L3 is a leaving group described herein. In certain embodiments, R^L3 is a NH _{trihaloacetimidate leaving group of the formula:} ^{O CX3} _{, wherein each X is halogen. In certain embodiments, R} ^L3 _{is a trichloroacetimidate leaving group of the formula:}

[151] In certain embodiments, at least one R¹ is optionally substituted acyl. In certain embodiments, each R¹ is optionally substituted acyl. In certain embodiments, at least one R¹ is –C(O)C_1-6 alkyl. In certain   embodiments, each R¹ is –C(O)C_1-6 alkyl. In certain embodiments, at least one R¹ is Ac (i.e., –C(O)Me). In certain embodiments, each R¹ is Ac. [152] In certain embodiments, each R^1C is independently optionally substituted C_1-6 alkyl. In certain embodiments, each R^1C is independently unsubstituted C_1-6 alkyl. In certain embodiments, each R^1C is independently optionally substituted C_1-4 alkyl. In certain embodiments, each R^1C is independently unsubstituted C_1-4 alkyl (e.g., methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl). In certain embodiments, each R^1C is t-Bu. [153] In certain embodiments, R^N is a nitrogen protecting group. In certain embodiments, R^N is a carbamate protecting group. In certain embodiments, R^N is fluorenylmethyloxycarbonyl (Fmoc). [154] In certain embodiments, R^O is optionally substituted C_1-6 alkyl. In certain embodiments, R^O is unsubstituted C_1-6 alkyl. In certain embodiments, R^O is optionally substituted C_1-4 alkyl. In certain embodiments, R^O is unsubstituted C_1-4 alkyl (e.g., methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl). In certain embodiments, R^O is tert-butyl (t-Bu). [155] In certain embodiments, the compound of Formula (7) is:

, or a salt thereof; the compound of Formula (8) is:

, or a salt thereof; and the compound of Formula (9) is:

, or a salt thereof.   [156] In certain embodiments, the reaction is carried out in the presence of a Lewis acid. In certain embodiments, the reaction is carried out in the presence of a trialkyl silyl Lewis acid. In certain embodiments, the Lewis acid is trimethylsilyl trifluoromethanesulfonate (TMSOTf). Other non-limiting examples of acids include trifluoromethanesulfonic acid (TfOH), boron trifluoride diethyl etherate (BF₃•Et₂O), silver triflate (AgOTf), methyl triflate (MeOTf), triflic anhydride (Tf2O), and trimethylsilyl trifluoromethanesulfonate (TESOTf). [157] In other embodiments, the reaction is carried out in the presence of a Brønsted acid and an N- halosuccinimide. [158] The reaction may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the solvent is an aprotic solvent. In certain embodiments, the reaction is carried out in dichloromethane (DCM). [159] In certain embodiments, the reaction is carried out at a temperature below room temperature. In certain embodiments, the reaction is carried out at a temperature of from approximately -10 °C to approximately room temperature. In certain embodiments, the reaction is carried out at a temperature of approximately 0 °C. [160] In certain embodiments, the reaction is allowed to run for under 10 hours. In certain embodiments, the reaction is allowed to run for 0.1-1 hour. In certain embodiments, the reaction is allowed to run for approximately 0.5 hour. [161] In certain embodiments, the method further comprises deprotecting the compound of Formula (7), or a salt thereof, to yield a compound of Formula (3):

or a salt thereof. [162] In certain embodiments, the compound of Formula (7) is:

, or a salt thereof; and the compound of Formula (3) is:  

, or a salt thereof. [163] In certain embodiments, the reaction is carried out in the presence of a fluoride source. In certain embodiments, the fluoride source is tetrabutylammonium fluoride (TBAF). In certain embodiments, the fluoride source is tributylamine hydrofluoride (TBAHF). [164] The reaction may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the solvent is an aprotic solvent. In certain embodiments, the reaction is carried out in tetrahydrofruan (THF). [165] In certain embodiments, the reaction is carried out at a temperature from approximately 0 °C to approximately 30 °C. In certain embodiments, the reaction is carried out at approximately room temperature. [166] In certain embodiments, the reaction is allowed to run for under 10 hours. In certain embodiments, the reaction is allowed to run for 0.5-4 hours. In certain embodiments, the reaction is allowed to run for approximately 2 hours. Methods for Preparing Compounds of Formula (8) [167] Compounds of Formula (8) can be prepared via compounds of Formula (10) as shown in Scheme 4. Glycosylation of compounds of Formula (11) with compounds of Formula (12) yields compounds of Formula (10). In certain embodiments, a compound of Formula (10) is formed in high yield (e.g., greater than 70%, greater than 80%) and/or with high selectivity for the α-anomer (e.g., 10:1 or greater, 20:1 or greater, 30:1 or greater). In certain embodiments, the reaction to form a compound of Formula (10) is stereoselective (e.g., stereospecific) for the α-anomer. In certain embodiments, the ratio of α:β anomers is 30:1 or greater, e.g., 32:1 or greater. Subsequent deprotection of the compound of Formula (10) (i.e., to remove the R¹ group) yields a compound of Formula (8). In certain embodiments, a compound of Formula (8) is obtained in greater than 70% yield, e.g., 70-80% yield, from a compound of Formula (11). In certain embodiments, the compound of Formula (8) is purified by crystallization. In certain embodiments, the two step reaction sequence represented in Scheme 4 can be carried out at a scale of 100 g or more.   Scheme 4

  [168] Provided herein is a method of preparing a compound of Formula (10):

or a salt thereof, comprising reacting a compound of Formula (11):

or a salt thereof, with a compound of Formula (12):

or a salt thereof, wherein: R^L4 is a leaving group;   R¹ is independently optionally substituted acyl or an oxygen protecting group; each R^1C is independently optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; R^N is optionally substituted acyl or a nitrogen protecting group; and R^O is optionally substituted alkyl, optionally substituted acyl, or an oxygen protecting group. [169] In certain embodiments, R^L4 is –SR^S4, wherein R^S4 is optionally substituted phenyl. In certain embodiments, R^L4 is –SR^S4, wherein R^S4 is substituted phenyl. In certain embodiments, R^S4 is mono-, di-, or tri-substituted phenyl. In certain embodiments, R^S4 is disubstituted phenyl. In certain embodiments, R^S4 is 2,6-disubstituted phenyl. In certain embodiments, R^S4 is of the formula:

, wherein each instance of R'' is independently C_1-6 alkyl. In certain embodiments, R^S4 is:

dimethylphenyl; “DMP”). In certain embodiments, R^L4 is phenyl (Ph). In certain embodiments, R^L4 is – SPh. [170] In certain embodiments, R¹ is optionally substituted acyl. In certain embodiments, R¹ is –C(O)C_1-6 alkyl. In certain embodiments, R¹ is Ac (i.e., –C(O)Me). [171] In certain embodiments, each R^1C is independently optionally substituted C_1-6 alkyl. In certain embodiments, each R^1C is independently unsubstituted C_1-6 alkyl. In certain embodiments, each R^1C is independently optionally substituted C_1-4 alkyl. In certain embodiments, each R^1C is independently unsubstituted C_1-4 alkyl (e.g., methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl). In certain embodiments, each R^1C is independently t-Bu. [172] In certain embodiments, R^N is a nitrogen protecting group. In certain embodiments, R^N is fluorenylmethyloxycarbonyl (Fmoc). [173] In certain embodiments, R^O is optionally substituted C_1-6 alkyl. In certain embodiments, R^O is unsubstituted C_1-6 alkyl. In certain embodiments, R^O is optionally substituted C_1-4 alkyl. In certain embodiments, R^O is unsubstituted C_1-4 alkyl (e.g., methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl). In certain embodiments, R^O is tert-butyl (t-Bu).   [174] In certain embodiments, the compound of Formula (10) is:

, or a salt thereof; the compound of Formula (11) is:

, or a salt thereof; and the compound of Formula (12) is:

, or a salt thereof. [175] In certain embodiments, the reaction is carried out in the presence of an acid. In certain embodiments, the acid is a Brønsted acid. In certain embodiments, the acid is an organic Brønsted acid. In certain embodiments, the acid is a sulfonic acid. In certain embodiments, the acid is trifluoromethanesulfonic acid (TfOH). Other non-limiting examples of acids include trimethylsilyl trifluoromethanesulfonate (TMSOTf), boron trifluoride diethyl etherate (BF₃•Et₂O), silver triflate (AgOTf), methyl triflate (MeOTf), triflic anhydride (Tf2O), and trimethylsilyl trifluoromethanesulfonate (TESOTf). [176] In certain embodiments, the reaction is carried out in the presence of a halogenating reagent. In certain embodiments, the reaction is carried out in the presence of an N-halosuccinimide. In certain embodiments, the N-halosuccinimide is N-chlorosuccinimide, N-bromosuccinimide, or N- iodosuccinimide. In certain embodiments, the N-halosuccinimide is N-iodosuccinimide (NIS). [177] The reaction may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the reaction is carried out in dichloromethane (DCM). [178] In certain embodiments, the reaction is carried out at a temperature below room temperature. In certain embodiments, the reaction is carried out at a temperature of from approximately -10 °C to approximately room temperature. In certain embodiments, the reaction is carried out at a temperature of approximately 0 °C.   [179] In certain embodiments, the reaction is allowed to run for under 10 hours. In certain embodiments, the reaction is allowed to run for 0.5-2 hours. In certain embodiments, the reaction is allowed to run for approximately 1 hour. [180] In certain embodiments, the method further comprises deprotecting the compound of Formula (10), or a salt thereof, to yield a compound of Formula (8):

or a salt thereof. [181] In certain embodiments, the compound of Formula (10) is:

, or a salt thereof; and the compound of Formula (8) is:

, or a salt thereof. [182] In certain embodiments, R¹ is optionally substituted acyl (e.g., –C(O)C_1-6 alkyl, e.g., Ac), and the reaction is carried out in the presence of hydrazine (H₂NNH₂). In certain embodiments, hydrazine hydrate (H₂NNH₂•H₂O) is used.   [183] The reaction may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the solvent is an alcohol. In certain embodiments, the reaction is carried out in methanol (MeOH). [184] In certain embodiments, the reaction is carried out at a temperature from approximately 0 °C to approximately 30 °C. In certain embodiments, the reaction is carried out at approximately room temperature. [185] In certain embodiments, the reaction is allowed to run for under 10 hours. In certain embodiments, the reaction is allowed to run for 2-4 hours. In certain embodiments, the reaction is allowed to run for approximately 3 hours. Methods for Preparing Compounds of Formula (6) [186] Compounds of Formula (6) can be prepared via compounds of Formula (13) as shown in Scheme 5. [1+1] Glycosylation of compounds of Formula (15) with compounds of Formula (14) yields compounds of Formula (13). In certain embodiments, a compound of Formula (13) is formed with high selectivity for the α-anomer (e.g., 10:1 or greater, 20:1 or greater, 100:1 or greater). In certain embodiments, the reaction is stereospecific for the α-anomer. Subsequent deprotection of the compound of Formula (13) (i.e., to remove the R¹ group) yields a compound of Formula (8). In certain embodiments, a compound of Formula (8) is isolated in greater than 50% yield, e.g., greater than 60% yield, e.g., 60-70% yield, starting from the compound of Formula (15). Scheme 5

    [187] Provided herein are methods of preparing a compound of Formula (13):

or a salt thereof, comprising reacting a compound of Formula (14):

or a salt thereof, with a compound of Formula (15):

or a salt thereof, wherein: R^L1 and R^L5 are each independently a leaving group; R^1B is optionally substituted naphthylmethyl; R^1D is optionally substituted naphthyl; each R¹ is independently optionally substituted acyl or an oxygen protecting group; and R² is optionally substituted acyl or a nitrogen protecting group. [188] In certain embodiments, R^L1 is –SR^S1. In certain embodiments, R^S1 is mono-, di-, or tri-substituted phenyl. In certain embodiments, R^S1 is disubstituted phenyl. In certain embodiments, R^S1 is 2,6- S¹

disubstituted phenyl. In certain embodiments, R is of the formula: , wherein each instance of R'' is independently C_1-6 alkyl. In certain embodiments, R^S1 is:

dimethylphenyl; “DMP”). In certain embodiments, R^L1 is:

[189] In certain embodiments, R^L5 is –SR^S5, wherein R^S5 is optionally substituted alkyl or optionally substituted aryl. In certain embodiments, R^S5 is optionally substituted C_1-6 alkyl. In certain embodiments, R^S5 is unsubstituted C_1-6 alkyl. In certain embodiments, R^S5 is optionally substituted C_1-4 alkyl. In certain embodiments, R^S5 is unsubstituted C_1-4 alkyl (e.g., methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl). In certain embodiments, R^S5 is ethyl (Et). In certain embodiments, R^L5 is –SEt.   O N [190] In certain embodiments, R^L5 is of the formula: X₃C ^RL2 . _{In certain embodiments, R} ^L2 _is optionally substituted aryl. In certain embodiments, R^L2 is optionally substituted phenyl. In certain embodiments, R^L2 is unsubstituted phenyl (Ph). In certain embodiments, each X is halogen. In certain embodiments, each X is –Cl. In certain embodiments, each X is –F. In certain embodiments, R^L2 is optionally substituted aryl; and each X is –F. In certain embodiments, R^L2 is optionally substituted phenyl; and each X is –F. In certain embodiments, R^L2 is Ph; and each X is –F. [191] In certain embodiments, at least one R¹ is optionally substituted acyl. In certain embodiments, each R¹ is optionally substituted acyl. In certain embodiments, at least one R¹ is –C(O)C_1-6 alkyl. In certain embodiments, each R¹ is –C(O)C_1-6 alkyl. In certain embodiments, at least one R¹ is Ac (i.e., –C(O)Me). In certain embodiments, each R¹ is Ac. [192] In certain embodiments, R² is a nitrogen protecting group. In certain embodiments, R² is a carbamate protecting group. In certain embodiments, R² is Troc (2,2,2-trichloroethoxycarbonyl). [193] In certain embodiments, each R^1B is independently optionally substituted naphthylmethyl. In certain embodiments, each R^1B is independently unsubstituted naphthylmethyl. In certain embodiments, each R^1B is:

(2-naphthylmethyl; “Nap”). [194] In certain embodiments, R^1D is optionally substituted naphthyl. In certain embodiments, R^1D is unsubstituted naphthyl. In certain embodiments, R^1D is:

(2-naphthyl). [195] In certain embodiments, the compound of Formula (13) is:

, or a salt thereof; the compound of Formula (14) is:

, or a salt thereof; and the compound of Formula (15) is of the formula:

,   or a salt thereof, wherein R^L5 is –SEt or –OC(=NPh)CF₃. [196] In certain embodiments, the reaction is carried out in the presence of an acid. In certain embodiments, the acid is a Brønsted acid. In certain embodiments, the acid is an organic Brønsted acid. In certain embodiments, the acid is a sulfonic acid. In certain embodiments, the acid is trifluoromethanesulfonic acid (TfOH). Other non-limiting examples of acids include trimethylsilyl trifluoromethanesulfonate (TfOH), boron trifluoride diethyl etherate (BF₃•Et₂O), silver triflate (AgOTf), methyl triflate (MeOTf), triflic anhydride (Tf2O), and trimethylsilyl trifluoromethanesulfonate (TESOTf). [197] In certain embodiments, the reaction is carried out in the presence of a halogenating reagent. In certain embodiments, the reaction is carried out in the presence of an N-halosuccinimide. In certain embodiments, the N-halosuccinimide is N-chlorosuccinimide, N-bromosuccinimide, or N- iodosuccinimide. In certain embodiments, the N-halosuccinimide is N-iodosuccinimide (NIS). [198] The reaction may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the solvent is an aprotic solvent. In certain embodiments, the reaction is carried out in dichloromethane (DCM). [199] In certain embodiments, the reaction is carried out at a temperature below room temperature. In certain embodiments, the reaction is carried out at a temperature of from approximately -10 °C to approximately room temperature. In certain embodiments, the reaction is carried out at a temperature of approximately 0 °C. [200] In certain embodiments, the reaction is carried out in the presence of a Lewis acid. In certain embodiments, the reaction is carried out in the presence of a trialkyl silyl Lewis acid. In certain embodiments, the Lewis acid is trimethylsilyl trifluoromethanesulfonate (TMSOTf). Other non-limiting examples of acids include trifluoromethanesulfonic acid (TfOH), boron trifluoride diethyl etherate (BF₃•Et₂O), silver triflate (AgOTf), methyl triflate (MeOTf), triflic anhydride (Tf2O), and trimethylsilyl trifluoromethanesulfonate (TESOTf). [201] The reaction may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the solvent is an aprotic solvent. In certain embodiments, the reaction is carried out in dichloromethane (DCM). [202] In certain embodiments, the reaction is carried out at a temperature below room temperature. In certain embodiments, the reaction is carried out at a temperature of from approximately -78 °C to approximately 0 °C. In certain embodiments, the reaction is carried out at a temperature of approximately -30 °C. [203] In certain embodiments, the reaction is allowed to run for under 10 hours. In certain embodiments, the reaction is allowed to run for 0.1-2 hours. In certain embodiments, the reaction is allowed to run for approximately 0.5 hours.   [204] In certain embodiments, the method further comprises deprotecting a compound of Formula (13), or a salt thereof, to yield a compound of Formula (6):

or a salt thereof. [205] In certain embodiments, the compound of Formula (13) is:

, or a salt thereof; and the compound of Formula (6) is:

, or a salt thereof. [206] In certain embodiments, the method is carried out in the presence of a hydride transfer reagent. In certain embodiments, the hydride transfer reagent is a trialkylsilane. In certain embodiments, the hydride transfer reagent is triethylsilane (Et₃SiH). Other non-limiting examples of hydride transfer reagents include tetramethyldisiloxnae (TMDS), polymethylhydrogen siloxane (PMHS), borane, DIBAL-H, and sodium cyanoborohydride (NaCNBH₃). [207] In certain embodiments, the reaction is carried out in the presence of an acid. In certain embodiments, the acid is a Brønsted acid. In certain embodiments, the acid is an organic acid. In certain embodiments, the acid is a sulfonic acid. In certain embodiments, the acid is trifluoromethanesulfonic acid (TfOH). [208] The reaction may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the solvent is an aprotic solvent. In certain embodiments, the reaction is carried out in dichloromethane (DCM). [209] In certain embodiments, the reaction is carried out at a temperature below room temperature. In certain embodiments, the reaction is carried out at a temperature of from approximately -110 °C to approximately 0 °C. In certain embodiments, the reaction is carried out at a temperature of approximately -78 °C.   [210] In certain embodiments, the reaction is allowed to run for under 10 hours. In certain embodiments, the reaction is allowed to run for 0.1-2 hours. In certain embodiments, the reaction is allowed to run for approximately 0.5 hours. Methods for Preparing Compounds of Formula (5) [211] Compounds of Formula (5) can be prepared via compounds of Formula (16) as shown in Scheme 6. [1+1] glycosylation of a compound of Formula (17) with a compound of Formula (18) yields a Compound of Formula (16). In certain embodiments, a compound of Formula (16) is formed with high selectivity for the α-anomer (e.g., 10:1 or greater, 20:1 or greater, 100:1 or greater). In certain embodiments, the reaction is stereospecific for the α-anomer. In certain embodiments, the compound of Formula (16) is isolated in high yield (e.g., 50% or greater, 60% or greater, 70% or greater, 80% or greater). In certain embodiments, the compound of Formula (16) is isolated in greater than 80% yield, e.g., 80-90% yield. Subsequent conversion of the compound of Formula (16) to a glycosyl donor of Formula (5) can be achieved by treatment with a reagent of Formula (19). In certain embodiments, the compound of Formula (5) can be purified by crystallization.

  [212] Provided herein is a method of preparing a compound of Formula (16):

or a salt thereof, comprising reacting a compound of Formula (17):

or a salt thereof, in the presence of a compound of Formula (18):  

or a salt thereof, wherein: R^L6 a leaving group; R^1E is optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group; each R¹ is independently optionally substituted acyl or an oxygen protecting group; R³ is optionally substituted alkyl, optionally substituted acyl, or an oxygen protecting group; and R⁴ is optionally substituted acyl or a nitrogen protecting group. [213] In certain embodiments, R^L6 is –SR^S6, wherein R^S6 is optionally substituted phenyl. In certain embodiments, R^L6 is –SR^S6, wherein R^S6 is substituted phenyl. In certain embodiments, R^S6 is mono-, di-, or tri-substituted phenyl. In certain embodiments, R^S6 is disubstituted phenyl. In certain embodiments, S^{6 S}

R is 2,6-disubstituted phenyl. In certain embodiments, R ⁶ is of the formula: , wherein each instance of R'' is independently C_1-6 alkyl. In certain embodiments, R^S6 is:

dimethylphenyl; “DMP”). In certain embodiments, R^L6 is phenyl (Ph). In certain embodiments, R^L6 is – SPh. [214] In certain embodiments, at least one R¹ is optionally substituted acyl. In certain embodiments, each R¹ is optionally substituted acyl. In certain embodiments, at least one R¹ is –C(O)C_1-6 alkyl. In certain embodiments, each R¹ is –C(O)C_1-6 alkyl. In certain embodiments, at least one R¹ is Ac (i.e., –C(O)Me). In certain embodiments, each R¹ is Ac. [215] In certain embodiments, R^S1 is mono-, di-, or tri-substituted phenyl; and each R¹ is optionally substituted acyl. In certain embodiments, R^S1 is disubstituted phenyl; and each R¹ is optionally substituted acyl. In certain embodiments, R^S1 is 2,6-disubstituted phenyl; and each R¹ is optionally S¹

substituted acyl. In certain embodiments, R is of the formula: , wherein each instance of R'' is independently C_1-6 alkyl; and each R¹ is –C(O)C_1-6 alkyl. In certain embodiments, R^S1 is DMP; and each R¹ is Ac. In certain embodiments, R^L1 is SDMP; and each R¹ is Ac. [216] In certain embodiments, R² is a nitrogen protecting group. In certain embodiments, R² is a carbamate protecting group. In certain embodiments, R² is Troc (2,2,2-trichloroethoxycarbonyl).   [217] In certain embodiments, R³ is optionally substituted alkyl. In certain embodiments, R³ is optionally substituted C_1-6 alkyl. In certain embodiments, R³ is unsubstituted C_1-3 alkyl. In certain embodiments, R³ is methyl (Me). [218] In certain embodiments, R⁴ is optionally substituted acyl. In certain embodiments, R⁴ is –C(O)C_1-6 alkyl. In certain embodiments, R⁴ is Ac (i.e., –C(O)Me). [219] In certain embodiments, R^1E is an oxygen protecting group. In certain embodiments, R^1E is a mono-, di-, or tri-alkoxy substituted phenyl. In certain embodiments, R^1E is a mono-, di-, or tri-methoxy substituted phenyl. In certain embodiments, R^1E is para-methoxyphenyl (MP). [220] In certain embodiments, the compound of Formula (16) is:

, or a salt thereof; the compound of Formula (17) is:

, or a salt thereof; and the compound of Formula (18) is:

, or a salt thereof. [221] In certain embodiments, the reaction is carried out in the presence of an acid. In certain embodiments, the acid is a Brønsted acid. In certain embodiments, the acid is an organic Brønsted acid. In certain embodiments, the acid is a sulfonic acid. In certain embodiments, the acid is trifluoromethanesulfonic acid (TfOH). Other non-limiting examples of acids include trimethylsilyl trifluoromethanesulfonate (TMSOTf), boron trifluoride diethyl etherate (BF₃•Et₂O), silver triflate (AgOTf), methyl triflate (MeOTf), triflic anhydride (Tf2O), and trimethylsilyl trifluoromethanesulfonate (TESOTf). [222] In certain embodiments, the reaction is carried out in the presence of a halogenating reagent. In certain embodiments, the reaction is carried out in the presence of an N-halosuccinimide. In certain embodiments, the N-halosuccinimide is N-chlorosuccinimide, N-bromosuccinimide, or N- iodosuccinimide. In certain embodiments, the N-halosuccinimide is N-iodosuccinimide (NIS). [223] The reaction may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the solvent is an aprotic solvent. In certain embodiments, the reaction is   carried out in dichloromethane (DCM). In certain embodiments, the reaction is carried out in acetonitrile (MeCN). In certain embodiments, the reaction is carried out in DCM and MeCN. [224] In certain embodiments, the reaction is carried out at a temperature below room temperature. In certain embodiments, the reaction is carried out at a temperature of from approximately -78 °C to approximately 0 °C. In certain embodiments, the reaction is carried out at a temperature of approximately -35 °C. In certain embodiments, the reaction is carried out at a temperature of approximately -35 °C. [225] In certain embodiments, the reaction is allowed to run for under 10 hours. In certain embodiments, the reaction is allowed to run for 0.1-2 hours. In certain embodiments, the reaction is allowed to run for 0.5-1 hour. [226] In certain embodiments, the method further comprises (a) deprotecting a compound of Formula (16):

or a salt thereof, to remove the group R^1E; and (b) reacting the product with a reagent of Formula (19):

(19), to yield a compound of Formula (5):

or a salt thereof, wherein: R^L2 is optionally substituted aryl or optionally substituted heteroaryl; and X and X^L are each independently halogen. [227] In certain embodiments, R^L2 is optionally substituted aryl. In certain embodiments, R^L2 is optionally substituted phenyl. In certain embodiments, R^L2 is unsubstituted phenyl (Ph). In certain embodiments, each X is halogen. In certain embodiments, each X is –Cl. In certain embodiments, each X is –F. In certain embodiments, R^L2 is optionally substituted aryl; and each X is –F. In certain embodiments, R^L2 is optionally substituted phenyl; and each X is –F. In certain embodiments, R^L2 is Ph; and each X is –F. In certain embodiments, X^L is –Cl. [228] In certain embodiments, the compound of Formula (16) is:

,   or a salt thereof; the compound of Formula (19) is: CF₃C(=NPh)Cl; and the compound of Formula (5) is:

, or a salt thereof. [229] In certain embodiments, R^1E is a mono-, di-, or tri-alkoxy substituted phenyl (e.g., mono-, di-, or tri-methoxy substituted phenyl, e.g., para-methoxyphenyl (MP)); and the reaction in step (a) is carried out in the presence of an oxidant. In certain embodiments, the oxidant is ceric ammonium nitrate (CAN). Other non-limiting examples of oxidants include lithium in liquid ethylamine, silver oxide/nitric acid, silver (II) dipicolinate, etc. [230] The reaction in step (a) may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the solvent is an aprotic solvent. In certain embodiments, the reaction in step (a) is carried out in acetonitrile (MeCN). In certain embodiments, the reaction in step (a) is carried out in MeCN and water. [231] In certain embodiments, the reaction in step (a) is carried out at a temperature below room temperature. In certain embodiments, the reaction in step (a) is carried out at a temperature of from approximately -10 °C to approximately room temperature. In certain embodiments, the reaction in step (a) is carried out at a temperature of approximately 0 °C. [232] In certain embodiments, the reaction in step (a) is allowed to run for under 10 hours. In certain embodiments, the reaction in step (a) is allowed to run for 2-4 hours. In certain embodiments, the reaction in step (a) is allowed to run for approximately 3 hours. [233] In certain embodiments, the reaction in step (b) is carried out in the presence of a base. In certain embodiments, the base is an inorganic case. In certain embodiments, the base is a carbonate. In certain embodiments, the base is cesium carbonate Cs₂CO₃. [234] The reaction in step (b) may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the solvent is an aprotic solvent. In certain embodiments, the reaction is carried out in dichloromethane (DCM). [235] In certain embodiments, the reaction in step (b) is carried out at a temperature below room temperature. In certain embodiments, the reaction in step (b) is carried out at a temperature of from approximately -10 °C to approximately room temperature. In certain embodiments, the reaction in step (b) is carried out at a temperature of approximately 0 °C to approximately room temperature. [236] In certain embodiments, the reaction in step (b) is allowed to run for under 10 hours. In certain embodiments, the reaction in step (b) is allowed to run for 1-3 hours. In certain embodiments, the reaction in step (a) is allowed to run for approximately 2 hours.   One-Pot Methods for Preparing Core 2 O-sialyl Lewis^X Polysaccharides [237] Also provided herein are streamlined methods for preparing Core 2 O-sialyl Lewis^X polysaccharides such as compounds of Formula (C) and (1-v) via glycosylation reactions carried out in “one pot” (i.e., via a sequence of reactions carried out in a single reaction vessel).. In certain embodiments, the glycosylation reactions represented in Scheme 1 and Scheme 2 can be carried out in one pot, i.e., to prepare compound of Formula (1) which can be converted to compounds of Formula (C). For another example, see Figure 4. [238] For example, provided herein are methods of preparing a compound of Formula (1-i):

or a salt thereof, with a compound of Formula (5):

or a salt thereof; and (b) reacting the resulting compound with a compound of Formula (3-i):  

or a salt thereof, wherein: R^L1 is –SR^S1, wherein R^S1 is substituted phenyl; R^L2 is optionally substituted aryl or optionally substituted heteroaryl; each X is independently halogen; each R¹ is independently optionally substituted acyl or an oxygen protecting group; each R^1B is independently optionally substituted naphthylmethyl; R² is optionally substituted acyl or a nitrogen protecting group; R³ is optionally substituted alkyl, optionally substituted acyl, or an oxygen protecting group; R⁴ is optionally substituted acyl or a nitrogen protecting group; R^N is optionally substituted acyl or a nitrogen protecting group; and R^O is optionally substituted alkyl, optionally substituted acyl, or an oxygen protecting group. [239] In certain embodiments, R^S1 is mono-, di-, or tri-substituted phenyl. In certain embodiments, R^S1 is disubstituted phenyl. In certain embodiments, R^S1 is 2,6-disubstituted phenyl. In certain embodiments, S¹

R is of the formula: , wherein each instance of R'' is independently C_1-6 alkyl. In certain

[240] In certain embodiments, R^L2 is optionally substituted aryl. In certain embodiments, R^L2 is optionally substituted phenyl. In certain embodiments, R^L2 is unsubstituted phenyl (Ph). In certain embodiments, each X is halogen. In certain embodiments, each X is –Cl. In certain embodiments, each X is –F. In certain embodiments, R^L2 is optionally substituted aryl; and each X is –F. In certain embodiments, R^L2 is optionally substituted phenyl; and each X is –F. In certain embodiments, R^L2 is Ph; and each X is –F. [241] In certain embodiments, at least one R¹ is optionally substituted acyl. In certain embodiments, each R¹ is optionally substituted acyl. In certain embodiments, at least one R¹ is –C(O)C_1-6 alkyl. In certain   embodiments, each R¹ is –C(O)C_1-6 alkyl. In certain embodiments, at least one R¹ is Ac (i.e., –C(O)Me). In certain embodiments, each R¹ is Ac. [242] In certain embodiments, each R^1B is independently optionally substituted naphthylmethyl. In certain embodiments, each R^1B is independently unsubstituted naphthylmethyl. In certain embodiments, each R^1B is:

(2-naphthylmethyl; “Nap”). [243] In certain embodiments, R² is a nitrogen protecting group. In certain embodiments, R² is a carbamate protecting group. In certain embodiments, R² is Troc (2,2,2-trichloroethoxycarbonyl). [244] In certain embodiments, R³ is optionally substituted alkyl. In certain embodiments, R³ is optionally substituted C_1-6 alkyl. In certain embodiments, R³ is unsubstituted C_1-3 alkyl. In certain embodiments, R³ is methyl (Me). [245] In certain embodiments, R⁴ is optionally substituted acyl. In certain embodiments, R⁴ is –C(O)C_1-6 alkyl. In certain embodiments, R⁴ is Ac (i.e., –C(O)Me). [246] In certain embodiments, R^N is a nitrogen protecting group. In certain embodiments, R^N is a carbamate protecting group. In certain embodiments, R^N is fluorenylmethyloxycarbonyl (Fmoc). [247] In certain embodiments, R^O is optionally substituted C_1-6 alkyl. In certain embodiments, R^O is unsubstituted C_1-6 alkyl. In certain embodiments, R^O is optionally substituted C_1-4 alkyl. In certain embodiments, R^O is unsubstituted C_1-4 alkyl (e.g., methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl). In certain embodiments, R^O is tert-butyl (t-Bu). [248] In certain embodiments, the compound of Formula (1-i) is:

, or a salt thereof; the compound of Formula (6) is:

, or a salt thereof; the compound of Formula (5) is:  

, or a salt thereof; and the compound of Formula (3-i) is:

, or a salt thereof. [249] In certain embodiments, the reaction in step (a) is carried out in the presence of a Lewis acid. In certain embodiments, the reaction in step (a) is carried out in the presence of a trialkyl silyl Lewis acid. In certain embodiments, the Lewis acid is trimethylsilyl trifluoromethanesulfonate (TMSOTf). Other non-limiting examples of acids include trifluoromethanesulfonic acid (TfOH), boron trifluoride diethyl etherate (BF₃•Et₂O), silver triflate (AgOTf), methyl triflate (MeOTf), triflic anhydride (Tf2O), and trimethylsilyl trifluoromethanesulfonate (TESOTf). [250] In certain embodiments, the reaciton in step (a) is carried out in the presence of a drying agent. In certain embodiments, the drying agent is molecular sieves (e.g., 4 Å activated molecular sieves). [251] In certain embodiments, the reaction in step (a) is carried out at a temperature below room temperature. In certain embodiments, the reaction in step (a) is carried out at a temperature of from approximately -10 °C to approximately room temperature. In certain embodiments, the reaction in step (a) is carried out at a temperature of approximately -5 °C. [252] In certain embodiments, the reaction of step (a) comprises dropwise addition of the compound of Formula (5), or salt thereof, to the compound of Formula (6), or salt thereof. [253] In certain embodiments, the reaction in step (a) is allowed to run for under 10 hours. In certain embodiments, the reaction in step (a) is allowed to run for 0.1-2 hours. In certain embodiments, the reaction in step (a) is allowed to run for approximately 0.5 hours. [254] In certain embodiments, the reaction in step (b) is carried out in the presence of an acid. In certain embodiments, the acid is a Brønsted acid. In certain embodiments, the acid is an organic Brønsted acid. In certain embodiments, the acid is a sulfonic acid. In certain embodiments, the acid is trifluoromethanesulfonic acid (TfOH). Other non-limiting examples of acids include trimethyl trifluoromethanesulfonate (TMSOTf), boron trifluoride diethyl etherate (BF₃•Et₂O), silver triflate (AgOTf), methyl triflate (MeOTf), triflic anhydride (Tf2O), and trimethylsilyl trifluoromethanesulfonate (TESOTf). [255] In certain embodiments, the reaction ion step (b) is carried out in the presence of a halogenating reagent. In certain embodiments, the reaction in step (b) is carried out in the presence of an N-   halosuccinimide. In certain embodiments, the N-halosuccinimide is N-chlorosuccinimide, N- bromosuccinimide, or N-iodosuccinimide. In certain embodiments, the N-halosuccinimide is N- iodosuccinimide (NIS). [256] In certain embodiments, the reaction in step (b) is carried out at a temperature below room temperature. In certain embodiments, the reaction is carried out at a temperature of from approximately - 30 °C to approximately 0 °C. In certain embodiments, the reaction is carried out at a temperature of approximately -15 °C to approximately -5 °C. [257] In certain embodiments, the reaction in step (b) is allowed to run for under 10 hours. In certain embodiments, the reaction in step (b) is allowed to run for 1-3 hours. In certain embodiments, the reaction in step (b) is allowed to run for approximately 2 hours. [258] As described herein, the reactions in steps (a) and (b) are carried out in one pot. For example, in certain embodiments, a compound of Formula (5) is reacted with a compound of Formula (6) (e.g., by dropwise addition of (5) to (6)), followed by addition of a compound of Formula (3-i) to the reaction vessel. [259] In certain embodiments, the reactions of steps (a) and (b) are carried out in a solvent. In certain embodiments, the solvent is an aprotic solvent. In certain embodiments, the solvent is dichloromethane (DCM). [260] In certain embodiments, the compound of Formula (1-i) is isolated in high yield (e.g., 50% or greater, 60% or greater, 70% or greater). In certain embodiments, a compound of Formula (1-i) is obtained in greater than 60% yield. In certain embodiments, a compound of Formula (1-i) is obtained in 60-70% yield. [261] In certain embodiments, the method further comprises: (a) deprotecting the compound of Formula (1-i) to yield a compound of Formula (1-ii):

or a salt thereof;   (b) protecting the compound of Formula (1-ii), or salt thereof, to yield a compound of Formula (1-iii):

or a salt thereof; (c) reducing and protecting the compound of Formula (1-iii), or a salt thereof, to yield a compound of Formula (1-iv):

or a salt thereof; and (d) hydrolyzing the compound of Formula (1-iv), or a salt thereof, to yield a compound of Formula (1-v):

  or a salt thereof, wherein R⁵ is optionally substituted acyl or a nitrogen protecting group. [262] In certain embodiments, the compound of Formula (1-i) is:

, or a salt thereof; the compound of Formula (1-ii) is:

, or a salt thereof; the compound of Formula (1-iii) is:

, or a salt thereof; the compound of Formula (1-iv) is:  

, or a salt thereof; and the compound of Formula (1-v) is:

, or a salt thereof. [263] In certain embodiments, the reaction in step (a) is carried out in the presence of an oxidant. In certain embodiments, the oxidant is 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). [264] The reaction in step (a) may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the reaction is carried out in dichloromethane (DCM). In certain embodiments, the reaction in step (a) is carried out in dichloromethane (DCM) and water. [265] In certain embodiments, the reaction in step (a) is carried out at a temperature below room temperature. In certain embodiments, the reaction in step (a) is carried out at a temperature of from approximately -10 °C to approximately room temperature. In certain embodiments, the reaction in step (a) is carried out at a temperature from approximately 0 °C to approximately 30 °C. In certain embodiments, the reaction in step (a) is carried out at a temperature of approximately room temperature. [266] In certain embodiments, the reaction in step (a) is allowed to run for under 24 hours. In certain embodiments, the reaction in step (a) is allowed to run for 8-16 hours. In certain embodiments, the reaction in step (a) is allowed to run for approximately 12 hours. [267] In certain embodiments, each R¹ is optionally substituted acyl; and the reaction in step (b) is carried out in the presence of an acylating reagent (e.g., an acid anhydride). In certain embodiments, each   R¹ is –C(O)C_1-6 alkyl; and the reaction in step (b) is carried out in the presence of (C_1-6 alkyl-C(O))₂O. In certain embodiments, each R¹ is –Ac; and the reaction in step (b) is carried out in the presence of Ac₂O. [268] In certain embodiments, the reaction is step (b) is carried out in the presence of a nucleophile capable of activating the acylating reagent. In certain embodiments, the reaction in step (b) is carried out in the presence of 4-dimethylaminopyridine (DMAP). In certain embodiments, the reaction in step (b) is carried out in the presence of a base. In certain embodiments, the reaction in step (b) is carried out in the presence of pyridine. In certain embodiments, the reaction in step (b) is carried out in the presence of DMAP and pyridine. [269] The reaction in step (b) may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the solvent is pyridine. [270] In certain embodiments, the reaction in step (b) is carried out at a temperature from approximately 0 °C to approximately 30 °C. In certain embodiments, the reaction is carried out at approximately room temperature. [271] In certain embodiments, the reaction in step (b) is allowed to run for under 12 hours. In certain embodiments, the reaction in step (b) is allowed to run for 6-12 hours. In certain embodiments, the reaction in step (b) is allowed to run for approximately 8 hours. [272] In certain embodiments, the reaction in step (c) is carried out in the presence of a reducing agent. Any reducing agent capable of reducing an azide to an amine may be suitable in the reaction. In certain embodiments, the reducing agent is zinc (Zn) metal or zinc-copper couple (ZnCu). In certain embodiments, the reducing agent is a phosphine reagent (e.g., a triarylphosphine such as triphenylphosphine or polymer-bound triphenylphosphine). Other non-limiting examples of reducing agents include 1,3-propanedithiol and other dithiol reagents (e.g., under basic conditions), sodium borohydride, dichloroindium hydridge, hydrogenation reagents, thioacetic acid, NaCNBH₃, BH₃/THF, H₂/Pd(OH)₂, Zn-Pb, and Cd-Pb. [273] In certain embodiments, R⁵ is optionally substituted acyl; and the reaction in step (c) is carried out in the presence of an acylating reagent (e.g., an acid anhydride). In certain embodiments, R⁵ is –C(O)C_1-6 alkyl; and the reaction in step (c) is carried out in the presence of (C_1-6 alkyl-C(O))₂O. In certain embodiments, R⁵ is –Ac; and the reaction in step (c) is carried out in the presence of Ac₂O. [274] The reaction in step (c) may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the solvent is THF and/or AcOH. In certain embodiments, the solvent is a mixture of THF and AcOH. [275] In certain embodiments, the reaction in step (c) is carried out at a temperature below room temperature. In certain embodiments, the reaction is carried out at a temperature of from approximately - 10 °C to approximately room temperature. In certain embodiments, the reaction is carried out at a temperature of approximately 0 °C to approximately room temperature. [276] In certain embodiments, the reaction in step (c) is allowed to run for under 12 hours. In certain embodiments, the reaction in step (c) is allowed to run for 2-6 hours. In certain embodiments, the reaction in step (c) is allowed to run for approximately 4 hours.   [277] In certain embodiments, the reaction in step (d) is carried out in the presence of an acid. In certain embodiments, the acid is a Brønsted acid. In certain embodiments, the acid is an organic Brønsted acid. In certain embodiments, the acid is a carboxylic acid. In certain embodiments, the acid is trifluoroacetic acid (TFA). Other possible acids include formic acid, acetic acid, etc. [278] The reaction in step (d) may be carried out in a solvent, such as any solvent or mixture of solvents described herein. In certain embodiments, the solvent is an aprotic solvent. In certain embodiments, the reaction in step (d) is carried out in dichloromethane (DCM). [279] In certain embodiments, the reaction in step (b) is carried out at a temperature from approximately 0 °C to approximately 30 °C. In certain embodiments, the reaction in step (b) is carried out at a temperature from approximately 0 °C to approximately room temperature. In certain embodiments, the reaction in step (b) is carried out at approximately room temperature. [280] In certain embodiments, the reaction in step (c) is allowed to run for under 12 hours. In certain embodiments, the reaction in step (c) is allowed to run for 4-8 hours. In certain embodiments, the reaction in step (b) is allowed to run for approximately 6 hours. Compounds [281] Compounds of any generic or specific formula recited herein are also provided. For example, provided herein are compounds of any one of Formulae (1), (2), (3-i), (4), (5), (6), (7), (8), (9), (10), (11), (13), (14), (15), (16), (18), (A), (B), (C), (D), (1-i), (1-ii), (1-iii), (1-iv), or (1-v), and salts thereof. Species of any of the foregoing formulae, and salts thereof, are also provided herein. EXAMPLES [282] The present disclosure describes the total synthesis of GSnP-6, an analogue of the N-terminal domain of PSGL-1. An efficient, scalable, hydrogenolysis-free synthesis of C2-O-sLe^X-Thr-COOH was prepared by both convergent and orthogonal one-pot assembly, which afforded this crucial building block ready for direct use in solid phase peptide synthesis (SPPS). C2-O-sLe^X-Thr-COOH was synthesized in 10 steps with an overall yield of 23% from 4-O,5-N oxazolidinone thiosialoside donor. The synthesis represents an 80-fold improvement in reaction yield as compared to prior reports, achieving the first gram scale synthesis of SPPS ready C2-O-sLe^X-Thr-COOH. The insights gained in formulating this design strategy could be broadly applied to the synthesis of a wide variety of biologically important oligosaccharides and O-glycan bearing glycopeptides. [283] Many cell-cell recognition processes are dependent upon the presentation of unique glycans in the context of other aglycone components, but the combined recognition functions of such determinants are poorly understood. Glycosulfopeptides represent a novel class of such complex glycoconjugates that are present in a wide variety of cell surface receptors, including P-selectin glycoprotein ligand-1 (PSGL-1),^1-5 GPIbα,^6-9 endoglycan,^10-13 and CCR5,^14-18 among other related biomacromolecules. All told, glycosulfopeptides play critical roles in disorders of innate immunity, thrombosis, cancer, viral   infections, and ischemia-reperfusion syndrome.¹⁹ Detailed structural and mechanistic studies have revealed the presence of a recognition motif common to many glycosulfopeptides that consist of clustered tyrosine sulfates and a Core 2 O-glycan that bears a sialyl Lewis^X-containing hexasaccharide epitope (C2-O-sLe^X).^2-5 Despite the potential of glycosulfopeptides to serve as tools for biological studies and their promise as therapeutic agents, their utility has been limited by the absence of chemical schemes for their synthesis on scale. [284] As a representative biological molecule with a glycosulfopeptide domain, PSGL-1 is a cell surface glycoprotein that is expressed on all leukocytes and supports leukocyte recruitment in the context of a broad range of inflammatory and immune responses. PSGL-1 is a ligand for P-, E-, and L-selectins, but binds with highest affinity to P-selectin that is expressed on activated platelets and endothelial cells.^{1,4,20- 25} Ligation of P-selectin by PSGL-1 constitutes the initial “capture and rolling” step in the leukocyte- endothelial cell adhesion cascade.^22,24-27 Likewise, the interaction of PSGL-1 with P-selectin on activated platelets leads to leukocyte-platelet, platelet-platelet, and tumor-platelet aggregates that promote the adhesion and infiltration of both inflammatory and tumor cells with the generation of metastatic niches.^{28- 30} An anti-P-selectin antibody for the treatment of sickle cell disease has confirmed that P-selectin may be a druggable target for human disease.³¹ [285] A rationally designed novel glycosulfopeptide mimic of N-terminal PSGL-1, GSnP-6, has been reported as the first synthetic high affinity (Kd 22 nM) and specific P-selectin antagonist for human therapy.³² Moreover, it has been demonstrated that the ability of a pegylated form of GSnP-6 (P-G6) to prevent venous thrombosis in an established preclinical model of disease, without an attendant increase in bleeding risk, could be characteristically observed with anticoagulants.³³ Chemoenzymatic synthesis of GSnP-6 was accomplished from a synthetic glycopeptide intermediate, followed by enzymatic addition of galactose, sialic acid, and fucose residues using respective glycotransferases and nucleotide donors. Enzymatic synthesis offers great value in the context of protecting group free synthesis, but has a number of limitations, including a requirement for costly sugar nucleotide donors and recombinant enzymes, and a need for bioreactor process development and down-stream processing. Moreover, while glycosyltransferases are highly selective, they are associated with prolonged reaction times and often express poorly in E. coli. Consequently, glycosyltransferases have been widely used for lab scale preparation of complex carbohydrates,^4,32,34 but are not commonly used for large scale production processes. [286] In principle, total chemical synthesis should provide an expedient route to C2-O-sLe^X as a common building block for glycosulfopeptide mimics of PSGL-1, as well as many other biologically important glycopeptides. However, limitations of some reported schemes have hindered large scale synthesis of both an appropriately derivatized sLe^{X 38-47} intermediate and the related C2-O-glycan hexasaccharide bearing amino acid.^35-37 For example, Nicolau³⁸ and Danishefsky⁴⁷ reported the synthesis of related sLe^X intermediates for the production of more complex glycans with yields of 5% to 20%. Of the two reported synthetic schemes for C2-O-sLe^X hexasaccharide, Kunz et al. observed that [4+2] glycosylation led to significant loss of the desired product due to limited regioselectivity³⁶, with even   greater loss noted in the case of modified sLe^X mimetics.³⁷ In addition, late stage post glycosylation modifications, including hydrogenolysis for removal of benzyl protecting groups, the reintroduction of an Fmoc group, and a requirement for global acetylation, all contributed to further reductions in product yield.³⁷ While an important milestone, the reported protocol did not provide a practical route for scalable synthesis. Beginning from a benzylidene protected N-Troc glucosamine, the scheme required 15 steps to synthesize the C2-O-glycan intermediate ready for solid phase peptide synthesis (SPPS) with a mere overall yield of 0.29%.³⁷ Likewise, Boons et al.³⁵ reported the synthesis of a sLe^X derivative suitable for [4+2] glycosylation with an overall yield of 35%, which provided only 35 mg of the desired product. Similar to the aforementioned report, lack of a regioselective scheme for [4+2] glycosylation afforded 11.5 mg of final product at a reported yield of 55%. Yet, as a C2-O-glycan intermediate containing benzyl groups, further modifications would have been required to adequately prepare this intermediate for use in SPPS with an attendant reduction in synthetic efficiency and the capacity to achieve synthesis on scale. [287] In summary, an efficient and effective strategy for the scalable synthesis C2-O-sLe^X as a crucial intermediate for many glycopeptides of interest has not been achieved due to multiple shortcomings of existing schemes. In particular, inefficient sialylation strategies have been associated with poor stereo- and regioselectivity using diol or triol acceptors. Aglycone transfer side reactions often occur during glycosylation⁴⁸ and Chapmann rearrangement byproducts⁴⁹ are known to limit β-galactosylation. The synthesis of the C2-O-glycan hexasaccharide has been limited by poor regioselectivity of the β- glycosylation reaction, which is required to achieve efficient [4+2] coupling. Moreover, stereoselective synthesis of the Core-1-diol on a multigram scale has been difficult to accomplish because of challenges related to β-galactosylation. Further, incompatibility of protecting groups has often led to loss of fucose and cleavage of O-glycosidic linkages under acidic conditions required for deprotection of the Fmoc group,^50,51 which is necessary to incorporate the O-glycan-bearing amino acid into a peptide synthesis protocol. Finally, even after the synthesis of the protected glycopeptide, basic saponification conditions required for global deprotection of the glycan under harsher conditions risks β-elimination and loss of the entire glycan.⁵² All told, access to glycosylation ready disaccharides or tetrasaccharide donors required replacing protecting groups at multiple stages throughout the course of synthesis in order to extend the number of steps of the reaction sequence with associated product losses. In the process, reaction scalability and overall yield were significantly compromised in the generation of adequate quantities of C2-O-sLe^X bearing target glycopeptides necessary for fundamental biological investigations, as well as preclinical studies rendered all but inaccessible.^35-37,53 Total Synthesis of a PSGL-1 Analogue By Scalable Synthesis of a Core 2 O-Glycan Terminated with sLe^X [288] The present disclosure reports a practical, scalable, hydrogenolysis free and SPPS compatible assembly of C2-O-sLe^X-Thr-COOH. Key synthetic challenges were addressed through the design of disaccharide building blocks which were accessible through a highly efficient stereoselective route, in a   minimum number of steps, on a multigram scale, and were compatible with convergent and orthogonal one-pot strategies. The sLe^X derivative ready for [4+2] glycosylation was synthesized in >6 g quantity with an overall yield of 48% in 6 steps from a sialic acid 4-O, 5-N-oxazolidinone thiosialoside donor. The present disclosure describes a novel stereoselective scheme that led to multigram (>10 gm) scale synthesis of the Core-1-diol. The overall yield for the SPPS ready C2-O-sLe^X-Thr-COOH glycoamino acid starting from the oxazolidinone thiosialoside donor was 23% in 10 total steps with synthesis performed on a scale exceeding 1 gram. As a consequence of using a low temperature NIS/TfOH activation strategy, the synthetic approach does not suffer from any regioselective loss at the [4+2] glycosylation step with yields as high as 88%, and as the intermediate is not subject to hydrogenolysis, the principal Fmoc group remains intact. It was also demonstrated that C2-O-sLe^X-Thr-COOH can be synthesized through an orthogonal one-pot scheme. Solid phase peptide synthesis using the C2-O-sLe^X- Thr-COOH building block afforded GSnP-6 through a fragment-condensation strategy, followed by late stage deprotection of sulfonate and glycan protecting groups. Retrosynthetic analysis [289] The synthesis of glycosulfonopeptide GSnP-61 required the generation of C2-O-sLe^X-Thr-COOH 2 on multigram scale that was suitable for solid phase peptide synthesis. A retrosynthetic analysis identified three structural building blocks necessary to achieve this goal, including Core-1-diol 4, peracetylated sialyl galactose donor 5, and fucosylated glucosamine acceptor 6 (Figure 1). The synthesis of C2-O-sLe^X-Thr-COOH 2 from a regioselective [4+2] glycosylation between sLe^X tetrasaccharide 3 and a Core-1-diol 4 was hypothesized. To address the shortcoming of prior strategies, it was postulated that the sLe^X tetrasaccharide 3 would be best obtained through a [2+2] glycosylation between a peracetylated sialylated galactose donor 5 and a thio-2,6-dimethylphenyl (SDMP) aglycone bearing fucosylated galactosamine acceptor 6. This would afford a sLe^X tetrasaccharide 3 bearing thioglycoside prepared for [4+2] glycosylation. Moreover, it was postulated that these building blocks would facilitate assembly of the threonine hexasaccharide through either convergent block synthesis [2+2]+2 or through an orthogonal one pot strategy, enabling multigram synthesis (Figure 1). [290] A number of key elements were incorporated within the design of the synthetic scheme. First, an acetate (OAc) protected galactose acceptor was used for sialylation, which facilitated the use of milder basic conditions during global deprotection in order to avoid β-elimination. This strategy provided access to the sialylated galactose N-phenyl acetimidate donor 5 on multigram scale in a minimum number of steps and avoided the need for further functional group modifications. Second, being electron deficient, the peracetylated sialylated galactose N-phenyl acetimidate disaccharide donor provided access to multigram quantities of conjugation ready sLe^X tetrasaccharide 3 by suppressing orthoester formation,⁵⁴ Chapmann byproduct,⁴⁹ α-glycoside formation, as well as acyl migration from donor to acceptor,^55,56 which are common challenges during β-galactosylation, especially in the context of large-scale reaction conditions. Third, an optimally functionalized fucosylated glucosamine C4-OH acceptor, a building block recognized as less reactive and sterically less accessible due to C3-O-fucosylation, was identified   through a [2+2] parallel screening approach. This building block was able to avoid undesirable side reactions, including aglycone transfer reactions⁴⁸ and the loss of an acid labile fucose under Bronsted acidic conditions, which together often limit the ability to achieve higher yields and effective separation of the desired product. Finally, the Core-1-diol was accessed in a stereoselective fashion using ditertiary butyl silylene group (DTBS) mediated galactosamination^57,58 of a threonine acceptor with almost exclusive formation of the α-anomer on multigram scale, followed by galactosylation and removal of the DTBS group. Synthesis of disaccharide building blocks [291] The present disclosure describes the synthesis of an α-sialylated galactose donor 5. Stereoselective chemical synthesis of α-sialosides remains a significant challenge in carbohydrate chemistry and has been thoroughly explored over several decades.^59,60 Obstacles included the electron withdrawing nature of a carboxylate group linked to a tertiary anomeric center, the absence of a participating group at the C3 position, the E₁ elimination which led to a glycal byproduct, and the oxocarbenium ion favoring formation of a β-sialoside. In addition to the use of a variety of promoters for the sialylation reaction,^92-94 prior investigations have evaluated the modifications of the leaving group at C2,^65-70 the functionalization of the acetamide group at C5,^71-83 and the use of auxiliary groups at C1 and C3.^84-91 [292] Ultimately, the identification of an appropriate leaving group at C2 in combination with a highly electron withdrawing protecting group at N5 position led Takahashi,⁹⁵ Crich⁸¹ and De Meo⁹⁶ to develop α-selective 4-O,5-N-oxazolidinone and N-acetyl-4-O,5-N-oxazolidinone thiosialoside donors. Nonetheless, the low reactivity of thiosialoside donors has limited their use in programmable orthogonal one pot synthesis, which motivated Wong et al.⁹⁷ to employ a dibutyl phosphate leaving group with successful use of a highly reactive, α-selective phosphate donor in one pot synthesis of various sialic acid containing oligosaccharides. Ando et al. had reported that macrobicyclized constrained sialic acid donors were also able to achieve excellent yields with complete α-selectivity, and wide applicability to a variety of acceptors and complex sialoside targets.⁹⁸ In the context of the target, the rational design of a suitably functionalized acceptor was crucial to achieve α-sialylation on a multigram scale and minimize subsequent steps to obtain sialylated galactose donor 5 for use in either convergent or orthogonal one pot schemes. Most disarmed galactose acceptors led to high yielding α-sialylation incorporate benzoyl ester (OBz) protecting groups.⁹⁹ However, the use of OBz based building blocks proved to be incompatible with glycopeptide synthesis due to β-elimination of the entire glycan in the presence of basic conditions required for global deprotection (according to unpublished data). Therefore, the suitability of acceptors 8- 11 bearing acetate (OAc) protecting groups was evaluated under a variety of reaction conditions using a sialic acid phosphate donor 7 (Table 1).   Table 1. Stereoselective α-sialylation

^[a] Methods A-D in which sialylation was attempted using donor 7 [1equivalents], acceptors 8-11 [1.2equivalents], TMSOTf [1equivalent] and activated 4 Å MS. For 7a NIS [2equivalents], TfOH [0.2 equivalent] and method D was used. Method A [CH₂Cl₂, -78°C, 2 hours], Method B [CH₂Cl₂, -50°C, 1 hour], Method C [CH₂Cl₂:CH₃CN (2:1), -50°C, 1 hour], Method D [CH₂Cl₂:CH₃CN (1:10), -35°C, 0.5 hour].^[b] Depicts the isolated yields. α:β is the ratio from crude NMR. The reagents and present conditions were: [a] i. CAN, CH₃CN:H₂O [4:1], 0°C, 3 hours ii. CF₃C(NPh)Cl, Cs₂CO₃, 0°C, 2 hours, 68% over two steps. [293] Sialylation using acceptor 8 at -78°C in CH₂Cl₂ led to disaccharide 12 in 42% yield with 16% recovery of an aglycone transfer byproduct (Table 1. Entry 1).⁴⁸ Sialylation with acceptor 9, conducted under two different conditions in CH₂Cl₂, achieved greater selectivity and higher yield when acetonitrile was used as a co-solvent leading to disaccharide 13 (Table 1. Entry 2). The diol acceptor 10 was subjected to sialylation in a CH₂Cl₂:CH₃CN [2:1] solvent system at -50°C and produced disaccharide 14   in 62% yield with excellent selectivity (Table 1. Entry 3). Sialylation of the disarmed acceptor 11 under similar solvent and temperature conditions as that used for the diol acceptor generated disaccharide 15 with the exclusive α-anomer in 59% yield (Table 1. Entry 4). The disarmed acceptor 11 required the fewest protecting group manipulations to produce a peracetylated disaccharide donor ready for glycosylation. Further optimization, by modifying the ratio of CH₂Cl₂:CH₃CN from [2:1] to [1:10], together with an increase in reaction temperature to -35°C, afforded disaccharide 15 in 84% yield with exclusive α-selectivity (Table 1. Entry 4). The increase in yield was speculated to be due to acetonitrile stabilization of the oxocarbenium ion intermediate, in addition to the higher reactivity of acceptor 11 at - 35°C. Sialylation using donor 7a and acceptor 11 using NIS and TfOH afforded the desired disaccharide 11 in 83% yield with exclusive α-selectivity (Table 1. Entry 4), avoiding the extra step for phosphate donor synthesis. The OMP protected disaccharide 15 was converted to the N-phenyl trifluroacetimidate donor 5 in 68% yield over two steps. This is the first systematic study of sialylation using acetate (OAc) protected galactose acceptors and represents the shortest route for the synthesis of a peracetylated sialyl galactose disaccharide donor 5 suitable for glycosylation on multigram scale. [294] Synthesis of disaccharide acceptors 4 and 6 was observed. Three fucosylated glucosamine disaccharide acceptors 21, 22 and 6 were synthesized by [1+1] glycosylation, followed by regioselective opening of the naphthyl (Nap) acetal protecting group in a one pot scheme (Figure 2). The 4,6-Nap protected glucosamine C3-OH acceptors, 16, 17, and 18, displaying 3’-O-t-butyldiphenylsilyl (OTBDPS), thiophenyl (SPh) or SDMP aglycones, respectively, were synthesized from D- glucosamine^.HCl in six or fewer steps in good overall yield. Commencing with L-fucose, donors 19 and 20 were prepared in nine or fewer steps with an overall yield of 54% and 36%, respectively. The glucosamine acceptor 16 bearing an OTBDPS aglycone was coupled to donor 19 under NIS, TfOH activation conditions, and selective ring opening afforded 21 in 71% yield. Glucosamine acceptors 17 and 18, bearing SPh and SDMP aglycones, respectively, were coupled to donor 20 using TMSOTf as a promoter, followed by selective ring opening, which afforded 22 and 6, with yields of 64% and 61%, respectively. Stereoselectivity of the α-fucosidic linkage was confirmed using 1D and 2D NMR, with exclusive formation of the α-isomer due to a non-participating C2-ONap ether protecting group and remote participation of the 3,4-OAc protecting groups. The Core-1-diol acceptor 4 was synthesized on multigram scale (Figure 2). The ditertiary butyl silylene (DTBS) group favors stereoselective α-galactosylation by stabilization of the oxocarbenium ion via through-space electron donation, while limiting β-facial nucleophilic attack due to the presence of a bulky tert butyl group.^57,58 As a consequence, stereoselective attack from the α-face of the oxocarbenium ion leads to diastereoselective formation of an α-glycosidic linkage. As such, the DTBS protected donor 23 was coupled to the NHFmoc, tert butyl protected threonine acceptor 24 under NIS and TfOH activation conditions at 0°C. The threonine bearing galactosamine was synthesized with excellent α- selectivity [α:β = 32:1], which following deacetylation afforded 25 in 74% yield over two steps. The acceptor 25 was then coupled to peracetylated galactose trichloroacetimidate 26 to produce the DTBS   protected Core-1 disaccharide in 79% yield. Deprotection of DTBS group using tetrabutylammonium fluoride (TBAHF) at room temperature afforded the desired Core-1 diol in 86% yield. Multigram scale convergent assembly of C2-O-sLe^X-Thr-COOH suitable for solid phase peptide synthesis [295] Three distinct aglycone bearing fucosylated glucosamine acceptors 21, 22 and 6 were screened in a [2+2] glycosylation reaction with sialylated galactose donor 5 to provide the desired sLe^X tetrasaccharide (Figure 3). The [2+2] coupling of disaccharide donor 5 with disaccharide acceptor 21 bearing an OTBDPS aglycone was performed using TMSOTf as a promoter at 0°C and afforded the OTBDPS bearing tetrasaccharide 27 in 68% yield. The [2+2] glycosylation of disaccharide acceptor 22 bearing an SPh aglycone with donor 5 using TMSOTf as a promoter at 0°C afforded the SPh bearing tetrasaccharide 28 in 52% yield, but with an aglycone transfer byproduct isolated in 15% yield.⁴⁸ [296] In an attempt to suppress the aglycone transfer side reaction, glycosylation was performed at - 40°C while varying donor and acceptor equivalents, but the byproduct continued to be observed. As a consequence, [2+2] glycosylation was subsequently performed with donor 5 and disaccharide acceptor 6 bearing an SDMP aglycone at 0°C using TMSOTf as a promoter. The SDMP bearing sLe^X tetrasaccharide 29 was obtained in 77% yield without any trace of aglycone transfer byproduct, consistent with the ability of 2,6-dimethylphenyl (DMP) to effectively block aglycone transfer with thioglycosides.¹⁰⁰ Neither orthoester formation⁵⁴ or acyl migration from donor to acceptor^55,56 were observed, which was attributed to the highly disarmed nature of the donor and emphasizes the importance of rationally designed building blocks to circumvent side reactions that hinder higher glycosylation yields and facilitate product purification. The presence of a β-glycosidic linkage was confirmed by 1D and 2D NMR. Nap protecting groups were oxidatively cleaved using DDQ¹⁰¹ in aqueous CH₂Cl₂ and acetylated by reaction with acetic anhydride in pyridine to afford peracetylated sLe^X 3 and 31, bearing SPh and SDMP aglycones in 92% and 71% yields, respectively. This approach facilitated multigram synthesis of a sLe^X glycan, which can be readily conjugated to a variety of linkers at the reducing end, thereby, providing a means to generate large quantities of target compounds. [297] Peracetylated sLe^X tetrasaccharide donors 3 and 31 were coupled to Core-1-diol 4 under NIS, TfOH activation conditions at 0°C, which was followed by acetylation of C4-OH providing hexasaccharide 32 from 3 or 31 in 88% and 69% yields, respectively. Good reactivity of disarmed peracetylated sLe^X tetrasaccharides was observed under NIS activation conditions at 0°C.1D and 2D NMR confirmed regioselectivity and exclusive formation of a β-glycosidic linkage due to participation of the NHTroc group at the C2 position of glucosamine. Conversion of the NHTroc and N₃ protecting groups to acetamides in hexasaccharide 32 using Zn/AcOH/Ac₂O¹⁰², followed by cleavage of the tert butyl ester group of threonine afforded C2-O-sLe^X-Thr-COOH 2 in 55% yield over two steps (Figure 3). The overall yield for the SPPS ready C2-O-sLe^X-Thr-COOH starting from an oxazolidinone thiosialoside donor was 23% in 10 total steps, which afforded 1.27 g of the target compound in a single setting.   Orthogonal one-pot strategy [298] Disaccharide building blocks 4, 5, and 6 were designed to be compatible with either convergent [2+2]+2 synthesis or an orthogonal one pot strategy to afford C2-O-sLe^X-Thr-COOH 2. Screening of various parameters, including temperature, ratio of building block equivalents, and normal or inverse glycosylation approaches led to the successful synthesis of the desired hexasaccharide in very good yield on a 250 mg scale (Figure 4). [299] Initially, one-pot glycosylation was attempted under a standard glycosylation protocol with donor 5 and acceptor 6, followed by the addition of acceptor 4a. Due to the low reactivity of fucosylated C4- OH glucosamine acceptor 6, nearly half of the acceptor remained unreacted at -5°C after 30 minutes (Table 2. Entry 1). After the addition of the Core-1 acceptor under NIS/TfOH activation conditions, formation of various side products resulted in a yield of 27%. To address the low reactivity of 6, excess donor 5 (>2.5 to 3equivalents) would have been required under normal glycosylation conditions. To mitigate this requirement, a one pot reaction was performed at lower temperature with extended reaction times and slow warming of the reaction mixture. Conducting the reaction at -78°C to 0°C with 1.5 (Table 2. Entry 2) and 2 equivalents (Table 2. Entry 3) of donor 5 for a period of 4 hours led to yields of 30 to 34%. Table 2: Reaction screening for orthogonal one-pot synthesis of hexasaccharide 33 ^[

^a] Entry 1 in which both donor 5 and acceptor 6 were dried and activation was done using TMSOTf, followed by addition of acceptor 4a under NIS/TfOH activation. ^[b] shows that Donor 5 was added to a solution of acceptor 6 and 30 mol% TMSOTf, followed by addition of acceptor 4a under NIS/TfOH activation conditions. ^[c] shows the isolated yield after column chromatography. [300] Due to the low reactivity of acceptor 6, it was hypothesized that an inverse glycosylation protocol with dropwise addition of donor 5 to a reaction mixture of acceptor 6 and TMSOTf (30 mol%) would shift the equilibrium towards the formation of the desired sLe^X tetrasaccharide 29. The inverse glycosylation protocol was attempted with 2 equivalents of donor 5 (Table 2. Entry 4) and 1 equivalents of acceptor 6, leading to the total consumption of the fucosylated glucosamine acceptor in less than 30 minutes at -5°C. As a consequence of using excess acceptor (2equivalents), the desired sLe^X was   observed as the major product and also led to the formation of a hemiacetal. Addition of acceptor 4a under NIS and TfOH activation led to the formation of the desired hexasaccharide 33 in 52% yield. The inverse protocol was further optimized to minimize formation of a hemiacetal and tertiary butyl group cleavage under acidic glycosylation conditions. Use of 1.2 equivalents of donor 5 under the inverse protocol led to clean conversion of acceptor 6 to sLe^X, as demonstrated by TLC and MALDI within 15 minutes. The acceptor 4a was then added, followed by addition of NIS/TfOH at -10°C with slow warming to 0°C, resulting in the formation of the desired hexasaccharide 33 in 66% yield at 250 mg scale (Table 2. Entry 5). Hexasaccharide 33 was subjected to DDQ oxidation conditions to remove the Nap protecting groups,⁹⁸ followed by acetylation to provide the peracetylated hexasaccharide 32 in 72% yield over two steps. Compound 32 was subject to Zn/AcOH mediated acetamide formation⁹⁹ and tert butyl ester cleavage using TFA/Et₃SiH, which afforded C2-O-sLe^X-Thr-COOH 2 in 62% yield, ready for solid phase peptide synthesis (Figure 3). Solid phase peptide synthesis of GSnP-6 and Global deprotection [301] Solid phase peptide synthesis was accomplished on a 70 µmol scale via a fragment-condensation strategy. Common peptide synthesis reagents were used including NovaSyn®TGA resin, Fmoc-amino acids, 1-hydroxy benzotriazole (HOBt), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU), and 20% piperidine for Fmoc deprotection. Acid labile tyrosine sulfate building blocks were replaced with a bioisosteric sulfonate analogue, Fmoc Phe (p-CH₂SO₃H). In brief, Fmoc-Glu-OH and Fmoc-Pro-OH were coupled to NovaSyn®TGA resin preloaded with Fmoc-Leu-OH, followed by coupling of the Fmoc-hexasaccharide-Thr-OH 2 in the presence of O-(benzotriazol-1-yl)- N,N,N’,N’-tetramethyluronium tetrafluoroborate (TBTU), HOBT, and trimethylpyridine in DMF. To deprotect the Fmoc group, the resin was rinsed with 2% DBU and 1% dithiothreitol (DTT) in DMF, which also led to the opening of the 4O,5N-oxazolidinone ring of sialic acid. In order to maximize yield, the N-terminal fragment of GSnP-6 was then coupled directly to the resin. The fully protected 13 residue N-terminal fragment was synthesized separately on 2-CTC resin pre-loaded with Fmoc-Glu-OH in 63% yield. The synthesized peptide fragment displayed >90% purity on high-performance liquid chromatography (HPLC) and was used without further purification. After washing, the fragment was coupled in a solution of TBTU, HOBT, and trimethylpyridine in DMF. The final product was cleaved off the resin using aqueous 95% trifluoracetic acid (TFA), 1,2-ethanedithiol (EDT), and triethyl silane, precipitated by cold ether, and purified by reversed-phase high-performance liquid chromatography (RP- HPLC) to provide 122 mg of the protected glycosulfonopeptide in 38% overall yield. [302] Tricholoroethyl (TCE) protected phenylalanine sulfonates were initially deprotected by hydrogenation using palladium on carbon and the product purified by RP-HPLC with a yield of 76%. Acetate protecting groups and the methyl ester group were subsequently hydrolyzed using sodium methoxide at pH 8.0-8.5, followed by lithium hydroxide at pH 10.5-11, affording the fully deprotected glycosulfonopeptide, GSnP-6 (1) after RP-HPLC purification in 41% yield.   [303] A total chemical synthesis was described for C2-O-sLe^X-Thr-COOH, which was suitable for incorporation within a solid phase peptide synthesis scheme without further modification. The critical intermediate afforded the total chemical synthesis of GSnP-6, a glycosulfonopeptide analogue of the N- terminal domain of PSGL-1, which had been identified as a potent inhibitor of P-selectin, and facilitated the synthesis of a variety of other O-glycan bearing peptides and glycosulfopeptides for fundamental biological studies, as well as the design of therapeutic and diagnostic agents. Through the use of three disaccharide building blocks with compatible protecting groups, both convergent and one pot schemes for the scalable synthesis of the hexasaccharide bearing amino acid were designed. Beginning with an oxazolidinone thiosialoside donor, a sialyl Lewis^X derivative was initially synthesized on a scale exceeding 6 grams in 6 steps with an overall yield of 48%. This afforded C2-O-sLe^X-Thr-COOH on a scale exceeding 1 gram in 4 additional steps ready for SPPS with an overall yield of 23%. [304] Several innovations were helpful to improving efficiency and providing an 80-fold improvement in reaction yield as compared to prior reports, achieving the first gram scale synthesis of SPPS ready C2- O-sLe^X-Thr-COOH. In particular, the use of benzyl free peracetylated building blocks established an expedient, practical, and scalable route to a hexasaccharide bearing amino acid without the need for hydrogenolyis. Synthesis of the sialyl Lewis^X derivative benefited from the use of a peracetylated sialyated galactose N-phenyl acetimidate disaccharide donor, which suppressed orthoester formation, Chapmann rearrangement byproducts, and α-glycoside formation. Moreover, a thio-2,6-dimethylphenyl (SDMP) donor group was exploited and crucial to avoiding aglycone transfer and incorporation of naphthyl acetyl protecting groups further enhanced the stability of the [2+2] glycosylation reaction. Finally, employing a ditertiary butyl silylene (DTBS) group proved beneficial in the synthesis of the Core-1-diol by favoring stereoselective α-galactosylation, which provided access to a single glycosylated isomer. Total chemical synthesis of GSnP-6 was successfully achieved by a peptide fragment condensation protocol and by avoiding the use of benzoyl based building blocks, β-elimination of the entire glycan was averted during the late stage basic deprotection sequences. [305] In summary, longstanding challenges that have limited the ability to achieve a scalable synthetic pathway for an essential O-glycan bearing amino acid were overcome through the rational design of disaccharide building blocks. The assembly of these building blocks afforded hydrogenolysis-free synthesis of C2-O-sLe^X-Thr at gram scale, ready for solid phase peptide synthesis, which led to the total synthesis of GSnP-6, a high affinity P-selectin inhibitor with promising preclinical properties. 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S.; Rao, V. R.; Bertozzi, C. R. A Chemically Synthesized Version of the Insect Antibacterial Glycopeptide, Diptericin, Disrupts Bacterial Membrane Integrity. Biochemistry 1999, 38, 11700–11710. 103) Piel F. B.; Patil A. P.; Howes R. E.; et al. Global epidemiology of sickle haemoglobin in neonates: A contemporary geostatistical modelbased map and population estimates. Lancet 2013, 381, 142–151. 104) Ranque B.; Kitenge R.; Ndiaye D. D.; Ba M. D.; Adjoumani L.; Traore H.; Coulibaly C.; Guindo A.; Boidy K.; Mbuyi D.; Ly I. D.; Offredo L.; Diallo D. A.; Tolo A.; Kafando E.; Tshilolo L.; Diagne I. Estimating the risk of child mortality attributable to sickle cell anaemia in sub-Saharan Africa: A retrospective, multicentre, case-control study. Lancet Haematol 2022, 9, e208-e216. General Techniques [306] All reagents and solvents were purchased from commercial suppliers and were used without further purification unless otherwise specified. All reactions were performed in an atmosphere of dry argon. All organic extracts were dried over sodium sulfate and concentrated under vacuum. [307] The reactions were monitored by thin layer chromatography (TLC) carried out on Sigma-Aldrich pre-coated glass backed plates (w/UV 254) and visualized by UV irradiation (254 nm) or by staining with 25% H₂SO₄ in EtOH or a ceric ammonium molybdate solution. Chromatographic purifications were carried out over silica gel. Automated column chromatography separations were performed on a TELEDYNE CombiFlash R_f 150. [308] ¹H, ¹³C, ³¹P and 2D NMR spectra were recorded at 400, 600 MHz (Bruker). Chemical shifts were reported in δ (ppm) relative units to residual solvent peaks CDCl₃ (7.26 ppm for ¹H and 77.0 ppm for ¹³C), acetone-d₆ (2.09 ppm and 2.84 ppm for ¹H and 30.60 ppm and 205.87 ppm for ¹³C) and DMSO-d6 (2.50 ppm for ¹H and 39.52 ppm for ¹³C). NMR multiplicities were reported using the following abbreviations: [s (singlet), d (doublet), t (triplet), q (quartet), quint (quintet), multiplet (m), dd (doublet of   doublets), and td (triplet of doublets)]. Assignments of proton and carbon signals were achieved by additional COSY, TOCSY, HSQC, and HMBC experiments. [309] High resolution mass spectra were recorded with an electrospray source coupled to a time-of-flight mass analyzer (MALDI, Bruker) with 2-hydroxy-5-methoxybenzoic acid (Super- DHB) as matrix. Procedures and Characterization Data Methyl (5-acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl-2-(dibutylphosphoryl)-3,5-dideoxy-D-glycero-

[310] A solution of sialic acid-oxazolidinone derivative 7a¹ (4.0 g, 7.19 mmol, 1.0 equivalent.), dibutyl phosphate (7.46 g, 35.50 mmol, 5.0 equivalents), and activated 4 Å powdered molecular sieves (~4.0 g) in anhydrous CH₂Cl₂ (60 mL) was stirred for 1 hour under argon, and then cooled to 0°C followed by the simultaneous addition of NIS (3.11 g, 13.82 mmol, 2.0 equivalents.) and TfOH (0.24 mL, 1.41 mmol, 0.4 equivalents). After 20 minutes, a second lot of TfOH (0.24 mL, 1.41 mmol, 0.4 equivalents.) was added and the resulting reaction mixture stirred for 3 hours at 0°C and then quenched with sat. Na₂S₂O₃ and sat. NaHCO₃ solutions. The TLC system was 60% EtOAc : hexanes. The mixture was diluted with CH₂Cl₂, washed with sat. NaHCO₃ and brine, and filtered through a celite bed with the organic layer concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc : hexanes, 1:1) to afford the sialic acid-phosphate donor 7 (3.47 g, yield 73%) as a white foam in a 1:1 ratio (α:β). [311] [α]_D ²⁶= +82.5 (c=0.20, CH₂Cl₂); R_f 0.40 (EtOAc, Hexanes; 3:2); ¹H NMR (400 MHz, Chloroform- d) δ 5.67 – 5.55 (m, 2H), 5.32 – 5.17 (m, 2H), 4.70 (ddd, J = 11.8, 9.5, 1.8 Hz, 2H), 4.60 – 4.45 (m, 2H), 4.37 (dd, J = 12.3, 2.8 Hz, 1H), 4.20 – 4.08 (m, 2H), 4.04 (dtd, J = 9.6, 5.6, 4.6, 2.8 Hz, 5H), 3.86 – 3.77 (m, 5H), 3.74 (dd, J = 11.3, 9.5 Hz, 1H), 2.96 (dd, J = 12.2, 4.0 Hz, 1H), 2.85 (dd, J = 12.7, 3.7 Hz, 1H), 2.70 – 2.59 (m, 1H), 2.26 (td, J = 12.8, 2.9 Hz, 1H), 2.17 – 2.03 (m, 8H), 1.99 (d, J = 3.5 Hz, 4H), 1.64 (ddt, J = 14.7, 8.9, 5.3 Hz, 6H), 1.37 (hept, J = 7.3 Hz, 6H), 1.21 (d, J = 2.7 Hz, 2H), 0.90 (td, J = 7.4, 1.9 Hz, 9H); ¹³C NMR (100 MHz, Chloroform-d) δ 172.05, 171.73, 170.50, 170.47, 169.89, 169.77, 169.66, 167.24, 167.17, 165.47, 153.45, 153.41, 98.82, 98.76, 98.17, 98.11, 77.37, 77.16, 77.05, 76.73, 76.57, 74.13, 73.96, 72.49, 71.71, 71.43, 69.76, 68.48, 68.42, 68.32, 68.27, 68.08, 68.02, 67.97, 67.90, 62.78, 62.46, 58.84, 58.28, 53.42, 53.40, 53.37, 36.04, 35.98, 35.86, 35.82, 32.12, 32.09, 32.05, 32.02, 31.99, 29.62, 24.56, 24.54, 20.93, 20.89, 20.72, 20.66, 18.58, 18.55, 18.53, 13.50, 13.47; HR-MALDI- TOF/MS (positive, SuperDHB matrix): m/z calcd for C₂₇H₄₂NNaO₁₆P [M+Na]⁺ 690.2139, observed: 690.2149.   Phenyl 4,6-O-benzylidene-2-O-acetyl-1-thio-β-D-galactopyranoside (8)

[312] Tetrahydroxy thiogalactoside G1³(500.0 mg, 1.84 mmol, 1.0 equivalents) and camphor-10- sulfonic acid (86.0 mg, 0.370 mmol, 0.2 equivalents) were dissolved in 2,2-dimethoxypropane (15.0 mL) and stirred overnight at room temperature. The reaction was quenched by addition of triethylamine (0.5 mL) and the solvent was evaporated under reduced pressure. The product was purified by flash chromatography (1:1 ethyl acetate/hexanes, 0.1% triethylamine) to yield the galactose acetonide derivative G2 as a white solid (530.0 mg, 75% yield). The resulting compound was subjected to acetylation without further characterization. The galactose acetonide derivative G2 (310 mg, 0.81 mmol, 1.0 equivalent) was reacted with acetic anhydride (0.5 mL) and pyridine (1.2 mL) followed by DMAP (4.0 mg) and the solution was stirred at room temperature for 3.5 hours. The solvent was removed under reduced pressure and the product purified by flash chromatography (ethyl acetate/hexanes 1:3, with 0.1% triethylamine) to afford the acetylated compound G3 as a white solid (270.0 mg, 84% yield); R_f 0.7 (2:3 ethyl acetate/hexanes).2-Acetyl galactose derivative G3 (270 mg, 0.63 mmol) was dissolved in an aq. acetic acid solution (80%, 3.0 mL) and the reaction mixture stirred at 70°C for 1.5 hours. The solvent was evaporated and the residue dried by azeotropic co-distillation using toluene. The residue was then suspended in acetonitrile (4.0 mL) and treated with benzaldehyde dimethyl acetal (436.0 mg, 2.87 mmol, 5 equivalents) and camphorsulfonic acid (26 mg, 0.11 mmol, 0.2 equivalents). The mixture was stirred at room temperature for 2 hours and the reaction quenched by the addition of triethylamine (40 µL, 0.5 equivalents). The product was purified by chromatography (1:1 ethyl acetate/hexanes) to afford 8 as a white foam (201.0 mg, 62% yield for 3 steps). ^{[313] R} _f ^{0.4 (4:1 ethyl acetate/hexanes); 1}H NMR (400 MHz, Chloroform-d) δ 7.65 – 7.56 (m, 2H), 7.44 – 7.35 (m, 5H), 7.37 – 7.22 (m, 3H), 5.51 (s, 1H, Benzylidene), 5.04 (t, J = 9.6 Hz, 1H, H-2), 4.64 (d, J = 9.8 Hz, 1H, H-1), 4.39 (dd, J = 12.5, 1.6 Hz, 1H, CH₂), 4.22 (dd, J = 3.7, 1.1 Hz, 1H, H-5), 4.03 (dd, J = 12.5, 1.8 Hz, 1H, CH₂), 3.74 (ddd, J = 11.2, 9.5, 3.7 Hz, 1H, H-3), 3.55 (q, J = 1.6 Hz, 1H, H-4), 2.46 (d, J = 11.2 Hz, 1H, OH), 2.14 (s, 3H, OAc).¹³C NMR (100 MHz, Chloroform-d) δ 133.68, 129.38, 128.77, 128.24, 128.11, 126.53, 101.54 (Benzylidene), 84.78 (C-1), 75.53 (C-5), 72.77 (C-3), 70.03 (C-2), 69.92 (C-4), 69.11 (CH₂), 21.07 (CH₃CO); ESI/Mass: m/z calcd for C₂₆H₂₄NaO₆S [M+Na]⁺ 425.1035, observed: 487.1085.  

2-O-Napthyl-3,4-diacetate-1-thio-α-L-fucopyranoside (19) [314] Ethanethiol (8.62 mL, 2 equivalents, 119.6 mmol) was added to compound F1 (20 g, 1 equivalent, 59.8 mmol) in anhydrous CH₂Cl₂ (150 mL) and cooled to 0°C. After 10 minutes, BF₃ ^.Et₂O (22 mL, 1.5 equivalents, 89.8 mmol) was slowly added in a dropwise manner and the ice bath was removed after 20 minutes, with continued stirring at room temperature for an additional 2 hours. TLC analysis confirmed completion of the reaction. The reaction mass was slowly added to a cooled aq. NaHCO₃ solution (300 mL) with mild stirring and transferred into a separatory funnel. The aqueous layer was extracted with CH₂Cl₂ (50 mL) and all organic layers mixed, washed with aq. NaHCO₃ (250 mL) and brine (200 mL), and subsequently dried over Na₂SO₄, which was removed under reduced pressure. Flash silica gel column chromatography using 25% EtOAc in hexanes (gradient method) afforded the desired compound F2 (18 g, 90%). [315] Compound F2 (18 g, 1 equivalent, 54 mmol) was dissolved in methanol (120 mL), NaOMe (1.45 g, 0.5 equivalents, 26.9 mmol) added and stirred at room temperature for 2 hours with AcOH (pH~5) or Amberlyst® 15/Dowex® H⁺ resin added to adjust the pH to 5-6. Solvents were removed under reduced pressure and the triol was obtained through flash column chromatography to afford the desired triol intermediate (10.6 g, 95%). The triol was co-distilled with toluene (2 x 75 mL) and dried under high vacuum. [316] The triol intermediate (10.6 g, 1 equivalent, 50.9 mmol) was dissolved in acetonitrile (100 mL), and 2,2-dimethoxy propane (2,2-DMP) (9.35 mL, 1.5 equivalents, 76.44 mmol), and camphor-10- sulfonic acid (CSA), added to pH ~ 1, were combined and continually stirred at room temperature for 1 hour. Et₃N (pH ~ 9-10) was subsequently added, the solvents were removed under reduced pressure, the reaction mixture was diluted with EtOAc (400 mL) and washed with H₂O (2 x 100 mL), aq. NaHCO₃ (2 x 100 mL) and sat. NaCl (2 x 75 mL). The solvent was dried over Na₂SO₄, removed under reduced pressure, and a final co-distillation was performed with toluene (3 x 50 mL) to afford the isopropylidene intermediate (9.7 g, 78%), which was dried under vacuum and used without further purification. [317] The isopropylidene intermediate^4,5 (9.7 g, 1 equivalent, 39.11 mmol) was dissolved in DMF (60 mL) and cooled to 0°C. NaH (3.13 g, 2 equivalents, 78.22 mmol) was added slowly in portions, followed by the addition of 2-NapBr (10.37 g, 1.2 equivalents, 46.94 mmol). The ice bath was removed after 20 minutes and the reaction stirred for 2 hours at room temperature. MeOH (30 mL) was slowly added in a   dropwise manner at 0°C using a dropping funnel and the reaction mixture stirred for 30 minutes, followed by removal of solvents to one-half volume under vacuum. The reaction mixture was diluted with EtOAc (200 mL) and washed with ice cold water (3 x 100 mL) and sat. NaCl wash (100 mL). The solvent was dried over Na₂SO₄, which was then removed under reduced pressure to obtain the napthyl isopropylidene intermediate F3 (quantitative) that was used without further purification. [318] The napthyl isopropylidene intermediate F3 (10.35 g, 1 equivalent) was dissolved in AcOH (160 mL) and H₂O (40 mL), and heated to 65°C for 4 hours. Solvents were removed under vacuum and co- distilled with toluene (4 x 100 mL) to the dihydroxy napthyl intermediate (quantitative) that was used without further purification. [319] The dihydroxy napthyl intermediate (9.74 g, 1 equivalent) was dissolved in pyridine (70 mL) and Ac₂O (35 mL). DMAP (Cat.) was added and the reaction mixture stirred at room temperature for 4 hours, after which TLC confirmed consumption of the starting materials and formation of the product. Solvents were removed under vacuum, the product co-distilled with toluene (2 x 100 mL), and purified using flash silica gel chromatography with 20% EtOAc in hexanes (gradient method) to afford compound 19 (9.36 g, 78%). [320] [α]_D ²⁶= +45.1 (c=0.20, CH₂Cl₂); R_f 0.20 (EtOAc, Hexanes; 3:2); ¹H NMR (600 MHz, Chloroform- d) δ 7.81 – 7.76 (m, 4H, Ar-H), 7.47 – 7.44 (m, 3H, Ar-H), 5.26 – 5.25 (m, 1H, H-4), 5.06 – 5.02 (m, 2H, H-3, Nap CH₂), 4.78 – 4.76 (d, J = 11.3 Hz, 1H, Nap CH₂), 4.56 – 4.55 (d, J = 9.7 Hz, 1H, H-1), 3.79 – 3.77 (m, 1H, H-5), 3.71 – 3.68 (t, J = 9.7 Hz, 1H, H-2), 2.84 – 2.77 (m, 2H, SCH₂CH₃), 2.13 (s, 3H, OAc), 1.89 (s, 3H, OAc) 1.35 – 1.33 (t, J = 7.4 Hz, 3H, SCH₂CH₃) 1.21 – 1.20 (d, J = 6.2 Hz, 3H, H- 6/CH₃); ¹³C NMR (125 MHz, Chloroform-d) δ 170.7, 170.2, 135.6, 133.3, 133.1, 128.2, 127.9, 127.8, 126.7, 126.2, 126.1, 85.3, 76.4, 75.6, 74.6, 73.3, 72.9, 72.5, 71.1, 25.3, 20.9, 16.6, 15.1; HR-MALDI- TOF/MS (positive, SuperDHB matrix): m/z calcd for C₁₂H₁₉O₅S [M+Na]⁺ 275.0953, found: 275.0958. 2-O-Napthyl-3,4-diacetate-1-hydroxy-L-fucopyranoside (19a) [321] Compound 19 (9.36 g, 1 equivalent) was dissolved in acetone:water (4:1, 80 mL:20 mL) and powdered NBS was added in portions at 0°C for a period of 30 minutes. The ice bath was then removed, and the reaction mixture stirred at room temperature for 2 hours after which TLC confirmed depletion of the starting materials and formation of product. Solvents were removed under vacuum, the product was diluted with EtOAc (200 mL) and washed with sat aq. NaHCO₃ (2 x 100 mL), sat aq. Na₂S₂O₃ (2 x 75 mL), and brine (100 mL). The organic layer was separated and dried over Na₂SO₄, solvents were removed under vacuum, and the crude was purified using flash silica gel chromatography using 20% EtOAc in hexanes (gradient method) to afford compound 19a as a syrupy oil in 1:1 mixture of isomers (7.2 g, 84%). [322] [α]_D ²⁶= +61.3 (c=0.20, CH₂Cl₂); R_f 0.30 (EtOAc, Hexanes; 3:2); ¹H NMR (600 MHz, CDCl₃) δ 7.92 – 7.63 (m, 8H), 7.44 (dddd, J = 10.6, 8.8, 3.2, 1.4 Hz, 6H), 5.49 – 5.31 (m, 2H), 5.32 (d, J = 3.2 Hz, 1H), 5.25 (dd, J = 3.5, 1.2 Hz, 1H), 5.15 (dd, J = 3.5, 1.0 Hz, 1H), 5.10 – 4.94 (m, 2H), 4.84 (d, J = 11.9 Hz, 1H), 4.79 (s, 2H), 4.73 (d, J = 6.2 Hz, 2H), 4.26 (qd, J = 6.5, 1.3 Hz, 1H), 4.10 (q, J = 7.1 Hz, 1H),   3.98 (d, J = 2.9 Hz, 1H), 3.87 (dd, J = 10.4, 3.5 Hz, 1H), 3.70 – 3.49 (m, 2H), 2.08 (d, J = 2.2 Hz, 7H), 2.01 (s, 1H), 1.99 (s, 4H), 1.94 (s, 3H), 1.22 (t, J = 7.1 Hz, 1H), 1.06 (m, 6H); ¹³C NMR (151 MHz, CDCl₃) δ 171.39, 170.73, 170.68, 170.34, 170.32, 135.88, 135.26, 133.24, 133.19, 133.07, 132.98, 128.27, 127.99, 127.85, 127.84, 127.71, 127.66, 126.59, 126.43, 126.29, 126.12, 125.90, 125.66, 97.33, 91.50, 77.67, 74.72, 73.92, 73.10, 72.80, 71.64, 70.82, 70.02, 68.86, 64.34, 60.47, 20.99, 20.85, 20.73, 20.61, 20.60, 16.08, 15.88, 14.15. HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₂₁H₂₄NaO₇ [M+Na]⁺ 411.1420, found: 411.1418. 2-O-Napthyl-3,4-diacetate-1-trichloroacetimido-α-L-fucopyranoside (20) [323] Compound 19a (7.2 g, 1 equivalent) was dissolved in anhydrous CH₂Cl₂ (40 mL), and trichloroacetonitrile (9.3 mL, 92.7 mmol, 5 equivalents) was added followed by DBU (0.6 mL, 3.7 mmol, 0.2 equivalents) at 0°C. The reaction was stirred for 2 hours at room temperature after which TLC confirmed completion of the starting materials and formation of the product. Solvents were removed under vacuum and the crude was purified using flash silica gel chromatography using 30% EtOAc in hexanes (gradient method) to afford 20 as an off-white solid (8.21 g, 83%). [324] [α]_D ²⁶= +11.3 (c=0.20, CH₂Cl₂); R_f 0.20 (EtOAc, Hexanes; 3:2); ¹H NMR (600 MHz, CDCl₃) δ 8.62 (s, 1H, NH), 7.93 – 7.70 (m, 4H, Ar-H), 7.54 – 7.35 (m, 3H, Ar-H), 6.58 (d, J = 3.6 Hz, 1H, H-1), 5.53 – 5.30 (m, 2H, H-3, H-4), 4.96 – 4.70 (m, 2H, NAP CH₂), 4.47 – 4.28 (m, 1H, H-5), 4.20 – 3.98 (m, 1H, H-2), 2.11 (s, 3H, OAc), 2.01 (s, 3H, OAc), 1.15 (d, J = 6.5 Hz, 3H, H-6); ¹³C NMR (151 MHz, CDCl₃) δ 170.39, 170.06, 161.30, 135.25, 133.22, 133.03, 128.14, 127.81, 127.70, 126.22, 126.20, 125.99, 125.39, 94.57 (C-1), 91.23 (C-CCl₃), 72.91 (C-2), 72.67 (NAP CH₂), 70.97 (C-3), 69.92 (C-4), 67.37 (C-5), 20.83 (OAc), 20.58 (OAc), 15.97 (C-6). HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₂₃H₂₄Cl₃NNaO₇[M+Na]⁺ 554.0516, found: 554.0511 tert-Butyldiphenylsilyl-4,6-O-(2-naphthyl)methylidene-2-deoxy-2-(2,2,2-trichloroethoxycarbonylamino)- β-D- glucopyranoside (16)

[325] 2-Naphthaldehyde dimethylacetal Glc2 (588.0 mg, 2.910 mmol, 2.0 equivalents) and camphor-10- sulfonic acid (34.0 mg, 0.146 mmol, 0.1 equivalents) were added successively to a stirred solution of trihydroxy glucosamine derivative Glc1⁶ (860.0 mg, 1.45 mmol, 1.0 equivalent) in anhydrous acetonitrile (20.0 mL) and the solution was stirred for 15 hours at room temperature. The solution was quenched with triethylamine (0.2 mL) and the organic phase dried over Na₂SO₄, filtered, and concentrated under   reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/hexanes) to afford 16 (990.0 mg, yield 93%) as a transparent solid. [326] R_f 0.40 (EtOAc, Hexanes; 1:4); [α]_D ²⁶= +16.2 (c=0.10, CH₂Cl₂); ¹H NMR (600 MHz, Chloroform- d) δ 7.94 – 7.87 (m, 1H), 7.87 – 7.75 (m, 3H), 7.69 (ddt, J = 16.2, 6.6, 1.5 Hz, 4H), 7.58 – 7.46 (m, 1H), 7.51 – 7.32 (m, 7H), 5.63 (s, 1H, Naphthylidene), 4.94 (d, J = 7.7 Hz, 1H, NH), 4.66 (m, 2H, CH₂), 4.59 (d, J = 8.0 Hz, 1H, H-1), 4.16 – 4.07 (m, 1H, 6CH₂), 3.76 – 3.63 (m, 3H, H-2, 6CH₂, H-5), 3.56 (t, J = 8.9 Hz, 1H, H-4), 3.13 (td, J = 9.7, 5.0 Hz, 1H, H-3), 2.92 (br s, 1H, OH), 1.10 (s, 9H, H-t-butyl); ¹³C NMR (151 MHz, Chloroform-d) δ 135.93, 135.82, 134.33, 132.84, 130.09, 129.98, 128.31, 128.18, 127.72, 127.66, 127.52, 126.51, 126.23, 125.86, 123.70, 101.91 (C-Naphthylidene), 95.20 (C-1), 81.44 (C-4), 74.90 (Troc-CH₂), 71.64 (C-5), 68.44 (6CH₂), 66.03 (C-3), 50.20 (C-2), 26.78 (CH₃), 19.12 (t- butyl); HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₃₆H₃₈C_l3NNaO₇Si [M+Na]⁺ 752.1381, found: 752.1369. Phenyl-4,6-O-(2-naphthyl)methylidene-2-deoxy-2-(2,2,2-trichloroethoxycarbonyl-amino)-1-thio-β-D- glucopyranoside (17)

[327] Camphor-10-sulfonic acid (603 mg, 2.6 mmol, 0.4 equivalents) was added to a solution of starting material Glc3 (2.9 g, 6.49 mmol, 1 equivalent) in anhydrous CH₃CN (50 mL), followed by 2- Napthaldeldehyde dimethyl acetal Glc2 (5.25 g, 25.96 mmol, 4 equivalents). The resulting mixture was stirred at room temperature for 18 hours and then quenched with Et₃N. Solvents were evaporated and the residue was subjected to column chromatography over silica gel eluting with a gradient mixture of ethyl acetate and hexanes to obtain 17 as fluffy white solid (3.58 g, 91%). [328] R_f 0.40 (EtOAc, Hexanes; 1:4); [α]_D ²⁶= +28.2 (c=0.10, CH₂Cl₂); ¹H NMR (600 MHz, Acetone-d₆) δ 8.07 – 7.94 (m, 1H), 7.97 – 7.78 (m, 3H), 7.64 (dd, J = 8.5, 1.7 Hz, 1H), 7.58 – 7.43 (m, 4H), 7.44 – 7.21 (m, 3H), 7.16 (d, J = 9.5 Hz, 1H), 5.80 (s, 1H, CH Napthylidene), 5.12 (d, J = 10.5 Hz, 1H, NH), 5.01 – 4.81 (m, 2H, CH₂Troc), 4.75 (d, J = 12.2 Hz, 1H, H-1), 4.34 (dd, J = 10.3, 4.8 Hz, 1H, H-6), 4.03 (dd, J = 9.2, 4.8 Hz, 1H, H-6), 3.85 (t, J = 10.0 Hz, 1H, H-3), 3.77 – 3.51 (m, 3H, H-2, H-4, H-5), 2.86 (s, 1H, OH), 1.12 (d, J = 6.1 Hz, 1H, H-t-butyl); ¹³C NMR (151 MHz, Acetone-d₆) δ 154.63, 135.60, 134.24, 133.65, 132.93, 131.20, 130.99, 128.92, 128.22, 127.66, 127.64, 127.23, 126.38, 126.18, 125.66, 125.65, 124.24, 101.36 (C-Napthylidene), 96.15 (C-1), 87.54 (C-4), 81.58, 74.11 (Troc-CH₂), 72.47 (C- 5), 70.49 (6CH₂), 68.26 (C-3), 57.71 (C-2), 24.93; HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₂₆H₂₄Cl₃NNaO₆S [M+Na]⁺ 606.0288, found: 606.0271.  

2,6-Dimethyl-3,4,6-tri-O-acetate-2-deoxy-2-(2,2,2-trichloroethoxycarbonylamino)-β-D- glucopyranoside (Glc5) [329] 2,6-Dimethyl thiophenol (1 mL, 2 equivalents, 7.68 mmol) was added to compound Glc4 (2 g, 1 equivalent, 3.84 mmol) in anhydrous dichloromethane (10 mL) and the solution was cooled to 0°C. BF₃ ^.Et₂O (1.5 mL, 1.5 equivalents, 5.76 mmol) was slowly added in a dropwise manner, the ice bath was removed, and the solution was brought to room temperature (RT) after 15 minutes. After stirring at room temperature for 16 hours, BF₃ ^.Et₂O (1.5 mL, 1.5 equivalents, 5.76 mmol) was added and the solution stirred for an additional 16 hours. After TLC showed complete consumption of the starting material, the solution was diluted with dichloromethane (75 mL), the organic layer washed with H₂O (3 x 30 mL), followed by aq. NaHCO₃ (3 x 30 mL), and dried over Na₂SO₄. The solvent was removed under reduced pressure to afford a crude solid. Ether trituration (40 mL) afforded the desired compound Glc5 as a fluffy white solid (1.8 g, 78%) without column purification. [330] R_f 0.40 (EtOAc, Hexanes; 1:4); [α]_D ²⁶= +16.2 (c=0.10, CH₂Cl₂); ¹H NMR (600 MHz, Chloroform- d) δ 7.15 – 7.14 (m, 1H, Ar-H), 7.09 – 7.08 (m, 2H, Ar-H), 5.60 – 5.59 (d, J = 9.5 Hz, 1H, NH), 5.23 – 5.20 (t, J = 9.6 Hz, 1H, H-3), 5.04 – 5.01 (t, J = 9.7 Hz, 1H, H-4), 4.79 -4.74 (q, J = 8.8 Hz, 2H, CH₂), 4.51 – 4.49 (d, J = 10.4 Hz, 1H, H-1), 4.15 – 4.12 (m, 1H, H-6), 4.03 – 4.01 (dt, J = 2.2 , 8.4 Hz, 1H, H- 6), 3.91 – 3.86 (q, J = 9.8 Hz, 1H, H-2), 3.53 – 3.50 (m, 1H, H-5), 2.52 (s, 6H, Ar-dimethyl), 2.03 (s, 3H, OAc), 1.99 (s, 3H, OAc), 1.89 (s, 3H, OAc); ¹³C NMR (125 MHz, Chloroform-d) δ 171.25,170.69, 169.51, 154.3, 144.3, 130.8, 129.4, 128.4, 95.45, 89.30, 77.3, 77.1, 76.9, 75.5, 74.8, 73.4, 68.9, 62.5, 55.9, 55.9, 22.5, 20.8, 20.7, 20.5; HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₂₃H₂₈Cl₃NO₉S [M+Na]⁺ 599.0550, found: 599.0539. 2,6-Dimethylthiophenyl-2-deoxy-2-(2,2,2- trichloroethoxy-carbonylamino)-β-D-glucopyranoside (Glc6) [331] Method 1: Sodium methoxide (0.32 g, 0.5 equivalents, 5.84 mmol) was added to compound Glc5 (7 g, 1 equivalent, 11.69 mmol) in methanol (120 mL), which was initially an insoluble mass, and the reaction mixture was stirred at room temperature for 30 to 40 minutes until an almost clear solution was noted. It was observed that adherence to the use of 0.5 equivalents of NaOMe, as well as a reaction time of 30 to 40 minutes were important variables. Prolonged reaction times led to transesterification of NHTroc with methanol. Acetic acid was added (pH ~ 5) and the solvent was removed under reduced   pressure to obtain a white solid. Co-distillation with toluene (3 x 50 mL) was used to remove any trace of methanol and the white solid was filtered with EtOAc:ether (1:1, 50 mL) to afford Glc6 (5.24 g, 95%) as a crystalline white solid. [332] Method 2: To a solution of starting material Glc5 (20.0 g, 33.285 mmol, 1 equivalent) in MeOH (160 mL) was added Et₃N (40 mL) followed by H₂O (40 mL). The resulting white solid emulsion was stirred at room temperature for 85 h. The solvents were then evaporated from the solid emulsion. Co- distillation with toluene (3 x 180 mL) was used to remove any trace of methanol and H₂O, and the white solid was filtered with EtOAc:ether (1:1, 180 mL) to afford Glc6 (11.47 g, 97%) as a crystalline white solid. [333] R_f 0.20 (EtOAc); [α]_D ²⁶= +5.2 (c=0.10, MeOH); ¹H NMR (600 MHz, Chloroform-d) δ 7.14 – 7.09 (m, 3H, Ar-H), 4.91 – 4.88 (d, J = 12 Hz, 1H, CHHTroc), 4.75 – 4.73 (d, J = 12 Hz, 1H, CHHTroc), 4.42 – 4.41 (d, J = 10.4 Hz, 1H, H-1), 3.78 – 3.76 (dd, J = 2.4, 12 Hz, 1H, H-6), 3.71 -3.66 (dd, J = 2.4, 12 Hz, 1H, H-6), 3.56 – 3.53 (t, J = 9.8 Hz, 1H, H-2), 3.76 – 3.41 (m, 2H, H-3, H-4), 3.09 – 3.07 (m, 1H, H-5), 2.57 (s, 6H, Ar-dimethyl); ¹³C NMR (125 MHz, Chloroform-d) δ 156.8, 145.3, 133.1, 129.9, 129.1, 97.1, 91.3, 81.5, 77.1, 75.8, 71.8, 62.8, 59.2, 22.9; HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₁₇H₂₂Cl₃NO₆S [M+Na]⁺ 473.0233, found: 473.0241. Dimethoxy 2-Napthalene acetal (Glc2) [334] 2-Naphthaldehyde (13 g, 1 equivalent, 83.3 mmol) was dissolved in trimethyl orthoformate (50 mL), followed by the addition of CSA (0.97 g, 0.05 equivalent, 4.16 mmol, pH~1-2), and stirred for 90minutes. TLC analysis confirmed completion of the reaction and formation of the product. It bears noting that TLC analysis was conducted by diluting the reaction sample into an ethyl acetate solution with excess Et₃N to avoid a reverse reaction on the TLC plate. The solvent was reduced to half volume under reduced pressure and the reaction mixture diluted with EtOAc (100 mL), followed by washes with H₂O (2 x 50 mL), aq. NaHCO₃ (2 x 50 mL) and sat. NaCl (2 x 50 mL). The solvent was dried over Na₂SO₄, removed under reduced pressure, and a final co-distillation performed with toluene (3 x 20 mL) to afford Glc2 (quantitative), which was used without further purification. 2,6-Dimethyl thiophenyl-4,6-O-(2-napthyl)methylidene-2-deoxy-2-(2,2,2-trichloroethoxycarbonylamino)- β-D- glucopyranoside (18) [335] Compound Glc6 (5.5 g, 1 equivalent, 11.63 mmol) was dissolved in anhydrous DMF (35 mL) and Napthaldehyde dimethyl acetal Glc2 (3.3 mL, 1.5 equivalents, 17.44 mmol), followed by the addition of camphor-10-sulfonic acid to pH ~1. The reaction mixture was heated to 85°C for 3 hours and the reaction mixture subsequently removed from the oil bath and stirred for 30 minutes to slowly reach room temperature. The reaction mixture was cooled to 0°C for 10 to 15 minutes using an ice bath and ice cold water (100 mL) slowly added. The formation of a precipitate was observed within 5 minutes and the solid stirred for 30 minutes until the formation of a fine powder-like solid was observed. The solid was filtered to remove the water, washed with 10% acetone in ether (3 x 50 mL), and dried overnight to obtain pure   compound 18 (6.2 g, 87%). Compound 18 was only partially soluble in an acetone/dichloromethane mixture. As a consequence, NMR analysis was performed in DMSO-d6 as complete solubility of compound 18 was observed. [336] R_f 0.40 (EtOAc, Hexanes; 1:4); [α]_D ²⁶= +55.2 (c=0.10, CH₂Cl₂); ¹H NMR (600 MHz, DMSO-d6) δ 7.96 – 7.89 (m, 5H, Ar-H), 7.56 – 7.52 (m, 3H, Ar-H), 7.18 – 7.13 (m, 3H, Ar-H), 5.77 (s, 1H, CH), 5.57 – 5.56 (d, J = 6 Hz, 1H, NH), 4.95 -4.93 (d, J = 12 Hz, 1H, CHHTroc), 4.75 – 4.73 (d, J = 12 Hz, 1H, CHHTroc), 4.52 – 4.50 (d, J = 10.5 Hz, 1H, H-1), 4.12 – 4.01 (m, 1H, H-6), 3.77 – 3.74 (t, J = 10.1 Hz, 1H, H-6), 3.68 – 3.65 (q, J = 9.1 Hz, 1H, H-3), 3.59 – 3.57 (d, J = 9.2 Hz, 1H, H-4) 3.52 – 3.47 (q, J = 9.8 Hz, 1H, H-2), 3.21 – 3.17 (m, 1H, H-5), 2.49 (s, 6H, Ar-dimethyl); ¹³C NMR (125 MHz, DMSO- d6) δ 154.4, 143.6, 135.0, 133.0, 132.3, 131.3, 129.1, 128.2, 127.7, 127.6, 126.5, 126.3, 125.4, 124.2, 100.6 (C-Napthylidene), 96.1 (C-1), 89.8, 80.8 (C-4), 73.7 (Troc-CH₂), 71.3 (C-5), 69.7 (6CH₂), 67.6 (C- 3), 58.2 (C-2), 22.2 (CH₃); HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₁₈H₂₁Cl₃NO₆S [M+Na]⁺ 484.0155, found: 484.0148. [1+1)] glycosylation and further modifications Methyl (5-acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl)-3,5-dideoxy-D-glycero-α-D-galacto-non-2-

[337] A reaction mixture containing sialylphosphate donor 7 (480.0 mg, 0.72 mmol, 1.0 equivalent), galactose acceptor 8 (260.0 mg, 0.646 mmol, 0.9 equivalent), and activated 3 Å powdered molecular sieves (~500.0 mg) in anhydrous acetonitrile (10.0 mL) was stirred for 1 hour under an argon atmosphere, and then cooled to -20°C. TMSOTf (160.0 mg, 0.719 mmol, 1.0 equivalent) was added in a dropwise manner under an argon atmosphere at the same temperature. The resulting reaction mixture was stirred for 30 minutes at -20°C before quenching with Hünig's base (2.0 equivalents). The mixture was diluted with CH₂Cl₂, filtered through a pad of celite, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluting with an EtOAc : hexanes system to afford sialic acid-galactose disaccharide 12 (406.0 mg, yield 42%) along with an aglycon transfer product (65.0 mg, 16%) as a white foam. [338] R_f 0.65 (2:3 acetone/toluene-double elution); [α]_D ²⁶= +14.5 (c=0.20, CH₂Cl₂); ¹H NMR (600 MHz, Chloroform-d) δ 7.64 – 7.59 (m, 2H), 7.43 – 7.34 (m, 5H), 7.37 – 7.27 (m, 3H), 7.31 – 7.26 (m, 1H), 5.80 (t, J = 1.9 Hz, 1H, H-7ʼ), 5.65 (s, 1H, Benzylidene), 5.52 (dt, J = 9.3, 2.2 Hz, 1H, H-8ʼ), 5.21 (t, J = 9.7 Hz, 1H, H-2), 5.06 (dd, J = 12.1, 2.6 Hz, 1H, 9ʼ-CH₂), 4.68 (d, J = 8.0 Hz, 1H, H-1), 4.55 – 4.48 (m, 2H, H-4ʼ, H-6ʼ), 4.46 (dd, J = 3.8, 1.1 Hz, 1H, H-4), 4.35 (dd, J = 12.3, 1.6 Hz, 1H, 6CH₂), 4.25   (dd, J = 9.5, 3.8 Hz, 1H, H-3), 4.18 – 4.10 (m, 1H, 6CH₂), 3.90 (dd, J = 12.1, 9.3 Hz, 1H, 9ʼ-CH₂), 3.86 (s, 3H, CO₂Me), 3.65 (q, J = 1.5 Hz, 1H, H-5), 3.57 (dd, J = 11.4, 9.5 Hz, 1H, H-5ʼ), 2.69 (dd, J = 12.1, 3.6 Hz, 1H, 3ʼe-CH₂), 2.38 (s, 3H, NHAc), 2.17 (s, 3H, OAc), 2.12 (d, 6H, OAc), 2.04 (s, 3H, OAc), 1.97 (t, J = 12.4 Hz, 1H, 3ʼa-CH₂); ¹³C NMR (100 MHz, Chloroform-d) δ 227.14, 171.61, 171.17, 170.86, 169.33, 169.02, 166.22, 133.31, 129.17, 128.72, 128.16, 127.97, 126.38, 100.96 (Benzylidene), 99.77 (C- 2ʼ), 84.95 (C-1), 76.25 (C-4ʼ), 75.21 (C-3, C-4), 74.37 (C-7ʼ), 74.20 (C-6ʼ), 71.96 (C-8ʼ), 69.70 (C-5), 69.01 (6CH₂), 67.57 (C-2), 63.16 (9ʼCH₂), 59.03 (C-9ʼ), 52.97(C-5ʼ), 36.80(9ʼCH₂), 24.40 (NHAc), 21.06 (OAc), 21.02 (OAc), 20.85 (OAc), 20.63 (OAc); HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₄₀H₄₅NNaO₁₈S [M+Na]⁺ 882.2255, found: 882.2268. Methyl (5-acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl)-3,5-dideoxy-D-glycero-α-D-galacto-non-2- ulopyranosylonate-(2→3)-phenyl-2-O-acetyl-4,6-O-benzylidene-1-p-methoxy phenyl-β-D- galactopyranoside (13)

[339] A reaction mixture containing sialylphosphate donor 7 (125.0 mg, 0.32 mmol, 1.0 equivalent), galactose acceptor 9 (301.0 mg, 0.45 mmol, 1.5 equivalents), and activated 4 Å powdered molecular sieves (~300.0 mg) in a mixture of anhydrous acetonitrile (10.0 mL) and anhydrous CH₂Cl₂ was stirred for 1 hour under an argon atmosphere, and then cooled to -50°C. TMSOTf (98 μL, 0.54 mmol, 1.8 equivalents) was added in a dropwise manner under an argon atmosphere at the same temperature. The resulting reaction mixture was stirred for 30 minutes at -50°C before quenching with Et₃N (1.5 mL). The mixture was diluted with CH₂Cl₂, filtered through a pad of celite, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluting with an EtOAc: hexanes system to afford sialic acid-galactose disaccharide 13 (168 mg, yield 64%). [340] R_f 0.35 (EtOAc, Hexanes; 1:4); [α]_D ²⁶= -36.2 (c=0.10, CH₂Cl₂); ¹H NMR (600 MHz, CDCl₃) δ 7.62 – 7.44 (m, 2H), 7.43 – 7.28 (m, 3H), 7.08 – 6.95 (m, 2H), 6.86 – 6.68 (m, 2H), 5.70 – 5.53 (m, 2H), 5.53 – 5.39 (m, 1H), 5.38 (s, 1H, Benzylidene), 5.09 – 4.96 (m, 1H, H-8’), 4.57 – 4.40 (m, 3H, H-2), 4.37 – 4.24 (m, 1H, H-6’), 4.10 (dd, J = 12.4, 1.8 Hz, 1H, 9’CH₂), 3.97 (dd, J = 12.2, 7.3 Hz, 1H, 6CH₂), 3.91 (dd, J = 3.7, 1.0 Hz, 1H, H-3), 3.88 – 3.78 (m, 2H, 6CH₂, H-4’), 3.75 (s, 3H, CO₂Me), 3.74 – 3.65 (m, 1H, H-5’), 3.63 (s, 3H, Me/OMP), 3.03 (dd, J = 12.0, 3.3 Hz, 1H, 3’e-CH₂), 2.47 (s, 3H, OAc), 2.17 (d, 6H, OAc), 2.15 (s, 3H, OAc), 2.11 (s, 3H, OAc), 1.93 (t, J = 12.4 Hz, 1H, 3’a-CH2)); ¹³C NMR (151 MHz, CDCl₃) δ 171.87, 170.62, 170.49, 169.70, 169.35, 168.51, 155.43, 153.42, 151.50, 137.64, 129.01, 128.12, 126.45, 119.06, 114.37, 101.08, 100.71 (Benzylidene), 97.25 (C-2’), 75.23 (C-4’), 75.01 (C-4), 73.41 (C-3), 72.41 (C-7’), 71.88 (C-6’), 69.04 (C-8’), 69.00 (C-5), 68.30 (6CH₂), 66.12 (C-2), 63.65 (9’-   CH₂), 59.03 (C-9’), 55.62 (Me/OMP), 52.98 (C-5’), 36.88 (9-CH₂), 30.86, 29.26, 24.59 (NHAc), 21.39 (OAc), 20.96 (OAc), 20.94 (OAc), 20.66 (OAc); HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₄₁H₄₇NNaO₂₀ [M+Na]⁺ 896.2589, found: 896.2572. Methyl (5-acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl)-3,5-dideoxy-D-glycero-α-D-galacto-non-2-

[341] Method 1: Sialic acid SPh donor 7a (5.4 g, 9.51 mmol, 1 equivalent) and galactose 3-OH acceptor 11 (5.49 g, 13.32 mmol, 1.8 equivalents) were dissolved in anhydrous CH₂Cl₂ (120 mL) and anhydrous CH₃CN (60 mL), activated 4 Å molecular sieves (5.5 g) added, and the contents stirred at room temperature for 1 h. The reaction mixture was then cooled to -78°C and NIS (4.29 g, 19.02 mmol, 2 equivalents) followed by TfOH (0.17 mL, 1.89 mmol, 0.2 equivalent) was added. The reaction mixture was stirred at -78°C for 2 h, then quenched by sat. aq. NaHCO₃. The reaction mixture was then filtered over a bed of Celite, diluted with CH₂Cl₂ and washed with 20% aq. Na₂S₂O₃. Organics were collected, dried (Na₂SO₄) and evaporated in vacuo to afford a crude compound. The compound was dissolved in pyridine (60 mL), and Ac₂O (30 mL) was added with continued stirring for 3hours. TLC confirmed acetylation of the excess acceptor. The reaction mixture was diluted with CH₂Cl₂ (250 mL), washed with sat aq. NaHCO₃ (2 x 250 mL), and the organic layer separated, and dried over Na₂SO_4. Solvents were removed under vacuum and co-distilled with toluene to remove excess pyridine to afford the crude mixture. Flash column purification using gradient ethyl acetate and hexanes afforded the desired compound 15 in a single isomer as a foamy white solid (6.92 g, 83%).

[342] Method 2: Phosphate donor 7 (2 g, 3.07 mmol, 1 equivalent) and acceptor 11 (1.89 g, 4.61 mmol, 1.5 equivalents) were dissolved in anhydrous CH₃CN:CH₂Cl₂ (9:1, 90 mL:10 mL), activated 4 Å molecular sieves (4 g) were added, and the contents stirred at room temperature for 30minutes. The reaction mixture was cooled to -35°C, and TMSOTf (0.61 mL, 3.38 mmol, 1.1 equivalents) slowly added in a dropwise manner with continued stirring at -35°C for 2hours. The reaction mixture was quenched with triethylamine/pyridine (3 mL) at -35 ˚C, filtered over a bed of Celite, and solvents removed under vacuum to afford the crude compound. The compound was dissolved in pyridine (20 mL), and Ac₂O (10 mL) was added with continued stirring for 3 hours. TLC confirmed acetylation of the excess acceptor.   The reaction mixture was diluted with CH₂Cl₂ (100 mL), washed with sat aq. NaHCO₃ (2 x 75 mL), the organic layer separated, and dried over Na₂SO₄. Solvents were removed under vacuum and co-distilled with toluene to remove pyridine affording a crude mixture. Flash column purification using the gradient ethyl acetate and hexanes system afforded the desired compound 15 as a foamy white solid (1.84 g, 70%). [343] R_f 0.40 (EtOAc, Hexanes; 1:4); [α]_D ²⁴= -36.4 (c=1, CHCl₃); ¹H NMR (600 MHz, Chloroform-d) δ 6.93 – 6.91 (m, 2H, Ar-H), 6.82 – 6.79 (m, 2H, Ar-H), 5.52 – 5.51 (m, 1H, H-7’’), 5.41 – 5.37 (m, 3H, H-8’’, H-2’, H-4’), 4.96 – 4.95 (dd, J = 1.9, 9.2 Hz, 1H, H-6’’), 4.92 – 4.91 (d, J = 8.1 Hz, 1H, H-1’), 4.88 – 4.87 (dd, J = 3.1, 10.6 Hz, 1H, H-3’), 4.84 – 4.81 (dd, J = 2.8, 11.9 Hz, 1H, H-9’’) 4.38 – 4.34 (m, 1H, H-4’’), 4.21 – 4.08 (m, 3H, H-6’, H-6’, H-5’), 3.84 (s, 3H, CO₂Me), 3.78 (s, 3H, Me/OMP), 3.80 – 3.75 (m, 1H, H-9’’), 3.61 – 3.57 (m, 1H, H-5’’) 2.76 – 2.73 (dd, J = 3.7, 12.8 Hz, 1H, H-3’’ eq) 2.50 (s, 3H, N-Ac) 2.21 (s, 3H, OAc), 2.12 (s, 3H, OAc), 2.11 (s, 3H, OAc), 2.06 (s, 3H, OAc), 2.03 (s, 3H, OAc) 2.0 (s, 3H, OAc); ¹³C NMR (125 MHz, Chloroform-d) δ 172.7, 171.2, 171.2, 171.1, 170.5, 169.8, 169.6, 166.9, 155.6, 153.9, 151.4, 118.7, 118.2, 114.6, 114.5, 100.5, 99.7, 74.5, 73.3, 71.5, 71.01, 70.9, 70.5, 69.8, 63.1, 62.4, 60.5, 59.2, 55.8, 52.7, 36.5, 24.8, 21.3, 21.1, 20.9, 20.8, 20.7; HR-MALDI- TOF/MS (positive, SuperDHB matrix): m/z calcd for C₃₈H₄₇NNaO₂₂ [M+Na]⁺ 892.2487, found: 892.2472. Methyl (5-acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl)-3,5-dideoxy-D-glycero-α-D-galacto-non-2-

[344] Ceric ammonium nitrate (2.65 g, 4.83 mmol, 3 equivalents) in 50 mL H₂O was added slowly to compound 15 (6.75 g, 3.05 mmol, 1 equivalent) in CH₃CN:H₂O (198 mL; 10:1) and the contents stirred from 0°C to room temperature over a 3 hour period. TLC confirmed the completion of the reaction and acetonitrile removed under vacuum. The crude product was diluted with EtOAc (150 mL) and washed with water (100 mL), brine (100 mL), and aq. NaHCO₃ (50 mL). The organic layer was separated and dried over Na₂SO₄ and the solvent removed under vacuum. Flash column chromatography over silica gel using 40% ethyl acetate in hexanes afforded the desired hemiacetal compound as a yellow fluffy solid (5.61 g). The yellow fluffy solid (5.61 g) was dissolved in CH₂Cl₂ (100 mL), cooled to 0°C, and Cs₂CO₃ (5.89 g, 18.40 mmol, 2.5 equivalents) added. This was followed by dropwise addition of N-phenyl trifluoroacetimidoyl chloride (PTFACl) (4.49 mL, 22.10 mmol, 3 equivalents) with continued stirring for 3 hours at room temperature. After 3hours, another batch of N-phenyl trifluoroacetimidoyl chloride (PTFACl) (1.5 mL, 7.37 mmol, 1 equivalent) was added and the reaction mixture was further stirred for 2 hours. After TLC confirmed the completion of the reaction, the solvent was removed under vacuum to afford the crude compound. Flash column chromatography of the crude mixture over a neutralized silica   gel with Et₃N, eluting with a gradient mixture of ethyl acetate and hexanes, afforded the desired compound 5 as a white fluffy solid (5.58 g, 82% yield). [345] [α]_D ²⁴= -72.1 (c=1, CHCl₃); ¹H NMR (600 MHz, CDCl₃) δ 7.40 – 7.18 (m, 3H), 7.19 – 7.02 (m, 1H), 6.85 – 6.66 (m, 2H), 6.45 (s, 1H), 5.55 (ddd, J = 8.2, 3.2, 1.8 Hz, 2H, H-7’, H-4’), 5.50 – 5.34 (m, 1H, H-8’), 5.25 (dd, J = 10.8, 3.5 Hz, 1H, H-2), 5.11 (dd, J = 10.8, 3.0 Hz, 1H, H-3), 4.98 (dd, J = 9.2, 2.4 Hz, 1H, H-4), 4.63 (dd, J = 12.0, 2.7 Hz, 1H, 6CH₂), 4.47 (dd, J = 7.1, 5.3 Hz, 1H, 6CH₂), 4.36 (ddd, J = 12.8, 11.2, 3.7 Hz, 1H, 9’CH₂), 4.26 – 4.06 (m, 3H, 6CH₂, H-4), 3.96 (dd, J = 11.9, 9.1 Hz, 1H, H- 5’), 3.86 (s, 3H, CO₂Me), 3.63 (dd, J = 11.2, 9.1 Hz, 1H, H-5), 2.72 (dd, J = 12.8, 3.7 Hz, 1H, 3’e-CH₂), 2.52 (s, 3H, NHAc), 2.19 (s, 3H, OAc), 2.12 (s, 3H, OAc), 2.11 (s, 3H, OAc), 2.09 (s, 3H, OAc), 2.07 (s, 3H, OAc), 2.01 (s, 3H, OAc), 1.25 (t, J = 7.1 Hz, 1H, 3’a-CH₂); ¹³C NMR (151 MHz, CDCl₃) δ 172.50, 170.87, 170.76, 170.64, 170.35, 169.90, 169.66, 166.59, 153.87, 143.02, 128.83, 128.80, 124.60, 119.14, 119.12, 99.77 (C-1), 93.25 (C-CCl₃), 77.19 (C-4’), 74.13 (C-6’), 73.30 (C-3), 71.07 (C-7’), 70.66 (C-8’), 69.98, 68.13 (6CH₂), 68.01 (C-2), 62.97 (C-4), 61.99 (9’CH₂), 60.33 (C-5), 59.34 (C-5’), 52.41 (CO₂Me), 36.44 (3’CH₂), 24.65 (NHAc), 20.99 (OAc), 20.91 (OAc), 20.87 (OAc), 20.85 (OAc), 20.63 (OAc), 20.61 (OAc), 20.38, 14.16. HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₃₉H₄₅F₃N₂NaO₂₁ [M+Na]⁺ 957.2365, found: 957.2361.

tert-Butyldiphenylsilyl-3-O-(3,4-di-O-acetyl-2-O-(2-naphthyl)methyl-α-L-fucopyranosyl)-4,6-O-(2- naphthyl)methylene-2-deoxy-2-(2,2,2-trichlorethoxycarbonylamino)-β-D-glucopyranoside (FG1) [346] A solution of glucosamine acceptor 16 (710.0 mg, 0.974 mmol, 1.0 equivalent), fucosyl donor 19⁷ (590.0 mg, 0.970 mmol, 1.5 equivalents), and activated 4 Å powdered molecular sieves (1.0 g) in anhyd. CH₂Cl₂ (22.0 mL) was stirred for 1 hour under an argon atmosphere, and then cooled to -20°C. NIS (307.0 mg, 1.36 mmol, 1.5 equivalents) and TfOH (14.6 mg, 0.097 mmol, 0.1 equivalents) were added at -20°C and the reaction mixture stirred for 30 minutes before quenching with excess TEA (0.5 equivalents). The mixture was diluted with CH₂Cl₂, washed with sat. Na₂S₂O₃ and brine and filtered through a pad of Celite. The organic layer was concentrated under reduced pressure and the residue   purified by silica gel column chromatography, eluting with an EtOAc: hexanes system to afford the desired fucosylated glucosamine derivative FG1 (772.0 mg, yield 96%) as a white foam. [α]_D ²⁴= -52.1 (c=1, CHCl₃); R_f 0.45 (EtOAc, Hexanes; 2:3); ¹H NMR (400 MHz, Acetone-d₆) δ 8.00 (d, J = 1.6 Hz, 1H), 7.95 – 7.83 (m, 8H), 7.82 – 7.68 (m, 5H), 7.63 (dd, J = 8.5, 1.6 Hz, 1H), 7.55 – 7.37 (m, 11H), 7.19 (d, J = 9.1 Hz, 1H), 5.84 (s, 1H, Naphthylidene), 5.39 (d, J = 3.5 Hz, 1H, H-1ʼ), 5.32 (dd, J = 10.6, 3.4 Hz, 1H, H-3ʼ), 5.07 – 4.94 (m, 3H, H-1, H-4ʼ, 2ʼ NAPCH₂), 4.74 (dd, J = 12.3, 7.2 Hz, 2H, 2ʼNAPCH₂, Troc CH₂), 4.57 (d, J = 12.1 Hz, 1H, Troc CH₂), 4.53 – 4.40 (m, 1H, H-5ʼ), 4.21 (t, J = 9.5 Hz, 1H, H-3), 4.13 – 4.01 (m, 2H, 6CH₂, H-2ʼ), 3.94 – 3.82 (m, 3H, H-2, H-3), 3.78 (t, J = 9.5 Hz, 1H, 6CH₂), 3.23 (td, J = 9.8, 5.0 Hz, 1H, H-5), 1.92 (s, 3H, OAc), 1.88 (s, 3H, OAc), 1.09 (s, 9H, t-butyl), 0.47 (d, J = 6.4 Hz, 3H, H-6ʼ); ¹³C NMR (100 MHz, Acetone-d₆) δ 169.91, 169.48, 154.41, 136.43, 135.85, 135.80, 135.40, 133.68, 133.33, 132.91, 129.83, 129.75, 128.18, 127.78, 127.71, 127.60, 127.53, 127.38, 126.35, 126.15, 126.03, 125.98, 125.74, 125.69, 124.19, 101.52 (Naphthylidene), 97.11 (C-1ʼ), 96.76 (C-1), 95.76 (C- CCl₃), 80.36 (C-4), 75.14 (C-3), 74.40 (Troc CH₂), 73.73 (C-2ʼ), 71.77 (2ʼNAPCH₂), 71.41(C-4ʼ), 69.59 (C-3ʼ), 68.13 (6CH₂), 66.34 (C-5), 64.23 (C-5ʼ), 60.60 (C-2), 26.39 (CH₃-t-butyl), 19.99 (OAc), 19.51 (OAc), 18.87 (4 ̊ C of t-butyl), 14.91(C-6ʼ); HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₅₇H₆₀Cl₃NNaO₁₃Si [M+Na]⁺ 1122.2797, found: 1122.2799. tert-Butyldiphenylsilyl-3-O-(3,4-di-O-acetyl-2-O-(2-naphthyl)methyl-α-L-fucopyranosyl)-6-O-(2- naphthyl)methyl-2-deoxy-2-(2,2,2-trichlorethoxycarbonylamino)-β-D-glucopyranoside (21) [347] Fucosylated glucosamine derivative FG1 (470 mg, 0.43 mmol, 1.0 equivalents) and anhydrous CH₂Cl₂ (20.0 mL) were added to a 100 mL round bottomed flask and the mixture stirred with 4 Å molecular sieves (500.0 mg) for 30 minutes at room temperature under an argon atmosphere. Triethylsilane (397.0 mg, 3.42 mmol, 8.0 equivalents) was added followed by the addition of BF₃OEt₂ (121.4 mg, 0.85 mmol, 2 equivalents) in a dropwise manner at -40°C with continued stirring for 9 hours before quenching with triethylamine. The reaction mixture was then diluted with CH₂Cl₂ and washed with sat. NaHCO₃ and brine solution. The organic layer was concentrated under reduced pressure and the residue was purified by silica gel chromatography using an EtOAc : hexanes gradient to afford fucosylated-glucosamine derivative 21 (308.0 mg, yield : 65 %) as a white foam. [348] [α]_D ²⁴= -46.1 (c=1, CHCl₃); R_f 0.40 (EtOAc, Hexanes; 2:3); ¹H NMR (600 MHz, Chloroform-d) δ 7.91 – 7.76 (m, 8H), 7.76 – 7.71 (m, 2H), 7.71 – 7.60 (m, 4H), 7.55 – 7.42 (m, 6H), 7.37 (ddt, J = 6.6, 5.0, 1.5 Hz, 4H), 7.34 – 7.21 (m, 3H), 5.34 (dd, J = 10.6, 3.3 Hz, 1H, H-3'), 5.31 – 5.21 (m, 2H, H-4', NH-Troc), 5.06 (brs, 1H, H-1'), 4.86 – 4.76 (m, 2H, NAP CH₂), 4.69 (d, J = 7.6 Hz, 1H, H-1), 4.67 – 4.54 (m, 3H, NAP CH_2, Troc CH₂), 4.47 (d, J = 11.9 Hz, 1H, NAP CH₂), 4.41 (q, J = 6.6 Hz, 1H, H-5'), 3.91 (dd, J = 10.5, 3.6 Hz, 1H, H-2'), 3.72 – 3.43 (m, 7H, H-3, H-2, H-6-CH₂), 3.09 (dd, J = 8.8, 4.7 Hz, 1H, H-5), 2.10 (s, 3H, CH₃), 1.99 (s, 3H, CH₃), 1.10 (d, J = 6.7 Hz, 3H, H-6ʼ), 1.07 (br s, 9H, t-butyl); ¹³C NMR (151 MHz, Chloroform-d) δ 170.39, 169.92 (Carbonyl of OAc) 135.99, 135.88, 129.80, 129.68, 128.53, 128.11, 127.88, 127.81, 127.75, 127.70, 127.52, 127.37, 126.45, 126.32, 126.26, 126.06, 125.82, 125.73 (NAP, TBDPS C's), 98.05 (C-1'), 95.63 (C-1), 95.37 (C-CCl₃), 82.92 (C-3), 74.48 (C-5), 74.45   (C-NAP CH₂), 73.80 (C-NAP CH₂), 73.69 (C-2'), 71.38 (C-2), 70.02, 69.43, 65.86 (C-5'), 26.80 (CH₃-t- butyl), 20.84 (OAc), 20.57 (OAc),19.16 (4 ̊ C of t-butyl), 15.95 (C-6'); HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₅₇H₆₂Cl₃NNaO₁₃Si [M+Na]⁺ 1124.2954, found: 1124.2957. 2,6-Dimethyl thiophenyl-3-O-(3,4-di-O-acetyl-2-O-p-methoxybenzyl-α-L-fucopyranosyl))-6-O-p-

[349] Compound 18 (3 g, 4.91 mmol, 1 equivalents) and donor 20 (5.2 g, 9.82 mmol, 2 equivalents) were dissolved in anhydrous CH₂Cl₂ (800 mL, excess solvent due to solubility of the acceptor) with the addition of activated 4 Å molecular sieves (10 g). The mixture was stirred at room temperature for 30 minutes, followed by cooling to 0°C, with slow dropwise addition of TMSOTf (0.2 mL, 0.2 equivalents w.r.t. donor) over a period of 5 minutes. The reaction mixture was then stirred at 0°C for 30 minutes until completion of the reaction was confirmed by TLC. The reaction mixture was then cooled to -78°C, followed by dropwise addition of Et₃SiH (4 mL) and TfOH (2 mL) over a period of 15 minutes with continued stirring at -78°C for an additional 5 hours. The reaction mixture was then quenched by initial slow dropwise addition of methanol (8 mL), followed by slow dropwise addition of pyridine (6 mL) with stirring at -78°C for 15minutes. The reaction mixture was then filtered over a pad of Celite and solvents removed under vacuum to afford the crude reaction mixture. Column chromatography over silica gel eluting with 35% EtOAc in hexanes afforded the desired compound as a white solid (3.05 g, 63%). [350] [α]_D ²⁴= -43.6 (c=1, CHCl₃); R_f 0.40 (EtOAc, Hexanes; 2:3; ¹H NMR (600 MHz, Chloroform-d) δ 7.84 – 7.81 (m, 7H, Ar-H), 7.79 (s, 1H, Ar-H), 7.72 (s, 1H, Ar-H), 7.51 – 7.47 (m, 6H, Ar-H), 7.42 – 7.41 (dd, J = 1.4, 8.4 Hz, 1H, Ar-H), 7.10 – 7.08 (t, J = 7.6 Hz, 1H, Ar-H), 7.01 – 7.00 (m, 2H, Ar-H), 5.63 – 5.62 (d, J = 7.4 Hz, 1H, NH), 5.35 – 5.33 (dd, J = 3.2, 10.5 Hz, 1H, H-3’’), 5.29 – 5.28 (d, J = 2.3 Hz, 1H, H-4’’), 5.18 – 5.17 (d, J = 3.4 Hz, 1H, H-1’’), 4.89 – 4.87 (d, J = 11.9 Hz, 1H, Nap CH₂/Fuc) 4.81 – 4.79 (d, J = 11.8 Hz, 1H, Nap CH₂/Fuc), 4.76 – 4.74 (d, J = 12 Hz, 1H, CHHTroc), 4.68 – 4.58 (m, 3H, Nap CH₂/Glc, H-1’), 4.52 – 4.49 (d, J = 12 Hz, 1H, CHHTroc), 4.41 – 4.39 (q, J = 6.6 Hz, 1H, H-5’’), 3.97 – 3.94 (dd, J = 3.4, 10.5 Hz, 1H) 3.82 – 3.79 (t, J = 9.1 Hz, 1H, H-3’) 3.75 – 3.69 (m, 2H, H-6’, H- 6’) 3.70 – 3.61 (m, 2H, OH, H-4’), 3.51 – 3.48 (m, 3H, OAc), 1.99 (s, 3H, OAc), 1.11 – 1.10 (d, J = 6.2 Hz, 3H, H-6’/CH₃); ¹³C NMR (125 MHz, Chloroform-d) δ 171.3, 170.5, 170.1, 154.3, 144.2, 135.6, 134.9, 133.3, 133.3, 133.2, 133.1, 129.1, 128.8, 128.3, 128.0, 127.9, 127.9, 127.8, 127.8, 127.0, 126.6, 12+6.5, 126.5, 126.4, 126.2, 126.1, 125.8, 125.7, 98.1, 95.5, 88.3, 83.4, 78.3, 74.6, 74.3, 73.8, 71.5, 70.9,   70.3, 70.3, 66.1, 60.5, 56.6, 22.5, 20.7, 16.1, 14.3; HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₄₉H₅₂Cl₃NNaO₁₂S [M+Na]⁺ 1006.2173, found: 1006.2167. Phenyl-3-O-(3,4-di-O-acetyl-2-O-p-methoxybenzyl-α-L-fucopyranosyl))-6-O-p-methoxybenzyl-2-deoxy-

[351] To a solution of starting material 17 (404 mg, 0.69 mmol, 1 equivalent) and fucose imidate acceptor 20 (731 mg, 1.38 mmol, 2 equivalents) in dry CH₂Cl₂ (12 mL), 4 Å MS (400 mg) was added, and stirred at RT for 1 hour. The reaction mixture was then cooled to 0°C and TMSOTf (23.6 μL; 0.14 mmol, 0.2 equivalents) was added dropwise. The resulting yellow-reddish solution was stirred at 0°C for 1 hour, then cooled to –78°C and Et₃SiH (352 μL, 2.21 mmol, 3.2 equivalents) and TfOH (170.4 μL, 1.93 mmol, 2.8 equivalents) were added dropwise. The resulting reddish solution was stirred at – 78°C for 4 hours, then quenched with pyridine (2.0 mL) and MeOH (2.0 mL) and further stirred at – 78°C for 15 minutes. The reaction mixture was then warmed to RT, filtered through celite, solvents evaporated, and the residue was subjected to column chromatography, eluting with 45% EtOAc in hexanes to afford the product 22 as a white solid. (473 mg;71 %). [352] R_f 0.25 (EtOAc, Hexanes; 1:4); [α]_D ²⁴= -42.2 (c=1, CHCl₃); ¹H NMR (600 MHz, Chloroform-d) δ 7.81 (m, 6H), 7.65 – 7.31 (m, 5H), 7.27 – 7.03 (m, 2H), 5.55 – 5.38 (m, 1H, NH), 5.40 – 5.16 (m, 2H, H- 3’, H-4’), 5.08 (dd, J = 13.2, 7.1 Hz, 1H, H-1’), 4.94 – 4.77 (m, 2H, NAPCH₂), 4.81 – 4.65 (m, 3H, NAPCH₂, TrocCH₂), 4.58 (d, J = 4.4 Hz, 1H, H-1), 4.50 – 4.30 (m, 1H, H-5’), 4.03 – 3.81 (m, 2H, H-3, H-2’), 3.80 – 3.69 (m, 2H, H-6, H-6), 3.67 – 3.46 (m, 2H, OH, H-4), 3.30 (q, J = 9.4 Hz, 1H, H-2), 2.17 – 2.04 (m, 3H, OAc), 1.97 (s, 3H, OAc), 1.09 (d, J = 6.5 Hz, 3H, H-6’); ¹³C NMR (151 MHz, Chloroform- d) δ 170.33, 169.93, 153.83, 135.58, 135.02, 133.25, 133.17, 133.08, 132.99, 132.80, 132.34, 128.89, 128.52, 128.15, 127.88, 127.79, 127.76, 127.74, 127.68, 126.47, 126.40, 126.29, 126.08, 125.85, 125.68, 98.32 (C-1’), 95.42 (C-1), 78.78 (C-CCl₃), 77.32 (C-3), 77.20 (C-5), 77.00, 76.68, 74.48 (C-NAP CH₂), 73.80 (C-NAP CH₂), 73.68 (C-2’), 71.32 (C-2), 70.57, 70.05, 69.88, 65.88, 55.72 (C-5’), 20.81 (OAc), 20.56 (OAc), 15.92 (C-6’), 14.18; ; HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₄₉H₅₂Cl₃NO₁₂S [M+Na]⁺ 983.2276, found: 983.2258; ; HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₄₇H₄₈Cl₃NNaO₁₂S [M+Na]⁺ 978.1860, found: 983.1871.   [2+2] glycosylation and further modifications

tert-Butyldiphenylsilyl [Methyl (5-acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl)-3,5-dideoxy-D- glycero-α-D-galacto-2-nonulopyranonate]-(2→3)-O-(2-O-acetyl-4,6-O-benzylidene-β-D- galactopyranosyl-(1→4)[(1→3)-(3,4-di-O-acetyl-2-O-(2-naphthyl)methyl-α-L-fucopyranosyl)]-O-[6-O- (2-naphthyl)methyl-2-deoxy-2-(2,2,2-trichlorethoxycarbonylamino)-β-D-glucopyranoside (27) [353] A solution of sialylated-galactose acetimidate donor 5 (156.0 mg, 0.167 mmol, 1.0 equivalent) and fucosylated-glucosamine acceptor 21 (276.0 mg, 0.250 mmol, 1.5 equivalents) in anhyd was made. CH₂Cl₂ (4.0 mL) with 4 Å molecular sieves (160.0 mg) was placed under an argon atmosphere and stirred at room temperature for 1 hour. The reaction mixture was then cooled to 0°C and TMSOTf (7.40 mg, 0.033 mmol, 0.2 equivalents) added with continued stirring for 45 minutes at 0°C. After TLC confirmed the completion of the reaction, the solution was quenched by the addition of triethylamine (50.0 µL), diluted with CH₂Cl₂ (5.0 mL), and filtered through a pad of celite. The filtrate was washed with sat. NaHCO₃ solution and brine, the organic layer was concentrated under vacuum, and the residue was purified by silica gel column chromatography (Hexanes : EtOAc, 1:1) to afford sLe^X derivative 27 (204.0 mg, yield 66%) as a white foam. [354] [α]_D ²⁴= -26.7 (c=1, CHCl₃); R_f 0.35 (2:3 ethyl acetate/hexanes*3 elution); ¹H NMR (600 MHz, CDCl₃) δ 7.99 – 7.93 (m, 1H), 7.91 – 7.87 (m, 1H), 7.86 (dd, J = 7.0, 1.7 Hz, 3H), 7.84 – 7.79 (m, 2H), 7.70 – 7.65 (m, 2H), 7.63 – 7.57 (m, 2H), 7.55 – 7.45 (m, 5H), 7.37 (td, J = 7.3, 1.0 Hz, 2H), 7.34 – 7.30 (m, 1H), 7.28 (dd, J = 6.9, 1.2 Hz, 1H), 7.25 (q, J = 7.8 Hz, 4H), 5.57 (dd, J = 3.7, 2.0 Hz, 1H, H-7’’’, H- 8’’’), 5.41 – 5.35 (m, 1H, H-3’), 5.35 – 5.30 (m, 3H, H-4’, H-1’, NH), 5.27 (dd, J = 3.2, 1.0 Hz, 1H, H- 2’’), 5.19 (d, J = 8.1 Hz, 1H, H-5’), 5.03 – 4.80 (m, 4H, H-1, CH₂, 9’’’CH₂), 4.76 (dd, J = 12.1, 2.7 Hz, 1H, H-1’’), 4.73 – 4.62 (m, 3H, H-4’’’, 6’’CH₂, TrocCH₂), 4.48 (d, J = 11.9 Hz, 1H, TrocCH₂), 4.40 – 4.24 (m, 3H, H-3’’, 6CH₂, 6’’CH₂), 4.12 (m, 1H, H-3), 4.03 (t, J = 9.1 Hz, 1H, H-4), 3.94 (dd, J = 9.9, 3.8 Hz, 1H, H-2’), 3.90 – 3.82 (m, 3H, H-5’’’, 9’’’CH₂, NAPCH₂), 3.66 (s, 3H, CO₂Me), 3.59 (dd, J = 11.2, 9.1 Hz, 1H, H-6’’’), 3.50 (dd, J = 11.7, 2.0 Hz, 2H, H-2’, NAPCH₂), 3.03 (dt, J = 10.0, 2.6 Hz, 1H, H-5), 2.67 (dd, J = 12.8, 3.7 Hz, 1H, 3’’’CH₂), 2.53 (s, 3H, NAc), 2.19 (s, 3H, OAc), 2.10 (s, 3H, OAc), 2.09 (s, 3H, OAc), 2.08 (s, 3H, OAc), 2.01 (s, 3H, OAc), 1.95 (s, 3H, OAc), 1.94 (s, 3H, OAc), 1.78 (s, 3H, OAc), 1.16 (d, J = 6.5 Hz, 3H, H-6’), 1.00 (s, 9H, t-butyl); ¹³C NMR (151 MHz, CDCl₃) δ 172.71,   171.14, 170.97, 170.70, 170.68, 169.73, 169.62, 168.97, 166.86, 153.92, 153.51, 135.86, 135.78, 135.72, 133.67, 133.56, 133.24, 133.23, 132.99, 132.64, 131.38, 129.87, 129.74, 128.65, 128.41, 128.25, 127.86, 127.74, 127.54, 127.40, 126.28, 126.26, 126.14, 126.04, 125.86, 125.82, 125.66, 125.30, 123.65, 99.97 (C-1’’), 99.61 (C-2’’’), 96.99 (C-1), 95.19 (C-CCl₃), 76.70 (C-5’), 75.58 (C-5), 74.71 (TrocCH₂), 74.56 (C-4’’), 74.19 (C-3), 73.79 (C-7’’’), 73.18 (C-4), 72.80 (C-4’’’), 72.01 (C-3’’), 71.97, 71.68 (C-8’’’), 71.05, 70.93 (C-4), 70.35 (C-2), 70.16 (C-2’’), 69.89 (C-3’), 67.11 (NAPCH₂), 64.33 (C-2’’), 62.89 (6’’CH₂), 61.75 (6CH₂), 59.22 (C-5’’’), 52.29 (CO₂Me), 36.50 (C-3’’’), 31.94, 29.72, 26.69 (CH₃-t- butyl), 24.74 (NAc), 22.71 (OAc), 21.11 (OAc), 20.99 (OAc), 20.90 (OAc), 20.80 (OAc), 20.69 (OAc), 20.57 (OAc), 19.10 (C-t-butyl), 15.80, 14.14 (C-6’); HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₈₈H₁₀₁Cl₃N₂NaO₃₃Si [M+Na]⁺ 1869.5019, found: 1869.5032.

Phenyl [Methyl (5-acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl)-3,5-dideoxy-D-glycero-α-D-galacto- 2-nonulopyranonate]-(2→3)-O-(2,3,4-O-triacetate-β-D-galactopyranosyl-(1→4)[(1→3)-(3,4-di-O- acetyl-α-L-fucopyranosyl)]-O-[2-deoxy-2-(2,2,2-trichlorethoxycarbonylamino)-1-thio-β-D- glucopyranoside (28a) [355] To a solution of starting material sialic acid-galactose disaccharide imidate donor 5 (220 mg, 0.24 mmol, 1 equivalent) and galactose-fucose acceptor 22 (338 mg, 0.35 mmol, 1.45 equivalents) in anhydrous CH₂Cl₂ (25 mL) was added 4 Å MS (500 mg) and stirred at room temperature for 1 hour. The reaction mixture was then brought to -10°C and TMSOTf (8 μL, 0.047 mmol, 0.2 equivalents) was added. The reaction mixture was stirred at -10°C to 0°C for 1 hour, then quenched with pyridine and brought to room temperature. Molecular sieves were filtered off through a pad of Celite and the filtrate was evaporated to dryness. The residue was subjected to column chromatography over silica gel eluting with 60% EtOAc in hexanes to provide a crude mixture of sLe^X 28 and the aglycon transfer (SG-SPh) byproduct (252 mg). To a solution of the crude mixture (252 mg, 0.15 mmol, 1 equivalents) in CH₂Cl₂ : H₂O (21 mL; 20:1) was added DDQ (122.6 mg, 0.54 mmol, 3.6 equivalents). The resulting mixture was stirred at room temperature for 18 hours then diluted with CH₂Cl₂ and washed with sat. aq. NaHCO₃. Organics were collected, dried (Na₂SO₄) and evaporated in vacuo. The residue was subjected to column   chromatography over silica gel eluting with 70% EtOAc in hexanes to obtain the product 28a as a white solid (175 mg; 52% (2 steps)) and an aglycon transfer byproduct as a white solid (22 mg; 11%). [356] R_f 0.45 (EtOAc, Hexanes; 3:2); [α]_D ²⁴= -32.1 (c=1, CHCl₃); ¹H NMR (600 MHz, CDCl₃) δ 7.46 (m, 2H, Ar-H), 7.30 (m, 3H, Ar-H), 5.48 (dd, J = 2.9, 1.9 Hz, 1H, H-7’’’), 5.38 (d, J = 3.0 Hz, 1H, H-1’), 5.35 – 5.23 (m, 2H, H-8’’’, H-3’), 5.25 – 5.10 (m, 1H, H-4’), 5.04 (dd, J = 10.5, 8.3 Hz, 1H, H-2’’), 4.98 – 4.57 (m, 5H, 9’’’CH₂, H-1, H-2, TrocCH₂, NH), 4.51 (dd, J = 11.7, 7.6 Hz, 1H, H-3’’), 4.44 – 4.24 (m, 1H, H-1), 4.11 (dd, J = 11.7, 4.7 Hz, 1H, 6CH₂), 4.02 – 3.89 (m, 1H, H-4), 3.91 – 3.82 (m, 4H, H-2, CO₂Me), 3.84 – 3.70 (m, 2H, H-5’’, 9’’CH₂), 3.60 (ddd, J = 11.2, 9.0, 4.6 Hz, 1H, H-5’’’), 3.36 (dt, J = 9.7, 2.7 Hz, 1H, H-5), 2.85 – 2.63 (m, 1H, H-3’’’), 2.50 (s, 3H, NAc), 2.20 – 2.00 (m, 24, 8 of OAc’s) 1.18 (d, J = 6.6 Hz, 3H, H-6’).¹³C NMR (151 MHz, CDCl₃) δ 172.53, 171.17, 171.03, 170.82, 170.74, 170.67, 170.61, 170.29, 169.62, 169.58, 169.05, 166.88, 156.16, 153.92, 153.83, 132.99, 132.17, 128.90, 128.00, 100.83 (C-1’’), 99.77 (C-2’’’), 95.52 (C-1’), 95.26 (C-CCl₃), 77.30 (C-5’), 76.98, 76.90 (C-5), 76.67, 75.15 (C-5’’), 74.73 (TrocCH₂), 74.11 (C-7’’’), 73.12 (C-4’’’), 71.53 (C-3’’), 71.34 (C-8’’’), 70.88 (C-4), 70.11 (C-2’), 69.84 (C-5’), 68.11 (C-2’’), 64.36 (C-5’), 62.81 (9’’’CH₂), 62.37 (6’’CH₂), 61.40 (6CH₂), 59.16 (C-5’’’), 57.21, 52.71, 36.44, 32.18, 29.66, 26.37, 24.66 (NAc), 23.39 (OAc), 21.02 (OAc), 20.93 (OAc), 20.90 (OAc), 20.88 (OAc), 20.84 (OAc), 20.69 (OAc), 20.64 (OAc), 20.57 (OAc), 15.79 (C-6’); HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₅₆H₇₁Cl₃N₂NaO₃₂S [M+Na]⁺ 1443.2674, found: 1443.2687.

tert-Butyldiphenylsilyl [Methyl (5-acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl)-3,5-dideoxy-D- glycero-α-D-galacto-2-nonulopyranonate]-(2→3)-O-(2,4,6-tri-O-acetyl-2-β-D-galactopyranosyl- (1→4)[(1→3)-(2,3,4-tri-O-acetyl-α-L-fucopyranosyl)]-O-[6-O-acetyl-2-deoxy-2-(2,2,2- trichlorethoxycarbonylamino)-β-D-glucopyranoside (30) [357] DDQ (140.0 mg, 0.62 mmol, 3.0 equivalents) was added to a stirred solution of sLe^x derivative 27 (300 mg, 0.21 mmol, 1.0 equivalents) in CH₂Cl₂:methanol (18.0 mL, 4:1) at room temperature with continued stirring for 4 hours. Upon consumption of the starting material as determined by TLC, the reaction mixture was diluted with CH₂Cl₂, and washed with sat. NaHCO₃, followed by brine. The solvent was removed under vacuum and the crude was purified by silica gel chromatography (1:1 ethyl acetate/hexanes) to afford the dihydroxy sLe^X derivative (160.0 mg, yield 62%) as a white foam with an   R_f 0.32 (acetone : toluene, 1:4). The purified compound was dissolved in pyridine (1.0 mL), followed by the addition of acetic anhydride (0.5 mL) and N,N-dimethyl pyridine (DMAP) (2.0 mg, cat.), with continued stirring at room temperature for 15 hours. The solvent was concentrated under vacuum and the product purified by silica gel chromatography (1:1 ethyl acetate/hexanes) to provide the desired product 30 as a white foam (140.0 mg, 52% overall yield for 3 steps). [358] [α]_D ²⁴= -24.2 (c=1, CHCl₃); R_f 0.35 (acetone : toluene, 1:4); ¹H NMR (600 MHz, Chloroform-d) δ 7.76 – 7.67 (m, 2H), 7.67 – 7.56 (m, 2H), 7.52 – 7.41 (m, 3H), 7.38 (q, J = 7.6 Hz, 4H), 5.57 (dd, J = 3.1, 1.8 Hz, 1H, H-7ʼʼʼ), 5.44 (d, J = 4.2 Hz, 1H, H-1ʼʼʼ), 5.38 (dd, J = 10.0, 2.9 Hz, 2H, H-8ʼʼʼ, NH), 5.30 (d, J = 3.2 Hz, 1H, H-4ʼʼ), 5.22 (dd, J = 10.8, 3.5 Hz, 1H, H-3ʼ), 5.04 – 4.95 (m, 3H, H-2ʼ, H-2ʼ, H-6ʼʼʼ), 4.94 – 4.85 (m, 2H, H-5ʼ, 9ʼʼʼCH₂), 4.80 (dd, J = 10.5, 3.1 Hz, 1H, H-3ʼʼ), 4.75 (d, J = 11.8 Hz, 1H, Troc CH₂), 4.60 – 4.50 (m, 2H, Troc CH₂, H-4ʼ), 4.45 (dd, J = 11.7, 7.9 Hz, 1H, 6ʼʼ CH₂), 4.38 (d, J = 8.3 Hz, 1H, H-1ʼʼ), 4.37 – 4.26 (m, 5H, H-1, H-4ʼʼʼ, 6CH₂, 6ʼʼ CH₂), 4.07 (dd, J = 7.8, 6.0 Hz, 1H), 4.01 (dd, J = 11.7, 5.6 Hz, 1H, 6CH₂), 3.94 (q, J = 9.7 Hz, 1H, H-5ʼʼʼ), 3.87 (s, 3H, CO₂Me), 3.84 – 3.74 (m, 2H, 9ʼʼʼCH₂, H-4), 3.65 – 3.52 (m, 2H, H-3, H-5), 3.17 (ddd, J = 9.9, 5.6, 2.1 Hz, 1H, H-5), 2.69 (dd, J = 12.9, 3.7 Hz, 1H, H-3ʼʼʼ), 2.53 (s, 3H, NAc), 2.22 (s, 3H, OAc), 2.17 – 2.10 (m, 15H, 5 of OAc's), 2.08 (s, 3H. OAc), 2.05 (s, 3H, OAc), 2.02 (s, 3H, OAc), 1.96 (s, 3H, OAc), 1.15 (d, J = 6.6 Hz, 4H), 1.08 (s, 9H, t-butyl); ¹³C NMR (151 MHz, Chloroform-d) δ 172.64, 171.04, 170.94, 170.75, 170.72, 169.67, 168.99, 166.90, 136.08, 135.75, 132.52, 130.13, 130.03, 127.71, 127.54, 100.86 (C-1ʼʼ), 99.76 (C-2ʼʼʼ), 96.13 (C-1), 95.29 (C-1ʼ), 94.88 (C-CCl₃), 76.91 (C-2ʼ), 75.31 (C-4), 75.20 (Troc CH₂), 74.16 (C-7ʼʼʼ), 73.75 (C-3), 73.16 (C-5), 73.11, 71.58, 71.34 (C-3ʼʼ), 70.88, 70.80 (C-8ʼʼʼ), 70.10 (C-2ʼʼ), 69.89, 68.17 (C-6ʼʼʼ), 67.95 (C-3ʼ), 64.20 (C-5), 62.82 (9ʼʼʼCH₂), 61.98 (6CH₂), 61.48 (6ʼʼCH₂), 59.88 (C-5ʼʼʼ), 59.16 (C-2), 52.70 (CO₂Me), 36.47 (3ʼʼʼCH₂), 29.71 (CH₃-t-butyl), 24.73, 22.70, 22.67, 21.15, 21.02, 20.94, 20.89, 20.75, 20.69, 20.61, 20.60 (11 C's of OAc), 15.77 (t-butyl), 14.13 (C-6ʼ); HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₇₀H₈₉Cl₃N₂NaO₃₅Si [M+Na]⁺ 1673.3978, found: 1673.3992. Phenyl [Methyl (5-acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl)-3,5-dideoxy-D-glycero-α-D-galacto- 2-nonulopyranonate]-(2→3)-O-(2,4,6-tri-O-acetyl-β-D-galactopyranosyl-(1→4)[(1→3)-(2,3,4-tri-O- acetyl-α-L-fucopyranosyl)]-O-[6-O-acetyl-2-deoxy-2-(2,2,2-trichlorethoxycarbonylamino)-1-thio-β-D- glucopyranoside (31) [359] From compound 30: sLe^x derivative 30 (194.5 mg, 0.119 mmol, 1.0 equivalent) was dissolved in anhyd. The THF (10.0 mL) followed by the simultaneous addition of TBAF (1M THF solution, 46.2 mg, 0.177 mmol, 1.5 equivalents) and acetic acid (21.2 mg, 0.353 mmol, 3.0 equivalents) at ice cooled temperature was continually stirred at ice cooled temperature for 30 minutes, and at RT for 4 hours. The mixture was diluted with CH₂Cl₂ and washed with sat. NaHCO₃ followed by a brine solution. The organic layer was concentrated under reduced pressure and the residue was purified by silica gel flash column chromatography, eluting with an EtOAc : hexanes system to afford the desired sLe^x hemiacetal (132.5 mg) as a white foam. Without further characterization, the product underwent acetylation followed by thioglycosylation. The sLe^x hemiacetal was dissolved in pyridine (1.5 mL) with subsequent addition   of acetic anhydride (0.5 mL) and DMAP (1.9 mg, cat.). The resulting reaction mixture was stirred for 2 hours with confirmation of consumption of the starting material by TLC, and the reaction mixture was concentrated under reduced pressure and multiple runs of azeotropic co-evaporation using toluene. The crude was dissolved in anhydrous CH₂Cl₂ (4.0 mL) and the solution was treated with thiophenol (10.6 mg, 0.096 mmol, 1.3 equivalents) and borontrifluoride etherate (26.4 mg, 0.186 mmol, 2.5 equivalents) at 0°C under an argon atmosphere. The reaction mixture was stirred overnight (15 hours) before it was diluted with CH₂Cl_2. The organic layer was washed with sat. NaHCO₃ (twice), followed by brine solution, and concentrated under reduced pressure. The residue was purified by silica gel flash column chromatography, eluting with an EtOAc: hexanes system to afford the desired product 31 (67.0 mg, 38% overall 3 steps) as a white foam with an R_f 0.35 (acetone : toluene, 1:4). [360] From compound 28a: To a solution of starting material 28a (110 mg; 0.77 mmol) in dry CH₂Cl₂ (15 mL) was added DMAP (1 mg; 0.008 mmol) followed by pyridine (37 μL; 0.46 mmol) and Ac₂O (29 μL; 0.31 mmol). The resulting mixture was stirred at RT for 3 hours, followed by the addition of 0.1 mL of pyridine and 0.1 mL of Ac2O, with further stirring for 3 hours. The solvents were then evaporated and the residue was subjected to column chromatography over silica gel eluting with 60% EtOAc in hexanes to afford product 30 as a white solid (102 mg; 88%). [361] R_f 0.40 (EtOAc, Hexanes; 3:2); [α]_D ²⁴= -23.5 (c=1, CHCl₃); ¹H NMR (600 MHz, Chloroform-d) δ 7.53 – 7.44 (m, 2H), 7.34 – 7.27 (m, 3H), 5.57 (dd, J = 3.1, 1.8 Hz, 1H, H-7ʼʼʼ), 5.53 (d, J = 4.1 Hz, 1H, H-1ʼ), 5.42 – 5.33 (m, 2H, H-8ʼʼʼ), 5.31 (m, 1H, H-3ʼ), 5.22 (dd, J = 10.8, 3.5 Hz, 1H, H-4ʼ), 5.12 (d, J = 9.7 Hz, 1H, NH), 5.03 (m, 3H, H-2ʼʼ, H-2ʼ, Troc CH₂), 5.01 – 4.87 (m, 3H, H-5ʼ, H-6ʼʼʼ), 4.90 (dd, J = 12.1, 2.9 Hz, 1H, 9ʼʼʼCH₂), 4.84 (dd, J = 10.5, 3.1 Hz, 1H, H-3ʼʼ), 4.66 (m, 1H, H-1), 4.60 – 4.54 (m, 2H, Troc CH₂, 6ʼʼCH₂), 4.48 – 4.39 (m, 2H, H-1ʼʼ, 6’’CH₂), 4.34 (ddd, J = 13.0, 11.2, 3.7 Hz, 1H, H-4ʼʼʼ), 4.27 (dd, J = 11.6, 6.1 Hz, 1H, 6CH₂), 4.16 – 4.10 (m, 1H, 6CH₂), 4.08 (t, J = 6.9 Hz, 1H, H-4), 3.90 (s, 4H, H-2, CO₂Me), 3.84 – 3.73 (m, 2H, H-5ʼʼ, 9ʼʼʼCH₂), 3.58 (dd, J = 11.3, 9.2 Hz, 1H, H-5ʼʼʼ), 3.55 – 3.48 (m, 1H, H-5), 2.71 (dd, J = 12.8, 3.7 Hz, 1H, H-3ʼʼʼ), 2.52 (s, 3H, NAc), 2.23 (s, 3H, OAc), 2.22 – 2.03 (m, 24H, 8 of OAc's), 1.96 (s, 3H, OAc), 1.20 (d, J = 6.5 Hz, 3H, H-6ʼ); ¹³C NMR (151 MHz, Chloroform-d) δ 172.62, 171.21, 170.90, 170.80, 170.35, 169.67, 169.13, 166.90, 154.00, 153.89, 132.15, 128.93, 128.01, 100.85 (C-1ʼʼ), 99.76 (C-2ʼʼʼ), 95.52 (C-1ʼ), 95.31 (C-CCl₃), 87.4 (C-1), 77.23 (C-5ʼ), 76.95 (C-5), 75.17 (C-5ʼʼ), 74.71 (Troc CH₂), 74.19 (C-7ʼʼʼ), 73.15 (C-4ʼʼʼ), 71.51 (C-3ʼʼ), 71.34 (C-8ʼʼʼ), 70.92, 70.83 (C-4), 70.12 (C-2ʼ), 69.86 (C-3ʼ), 68.11 (C-2ʼʼ), 64.34 (C-5ʼ), 62.81 (9ʼʼʼCH₂), 62.36 (6ʼʼCH₂), 61.41 (6CH₂), 59.15 (C-5ʼʼʼ), 57.18, 52.76 (CO₂Me), 36.45 (C-3ʼʼʼ), 24.73 (NAc), 21.08, 20.95, 20.90, 20.75, 20.70, 20.62, 15.84 (C-6ʼ); HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₆₀H₇₅Cl₃N₂NaO₃₄S [M+Na]⁺ 1527.2885, found: 1527.2843. 2,6-Dimethyl Thiophenyl [Methyl (5-acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl)-3,5-dideoxy-D- glycero-α-D-galacto-2-nonulopyranonate]-(2→3)-O-(2,3,4-O-triacetate-β-D-galactopyranosyl- (1→4)[(1→3)-(2-O-napthyl-3,4-di-O-acetyl-α-L-fucopyranosyl)]-O-[2-deoxy-2-(2,2,2- trichlorethoxycarbonylamino)-6-O-napthyl-β-D-glucopyranoside (29)  

[362] Donor 5 (5.4 g, 5.74 mmol, 1 equivalent) and acceptor 6 (9.78 g, 10.125 mmol, 1.8 equivalents) were dissolved in anhydrous CH₂Cl₂ (200 mL) in the presence of activated 4 Å molecular sieves (5.4 g). The reaction mixture was stirred at room temperature for 30 minutes, followed by cooling to 0°C with slow dropwise addition of TMSOTf (0.16 mL, 0.15 equivalents w.r.t. donor) at 0°C. The reaction mixture was stirred at 0°C for 1 hour with completion of the reaction confirmed by TLC. The reaction mixture was quenched with pyridine (0.8 mL), filtered over a pad of Celite, and solvents were removed under vacuum. To achieve the desired compound 29 as a white solid (7.7 g, 77%), dry silica gel loading of the crude reaction mixture was followed by silica gel flash column chromatography purification eluting with ethyl acetate and hexanes. [363] R_f 0.40 (EtOAc, Hexanes; 3:2); [α]_D ²⁴= -26.8 (c=1, CHCl₃);¹H NMR (600 MHz, CDCl₃) δ 7.99 – 7.77 (m, 7H), 7.74 (s, 1H), 7.61 – 7.45 (m, 5H), 7.44 (dd, J = 8.4, 1.7 Hz, 1H), 7.26 – 7.13 (m, 1H), 7.07 (dd, J = 8.1, 6.9 Hz, 1H), 6.99 (d, J = 7.5 Hz, 2H), 5.57 (dd, J = 3.5, 1.9 Hz, 1H, H-7’’’), 5.49 (d, J = 7.9 Hz, 1H, H-1’), 5.42 – 5.27 (m, 5H, H-8’’’, H-3’, H-4’, NH, H-2’’), 5.06 (dd, J = 10.5, 8.2 Hz, 1H, H-2’), 4.99 (dd, J = 9.2, 2.0 Hz, 1H, H-6’), 4.94 – 4.67 (m, 8H, H-5’, H-6’’’, 9’’’CH₂, H-3’’, H-1, TrocCH₂, 6’’CH₂, H-1’’, H-4’’’), 4.56 (d, J = 12.0 Hz, 1H, NAP CH₂), 4.40 – 4.26 (m, 3H, NAP CH₂, 6CH₂, H-2), 4.20 (d, J = 8.8 Hz, 1H, 6CH₂), 4.09 – 3.92 (m, 3H, H-5’’, 9’’’CH₂, H-4), 3.82 (s, 3H, CO₂Me), 3.81 – 3.77 (m, 1H, H-5’’’) 3.29 (dt, J = 9.0, 3.0 Hz, 2H, H-5, NAP CH₂), 2.70 (dd, J = 12.8, 3.7 Hz, 1H, H- 3’’’), 2.53 (s, 3H, NAc), 2.43 (s, 6H, 2 XCH₃SPh), 2.21 – 1.78 (s, 18H, 6 X OAc) 1.18 (d, J = 6.5 Hz, 3H, H-6’); ¹³C NMR (151 MHz, CDCl₃) δ 172.69, 171.17, 170.99, 170.78, 170.68, 170.63, 169.78, 169.66, 169.15, 166.95, 153.89, 144.06, 135.51, 135.44, 133.26, 133.22, 133.07, 133.01, 129.05, 128.93, 128.40, 128.28, 128.11, 127.95, 127.83, 127.77, 127.73, 126.44, 126.31, 126.14, 126.12, 126.07, 125.71, 125.41, 125.31, 99.99 (C-1’’), 99.67 (C-2’’’), 97.08 (C-1’) 95.28 (C-CCl₃), 79.37 (C-5’’), 74.70 (Troc_CH₂), 74.46 (Nap CH₂), 74.31 (Nap CH₂), 74.01 (C-7’’’), 73.60 (C-4’’’), 73.09 (C-3’’), 71.94 (C- 8’’’), 71.63 (C-4), 71.20 (C-2’), 70.94 (C-3’), 70.46 (C-2’’), 70.21 (C-5’), 70.13, 64.58 (9’’’CH₂), 62.93 (6’’CH₂), 61.88 (6CH₂), 59.15 (C-5’’’), 52.45 (CO₂Me), 36.53 (C-3’’’), 29.72, 24.74 (NAc), 22.42 (OAc), 21.12 (OAc), 21.02 (OAc), 20.94 (OAc), 20.91 (OAc), 20.75 (OAc), 20.71 (OAc), 20.68 (OAc), 20.55 (OAc), 15.85 (C-6’); HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₈₀H₉₁Cl₃N₂NaO₃₂S [M+Na]⁺ 1751.4239, found: 1751.4226.   2,6-Dimethyl Thiophenyl [Methyl (5-acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl)-3,5-dideoxy-D- glycero-α-D-galacto-2-nonulopyranonate]-(2→3)-O-(2,3,4-O-triacetate-β-D-galactopyranosyl- (1→4)[(1→3)-(2,3,4-Tri-O-acetyl-α-L-fucopyranosyl)]-6-O-Acetyl-[2-deoxy-2-(2,2,2-

[364] DDQ (5.1 g, 22.33 mmol, 5 equivalents) was added to compound 29 (7.7 g, 4.39 mmol, 1 equivalent) in CH₂Cl₂:H₂O (20:1, 220 mL), with continued stirring from 0°C to room temperature for 12 hours. After TLC confirmed consumption of the starting material, the mixture was diluted with CH₂Cl₂ (150 mL), washed with sat. aq. NaHCO₃ (250 mL), and followed by water and brine. The organic layer was separated, dried over Na₂SO₄, and the solvent was removed under vacuum to afford the crude compound. Flash chromatography of the crude mixture afforded the desired compound as a fluffy solid (6.06 g), which was then dissolved in pyridine (60 mL), Ac₂O (30 mL), and DMAP (120 mg) with continued stirring at room temperature for 3 hours. Upon confirmation of the completion of the reaction by TLC, the solvent was removed under vacuum, and the product co-distilled with toluene (2x150 mL) to afford the crude compound. Silica gel flash column chromatography afforded the desired compound 3 as a white solid (6.2 g, 92% yield). [365] R_f 0.40 (EtOAc, Hexanes; 3:2); [α]_D ²⁴= -22.1 (c=1, CHCl₃); ¹H NMR (600 MHz, Chloroform-d) δ 7.15 – 7.13 (m, 1H, Ar-H), 7.08 – 7.07 (m, 2H, Ar-H), 5.56 – 5.53 (m, 2H, Ar-H), 5.39 (d, J = 2.8 Hz, 1H, H-1), 5.36 – 5.34 (m, 1H, H-8’’’), 5.30 – 5.29 (d, J = 2.8 Hz, 1H, H-3’) 5.23 – 5.21 (dd, J = 3.4, 10.9 Hz, 1H, H-4’), 5.11 (d, J = 9.9 Hz, 1H, H-4’), 5.06 – 4.90 (m, 5H, H-2’’, H-2’, TrocCH₂, H-5’, H-6’’’), 4.88 – 4.85 (dd, J = 2.8, 12 Hz, 1H, 9’’’ CH₂), 4.82 – 4.79 (dd, J = 3.1, 10.5 Hz, 1H, H-3’’), 4.53 (d, J = 12 Hz, 1H, H-1), 4.43 – 4.38 (m, 3H, TrocCH₂, 6’’CH₂, 6’’CH₂), 4.34 – 4.25 (s, 3H, H-1’’, H-4’’’, 6CH₂) 4.13 – 4.09 (d, J = 7.2 Hz, 1H, 6CH₂), 4.06 – 4.01 (m, 2H, H-2, H-4), 3.84 (s, 3H, CO₂Me), 3.78 – 3.73 (m, 2H, H-5’’, 9’’’CH₂), 3.57 – 3.54 (m, 1H, H-5’’’), 3.26 – 3.24 (m, 1H, H-5), 2.69 – 2.67 (dd, J = 3.7, 12 Hz, 1H, H-3’’’), 2.51 (s, 6H, 2xCH₃SPh) 2.50 (s, 3H, NAc), 2.21 – 1.95 (10 X OAc’s), 1.17 – 1.16 (d, J = 6.2 Hz, 3H, H-6’) ; ¹³C NMR (151 MHz, Chloroform-d) δ 172.67, 171.24, 171.00, 170.87, 170.75, 170.72, 170.38, 169.70, 169.10, 166.90, 154.04, 153.91, 144.15, 129.31, 128.25, 100.80 (C-1’’), 99.74 (C-2’’’), 95.36 (C-1’), 95.19 (C-CCl₃), 76.97 (C-5’), 75.30 (C-5’’), 74.92 (Troc CH₂), 74.26 (C-7’’’), 73.16 (C-4’’’), 71.47 (C-3’’), 71.35 (C-8’’’), 70.91 (C-4), 70.18 (C-2’), 69.86 (C-3’), 68.12 (C-2’’), 64.34 (C-5’), 62.83 (9’’’CH₂), 62.33 (6’’CH₂), 61.56 (6CH₂), 59.15 (C-5’’’), 52.69 (CO₂Me), 36.45 (C-   3’’’), 31.94, 29.71, 29.37, 24.74 (NAc), 22.70 – 20.61 (10 X OAc’s) 15.79 (C-6’), 14.20 (CH₃), 14.14 (CH₃); HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₆₂H₇₉Cl₃N₂NaO₃₄S [M+Na]⁺ 1555.3198, found: 1555.3191. [4+2] glycosylation and further functional groups modification

N-(9-Fluorenylmethyloxycarbonyl)-O-[4-O-acetyl-2-deoxy-2-azido-3-O-(2,3,4,6-tetra-O-acetyl-β-D- galactopyranosyl)-6-O-(methyl-5-acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl)-3,5-dideoxy-D- glycero-α-D-galacto-2-nonulopyranonate)-(2→3)-O-(2,4,6-tri-O-acetyl-β-D-galactopyranosyl)-(1→4)- [(1→3)-(2,3,4-tri-O-acetyl-α-L-fucopyranosyl)]-O-[6-O-acetyl-2-deoxy-2-(2,2,2- trichloroethoxycarbonylamino)-β-D-glucopyranosyl-(1→6)]-α-D-galactopyranosyl]-L-threonine-tert- butyl ester (32) [366] From donor 3: Donor 3 (2.2 g, 1.44 mmol, 1 equivalent) and core-1-diol acceptor 4 (2.3 g, 2.57 mmol, 1.8 equivalents) were dissolved in anhydrous CH₂Cl₂ (100 mL), activated 4 Å molecular sieves (2.3 g) added, and the mixture stirred at room temperature for 30 minutes. The reaction mixture was cooled to -15°C, NIS (1.28 g, 5.72 mmol, 4.0 equivalents) and TfOH (50 µL, 0.57 mmol, 0.4 equivalents)   were added, and the reaction was stirred with slow warming to -5°C for 1.5 hours followed by quenching with aq. NaHCO₃. The reaction mixture was then filtered over a bed of Celite and washed with dichloromethane. After twice repeating the work up with aq. Na₂S₂O₃, the organic layer was separated, dried over Na₂SO₄, and the solvent removed under vacuum to afford the crude compound. The crude compound was dissolved in pyridine/Ac₂O (50 mL/35 mL) and cat. DMAP (60 mg) added and stirred for 3 hours. Solvents were removed under vacuum, co-distilled with toluene (3 x 100 mL), and flash column purification afforded compound 32 as a foamy white solid (3.1 g, 88% over two steps). [367] From donor 31: A mixture of sLe^X thioglycoside donor 31 (67.0 mg, 0.044 mmol, 1.0 equivalent), core-1 diol acceptor 4 (61 mg, 0.067 mmol, 1.5 equivalents) and freshly activated 4 Å molecular sieve (100 mg) were stirred in anhydrous CH₂Cl₂ (4.5 mL) for 1 hour at room temperature under an argon atmosphere. The reaction mixture was then cooled to -10°C. NIS (20.0 mg, 0.089 mmol, 2.0 equivalents) and TfOH (1.34 mg, 0.010 mmol, 0.2 equivalents) were added sequentially, and the mixture stirred for 30 minutes at -10°C. The progress of the reaction was monitored by TLC and MALDI-ToF. The reaction was diluted with CH₂Cl₂, filtered, and washed with sat. Na₂S₂O₃ solution, sat. NaHCO₃ solution, and brine. The organic layer was dried (Na₂SO₄) and filtered, and the filtrate concentrated under vacuum. The residue was dissolved in pyridine (1.0 mL), acetic anhydride (0.3 mL), and DMAP (2.0 mg), and the reaction mixture stirred for 2 hours until the starting material was consumed as determined by TLC. The product underwent azeotropic co-distillation under the reduced pressure using toluene. The residue was purified by silica gel column chromatography (hexanes: EtOAc, 1:4) to afford compound 32 (70.0 mg, yield : 67%) as a white foam. [368] [α]_D ²⁴= -16.4 (c=1, CHCl₃); R_f 0.55 (acetone : toluene, 2:3); ¹H NMR (600 MHz, Chloroform-d) δ 7.79 (d, J = 7.5 Hz, 2H), 7.64 (d, J = 7.4 Hz, 2H), 7.42 (td, J = 7.5, 2.7 Hz, 2H), 7.33 (ddd, J = 9.2, 6.7, 1.8 Hz, 2H), 5.64 (d, J = 9.6 Hz, 1H, NHTroc), 5.58 (m, 1H, H-7ʼʼʼʼʼ), 5.47 – 5.40 (m, 2H, H-1ʼʼʼ, H- 8ʼʼʼʼʼ), 5.38 (d, J = 3.5 Hz, 2H, H-4ʼ, H-4ʼʼʼʼ), 5.33 – 5.16 (m, 4H, H-3ʼʼʼʼ, H-3ʼʼʼ, H-2ʼʼʼʼ, H-3ʼ), 5.10 – 4.92 (m, 5H, H-4ʼʼʼ, H-1ʼʼ, H-6ʼʼʼʼʼ, H-5ʼʼʼ, H-2ʼ), 4.92 – 4.85 (m, 2H, 9ʼʼʼʼʼCH₂), 4.83 – 4.78 (m, 2H, Troc CH₂), 4.75 (t, J = 6.8 Hz, 1H, H-1ʼʼʼʼ), 4.69 (d, J = 12.0 Hz, 1H, Troc CH₂), 4.55 – 4.36 (m, 6H, H- 1, H-1ʼ, Thr OCH, Fmoc CH₂, 6ʼCH₂, 6ʼʼʼʼCH₂), 4.36 – 4.18 (m, 7H, H-4ʼʼʼʼʼ, H-5ʼ, H-5ʼʼ, 6ʼCH₂, 6ʼʼʼCH₂, FmocCH₂), 4.18 – 3.95 (m, 7H, H-2ʼʼʼ, H-3, H-5ʼʼʼʼ, H-4, H-2ʼʼ, 6ʼʼʼʼCH₂, 6ʼʼʼCH₂), 3.92 (t, J = 6.8 Hz, 1H, H-4ʼʼ), 3.90 – 3.81 (m, 4H, CO₂Me, 6CH₂), 3.78 (td, J = 9.3, 3.6 Hz, 2H, H-3ʼʼ, 9ʼʼʼʼʼCH₂), 3.58 – 3.50 (m, 2H, H-5ʼʼʼʼʼ, H-2), 3.48 – 3.36 (m, 2H, H-5, 6CH₂), 2.70 (dd, J = 12.9, 3.7 Hz, 1H, H- 3ʼʼʼʼʼ), 2.52 (s, 3H, NAc), 2.22 – 1.95 (m, 46H, 15x OAc, H-3ʼʼʼʼʼ), 1.51 (s, 9H, t-butyl), 1.35 (m, 3H, Fmoc CH₃), 1.21 (d, J = 6.6 Hz, 3H, H-6ʼʼ); ¹³C NMR (151 MHz, Chloroform-d) δ 171.01, 170.73, 170.71, 170.46, 170.34, 170.21, 170.08, 169.70, 169.63, 169.54, 166.89, 156.76, 153.87, 143.88, 143.73, 141.29, 141.28, 127.77, 127.11, 127.03, 125.22, 125.15, 120.04, 120.01, 101.54 (C-1), 100.69 (C-1ʼʼʼʼ) , 99.99 (C-1ʼ), 99.74 (C-2ʼʼʼʼʼ), 99.32 (C-1ʼʼ), 95.52 (C-CCl₃), 95.43 (C-1ʼʼʼ), 82.92 (C-C(CH₃)₃), 77.01 (C-5ʼʼʼ), 76.16 (Thr OCH), 75.07 (C-3ʼʼ), 74.63 (Troc CH₂), 74.02 (C-4ʼʼ), 73.13 (C-4ʼʼʼʼʼ), 71.53 (C- 3ʼʼʼ), 71.38 (C-4ʼʼ), 70.70 (C-4ʼʼʼʼ), 70.10 (C-6ʼʼʼʼʼ), 69.90 (C-2ʼ), 69.39, 68.76 (6CH₂), 68.07, 67.34 (6ʼCH₂), 66.70, 64.35, 62.78 (9ʼʼʼʼʼCH₂), 61.91 (6ʼʼʼʼCH₂), 61.38 (Fmoc CH₂), 60.83 (C-6ʼʼʼ), 59.55 (C-   2ʼʼ), 59.27 (C-5ʼʼʼʼʼ), 59.17 (C-2), 52.74 (CO₂Me), 47.15 (CH₂CHFmoc), 36.50 (C-3ʼʼʼʼʼ), 28.08 (C-t- butyl), 24.72 (C-NAc), 21.29 – 20.34 (15 x OAc's), 19.16 (Thr CH₃), 15.80 (C-6ʼ’’); HR-MALDI- TOF/MS (positive, SuperDHB matrix): m/z calcd for C₉₉H₁₂₅Cl₃N₆NaO₅₃ [M+Na]⁺ 2373.6234, found: 2373.6310. N-(9-Fluorenylmethyloxycarbonyl)-O-[2-(N-acetamido)-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-β-D- galactopyranosyl)-6-O-(methyl-5-acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl)-3,5-dideoxy-D- glycero-α-D-galacto-2-nonulopyranonate)-(2→3)-O-(2,4,6-tri-O-acetyl-β-D-galactopyranosyl)-(1→4)- [(1→3)-(2,3,4-tri-O-acetyl-α-L-fucopyranosyl)]-O-[6-O-acetyl-2-deoxy-2-(N-acetamido)-β-D- glucopyranosyl-(1→6)]-α-D-galactopyranosyl]-L-threonine-tert-butyl ester (34) [369] Acetic anhydride (50 mL), Zn-Cu couple (12.0 g), and acetic acid (50 mL) were added to a stirred solution of hexasaccharide 32 (2.6 g, 10.77 mmol, 1.0 equivalent) in anhydrous THF (120 mL) at room temperature. The reaction mixture was stirred for 5 hours at room temperature followed by dilution with CH₂Cl₂ and filtration through a pad of Celite. The filtrate was washed with sat. aq. NaHCO₃ and brine, and the organic layer concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexanes: EtOAc, 1:4) to afford compound 34 (1.83 g, yield 73%) as a white foam. [370] R_f 0.30 (acetone : toluene, 1:1); [α]_D ²⁴= -18.2 (c=1, CHCl₃); ¹H NMR (600 MHz, Acetone-d₆) δ 7.91 (d, J = 7.5 Hz, 2H), 7.72 (d, J = 7.5 Hz, 2H), 7.45 (q, J = 5.8, 4.3 Hz, 2H), 7.37 (t, J = 6.9 Hz, 2H), 7.07 (dd, J = 13.4, 9.7 Hz, 1H, NH, GlcNAc), 6.97 (d, J = 10.0 Hz, 1H, NH, GalNAc), 6.53 (d, J = 9.7 Hz, 1H, NHFmoc), 5.84 (m, 1H, H-8ʼʼʼʼʼ), 5.53 (ddt, J = 7.8, 4.7, 2.9 Hz, 1H, H-7ʼʼʼʼʼ), 5.47 – 5.35 (m, 4H, H-1ʼʼʼ, H-3ʼʼʼ, H-4), 5.35 – 5.26 (m, 2H, H-4ʼʼʼ), 5.18 – 5.04 (m, 2H, H-2ʼʼʼʼ, H-5ʼʼʼ), 5.04 – 4.92 (m, 3H, H-6ʼʼʼʼʼ, H-4ʼʼʼʼ, H-4), 4.84 (d, J = 3.9 Hz, 1H, H-1), 4.82 – 4.77 (m, 2H, 9ʼʼʼʼʼCH₂, H-5), 4.76 (d, J = 7.5 Hz, 1H, H-1ʼʼ), 4.62 (d, J = 8.2 Hz, 1H, H-1ʼʼʼʼ), 4.56 – 4.34 (m, 7H, 6ʼʼʼCH₂, 6ʼCH₂, H-2ʼʼ, H-4ʼʼʼʼʼ, H-3ʼʼʼʼ, H-5ʼʼʼʼ, H-5), 4.34 – 4.24 (m, 4H, 6ʼCH₂, Fmoc CH), 4.21 – 4.12 (m, 4H, CH₂), 4.06 (tdd, J = 5.1, 3.9, 2.2 Hz, 4H, H-2, H-2ʼʼʼ, CH₂), 4.01 – 3.78 (m, 8H, 9ʼʼʼʼʼCH₂, CO₂Me, H-5ʼʼʼʼʼ, 6CH_2, H-3ʼʼ, H-4ʼʼ), 3.63 (ddd, J = 10.1, 6.1, 3.2 Hz, 1H, H-5ʼʼ), 3.43 (dd, J = 10.6, 8.3 Hz, 1H, 6CH₂), 2.56 (dt, J = 12.7, 3.5 Hz, 1H, H-3ʼʼʼʼʼ), 2.42 (s, 3H, NAc), 2.29 (t, J = 12.8 Hz, 1H, H-3ʼʼʼʼʼ), 2.25 – 1.76 (17s, 51H, 15x OAc, 2x NHAc), 1.48 (s, 9H, t-butyl), 1.31 (m, Fmoc CH₃), 1.25 – 1.05 (m, 3H, H-6ʼʼʼ); ¹³C NMR (151 MHz, Acetone-d₆) δ 171.47, 170.63, 170.50, 170.27, 170.22, 170.09, 169.91, 169.68, 169.55, 169.36, 169.32, 169.03, 168.87, 168.81, 167.14, 153.79, 144.05, 141.24, 127.72, 127.12, 125.14, 120.02, 101.83 (C-1ʼ), 101.31 (C-1), 100.74 (C-1ʼʼʼʼ), 100.07 (C-2ʼʼʼʼʼ), 95.50 (C-1ʼʼʼ), 81.80 (C- C(CH₃)₃), 76.46 (C-5ʼʼ), 75.21 (C-4ʼʼ)74.78 (OCH Thr), 73.67 (C-8ʼʼʼʼʼ), 73.10 (C-5ʼʼ), 73.07 (C-4ʼʼʼʼʼ), 72.96 (C-3ʼʼʼ), 71.79 (C-4), 71.50 (C-3), 70.91 (C-7ʼʼʼʼʼ), 70.69, 70.57, 70.38, 69.83, 69.19 (6CH₂), 68.61 (Fmoc CH₂), 67.92, 67.74, 67.04 (C-5ʼʼʼ), 66.27 (6ʼʼʼʼCH₂), 63.96, 62.81 (9ʼʼʼʼʼCH₂), 62.32 (6CH₂), 61.26 (Thr-OCH), 60.87 (6ʼʼCH₂), 58.87 (C-5ʼʼʼʼʼ), 52.32 (CO₂Me), 48.47 (CH₂CHFmoc), 35.90 (3ʼʼʼʼʼCH₂), 27.37 (C-t-butyl), 23.65 (NAc), 22.79 - 19.18 (17c of OAc and NHAc), 19.13 (Thr CH₃), 15.45 (C-6ʼʼʼ); HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₁₀₀H₁₃₀N₄NaO₅₃ [M+Na]⁺ 2257.7498, found: 2257.7399.   N-(9-Fluorenylmethyloxycarbonyl)-O-[4-O-acetyl-2-deoxy-2-(N-acetamido)-3-O-(2,3,4,6-tetra-O-acetyl- β-D-galactopyranosyl)-6-O-(methyl-5-acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl)-3,5-dideoxy-D- glycero-α-D-galacto-2-nonulopyranonate)-(2→3)-O-(2,4,6-tri-O-acetyl-β-D-galactopyranosyl)-(1→4)- [(1→3)-(2,3,4-tri-O-acetyl-α-L-fucopyranosyl)]-O-[6-O-acetyl-2-deoxy-2-(N-acetamido)-β-D- glucopyranosyl-(1→6)]-α-D-galactopyranosyl]-L-threonine (2) [371] Hexasaccharide tert-butyl ester 34 (1.7 g, 0.16 mmol, 1.0 equivalent) was dissolved in anhyd. CH₂Cl₂ (45 mL). TFA (35 mL) and anisole (6.5 mL) were added to the reaction mixture at room temperature under argon atmosphere. The reaction mixture was then stirred for 6 hours at room temperature. Solvent was removed azeotropically with toluene under reduced pressure after confirming that the starting material was consumed on TLC analysis. The residue was purified by silica gel flash chromatography (0 → 10% MeOH in CH₂Cl₂), affording the glycoamino acid 2 (1.27 g, 75 %). [372] [α]_D ²⁴= -12.4 (c=1, CHCl₃); R_f = 0.35 (methanol : CH₂Cl₂, 1:9); ¹H NMR (600 MHz, Acetone-d₆) δ 7.90 (d, J = 7.6 Hz, 2H), 7.73 (d, J = 7.5 Hz, 2H), 7.45 (t, J = 7.5 Hz, 2H), 7.37 (t, J = 7.5 Hz, 2H), 5.83 (td, J = 6.0, 5.4, 2.6 Hz, 1H, H-8’’’’’), 5.53 (ddt, J = 8.1, 4.9, 2.8 Hz, 1H, H-7’’’’’), 5.44 – 5.28 (m, 5H, H-1’’’, H-3’’’, H-4, H-4’’’, H-2’’’’), 5.09 (ddd, J = 12.8, 12.1, 7.6 Hz, 1H, H-5’’’), 4.99 (td, J = 11.4, 10.3, 4.4 Hz, 3H, H-6’’’’’, H-4’’’’, H-4), 4.85 – 4.76 (m, 3H, H-1, 9’’’’’CH₂, H-5), 4.63 (t, J = 8.3 Hz, 1H, H-1’’’’), 4.38 (ddt, J = 11.0, 6.1, 3.5 Hz, 1H, H-1’’), 4.30 (dq, J = 11.5, 6.8, 6.1 Hz, 2H, 6CH₂, 6’’’CH₂), 4.21 – 4.13 (m, 8H, H-2’’, H-4’’’’’, H-3’’’’, H-5’’’, H-5, 6’CH₂, FmocCH), 4.07 – 3.8 (m, 12H, H-2, H-2’’’, CH₂, 9’’’’’CH₂, CO₂Me, H-5’’’’’, 6CH₂, H-3’’, H-4’’) 2.59 – 2.51 (m, 2H, H-3’’’’’, H-5’’), 2.42 (s, 3H, NAc), 2.29 (t, J = 12.8 Hz, 1H, H-3’’’’’) 2.19 – 1.87 (17s, 51H, 15XOAc, 2XNHAc), 1.37 – 1.26 (m, 3H, Fmoc CH₃), 1.21 (dd, J = 11.5, 6.8 Hz, 3H, H-6’’’); ¹³C NMR (151 MHz, Acetone- d₆) 171.44, 170.78, 170.63, 170.48, 170.26, 170.23, 170.07, 169.90, 169.81, 169.70, 169.35, 169.30, 169.03, 168.92, 168.81, 167.14, 153.77, 150.95, 149.99, 149.66, 148.91, 144.09, 141.23, 128.85, 127.69, 127.14, 125.18, 119.97, 101.21 (C-1), 100.75 (C-1’’’’), 100.09 (C-2’’’’’), 95.52 (C-1’’’), 76.44 (C-5’’), 75.46 (C-4’’), 73.10 (OCHThr), 73.03 (C-8’’’’’), 71.84 (C-5’’), 71.51 (C-4’’’’’), 70.94 (C-3’’’), 70.65 (C-4), 70.37 (C-3), 69.83 (C-7’’’’’), 68.71 (Fmoc CH₂), 67.95 , 67.73, 67.08 (C-5’’’), 66.33 (6’’’’CH₂), 63.98, 62.81 (9’’’’’ CH₂), 62.28 (6CH₂), 61.26 (Thr-OCH), 60.87 (6’CH₂), 58.88 (C-5’’’’’), 52.29 (CO₂Me), 47.18 (CH₂CHFmoc), 35.89 (3’’’’’CH₂), 23.59 - 19.60 (17c of OAc and NHAc), 19.58 (ThrCH₃), 15.43 (C-6’’’); HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₉₅H₁₂₂N₄NaO₅₃ [M+Na]⁺ 2201.6872, found: 2201.6362.   Procedures and characterization of Core-1-diol intermediates

Phenyl 2-deoxy-2-azido-4,6-O-di-tert-butyl silyl-D-galactopyranoside (23) [373] Di-tert butyl silyl bistriflate (16.9 mL, 51.84 mmol, 2.2 equivalents) was added in a dropwise manner to a solution of starting material, phenyl 2-deoxy-2-azido-3,4,6-thio-D-galactopyranoside⁹ (7.0 g, 23.56 mmol, 1.0 equivalent), in dry pyridine at 0°C. The resulting mixture was brought to room temperature and further stirred for 1 hour until TLC analysis demonstrated complete consumption of the starting material (TLC of SM: 15% MeOH in CH₂Cl₂; Product: 15% EtOAc in hexanes). The reaction mixture was then cooled to 0°C, Ac₂O (25 mL) added, and the solution rewarmed to room temperature and was stirred for 3 hours (TLC: 10% EtOAc in hexanes). Solvents were evaporated and the residue co- evaporated with toluene, twice, to obtain a crude product. The crude product was purified over silica gel column chromatography by eluting with 10% EtOAc in hexanes to obtain product 23, as mixture of isomers, as an off-white oil (10.5 g; 99%; 1:1 α:β). Two distinct product spots of isomers 23α- and 23β- were observed on TLC, which were easily separated via silica gel flash column chromatography. However, as both isomers afforded the same product 25 in the next step of the reaction sequence, there was no need to further separate these products. [374] β-isomer (23β): [α]_D ²⁶= +13.5 (c=0.20, CH₂Cl₂); R_f 0.10 (EtOAc, Hexanes; 1:4); ¹H NMR (600 MHz, CDCl₃) δ 7.69 – 7.48 (m, 2H, Ar-H), 7.44 – 7.26 (m, 3H, Ar-H), 4.73 – 4.57 (m, 2H, H-1, H-3), 4.51 (d, J = 10.3 Hz, 1H, H-4), 4.21 (dd, J = 2.1, 1.1 Hz, 2H, H-6, H-6), 3.89 (dd, J = 10.3, 9.5 Hz, 1H, H-2), 3.40 (q, J = 1.7 Hz, 1H, H-5), 2.17 (s, 3H, OAc), 1.09 (s, 9H, tBu), 1.01 (s, 9H, tBu); ¹³C NMR (151 MHz, CDcl₃) δ 170.27, 132.95, 132.91, 128.98, 128.12, 87.70 (C-1), 76.20 (C-3), 74.80 (C-4), 69.14 (C-5), 67.09 (C-6), 59.99 (C-2), 27.51 (2 X Si-C-Me₃), 23.19 (OAc), 20.79 (Si-C-Me₃), 20.64 (Si- C-Me₃); HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₂₂H₃₃N₃NaO₅SSi [M+Na]⁺ 502.1808, found: 502.1804.   [375] α-isomer (23α): [α]_D ²⁶= +18.5 (c=0.20, CH₂Cl₂); R_f 0.10 (EtOAc, Hexanes; 1:4); ¹H NMR (400 MHz, CDCl₃) δ 7.57 – 7.39 (m, 2H, Ar-H), 7.30 (qq, J = 7.1, 1.4 Hz, 3H, Ar-H), 5.67 (d, J = 5.5 Hz, 1H, H-1), 4.94 (dd, J = 10.9, 3.0 Hz, 1H, H-3), 4.78 (d, J = 3.0 Hz, 1H, H-4), 4.46 (dd, J = 10.9, 5.4 Hz, 1H, H-6), 4.28 (d, J = 12.2 Hz, 2H, H-6, H-2), 4.17 – 3.92 (m, 1H, H-5), 2.17 (s, 3H, OAc), 1.07 – 0.88 (m, 18H, 2 X tBu); ¹³C NMR (100 MHz, CDCl₃) δ 170.18, 133.31, 132.04, 129.11, 127.68, 87.61 (C-1), 73.18 (C-3), 69.86 (C-4), 68.13 (C-5), 66.86 (C-6), 57.66 (C-2), 27.52 (Si-C-Me₃), 27.23 (Si-C-Me₃), 23.20 (OAc), 20.77 (Si-C-Me₃), 20.70 (Si-C-Me₃); HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₂₂H₃₃N₃NaO₅SSi [M+Na]⁺ 502.1808, found: 502.1816. N^α-(Fluoren-9-ylmethoxycarbonyl)-O-2-azido-2-deoxy-4,6-di-tert-butyl silyl-α-D-galactopyranosyl]-L- threonine tert-butyl ester (25) [376] A reaction mixture of starting material 23 (10.5 g, 23.25 mmol, 1.0 equivalent) and Fmoc-Thr- COOtBu (compound 24) (13.85 g, 34.87 mmol, 1.5 equivalents) in anhydrous CH₂Cl₂ (300 mL), which contained 4 Å molecular sieves (10.5 g), was stirred at room temperature for 1 hour under argon. The reaction mixture was cooled to -10°C, NIS (10.46 g, 46.50 mmol, 2.0 equivalents) added, followed by TfOH (0.41 mL, 4.65 mmol, 0.2 equivalents), and the mixture stirred under argon at -10°C for 1 hour, and then quenched with sat. aq. NaHCO₃ and passed through a bed of Celite. The filtrate was washed with 20% aq. Na₂S₂O₃ (2 X 200 mL) and brine solution. Organics were collected, dried (Na₂SO₄), and evaporated in vacuo to obtain a residue. The residue was subjected to silica gel column chromatography eluting with 15% EtOAc in hexanes to obtain the product 25 as an off-white solid in the form of single isomer (12.0 g; 70%). [377] [α]_D ²⁶= +41.5 (c=0.20, CH₂Cl₂); R_f 0.10 (EtOAc, Hexanes; 1:4); ¹H NMR (600 MHz, CDCl₃) δ 7.88 – 7.69 (m, 2H), 7.64 (d, J = 7.5 Hz, 2H), 7.39 (tt, J = 7.6, 1.6 Hz, 2H), 7.31 (tdd, J = 7.4, 2.3, 1.2 Hz, 2H), 5.71 (d, J = 9.5 Hz, 1H, NH-Fmoc), 5.19 – 4.98 (m, 2H, H-3, H-1), 4.75 (d, J = 3.0 Hz, 1H, H- 4), 4.53 – 4.43 (m, 1H, Thr-CH), 4.43 – 4.37 (m, 1H, CH₂-Fmoc), 4.34 (dd, J = 10.3, 7.3 Hz, 1H, CH₂- Fmoc), 4.29 – 4.20 (m, 3H, H-6, CH-Fmoc, O-CH-Thr), 4.20 – 4.05 (m, 1H, H-6), 3.90 – 3.72 (m, 2H, H-2, H-5), 2.18 (s, 3H, OAc), 1.51 (s, 9H, COOtBu), 1.38 – 1.19 (m, 3H, Thr-CH₃), 1.04 (d, J = 7.0 Hz, 18H, 2 X tBu); ¹³C NMR (100 MHz, CDCl₃) δ 170.43, 169.41, 156.83, 143.94, 143.88, 141.27, 127.66, 127.09, 127.06, 125.28, 119.93, 119.90 (Ar-H), 98.87 (C-1), 82.74 (O-CH-Thr), 75.31 (C-4), 71.13 (C- 3), 70.13 (C-5), 67.51 (C-6), 67.43 (CH₂-Fmoc), 66.75 (Thr-CH), 59.16 (C-Me₃), 57.28 (C-2), 47.15 (CH-Fmoc), 27.94 (Si-C-Me₃), 27.54 (Si-C-Me₃), 27.18 (COOtBu), 23.24 (OAc), 20.82 (Si-C-Me₃), 20.67 (Si-C-Me₃), 19.21 (CH₃); HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₃₇H₅₂N₄NaO₉Si [M+Na]⁺ 747.3401, found: 747.3408. N^α-(Fluoren-9-ylmethoxycarbonyl)-O-[(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-(1→3)]-O-2- azido-2-deoxy-α-D-galactopyranosyl]-L-threonine tert-butyl ester (4) [378] Hydrazine monohydrate (9.45 mL, 194.88 mmol, 12.0 equivalents) was added to a solution of starting material 25 (12.0 g, 16.24 mmol, 1.0 equivalent) in methanol (400 mL). The resulting mixture   was stirred at room temperature for 3 hours (TLC: 20% EtOAc in hexanes). Solvents were evaporated in vacuo and the reaction mixture concentrated to about 50 mL. The reaction mixture was then diluted with CH₂Cl₂ and washed with H₂O followed by sat. aq. brine solution. Organics were collected, dried (Na₂SO₄), and evaporated in vacuo to obtain a crude product (10.5 g). The crude deacetylated acceptor (10.5 g, 15.07 mmol, 1.0 equivalent) was dissolved in anhydrous CH₂Cl₂ (300 mL). Galactose imidate donor 26 (11.13 g, 22.6 mmol, 1.5 equivalents) and 4 Å molecular sieves (10.5 g) were added and the reaction mixture stirred at room temperature under argon for 1 hour. The reaction mixture was brought to 0°C and TMSOTf (0.41 mL, 2.26 mmol, 0.15 equivalents) was added in a dropwise manner. The resulting mixture was stirred at 0°C for 1 hour, quenched with pyridine (0.36 mL, 4.52 mmol, 0.3 equivalents), brought to room temperature, filtered through a bed of Celite, and washed with CH₂Cl₂. Organics were collected, dried (Na₂SO₄), and evaporated in vacuo to obtain a crude residue. The residue was subjected to column chromatography over silica gel eluting with 35% EtOAc in hexanes to obtain the 4,6-O-di-tert-butyl silyl core-1-diol intermediate as an off-white solid (11.5 g, 75%). To a solution of the 4,6-O-di-tert-butyl silyl core-1-diol (11.5 g, 10.90 mmol, 1.0 equivalent) in THF (200 mL) was added TBAHF (1M; 47 mL in 200 mL of THF) (Preparation of 1 M TBAHF: A total of 200 mL of THF was added to 40 mL of Bu₃N. To this stirred solution of Bu₃N, 7 mL of HF was slowly added and was continually stirred for another 10 minutes). The resulting mixture was stirred at room temperature for 1 hour and solvents were then evaporated in vacuo. The residue was redissolved in EtOAc and washed with 10% aq HCl and sat. aq NaHCO₃. Organics were collected, dried (Na₂SO₄), and evaporated in vacuo to obtain a crude residue. The crude residue was subjected to column chromatography over silica gel eluting with 70% EtOAc in hexanes to obtain Core-1-diol 4 as an off-white solid. Spectral data matched that reported in the literature (7.37 g, 74%).¹⁰ [379] [α]_D ²⁶= + 66.0 (c 1, CHCl₃); ¹H NMR (CDCl₃):

1.33 (3H, d, J 6.7 Hz, Thr -CH₃); 1.51 (9H, s, – NHBoc), 2.00 (3H, s, OAc), 2.06 (3H, s, OAc), 2.10 (3H, s, OAc), 2.17 (3H, s, OAc), 3.57 (1H, dd, J 3.3 Hz, 10.5 Hz, H-2), 3.81 (1H, d, J 7.6 Hz, H-5), 3.93 (1H, s, H-5′), 3.95 (2H, m, 6-H₂), 4.02 (1H, dd, J 2.9 Hz, 10.5 Hz, H-3), 4.11 (1H, d, J 5.3 Hz, H-6′), 4.17 (1H, dd, J 4.1 Hz, 11.7 Hz), 4.21 (1H, d, J 2.5 Hz, H-4), 4.26 (1H, J 7.1 Hz, 7.6 Hz, Fmoc -CH₂), 4.30 (1H, d, J 8.4 Hz, Thr -CHα), 4.45 (1H, s, Fmoc -CH), 4.47 (1H, dd, J 1.5 Hz, 6.1 Hz, Thr -CHβ), 4.76 (1H, d, J 7.6 Hz, H-1′), 5.04 (1H, dd, J 3.3 Hz, 10.5 Hz, H-3′), 5.08 (1H, d, J 3.8 Hz, H-1), 5.30 (1H, dd, J 8.1 Hz, 10.5 Hz, H-2′), 5.41 (1H, d, J 3.3 Hz, H-4′), 5.70 (1 H, d, J 9.5 Hz, –NH), 7.31 (2H, at, J 7.6 Hz, 7.1 Hz, Fmoc -Ar), 7.40 (2H, dt, J 3.8 Hz, 7.1 Hz, Fmoc -Ar), 7.63 (2H, d, J 6.7 Hz, Fmoc -Ar), 7.77 (2H, d, J 7.2 Hz, Fmoc -Ar), ¹³C NMR (CDCl₃): δ_C 19.2, 20.7, 20.8, 20.9, 28.2, 47.3, 58.7, 59.2, 61.8, 62.9, 67.5, 68.5, 69.4, 69.7, 70.8, 71.5, 76.0, 77.0, 77.2, 77.4, 78.0, 83.2, 99.4, 102.1, 120.2, 124.5, 125.4, 127.2, 127.3, 127.9, 141.5, 143.9, 144.1, 156.9, 169.4, 169.8, 170.2, 170.3, 170.7; HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₄₅H₅₆N₄NaO₁₉ [M+Na]⁺ 979.3325, found: 979.3335. N^α-(Fluoren-9-ylmethoxycarbonyl)-O-[(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-(1→3)]-O-2- azido-2-deoxy-4-O-acetyl-α-D-galactopyranosyl]-L-threonine tert-butyl ester (4a)   [380] Imidazole (476 mg, 7 mmol, 2 equivalents) and N,N-dimethyl amino pyridine (DMAP) (42 mg, 0.35 mmol, 0.1 equivalents) were added to Core-1-diol 4 (3.2 g, 3.5 mmol, 1 equivalent) in DMF (12 mL), followed by the addition of t-butyl silyl chloride (TBSCl) (850 mg, 5.25 mmol, 1.5 equivalents). The reaction mixture was stirred for 3 hours, diluted with H₂O (50 mL), extracted with EtOAc (2 x 50 mL), and washed with ice cold water, followed by brine. The organic layer was separated, dried over Na₂SO₄, and the solvent was removed under vacuum. The crude compound was dissolved in pyridine (6 mL) and Ac₂O (4 mL), cat. DMAP was then added and the reaction mixture stirred for 8 hours at room temperature. Solvents were removed under vacuum and co-distillation with toluene (3 x 30 mL) afforded the crude compound. Flash column chromatography over silica gel with gradient solvents of ethyl acetate and hexane afforded the 4-OAc-6-OTBS-Core 1 disaccharide (3.2 g). The 4-OAc-6-OTBS-Core 1 disaccharide (3.2 g) was dissolved in THF (20 mL), followed by sequential addition of AcOH (0.8 mL) and TBAF (4.49 mL, 4.49 mmol, 1.5 equivalents), and then stirred for 16 hours at room temperature. THF was subsequently removed under vacuum, the reaction diluted with EtOAc (80 mL), washed with H₂O (50 mL), brine (25 mL), and aq. NaHCO₃ (30 mL). The organic layer was separated, dried over Na₂SO₄, and evaporated to afford the desired crude compound, which was purified over a silica gel column using 55% ethyl acetate and hexanes to provide the desired compound 4a (2.6 g, 76% over three steps). [381] [α]_D ²⁶= +33.6 (c=0.20, CH₂Cl₂); R_f 0.35 (EtOAc, Hexanes; 3:2)¹H NMR (600 MHz, Chloroform- d) δ 7.77 – 7.76 (m, 2H, Ar-H), 7.63 – 7.62 (m, 2H, Ar-H), 7.41 - 7.40 (m, 2H, Ar-H), 7.40 – 7.39 (m, 2H, Ar-H), 5.69 – 5.68 (d, J = 9 Hz, 1H, NH), 5.45 – 5.44 (s, 1H, H-4’), 5.37 – 5.36 (d, J = 3.4 Hz, 1H, H-4’’), 5.26 – 5.25 (m, 1H, H-2’’), 5.04 – 5.03 (d, J = 3.6 Hz, 1H, H-1’), 5.02 – 5.01 (d, J = 2.3 Hz, 1H, H-3’’), 4.74 – 4.73 (d, J = 7.9 Hz, 1H, H-1’’), 4.49 – 4.48 (t, J = 11.9 Hz, 1H, Fmoc CH₂) 4.41 – 4.40 (m, 1H, Thr-β-H), 4.34 – 4.33 (t, J = 12 Hz, 1H, CH₂Fmoc), 4.30 – 4.28 (m, 2H, CHFmoc, Thr-α-H), 4.12 – 4.09 (m, 3H, H3’, H-6’’, H-6’’), 3.98 – 3.94 (m, 1H, H-5’), 3.94 – 3.93 (m, 1H, H-5’’) 3.62 – 3.60 (dd, J = 2.8, 8.4 Hz, 1H, H-2’) 3.56 – 3.54 (m, 1H, H-6’) 3.41 – 3.39 (m, 1H, H-6’), 3.01(br s, 3H, OH), 2.18 (s, 3H, OAc), 2.13 (s, 3H, OAc), 2.08 (s, 3H, OAc), 2.03 (s, 3H, OAc), 1.98 (s, 3H, OAc), 1.32 – 1.31 (d, J = 6.2 Hz, 3H, Thr-CH₃); ¹³C NMR (125 MHz, Chloroform-d) δ 171.3, 170.5, 170.1, 154.3, 144.2, 135.6, 134.9, 133.3, 133.3, 133.2, 133.1, 129.1, 128.8, 128.3, 128.0, 127.9, 127.9, 127.8, 127.8, 127.0, 126.6, 12+6.5, 126.5, 126.4, 126.2, 126.1, 125.8, 125.7, 98.1, 95.5, 88.3, 83.4, 78.3, 74.6, 74.3, 73.8, 71.5, 70.9, 70.3, 70.3, 66.1, 60.5, 56.6, 22.5, 20.7, 16.1, 14.3; HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₄₅H₅₆N₄NaO₁₉ [M+Na]⁺ 979.3436, found: 979.3421. One-Pot Reaction General Procedure for one-pot glycosylation [382] Normal glycosylation protocol: Activated 4 Å molecular sieves (200 mg) were added to a mixture of dried donor 5 (1.5 equivalents) and acceptor 6 (1 equivalent) in anhydrous CH₂Cl₂ (4 mL). The reaction was stirred at room temperature for 30 minutes, followed by cooling of the reaction mixture to 0°C with slow dropwise addition of TMSOTf (15 mol% or 0.15 equivalents w.r.t. donor) at 0°C. The   reaction mixture was stirred at 0°C for 30 minutes, followed by sequential addition of Core-1 disaccharide acceptor 4a, NIS (3 equivalents), and TfOH (0.2 equivalents) at -15°C under an argon atmosphere. The reaction was stirred between -15°C to -5°C for 2 hours, after which TLC confirmed completion of the reaction. The reaction mixture was quenched with aq. NaHCO₃, filtered over a bed of Celite, and washed with dichloromethane. After work up with aq. Na₂S₂O₃, the organic layer was separated, dried over Na₂SO₄, and solvents were removed under vacuum to afford the crude compound, which was subjected to flash column purification to afford the desired compound. Inverse glycosylation protocol: Synthesis of hexasaccharide 33 N-(9-Fluorenylmethyloxycarbonyl)-O-[4-O-acetyl-2-deoxy-2-azido-3-O-(2,3,4,6-tetra-O-acetyl-β-D- galactopyranosyl)-6-O-(methyl-5-acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl)-3,5-dideoxy-D- glycero-α-D-galacto-2-nonulopyranonate)-(2→3)-O-(4,6-tri-O-acetyl-2-O-benzoyl-β-D- galactopyranosyl)-(1→4)-[(1→3)-(2-O-napthyl-3,4-di-O-acetyl-α-L-fucopyranosyl)]-O-[6-O-napthyl-2- deoxy-2-(2,2,2-trichloroethoxycarbonylamino)-β-D-glucopyranosyl-(1→6)]-α-D-galactopyranosyl]-L- threonine-tert-butyl ester (33) [383] Activated 4 Å molecular sieve (0.5 g) was added to a mixture of dried acceptor 6 (250 mg, 0.254 mmol, 1 equivalent) in anhydrous CH₂Cl₂ (4 mL) and the reaction mixture stirred at room temperature for 30 minutes, followed by cooling to -5°C with slow dropwise addition of TMSOTf (16 µL, 0.3 equivalents, 0.076 equivalents). After 2 to 3 minutes, a fresh solution of donor 5 (288 mg, 0.305 mmol, 1.2 equivalents) in anhydrous CH₂Cl₂ (4 mL) was added via syringe at -5°C over a period of 12 minutes (1 mL/3 minutes). The reaction mixture was stirred at -5°C for 30 minutes and the 4-OAc-Core I disaccharide acceptor 4a (~340 mg, 0.381 mmol, 1.5 equivalents) was then added, followed by NIS (229 mg, 1.01 mmol, 4 equivalents) and TfOH (3 µL, 0.0254 mmol, 0.1 equivalents) at -15°C. The reaction vessel was flushed with argon and the reaction mixture stirred between -15°C to -5°C for 2 hours after which TLC confirmed completion of the reaction. The reaction mixture was quenched with aq. NaHCO₃ (10 mL), diluted with CH₂Cl₂ (40 mL), filtered over a bed of Celite, and washed with dichloromethane (20 mL). After work up with aq. Na₂S₂O₃ (2 x 50 mL), the organic layer was separated, dried over Na₂SO₄, and the solvent was removed under vacuum to afford the crude compound, which was subject to flash column purification to afford hexasaccharide 33 as a white foamy solid. (424 mg, 66% yield). [384] [α]_D ²⁴= -13.2 (c=1, CHCl₃); R_f 0.55 (acetone : toluene, 2:3); ¹H NMR (600 MHz, Acetone-d₆) δ 8.01 – 7.84 (m, 9H, Ar-H), 7.77 – 7.69 (d, J = 7.32 Hz, 1H, Ar-H), 7.62 – 7.60 (d, J = 8.34 Hz, 1H, Ar- H), 7.55 – 7.41 (m, 4H, Ar-H), 7.42 – 7.40 (m, 2H, Ar-H), 7.35 - 7.31 (m, 2H, Ar-H), 7.02 – 7.01 (d, 1H, Ar-H), 6.09 – 6.08 (d, J = 9.4 Hz, 1H), 5.80 – 5.79 (m, 1H), 5.55 – 5.54 (d, J = 9.36 Hz, 1H, H-1ʼʼ’’), 5.51 – 5.39 (m, 1H, H-1ʼʼʼ), 5.46 – 5.45 (d, J = 2.64 Hz, 2H, H-4ʼ, H-4ʼʼʼʼ), 5.39 – 5.34 (m, 4H, H-3ʼʼʼʼ, H-3ʼʼʼ, H-2ʼʼʼʼ, H-3ʼ), 5.33 – 5.32 (d, 1H, H-4ʼʼʼ), 5.14 – 5.07 (m, 5H, 9ʼʼʼʼʼCH_2, H-3’’, H-4’’’’, H-5’’, H-2’’’), 4.98 – 4.92 (m, 4H, Troc CH₂, H-5ʼ, H-5ʼʼ, 6ʼCH₂), 4.86 (s, 3H, Me), 4.85 – 4.78 (m, 2H, H-4, H-2ʼʼ), 4.76 – 4.68 (m, 3H, Fmoc CH₂, 6ʼCH₂, 6ʼʼʼʼCH₂), 4.40 – 4.36 (m, 4H, H-4ʼʼʼʼʼ, H-3’’’, 6ʼʼʼCH₂, FmocCH₂), 4.33 – 4.28 (m, 3H, H-2ʼʼʼ, H-3, H-5ʼʼʼʼ), 4.26 – 4.22 (m, 3H, H-4ʼʼ, H-3’’’’, H-2), 4.19 –   4.12 (m, 2H, H-5’’, H-3’’’), 4.04 -4.03 (m, 3H, H-3ʼʼ, H-2’’’’, 9ʼʼʼʼʼCH₂), 4.01 – 3.98 (m, 7H, H-5ʼʼʼʼʼ, H-2, H-4, H-2ʼʼ, H-2ʼʼʼ, H-3, H-5ʼʼʼ), 3.95 – 3.87 (m, 4H, H-5, H-3ʼʼʼʼ, H-5’’, 6CH₂), 2.57 – 2.41 (dd, J = 3.6, 12.7 Hz, 1H, H-3ʼ’ʼʼ), 2.33 – 2.28 (t, J = 9.2 Hz, 1H, H-2’’’), 2.19 (s, 3H, OAc), 2.12 (s, 3H, OAc), 2.10 (s, 3H, OAc), 2.06 (s, 3H, OAc), 2.02 (s, 3H, OAc), 1.99 (s, 3H, OAc), 1.92 (s, 3H, OAc), 1.89 (s, 3H, OAc), 1.84 (s, 3H, OAc), 1.71 (s, 3H, OAc), 1.51 (s, 3H, OAc), 1.41 – 1.40 (d, J = 6.4 Hz, 3H, Me), 1.19 – 1.18 (d, J = 6.2 Hz, 3H, Me); ¹³C NMR (151 MHz, Chloroform-d) δ 205.3, 171.5, 170.8, 170.3, 170.2, 170.1, 169.7, 169.6, 169.4, 169.4, 169.4, 169.3, 168.9, 168.8, 167.2, 156.5, 154.1, 153.7, 144.1, 141.2, 236.6, 136.2, 133.4, 133.4, 133.1, 133.0, 128.2, 127.9, 127.8, 127.7, 127.6, 127.1, 127.0, 126.2, 126.1, 125.9, 125.9, 125.8, 125.6, 125.5, 125.2, 125.2, 119.9, 101.2, 100.9, 100.3, 100.1, 99.6, 96.5, 96.2, 81.8, 76.4, 76.2, 75.1, 75.0, 74.5, 74.1, 73.8, 73.0, 72.9, 71.8, 71.5, 71.3, 70.7, 70.5, 70.4, 70.3, 70.1, 69.7, 69.4, 69.1, 68.8, 68.2, 67.0, 66.7, 63.9, 62.7, 61.6, 60.7, 59.8, 59.7, 59.6, 58.9, 58.8, 58.6, 55.05, 52.3, 47.1, 27.3, 23.6, 20.5, 20.3, 20.1, 19.9, 19.9, 19.8, 19.8, 19.6, 19.6, 19.0, 15.5, 13.6; HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₁₁₃H₁₂₈Cl₃N₆O₅₀ [M+Na]⁺ 2496.6621, found: 2496.6609. N-(9-Fluorenylmethyloxycarbonyl)-O-[4-O-acetyl-2-deoxy-2-azido-3-O-(2,3,4,6-tetra-O-acetyl-β-D- galactopyranosyl)-6-O-(methyl-5-acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl)-3,5-dideoxy-D- glycero-α-D-galacto-2-nonulopyranonate)-(2→3)-O-(4,6-tri-O-acetyl-2-O-benzoyl-β-D- galactopyranosyl)-(1→4)-[(1→3)-(2,3,4-tri-O-acetyl-α-L-fucopyranosyl)]-O-[6-O-acetyl-2-deoxy-2- (2,2,2-trichloroethoxycarbonylamino)-β-D-glucopyranosyl-(1→6)]-α-D-galactopyranosyl]-L-threonine-

[385] DDQ (45 mg, 0.21 mmol, 6 equivalents) was added to compound 33 (100 mg, 0.035 mmol, 1 equivalent) in CH₂Cl₂:H₂O (20:1, 2 mL) and the reaction mixture stirred from 0°C to room temperature for 12 hours. After TLC confirmed completion of the reaction, the mixture was diluted with CH₂Cl₂ (20 mL), and subsequently washed with water (3 mL) and brine (3 mL), followed by aq. NaHCO₃ (5 mL). The organic layer was separated and dried over Na₂SO₄ and the solvent was removed under vacuum. Flash chromatography of the crude mixture afforded the desired compound as a fluffy solid (84 mg), which was dissolved in pyridine (1 mL) and Ac₂O (1 mL), and the reaction mixture stirred at room temperature for 3 hours. After TLC showed completion of the reaction, the solvent was removed under vacuum and co-distilled with toluene (2 x 2 mL) to afford the crude compound. Silica gel flash chromatography afforded the desired compound 32 as a white solid (84 mg, 72% yield over two steps).   [386] [α]_D ²⁴= -16.4 (c=1, CHCl₃); R_f 0.55 (acetone : toluene, 2:3); ¹H NMR (600 MHz, Chloroform-d) δ 7.79 (d, J = 7.5 Hz, 2H), 7.64 (d, J = 7.4 Hz, 2H), 7.42 (td, J = 7.5, 2.7 Hz, 2H), 7.33 (ddd, J = 9.2, 6.7, 1.8 Hz, 2H), 5.64 (d, J = 9.6 Hz, 1H, NHTroc), 5.58 (m, 1H, H-7ʼʼʼʼʼ), 5.47 – 5.40 (m, 2H, H-1ʼʼʼ, H- 8ʼʼʼʼʼ), 5.38 (d, J = 3.5 Hz, 2H, H-4ʼ, H-4ʼʼʼʼ), 5.33 – 5.16 (m, 4H, H-3ʼʼʼʼ, H-3ʼʼʼ, H-2ʼʼʼʼ, H-3ʼ), 5.10 – 4.92 (m, 5H, H-4ʼʼʼ, H-1ʼʼ, H-6ʼʼʼʼʼ, H-5ʼʼʼ, H-2ʼ), 4.92 – 4.85 (m, 2H, 9ʼʼʼʼʼCH₂), 4.83 – 4.78 (m, 2H, Troc CH₂), 4.75 (t, J = 6.8 Hz, 1H, H-1ʼʼʼʼ), 4.69 (d, J = 12.0 Hz, 1H, Troc CH₂), 4.55 – 4.36 (m, 6H, H- 1, H-1ʼ, Thr OCH, Fmoc CH₂, 6ʼCH₂, 6ʼʼʼʼCH₂), 4.36 – 4.18 (m, 7H, H-4ʼʼʼʼʼ, H-5ʼ, H-5ʼʼ, 6ʼCH₂, 6ʼʼʼCH₂, FmocCH₂), 4.18 – 3.95 (m, 7H, H-2ʼʼʼ, H-3, H-5ʼʼʼʼ, H-4, H-2ʼʼ, 6ʼʼʼʼCH₂, 6ʼʼʼCH₂), 3.92 (t, J = 6.8 Hz, 1H, H-4ʼʼ), 3.90 – 3.81 (m, 4H, CO₂Me, 6CH₂), 3.78 (td, J = 9.3, 3.6 Hz, 2H, H-3ʼʼ, 9ʼʼʼʼʼCH₂), 3.58 – 3.50 (m, 2H, H-5ʼʼʼʼʼ, H-2), 3.48 – 3.36 (m, 2H, H-5, 6CH₂), 2.70 (dd, J = 12.9, 3.7 Hz, 1H, H- 3ʼʼʼʼʼ), 2.52 (s, 3H, NAc), 2.22 – 1.95 (m, 46H, 15x OAc, H-3ʼʼʼʼʼ), 1.51 (s, 9H, t-butyl), 1.35 (m, 3H, Fmoc CH₃), 1.21 (d, J = 6.6 Hz, 3H, H-6ʼʼ); ¹³C NMR (151 MHz, Chloroform-d) δ 171.01, 170.73, 170.71, 170.46, 170.34, 170.21, 170.08, 169.70, 169.63, 169.54, 166.89, 156.76, 153.87, 143.88, 143.73, 141.29, 141.28, 127.77, 127.11, 127.03, 125.22, 125.15, 120.04, 120.01, 101.54 (C-1), 100.69 (C-1ʼʼʼʼ) , 99.99 (C-1ʼ), 99.74 (C-2ʼʼʼʼʼ), 99.32 (C-1ʼʼ), 95.52 (C-CCl₃), 95.43 (C-1ʼʼʼ), 82.92 (C-C(CH₃)₃), 77.01 (C-5ʼʼʼ), 76.16 (Thr OCH), 75.07 (C-3ʼʼ), 74.63 (Troc CH₂), 74.02 (C-4ʼʼ), 73.13 (C-4ʼʼʼʼʼ), 71.53 (C- 3ʼʼʼ), 71.38 (C-4ʼʼ), 70.70 (C-4ʼʼʼʼ), 70.10 (C-6ʼʼʼʼʼ), 69.90 (C-2ʼ), 69.39, 68.76 (6CH₂), 68.07, 67.34 (6ʼCH₂), 66.70, 64.35, 62.78 (9ʼʼʼʼʼCH₂), 61.91 (6ʼʼʼʼCH₂), 61.38 (Fmoc CH₂), 60.83 (C-6ʼʼʼ), 59.55 (C- 2ʼʼ), 59.27 (C-5ʼʼʼʼʼ), 59.17 (C-2), 52.74 (CO₂Me), 47.15 (CH₂CHFmoc), 36.50 (C-3ʼʼʼʼʼ), 28.08 (C-t- butyl), 24.72 (C-NAc), 21.29 – 20.34 (15 x OAc's), 19.16 (Thr CH₃), 15.80 (C-6ʼ); HR-MALDI- TOF/MS (positive, SuperDHB matrix): m/z calcd for C₉₉H₁₂₅Cl₃N₆NaO₅₃ [M+Na]⁺ 2373.6234, found: 2373.6310. Solid phase peptide synthesis of GSnP-6 (1) via fragment condensation [387] A fragment-condensation strategy was adopted to optimize the yield of GSnP-6 (compound 1). The synthetic scheme is illustrated in Figure 8. Amino acids were coupled through a standard protocol unless otherwise specified. Coupling method A (Standard Protocol) [388] Fmoc-AA-OH (5.0 equivalents, 0.25 M in DMF), HBTU (5.0 equivalents, 0.25 M in DMF), and N-methylmorpholine (12.5 equivalents) were mixed in a falcon tube and allowed to shake for ~2 minutes until the solids were dissolved. The mixture was then added to the vessel which contained the resin. The coupling step proceeded for 1 hour at RT. The solution was then drained, and the resin was thoroughly washed five times with DMF. After each coupling step, Fmoc on the N-terminus was removed by 20% piperidine in DMF, twice. The resin was washed 5 times with DMF to prepare for the next coupling. Coupling method B (coupling of glycoamino acid Fmoc-hexasaccharide-Thr-OH 2)   [389] The resin was evenly split into Costar^® Spin-X^® Centrifuge Tube with a filter. Glycoamino acid Fmoc-hexasaccharide-Thr-OH 2 (1.1 equivalents, 110 mM), TBTU (1.1 equivalents, 110 mM), HOBT (1.1 equivalents, 110 mM) and trimethylpyridine (3 equivalents, 300 mM) were mixed in DMF and allow to shake for ~2 minutes. The resulting clear solution was distributed into the centrifuge tubes and allowed to react overnight on a shaker at RT. The resin was then washed 5 times with DMF. Coupling method C (coupling of the fragment) [390] The 13-mer peptide fragment (1.5 equivalents, 150 mM), TBTU (1.5 equivalents, 150 mM), HOBT (1.5 equivalents, 150 mM) and trimethylpyridine (3 equivalents, 300 mM) were mixed in DMF and allowed to shake for ~2 minutes. The resulting solution was pipetted into the centrifuge tubes and allowed to react for 3 hours on a shaker at RT. Synthesis of the 13-mer peptide fragment [391] A 13 residue peptide fragment was synthesized on a 2-CTC resin pre-loaded with Fmoc-Glu-OH (0.625 mmol/g) through standard SPPS. The product was cleaved by 5 mL of 2% (v/v) TFA in DCM for 5 minutes, three times. The cleavage cocktail was then drained and combined in a 50 mL falcon tube. A total of 500 mg of sodium bicarbonate was added to the cocktail and the solution was dried by blowing nitrogen through the tube. To the slurry was added 5 mL of acetonitrile and the peptide was precipitated by adding 40 mL of DI water. The product was collected by filtration and washed twice with DI water. The fully protected fragment was completely dried by lyophilization. The product displayed >90% purity on HPLC, with a yield of 63%, and was used without further purification. Synthesis of protected GSnP-6 [392] Protected GSnP-6 was synthesized on NovaSyn®TGA resin preloaded with Fmoc-Leu-OH (0.19 mmol/g, 368 mg, 70 μmol). Fmoc-Glu-OH and Fmoc-Pro-OH were coupled using a standard protocol (coupling method A) and glycoamino acid Fmoc-hexasaccharide-Thr-OH (compound 2) was coupled by coupling method B. The resin was treated three times with 2% DBU and 1% DTT in 4 mL of DMF for 5 minutes, which not only deprotected the Fmoc group but also cleaved the 4O,5N-oxazolidinone ring. After washing, the 13-mer peptide fragment was coupled by coupling method C to provide the full sequence. The peptide was cleaved using 4 mL of cleavage cocktail over a 2 hour period and the resin rinsed with another 2 mL of cleavage cocktail. The cocktail was drained and combined in a falcon tube and the peptide was precipitated in cold ether. The crude product was purified by RP-HPLC to afford 122 mg of the protected peptide (38% overall yield). HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₁₈₉H₂₅₈Cl₉N₂₁NaO₈₈S₃ [M+Na]⁺ 4663.262, found: 4662.720. Deprotection sequence to provide GSnP-6 (1) Deprotection of tricholoroethyl (TCE) protected the phenylalanine sulfonates. Palladium on carbon (Pd/C, 10 wt. % loading, 39 mg) was added to a scintillation vial which contained protected GSnP-6 (194 mg, 0.042 mmol, 1 equivalent) in methanol/water/acetic acid solution (8:1:0.1 v/v, 5 mL), which was   shaken under H₂ gas (40 PSI) and monitored over 5-minute intervals by analytical HPLC until the reaction was completed. The crude mixture was subsequently centrifugated and the supernatant was subjected to HPLC purification. The RP-HPLC gradient used for preparative purposes included a solvent (A) comprised of water and 0.1% TFA, and a solvent (B) comprised of acetonitrile: 0-2 minutes, 5% B, 2-5 minutes, 5-40% B, 5-16 minutes, 40-70% B, 16-17 minutes, 70-98% B, 17-18.5 minutes, 98% B, 18.5-20 minutes, 98-5% B. The protected GSnP-6 without TCE groups displayed an R_t = 9.78 minutes at a flow rate of 40 mL/minute. The RP-HPLC gradient used for analytical purposes included a solvent (A) comprised of water and 0.1% TFA, and a solvent (B) comprised of acetonitrile: 0-2 minutes, 5% B, 2-18 minutes, 5-95% B, 18-20 minutes, 95% B, 20-20.01 minutes, 95-5% B, 20.01-22 minutes, 5% B. The protected GSnP-6 without the TCE groups displayed an R_t = 8.42 minutes at a flow rate of 2.5 mL/minute. Preparative RP-HPLC afforded the protected GSnP-6 without the TCE groups (136 mg) in 76% yield. HR-MALDI-TOF/MS (negative, SuperDHB matrix): m/z calcd for C₁₈₃H₂₅₄N₂₁O₈₈S₃ [M-H]⁺ 4249.521, found: 4249.070. Deprotection of acetate protecting groups were observed. Sodium methoxide was added to a scintillation vial which contained protected GSnP-6 without the TCE groups (12 mg, 0.003 mmol, 1 equivalent) in dry methanol (2 mL) until the pH reached 8.0 - 8.5 and was shaken under Ar for 8 hours. The reaction was quenched using DOWEX® 50WX8. The crude mixture was centrifugated and the supernatant was subjected to RP-HPLC. The RP-HPLC gradient used for preparative purposes included a solvent (A) comprised of water and 0.1% TFA, and a solvent (B) comprised of acetonitrile: 0-2 minutes, 5% B, 2-5 minutes, 5-40% B, 5-16 minutes, 40-70% B, 16-17 minutes, 70-98% B, 17-18.5 minutes, 98% B, 18.5-20 minutes, 98-5% B. Partially O-acetylated GSnP-6 displayed an R_t = 8.03 minutes at a flow rate of 40 mL/minute. The RP-HPLC gradient used for analytical purposes included a solvent (A) comprised of water and 0.1% TFA, and a solvent (B) consisted of acetonitrile: 0-2 minutes, 5% B, 2-18 minutes, 5- 95% B, 18-20 minutes, 95% B, 20-20.01 minutes, 95-5% B, 20.01-22 minutes, 5% B. Partially O- acetylated GSnP-6 displayed an R_t = 5.92 minutes at a flow rate of 2.5 mL/minute. Preparative RP-HPLC gave partially O-acetylated GSnP-6 (7 mg) in 66% yield. HR-MALDI-TOF/MS (positive, SuperDHB matrix): m/z calcd for C₁₅₉H₂₃₂N₂₁O₇₆S₃ [M+H]⁺ 3747.410, found: 3747.695. Deprotection of the remaining acetate and methyl ester protecting groups was observed. Lithium hydroxide was added to a scintillation vial which contained partially O-acetylated GSnP-6 (7 mg, 0.002 mmol, 1 equivalent) in water (2 mL) until the pH reached 10.5 - 11.0 and was shaken under Ar for 3 hours. The reaction was quenched using DOWEX® 50WX8. The crude mixture was centrifugated and the supernatant was subjected to RP-HPLC. The RP-HPLC gradient used for preparative purposes included a solvent (A) comprised of water and 0.1% TFA, and a solvent (B) comprised of acetonitrile: 0- 2 minutes, 5% B, 2-5 minutes, 5-40% B, 5-16 minutes, 40-70% B, 16-17 minutes, 70-98% B, 17-18.5 minutes, 98% B, 18.5-20 minutes, 98-5% B (GSnP-6, R_t = 7.55 minutes at a flow rate of 40 mL/minute). The RP-HPLC gradient used for analytical purposes included a solvent (A) comprised of water and 0.1% TFA and a solvent (B) comprised of acetonitrile: 0-2 minutes, 5% B, 2-18 minutes, 5-95% B, 18-20 minutes, 95% B, 20-20.01 minutes, 95-5% B, 20.01-22 minutes, 5% B (GSnP-6, R_t = 5.80 minutes at a   flow rate of 2.5 mL/minute). Preparative RP-HPLC afforded GSnP-61 (4 mg) in 62% yield. HR-ESI- QTOF/MS (positive, SuperDHB matrix): m/z calcd for C₁₅₂H₂₂₄N₂₁O₇₃S₃ [M+H]⁺ 3607.3623, found: 3607.3782. References: 1) Crich, D.; Li, W. “O-Sialylation with N-acetyl-5-N,4-O-carbonyl-protected thiosialoside donors in dichloromethane: Facile and selective cleavage of the oxazolidinone ring” J. Org. Chem.2007, 72, 2387-2391. 2) Li, Z.; Gildersleeve, J. C. “Mechanistic studies and methods to prevent aglycon transfer of thioglycosides” J. Am. Chem. Soc.2006, 128, 11612-11619. 3) Khiar, N.; Martin-Lomas, M. “A highly convergent synthesis of the tetragalactose moiety of the GPI anchor of the VSG of trypanosoma brucei” J. Org. Chem.1995, 60, 7017-7021. 4) Mukherjee, A.; Palcic, M. M.; Hindsgaul, O. “Synthesis and enzymatic evaluation of modified acceptors of recombinant blood group A and B glycosyltransferases” Carbohydr. Res.2000, 326, 1-21. 5) Smid, P.; de Ruiter, G. A.; van der Marel, G. A.; Rombouts, F. M.; van Boom, J. H. “Iodonium- ion assisted stereospecific glycosylation: synthesis of oligosaccharides containing α(1-4)-linked l-fucopyranosyl units” J. Carbohydr. Chem.1991, 10, 833-849. 6) Hollaus, R.; Ittig, S.; Hofinger, A.; Haegman, M.; Beyaert, R.; Kosma, P.; Zamyatina, A. “Chemical synthesis of Burkholderia Lipid A modified with glycosyl phosphodiester-linked 4- amino-4-deoxy-β-L-arabinose and its immunomodulatory potential” Chem. Eur. J.2015, 21, 4102-4114. 7) Chinoy, Z. S.; Schafer, C. M.; West, C. M.; Boons, G.-J. “Chemical synthesis of a glycopeptide derived from Skp1 for probing protein specific glycosylation” Chem. Eur. J.2015, 21, 11779- 11787. 8) Mathieux, N.; Paulsen, H.; Meldal, M.; Bock, K. “Synthesis of glycopeptide sequences of repeating units of the mucins MUC2 and MUC 3 containing oligosaccharide side-chains with core 1, core 2, core 3, core 4 and core 6 structure” J. Chem. Soc., Perkin Trans.11997, 2359- 2368. 9) Bourgault, J. P.; Trabbic, K. R.; Shi, M; Andreana, P. R. "Synthesis of the tumor associative α- aminooxy disaccharide of the TF antigen and its conjugation to a polysaccharide immune stimulant" Org. Biomol. Chem.2014, 12, 1699-1702. 10) Sardar, M. Y. R.; Mandhapati, A. R.; Park, S.; Wever, W. J.; Cummings, R. D.; Chaikof, E. L. "Convergent synthesis of sialyl LewisX-O-Core-1-threonine" J. Org. Chem.2018, 83, 4963- 4972.   EQUIVALENTS AND SCOPE [393] In the claims, articles such as “a,” “an,” and “the” may mean one or more than one unless indicated to the contrary or otherwise evident from the context. Claims or descriptions that include “or” between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context. The present disclosure includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The present disclosure includes embodiments in which more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process. [394] Furthermore, the present disclosure encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, and descriptive terms from one or more of the listed claims is introduced into another claim. For example, any claim that is dependent on another claim can be modified to include one or more limitations found in any other claim that is dependent on the same base claim. Where elements are presented as lists, e.g., in Markush group format, each subgroup of the elements is also disclosed, and any element(s) can be removed from the group. It should it be understood that, in general, where the present disclosure, or aspects of the present disclosure, is/are referred to as comprising particular elements and/or features, certain embodiments of the present disclosure or aspects of the present disclosure consist, or consist essentially of, such elements and/or features. For purposes of simplicity, those embodiments have not been specifically set forth in haec verba herein. It is also noted that the terms “comprising” and “containing” are intended to be open and permits the inclusion of additional elements or steps. Where ranges are given, endpoints are included. Furthermore, unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or sub-range within the stated ranges in different embodiments of the present disclosure, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise. [395] This application refers to various issued patents, published patent applications, journal articles, and other publications, all of which are incorporated herein by reference. If there is a conflict between any of the incorporated references and the instant specification, the specification shall control. In addition, any particular embodiment of the present disclosure that falls within the prior art may be explicitly excluded from any one or more of the claims. Because such embodiments are deemed to be known to one of ordinary skill in the art, they may be excluded even if the exclusion is not set forth explicitly herein. Any particular embodiment of the present disclosure can be excluded from any claim, for any reason, whether or not related to the existence of prior art. [396] Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation many equivalents to the specific embodiments described herein. The scope of the present embodiments described herein is not intended to be limited to the above Description, but rather is as set forth in the appended claims. Those of ordinary skill in the art will appreciate that various changes   and modifications to this description may be made without departing from the spirit or scope of the present disclosure, as defined in the following claims.

Claims

  CLAIMS What is claimed is: 1. A method of preparing a compound of Formula (1):

or a salt thereof, comprising reacting a compound of Formula (2):

or a salt thereof, in the presence of a compound of Formula (3):

or a salt thereof, wherein: R^L1 is –SR^S1, wherein R^S1 is substituted phenyl; each R¹ is independently optionally substituted acyl or an oxygen protecting group; R² is optionally substituted acyl or a nitrogen protecting group; R³ is optionally substituted alkyl, optionally substituted acyl, or an oxygen protecting group; R⁴ is optionally substituted acyl or a nitrogen protecting group; R^N is optionally substituted acyl or a nitrogen protecting group; and R^O is optionally substituted alkyl, optionally substituted acyl, or an oxygen protecting group.   2. The method of claim 1, wherein the compound of Formula (1) is:

, or a salt thereof; the compound of Formula (2) is:

, or a salt thereof; and the compound of Formula (3) is:

, or a salt thereof. 3. The method of claim 1 or 2, wherein the reaction is carried out in the presence of an acid. 4. The method of claim 3, wherein the acid is trifluoromethanesulfonic acid (TfOH). 5. The method of any one of claims 1-4, wherein the reaction is carried out in the presence of an N- halosuccinimide. 6. The method of claim 5, wherein the N-halosuccinimide is N-iodosuccinimide (NIS).   7. The method of any one of claims 1-6, wherein the reaction is carried out in dichloromethane (DCM). 8. The method of any one of claims 1-7, further comprising protecting the compound of Formula (1), or a salt thereof, to yield a compound of Formula (A):

or a salt thereof, wherein R^1A is optionally substituted acyl or a nitrogen protecting group. 9. The method of claim 8, wherein the compound of Formula (1) is:

, or a salt thereof; and the compound of Formula (A) is:

,   or a salt thereof. 10. The method of claim 8, wherein R^1A is optionally substituted acyl; and the reaction is carried out in the presence of an acylating reagent. 11. The method of any one of claims 8-10, wherein R^1A is –Ac; and the reaction is carried out in the presence of Ac₂O. 12. The method of any one of claims 8-11, wherein the reaction is carried out in the presence of a base. 13. The method of any one of claims 8-12, wherein the reaction is carried out in the presence of 4- dimethylaminopyridine (DMAP) and/or pyridine. 14. The method of any one of claims 8-13, further comprising: (a) reducing and protecting the compound of Formula (A), or a salt thereof, to yield a compound of Formula (B):

or a salt thereof; and (b) hydrolyzing the compound of Formula (B), or a salt thereof, to yield a compound of

  or a salt thereof, wherein R⁵ is optionally substituted acyl or a nitrogen protecting group. 15. The method of claim 14, wherein the compound of Formula (A) is:

or a salt thereof; the compound of Formula (B) is:

, or a salt thereof; and the compound of Formula (C) is:

, or a salt thereof.   16. The method of claim 14 or 15, wherein the reaction in step (a) is carried out in the presence of a reducing agent. 17. The method of claim 16, wherein the reducing agent is zinc (Zn) metal or zinc-copper couple (ZnCu). 18. The method of any one of claims 14-17, wherein R⁵ is optionally substituted acyl; and the reaction in step (a) is carried out in the presence of an acylating reagent. 19. The method of claim 18, wherein R⁵ is –Ac; and the reaction in step (a) is carried out in the presence of Ac₂O. 20. The method of any one of claims 14-19, wherein the reaction in step (a) is carried out in THF and/or AcOH. 21. The method of any one of claims 14-19, wherein the reaction in step (b) is carried out in the presence of an acid. 22. The method of claim 21, wherein the acid is trifluoroacetic acid (TFA). 23. The method of any one of claims 14-22, wherein the reaction in step (b) is carried out in dichloromethane (DCM). 24. A method of preparing a compound of Formula (4):

or a salt thereof, comprising reacting a compound of Formula (5):

or a salt thereof, with a compound of Formula (6):  

or a salt thereof, wherein: R^L1 is a leaving group; R^L2 is optionally substituted aryl or optionally substituted heteroaryl; each X is independently halogen; each R^1B is independently optionally substituted naphthylmethyl; each R¹ is independently optionally substituted acyl or an oxygen protecting group; R² is optionally substituted acyl or a nitrogen protecting group; R³ is optionally substituted alkyl, optionally substituted acyl, or an oxygen protecting group; and R⁴ is optionally substituted acyl or a nitrogen protecting group. 25. The method of claim 24, wherein the compound of Formula (4) is:

, or a salt thereof; the compound of Formula (5) is:

, or a salt thereof; and the compound of Formula (6) is:

, or a salt thereof. 26. The method of claim 24 or 25, wherein the reaction is carried out in the presence of a Lewis acid.   27. The method of claim 26, wherein the Lewis acid is trimethylsilyl trifluoromethanesulfonate (TMSOTf). 28. The method of any one of claims 24-27, wherein the reaction is carried out in dichloromethane (DCM). 29. The method of any one of claims 24-28, further comprising: (a) deprotecting the compound of Formula (4), or a salt thereof, to yield a compound of Formula (D):

or a salt thereof; and (b) protecting the compound of Formula (D), or a salt thereof, to yield a compound of Formula (2):

or a salt thereof. 30. The method of claim 29, wherein the compound of Formula (4) is:

, or a salt thereof; the compound of Formula (D) is:

,   or a salt thereof; and the compound of Formula (2) is:

, or a salt thereof. 31. The method of claim 29 or 30, wherein the reaction in step (a) is carried out in the presence of an oxidant. 32. The method of claim 31, wherein the oxidant is 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). 33. The method of any one of claims 29-32, wherein the reaction in step (a) is carried out in dichloromethane (DCM). 34. The method of any one of claims 29-33, wherein each R¹ is optionally substituted acyl; and the reaction in step (b) is carried out in the presence of an acylating reagent. 35. The method of claim 34, wherein each R¹ is –Ac; and the reaction in step (b) is carried out in the presence of Ac₂O. 36. The method of any one of claims 29-35, wherein the reaction in step (b) is carried out in the presence of a base. 37. The method of any one of claims 29-36, wherein the reaction in step (b) is carried out in the presence of 4-dimethylaminopyridine (DMAP) and/or pyridine. 38. A method of preparing a compound of Formula (7):

  or a salt thereof, comprising reacting a compound of Formula (8):

or a salt thereof, with a compound of Formula (9):

or a salt thereof, wherein: R^L3 is a leaving group; each R¹ is independently optionally substituted acyl or an oxygen protecting group; each R^1C is independently optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; R^N is optionally substituted acyl or a nitrogen protecting group; and R^O is optionally substituted alkyl, optionally substituted acyl, or an oxygen protecting group. 39. The method of claim 38, wherein the compound of Formula (7) is:

, or a salt thereof; the compound of Formula (8) is:  

, or a salt thereof; and the compound of Formula (9) is:

, or a salt thereof. 40. The method of claim 38 or 39, wherein the reaction is carried out in the presence of a Lewis Acid. 41. The method of claim 40, wherein the Lewis acid is trifluoromethanesulfonate (TMSOTf). 42. The method of any one of claims 39-41, wherein the reaction is carried out in dichloromethane (DCM). 43. The method of any one of claims 39-42, further comprising deprotecting the compound of Formula (7), or a salt thereof, to yield a compound of Formula (3):

or a salt thereof. 44. The method of claim 43, wherein the compound of Formula (7) is:  

, or a salt thereof; and the compound of Formula (3) is:

, or a salt thereof. 45. The method of claim 43 or 44, wherein the reaction is carried out in the presence of a fluoride source. 46. The method of claim 45, wherein the fluoride source is tributylamine hydrofluoride (TBAHF). 47. The method of any one of claims 43-46, wherein the reaction is carried out in tetrahydrofruan (THF). 48. A method of preparing a compound of Formula (10):

or a salt thereof, comprising reacting a compound of Formula (11):  

or a salt thereof, with a compound of Formula (12):

or a salt thereof, wherein: R^L4 is a leaving group; R¹ is independently optionally substituted acyl or an oxygen protecting group; each R^1C is independently optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; R^N is optionally substituted acyl or a nitrogen protecting group; and R^O is optionally substituted alkyl, optionally substituted acyl, or an oxygen protecting group. 49. The method of claim 46, wherein the compound of Formula (10) is:

, or a salt thereof; the compound of Formula (11) is:

, or a salt thereof; and the compound of Formula (12) is:

, or a salt thereof.   50. The method of claim 48 or 49, wherein the reaction is carried out in the presence of an acid. 51. The method of claim 50, wherein the acid is trifluoromethanesulfonic acid (TfOH). 52. The method of any one of claims 48-51, wherein the reaction is carried out in the presence of an N-halosuccinimide. 53. The method of claim 52, wherein the N-halosuccinimide is N-iodosuccinimide (NIS). 54. The method of any one of claims 48-53, wherein the reaction is carried out in dichloromethane (DCM). 55. The method of any one of claims 48-54, further comprising deprotecting the compound of Formula (10), or a salt thereof, to yield a compound of Formula (8):

or a salt thereof. 56. The method of claim 55, wherein the compound of Formula (10) is:

, or a salt thereof; and the compound of Formula (8) is:  

, or a salt thereof. 57. The method of claim 55, wherein R¹ is optionally substituted acyl. 58. The method of any one of claims 55-57, wherein the reaction is carried out in the presence of hydrazine (H₂NNH₂). 59. The method of any one of claims 55-57, wherein the reaction is carried out in methanol (MeOH). 60. A method of preparing a compound of Formula (13):

or a salt thereof, comprising reacting a compound of Formula (14):

or a salt thereof, with a compound of Formula (15):

or a salt thereof, wherein: R^L1 and R^L5 are each independently a leaving group; R^1B is optionally substituted naphthylmethyl; R^1D is optionally substituted naphthyl; each R¹ is independently optionally substituted acyl or an oxygen protecting group; and R² is optionally substituted acyl or a nitrogen protecting group.   61. The method of claim 60, wherein the compound of Formula (13) is:

, or a salt thereof; the compound of Formula (14) is:

, or a salt thereof, and the compound of Formula (15) is of the formula:

, or a salt thereof, wherein R^L5 is –SEt or –OC(=NPh)CF₃. 62. The method of claim 60 or 61, wherein the reaction is carried out in the presence of an acid. 63. The method of claim 62, wherein the acid is trifluoromethanesulfonic acid (TfOH). 64. The method of any one of claims 60-61, wherein the reaction is carried out in the presence of an N-halosuccinimide. 65. The method of claim 64, wherein the N-halosuccinimide is N-iodosuccinimide (NIS). 66. The method of claim 60 or 61, wherein the reaction is carried out in the presence of a Lewis Acid. 67. The method of claim 66, wherein the Lewis acid is trifluoromethanesulfonate (TMSOTf). 68. The method of any one of claims 60-67, wherein the reaction is carried out in dichloromethane (DCM). 69. The method of any one of claims 60-68, further comprising deprotecting a compound of Formula (13), or a salt thereof, to yield a compound of Formula (6):  

or a salt thereof. 70. The method of claim 69, wherein the compound of Formula (13) is:

, or a salt thereof; and the compound of Formula (6) is:

, or a salt thereof. 71. The method of claim 69 or 70, wherein the reaction is carried out in the presence of a hydride transfer reagent. 72. The method of claim 71, wherein the hydride transfer reagent is triethylsilane (Et₃SiH). 73. The method of any one of claims 69-72, wherein the reaction is carried out in the presence of an acid. 74. The method of claim 73, wherein the acid is trifluoromethanesulfonic acid (TfOH). 75. The method of any one of claims 69-74, wherein the reaction is carried out in dichloromethane (DCM).   76. A method of preparing a compound of Formula (16):

or a salt thereof, comprising reacting a compound of Formula (17):

or a salt thereof, in the presence of a compound of Formula (18):

or a salt thereof, wherein: R^L6 a leaving group; R^1E is optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group; each R¹ is independently optionally substituted acyl or an oxygen protecting group; R³ is optionally substituted alkyl, optionally substituted acyl, or an oxygen protecting group; and R⁴ is optionally substituted acyl or a nitrogen protecting group. 77. The method of claim 76, where the compound of Formula (16) is:

, or a salt thereof; the compound of Formula (17) is:

, or a salt thereof; and the compound of Formula (18) is:

, or a salt thereof.   78. The method of claim 76 or 77, wherein the reaction is carried out in the presence of an acid. 79. The method of claim 78, wherein the acid is trifluoromethanesulfonic acid (TfOH). 80. The method of any one of claims 76-79, wherein the reaction is carried out in the presence of an N-halosuccinimide. 81. The method of claim 80, wherein the N-halosuccinimide is N-iodosuccinimide (NIS). 82. The method of any one of claims 76-81, wherein the reaction is carried out in dichloromethane (DCM) and acetonitrile (MeCN). 83. The method of any one of claims 76-82, further comprising (a) deprotecting a compound of Formula (16):

or a salt thereof, to remove the group R^1E; and (b) reacting the product with a reagent of Formula (19):

(19) to yield a compound of Formula (5):

or a salt thereof, wherein: R^L2 is optionally substituted aryl or optionally substituted heteroaryl; and X and X^L are each independently halogen. 84. The method of claim 83, wherein the compound of Formula (16) is:

, or a salt thereof; the compound of Formula (19) is: CF₃C(=NPh)Cl; and the compound of Formula (5) is:  

, or a salt thereof. 85. The method of claim 83 or 84, wherein step (a) is carried out in the presence of an oxidant; optionally wherein the oxidant is ceric ammonium nitrate (CAN). 86. The method of any one of claims 83-85, wherein the reaction in step (b) is carried out in the presence of a base. 87. The method of claim 86, wherein the base is cesium carbonate Cs₂CO₃. 88. The method of any one of claims 83-87, wherein the reaction is carried out in acetonitrile (MeCN). 89. A method of preparing a compound of Formula (1-i):

or a salt thereof, comprising: (a) reacting a compound of Formula (6):

or a salt thereof, with a compound of Formula (5):  

or a salt thereof; and (b) reacting the resulting compound with a compound of Formula (3-i):

or a salt thereof, wherein: R^L1 is –SR^S1, wherein R^S1 is substituted phenyl; R^L2 is optionally substituted aryl or optionally substituted heteroaryl; each X is independently halogen; each R¹ is independently optionally substituted acyl or an oxygen protecting group; each R^1B is independently optionally substituted naphthylmethyl; R² is optionally substituted acyl or a nitrogen protecting group; R³ is optionally substituted alkyl, optionally substituted acyl, or an oxygen protecting group; R⁴ is optionally substituted acyl or a nitrogen protecting group; R^N is optionally substituted acyl or a nitrogen protecting group; and R^O is optionally substituted alkyl, optionally substituted acyl, or an oxygen protecting group. 90. The method of claim 89, wherein the compound of Formula (1-i) is:

, or a salt thereof; the compound of Formula (6) is:  

, or a salt thereof; the compound of Formula (5) is:

, or a salt thereof; and the compound of Formula (3-i) is:

, or a salt thereof. 91. The method of claim 89 or 90, wherein the reaction in step (a) is carried out in the presence of a Lewis Acid. 92. The method of claim 91, wherein the Lewis acid is trifluoromethanesulfonate (TMSOTf). 93. The method of any one of claims 89-92, wherein the reaciton in step (b) is carried out in the presence of an acid. 94. The method of claim 93, wherein the acid is trifluoromethanesulfonic acid (TfOH). 95. The method of any one of claims 89-94, wherein the reaction in step (b) is carried out in the presence of an N-halosuccinimide. 96. The method of claim 95, wherein the N-halosuccinimide is N-iodosuccinimide (NIS). 97. The method of any one of claims 89-96, wherein the reaction is carried out in dichloromethane (DCM).   98. The method of any one of claims 89-97, wherein the reactions in steps (a) and (b) are carried out in one pot. 99. The method of any one of claims 89-98, further comprising: (a) deprotecting the compound of Formula (1-i) to yield a compound of Formula (1-ii):

or a salt thereof; (b) protecting the compound of Formula (1-ii), or salt thereof, to yield a compound of Formula (1-iii):

  (c) reducing and protecting the compound of Formula (1-iii), or a salt thereof, to yield a compound of Formula (1-iv):

iv), or a salt thereof; and (d) hydrolyzing the compound of Formula (1-iv), or a salt thereof, to yield a compound of Formula (1-v):

or a or a group. 100. The method of claim 99, wherein the compound of Formula (1-i) is:

,   or a salt thereof; the compound of Formula (1-ii) is:

or a salt thereof; the compound of Formula (1-iii) is:

, or a salt thereof; the compound of Formula (1-iv) is:

, or a salt thereof; and the compound of Formula (1-v) is:  

, or a salt thereof. 101. The method of claim 99 or 100, wherein the reaction in step (a) is carried out in the presence of an oxidant. 102. The method of claim 101, wherein the oxidant is 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). 103. The method of any one of claims 99-102, wherein the reaction in step (a) is carried out in dichloromethane (DCM). 104. The method of any one of claims 99-103, wherein each R¹ is optionally substituted acyl; and the reaction in step (b) is carried out in the presence of an acylating reagent. 105. The method of claim 104, wherein each R¹ is –Ac; and the reaction in step (b) is carried out in the presence of Ac₂O. 106. The method of any one of claims 99-105, wherein the reaction in step (b) is carried out in the presence of a base. 107. The method of any one of claims 99-106, wherein the reaction in step (b) is carried out in the presence of 4-dimethylaminopyridine (DMAP) and/or pyridine. 108. The method of claim 14 or 15, wherein the reaction in step (c) is carried out in the presence of a reducing agent. 109. The method of claim 108, wherein the reducing agent is zinc (Zn) metal or zinc-copper couple (ZnCu).   110. The method of any one of claims 99-109, wherein R⁵ is optionally substituted acyl; and the reaction in step (c) is carried out in the presence of an acylating reagent. 111. The method of claim 110, wherein R⁵ is –Ac; and the reaction in step (c) is carried out in the presence of Ac₂O. 112. The method of any one of claims 99-111, wherein the reaction in step (c) is carried out in THF and/or AcOH. 113. The method of any one of claims 99-112, wherein the reaction in step (d) is carried out in the presence of an acid. 114. The method of claim 113, wherein the acid is trifluoroacetic acid (TFA). 115. The method of any one of claims 99-114, wherein the reaction in step (d) is carried out in dichloromethane (DCM). 116. A compound of any one of Formulae (1), (2), (3-i), (4), (5), (6), (7), (8), (9), (10), (11), (13), (14), (15), (16), (18), (A), (B), (C), (D), (1-i), (1-ii), (1-iii), (1-iv), and (1-v); or a salt thereof.