WO2025221915A1 - Synthesis of gadusol and related compounds - Google Patents

Abstract

The present disclosure is concerned with methods of making Gadusol, making Gadusol derivatives, and methods of making the intermediates. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Description

Attorney Docket No.21101.0480P1 SYNTHESIS OF GADUSOL AND RELATED COMPOUNDS CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This Application claims the benefit of U.S. Application No.63/634,708, filed on April 16, 2024, the contents of which are hereby incorporated by reference in their entirety. BACKGROUND [0002] Gadusol is a natural product isolated from fish and primarily used by these species as a UV protective agent for their eggs. Initial isolation of the compound was done in 1981 by Plack, et al. in a natural product isolation journal. Following the initial discovery substantial research was conducted on the photophysical properties, antioxidant properties, and later on, the biochemical mechanisms of its synthesis in these species at Oregon State University. The biosynthetic pathway is a two-step synthesis from sedoheptulose 7-phosphate, an endogenous saccharide in these species. In a two-step process, two separate proteins cyclize the saccharide and then oxidize the resulting intermediate species, respectively. Having the biosynthetic process in hand, later work then introduced the genes responsible into a host production organism to produce gadusol biosynthetically in standard fermentation processes. [0003] New chemical routes and intermediates useful in the large-scale synthesis of gadusol and gadusol derivatives are needed. SUMMARY [0004] In accordance with the purpose(s) of the invention, as embodied and broadly described herein, the invention, in one aspect, relates to methods of making gadusol and gadusol derivatives, compounds useful as intermediates in the preparation thereof, and methods of making the intermediates. [0005] Thus, disclosed are methods comprising reducing a compound having a structure: to obtain a compound having a structure: Attorney Docket No.21101.0480P1 , wherein R1 is C1-C8 alkyl, wherein R² is C1-C8 alkyl, and wherein PG¹ is a hydroxyl protecting group. [0006] Also disclosed are compounds selected from: wherein R1 is C1-C8 alkyl, wherein R² is C1-C8 alkyl, wherein PG¹ is a hydroxyl protecting group, wherein PG² is a hydroxyl protecting group that is different from PG¹, and wherein the compound is not gadusol. [0007] Also disclosed are methods comprising oxidizing a compound having a structure: to obtain a compound having a structure: Attorney Docket No.21101.0480P1 , wherein R² is C1-C8 alkyl, and wherein PG² is a hydroxyl protecting group. [0008] Also disclosed are methods comprising protecting a compound having a structure: , wherein R² is C1-C8 alkyl, and wherein PG¹ is a hydroxyl protecting group, to obtain a compound having a structure: wherein PG³ is a hydroxyl protecting group that is different from PG¹. [0009] Also disclosed are compounds selected from: wherein R² is C1-C8 alkyl, wherein PG¹ is a hydroxyl protecting group, wherein PG³ is a hydroxyl protecting group that is different from PG¹, and wherein the compound is not gadusol. [0010] Also disclosed are methods comprising oxidizing a compound having a structure: Attorney Docket No.21101.0480P1 , to obtain a compound having a structure: , wherein R² is C1-C8 alkyl, and wherein PG³ is a hydroxyl protecting group. [0011] Also disclosed are products of the disclosed methods. [0012] While aspects of the present invention can be described and claimed in a particular statutory class, such as the system statutory class, this is for convenience only and one of skill in the art will understand that each aspect of the present invention can be described and claimed in any statutory class. Unless otherwise expressly stated, it is in no way intended that any method or aspect set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not specifically state in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including matters of logic with respect to arrangement of steps or operational flow, plain meaning derived from grammatical organization or punctuation, or the number or type of aspects described in the specification. BRIEF DESCRIPTION OF THE DRAWINGS [0013] The accompanying figures, which are incorporated in and constitute a part of this specification, illustrate several aspects and together with the description serve to explain the principles of the invention. [0014] FIG.1 shows a schematic of an example synthetic route for making Gadusol. [0015] FIG.1 shows a schematic of a further example synthetic route for making Gadusol. [0016] Additional advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or can be learned by practice of the invention. The advantages of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be Attorney Docket No.21101.0480P1 understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed. DETAILED DESCRIPTION [0017] The present invention can be understood more readily by reference to the following detailed description of the invention and the Examples included therein. [0018] Before the present compounds, compositions, articles, systems, devices, and/or methods are disclosed and described, it is to be understood that they are not limited to specific synthetic methods unless otherwise specified, or to particular reagents unless otherwise specified, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, example methods and materials are now described. [0019] While aspects of the present invention can be described and claimed in a particular statutory class, such as the system statutory class, this is for convenience only and one of skill in the art will understand that each aspect of the present invention can be described and claimed in any statutory class. Unless otherwise expressly stated, it is in no way intended that any method or aspect set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not specifically state in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including matters of logic with respect to arrangement of steps or operational flow, plain meaning derived from grammatical organization or punctuation, or the number or type of aspects described in the specification. [0020] Throughout this application, various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this pertains. The references disclosed are also individually and specifically incorporated by reference herein for the material contained in them that is discussed in the sentence in which the reference is relied upon. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of Attorney Docket No.21101.0480P1 publication provided herein may be different from the actual publication dates, which can require independent confirmation. A. DEFINITIONS [0021] As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a functional group,” “an alkyl,” or “a residue” includes mixtures of two or more such functional groups, alkyls, or residues, and the like. [0022] As used in the specification and in the claims, the term “comprising” can include the aspects “consisting of” and “consisting essentially of.” [0023] Ranges can be expressed herein as from “about” one particular value, and/or to “about” another particular value. When such a range is expressed, another aspect includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed. [0024] As used herein, the terms “about” and “at or about” mean that the amount or value in question can be the value designated some other value approximately or about the same. It is generally understood, as used herein, that it is the nominal value indicated ±10% variation unless otherwise indicated or inferred. The term is intended to convey that similar values promote equivalent results or effects recited in the claims. That is, it is understood that amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact, but can be approximate and/or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art. In general, an amount, size, formulation, parameter or other quantity or characteristic is “about” or “approximate” whether or not expressly stated to be such. It is understood that where “about” is used before a quantitative value, the parameter also includes the specific quantitative value itself, unless specifically stated otherwise. Attorney Docket No.21101.0480P1 [0025] References in the specification and concluding claims to parts by weight of a particular element or component in a composition denotes the weight relationship between the element or component and any other elements or components in the composition or article for which a part by weight is expressed. Thus, in a compound containing 2 parts by weight of component X and 5 parts by weight component Y, X and Y are present at a weight ratio of 2:5, and are present in such ratio regardless of whether additional components are contained in the compound. [0026] A weight percent (wt. %) of a component, unless specifically stated to the contrary, is based on the total weight of the formulation or composition in which the component is included. [0027] As used herein, the term “substituted” is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, and aromatic and nonaromatic substituents of organic compounds. Illustrative substituents include, for example, those described below. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this disclosure, the heteroatoms, such as nitrogen, can have hydrogen substituents and/or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms. This disclosure is not intended to be limited in any manner by the permissible substituents of organic compounds. Also, the terms “substitution” or “substituted with” include the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, e.g., a compound that does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. It is also contemplated that, in certain aspects, unless expressly indicated to the contrary, individual substituents can be further optionally substituted (i.e., further substituted or unsubstituted). [0028] In defining various terms, “A¹,” “A²,” “A³,” and “A⁴” are used herein as generic symbols to represent various specific substituents. These symbols can be any substituent, not limited to those disclosed herein, and when they are defined to be certain substituents in one instance, they can, in another instance, be defined as some other substituents. [0029] The term “aliphatic” or “aliphatic group,” as used herein, denotes a hydrocarbon moiety that may be straight-chain (i.e., unbranched), branched, or cyclic (including fused, bridging, and spirofused polycyclic) and may be completely saturated or may contain one or more units of unsaturation, but which is not aromatic. Unless otherwise specified, aliphatic Attorney Docket No.21101.0480P1 groups contain 1-20 carbon atoms. Aliphatic groups include, but are not limited to, linear or branched, alkyl, alkenyl, and alkynyl groups, and hybrids thereof such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl. [0030] The term “alkyl” as used herein is a branched or unbranched saturated hydrocarbon group of 1 to 24 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s- butyl, t-butyl, n-pentyl, isopentyl, s-pentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, dodecyl, tetradecyl, hexadecyl, eicosyl, tetracosyl, and the like. The alkyl group can be cyclic or acyclic. The alkyl group can be branched or unbranched. The alkyl group can also be substituted or unsubstituted. For example, the alkyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol, as described herein. A “lower alkyl” group is an alkyl group containing from one to six (e.g., from one to four) carbon atoms. The term alkyl group can also be a C1 alkyl, C1-C2 alkyl, C1-C3 alkyl, C1-C4 alkyl, C1-C5 alkyl, C1-C6 alkyl, C1-C7 alkyl, C1-C8 alkyl, C1-C9 alkyl, C1-C10 alkyl, and the like up to and including a C1-C24 alkyl. [0031] Throughout the specification “alkyl” is generally used to refer to both unsubstituted alkyl groups and substituted alkyl groups; however, substituted alkyl groups are also specifically referred to herein by identifying the specific substituent(s) on the alkyl group. For example, the term “halogenated alkyl” or “haloalkyl” specifically refers to an alkyl group that is substituted with one or more halide, e.g., fluorine, chlorine, bromine, or iodine. Alternatively, the term “monohaloalkyl” specifically refers to an alkyl group that is substituted with a single halide, e.g. fluorine, chlorine, bromine, or iodine. The term “polyhaloalkyl” specifically refers to an alkyl group that is independently substituted with two or more halides, i.e. each halide substituent need not be the same halide as another halide substituent, nor do the multiple instances of a halide substituent need to be on the same carbon. The term “alkoxyalkyl” specifically refers to an alkyl group that is substituted with one or more alkoxy groups, as described below. The term “aminoalkyl” specifically refers to an alkyl group that is substituted with one or more amino groups. The term “hydroxyalkyl” specifically refers to an alkyl group that is substituted with one or more hydroxy groups. When “alkyl” is used in one instance and a specific term such as “hydroxyalkyl” is used in another, it is not meant to imply that the term “alkyl” does not also refer to specific terms such as “hydroxyalkyl” and the like. [0032] This practice is also used for other groups described herein. That is, while a term such as “cycloalkyl” refers to both unsubstituted and substituted cycloalkyl moieties, the Attorney Docket No.21101.0480P1 substituted moieties can, in addition, be specifically identified herein; for example, a particular substituted cycloalkyl can be referred to as, e.g., an “alkylcycloalkyl.” Similarly, a substituted alkoxy can be specifically referred to as, e.g., a “halogenated alkoxy,” a particular substituted alkenyl can be, e.g., an “alkenylalcohol,” and the like. Again, the practice of using a general term, such as “cycloalkyl,” and a specific term, such as “alkylcycloalkyl,” is not meant to imply that the general term does not also include the specific term. [0033] The term “cycloalkyl” as used herein is a non-aromatic carbon-based ring composed of at least three carbon atoms. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornyl, and the like. The term “heterocycloalkyl” is a type of cycloalkyl group as defined above, and is included within the meaning of the term “cycloalkyl,” where at least one of the carbon atoms of the ring is replaced with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. The cycloalkyl group and heterocycloalkyl group can be substituted or unsubstituted. The cycloalkyl group and heterocycloalkyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol as described herein. [0034] The term “polyalkylene group” as used herein is a group having two or more CH2 groups linked to one another. The polyalkylene group can be represented by the formula — (CH₂)_a—, where “a” is an integer of from 2 to 500. [0035] The terms “alkoxy” and “alkoxyl” as used herein to refer to an alkyl or cycloalkyl group bonded through an ether linkage; that is, an “alkoxy” group can be defined as —OA¹ where A¹ is alkyl or cycloalkyl as defined above. “Alkoxy” also includes polymers of alkoxy groups as just described; that is, an alkoxy can be a polyether such as —OA¹—OA² or — OA¹—(OA²)a—OA³, where “a” is an integer of from 1 to 200 and A¹, A², and A³ are alkyl and/or cycloalkyl groups. [0036] The term “alkenyl” as used herein is a hydrocarbon group of from 2 to 24 carbon atoms with a structural formula containing at least one carbon-carbon double bond. Asymmetric structures such as (A¹A²)C=C(A³A⁴) are intended to include both the E and Z isomers. This can be presumed in structural formulae herein wherein an asymmetric alkene is present, or it can be explicitly indicated by the bond symbol C=C. The alkenyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol, as described herein. Attorney Docket No.21101.0480P1 [0037] The term “cycloalkenyl” as used herein is a non-aromatic carbon-based ring composed of at least three carbon atoms and containing at least one carbon-carbon double bound, i.e., C=C. Examples of cycloalkenyl groups include, but are not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, cyclohexadienyl, norbornenyl, and the like. The term “heterocycloalkenyl” is a type of cycloalkenyl group as defined above, and is included within the meaning of the term “cycloalkenyl,” where at least one of the carbon atoms of the ring is replaced with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. The cycloalkenyl group and heterocycloalkenyl group can be substituted or unsubstituted. The cycloalkenyl group and heterocycloalkenyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol as described herein. [0038] The term “alkynyl” as used herein is a hydrocarbon group of 2 to 24 carbon atoms with a structural formula containing at least one carbon-carbon triple bond. The alkynyl group can be unsubstituted or substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol, as described herein. [0039] The term “cycloalkynyl” as used herein is a non-aromatic carbon-based ring composed of at least seven carbon atoms and containing at least one carbon-carbon triple bound. Examples of cycloalkynyl groups include, but are not limited to, cycloheptynyl, cyclooctynyl, cyclononynyl, and the like. The term “heterocycloalkynyl” is a type of cycloalkenyl group as defined above, and is included within the meaning of the term “cycloalkynyl,” where at least one of the carbon atoms of the ring is replaced with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. The cycloalkynyl group and heterocycloalkynyl group can be substituted or unsubstituted. The cycloalkynyl group and heterocycloalkynyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol as described herein. [0040] The term “aromatic group” as used herein refers to a ring structure having cyclic clouds of delocalized electrons above and below the plane of the molecule, where the clouds contain (4n+2) electrons. A further discussion of aromaticity is found in Morrison Attorney Docket No.21101.0480P1 and Boyd, Organic Chemistry, (5th Ed., 1987), Chapter 13, entitled “Aromaticity,” pages 477-497, incorporated herein by reference. The term “aromatic group” is inclusive of both aryl and heteroaryl groups. [0041] The term “aryl” as used herein is a group that contains any carbon-based aromatic group including, but not limited to, benzene, naphthalene, phenyl, biphenyl, anthracene, and the like. The aryl group can be substituted or unsubstituted. The aryl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, NH₂, carboxylic acid, ester, ether, halide, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol as described herein. The term “biaryl” is a specific type of aryl group and is included in the definition of “aryl.” In addition, the aryl group can be a single ring structure or comprise multiple ring structures that are either fused ring structures or attached via one or more bridging groups such as a carbon- carbon bond. For example, biaryl can be two aryl groups that are bound together via a fused ring structure, as in naphthalene, or are attached via one or more carbon-carbon bonds, as in biphenyl. [0042] The term “aldehyde” as used herein is represented by the formula —C(O)H. Throughout this specification “C(O)” is a short hand notation for a carbonyl group, i.e., C=O. [0043] The terms “amine” or “amino” as used herein are represented by the formula — NA¹A², where A¹ and A² can be, independently, hydrogen or alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. A specific example of amino is NH₂. [0044] The term “alkylamino” as used herein is represented by the formula —NH(-alkyl) where alkyl is a described herein. Representative examples include, but are not limited to, methylamino group, ethylamino group, propylamino group, isopropylamino group, butylamino group, isobutylamino group, (sec-butyl)amino group, (tert-butyl)amino group, pentylamino group, isopentylamino group, (tert-pentyl)amino group, hexylamino group, and the like. [0045] The term “dialkylamino” as used herein is represented by the formula —N(-alkyl)2 where alkyl is a described herein. Representative examples include, but are not limited to, dimethylamino group, diethylamino group, dipropylamino group, diisopropylamino group, dibutylamino group, diisobutylamino group, di(sec-butyl)amino group, di(tert-butyl)amino group, dipentylamino group, diisopentylamino group, di(tert-pentyl)amino group, dihexylamino group, N-ethyl-N-methylamino group, N-methyl-N-propylamino group, N- ethyl-N-propylamino group and the like. Attorney Docket No.21101.0480P1 [0046] The term “carboxylic acid” as used herein is represented by the formula —C(O)OH. [0047] The term “ester” as used herein is represented by the formula —OC(O)A¹ or — C(O)OA¹, where A¹ can be alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. The term “polyester” as used herein is represented by the formula —(A¹O(O)C-A²-C(O)O)_a— or —(A¹O(O)C-A²-OC(O))_a—, where A¹ and A² can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group described herein and “a” is an integer from 1 to 500. “Polyester” is as the term used to describe a group that is produced by the reaction between a compound having at least two carboxylic acid groups with a compound having at least two hydroxyl groups. [0048] The term “ether” as used herein is represented by the formula A¹OA², where A¹ and A² can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group described herein. The term “polyether” as used herein is represented by the formula —(A¹O-A²O)a—, where A¹ and A² can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group described herein and “a” is an integer of from 1 to 500. Examples of polyether groups include polyethylene oxide, polypropylene oxide, and polybutylene oxide. [0049] The terms “halo,” “halogen,” or “halide” as used herein can be used interchangeably and refer to F, Cl, Br, or I. [0050] The terms “pseudohalide,” “pseudohalogen,” or “pseudohalo” as used herein can be used interchangeably and refer to functional groups that behave substantially similar to halides. Such functional groups include, by way of example, cyano, thiocyanato, azido, trifluoromethyl, trifluoromethoxy, perfluoroalkyl, and perfluoroalkoxy groups. [0051] The term “heteroalkyl” as used herein refers to an alkyl group containing at least one heteroatom. Suitable heteroatoms include, but are not limited to, O, N, Si, P and S, wherein the nitrogen, phosphorous and sulfur atoms are optionally oxidized, and the nitrogen heteroatom is optionally quaternized. Heteroalkyls can be substituted as defined above for alkyl groups. [0052] The term “heteroaryl” as used herein refers to an aromatic group that has at least one heteroatom incorporated within the ring of the aromatic group. Examples of heteroatoms include, but are not limited to, nitrogen, oxygen, sulfur, and phosphorus, where N-oxides, sulfur oxides, and dioxides are permissible heteroatom substitutions. The heteroaryl group can be substituted or unsubstituted. The heteroaryl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxy, Attorney Docket No.21101.0480P1 nitro, silyl, sulfo-oxo, or thiol as described herein. Heteroaryl groups can be monocyclic, or alternatively fused ring systems. Heteroaryl groups include, but are not limited to, furyl, imidazolyl, pyrimidinyl, tetrazolyl, thienyl, pyridinyl, pyrrolyl, N-methylpyrrolyl, quinolinyl, isoquinolinyl, pyrazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, pyridazinyl, pyrazinyl, benzofuranyl, benzodioxolyl, benzothiophenyl, indolyl, indazolyl, benzimidazolyl, imidazopyridinyl, pyrazolopyridinyl, and pyrazolopyrimidinyl. Further not limiting examples of heteroaryl groups include, but are not limited to, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiophenyl, pyrazolyl, imidazolyl, benzo[d]oxazolyl, benzo[d]thiazolyl, quinolinyl, quinazolinyl, indazolyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrazinyl, benzo[c][1,2,5]thiadiazolyl, benzo[c][1,2,5]oxadiazolyl, and pyrido[2,3-b]pyrazinyl. [0053] The terms “heterocycle” or “heterocyclyl” as used herein can be used interchangeably and refer to single and multi-cyclic aromatic or non-aromatic ring systems in which at least one of the ring members is other than carbon. Thus, the term is inclusive of, but not limited to, “heterocycloalkyl,” “heteroaryl,” “bicyclic heterocycle,” and “polycyclic heterocycle.” Heterocycle includes pyridine, pyrimidine, furan, thiophene, pyrrole, isoxazole, isothiazole, pyrazole, oxazole, thiazole, imidazole, oxazole, including, 1,2,3-oxadiazole, 1,2,5-oxadiazole and 1,3,4-oxadiazole, thiadiazole, including, 1,2,3-thiadiazole, 1,2,5-thiadiazole, and 1,3,4- thiadiazole, triazole, including, 1,2,3-triazole, 1,3,4-triazole, tetrazole, including 1,2,3,4- tetrazole and 1,2,4,5-tetrazole, pyridazine, pyrazine, triazine, including 1,2,4-triazine and 1,3,5-triazine, tetrazine, including 1,2,4,5-tetrazine, pyrrolidine, piperidine, piperazine, morpholine, azetidine, tetrahydropyran, tetrahydrofuran, dioxane, and the like. The term heterocyclyl group can also be a C2 heterocyclyl, C2-C3 heterocyclyl, C2-C4 heterocyclyl, C2-C5 heterocyclyl, C2-C6 heterocyclyl, C2-C7 heterocyclyl, C2-C8 heterocyclyl, C2-C9 heterocyclyl, C2-C10 heterocyclyl, C2-C11 heterocyclyl, and the like up to and including a C2-C18 heterocyclyl. For example, a C2 heterocyclyl comprises a group which has two carbon atoms and at least one heteroatom, including, but not limited to, aziridinyl, diazetidinyl, dihydrodiazetyl, oxiranyl, thiiranyl, and the like. Alternatively, for example, a C5 heterocyclyl comprises a group which has five carbon atoms and at least one heteroatom, including, but not limited to, piperidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, diazepanyl, pyridinyl, and the like. It is understood that a heterocyclyl group may be bound either through a heteroatom in the ring, where chemically possible, or one of carbons comprising the heterocyclyl ring. Attorney Docket No.21101.0480P1 [0054] The term “bicyclic heterocycle” or “bicyclic heterocyclyl” as used herein refers to a ring system in which at least one of the ring members is other than carbon. Bicyclic heterocyclyl encompasses ring systems wherein an aromatic ring is fused with another aromatic ring, or wherein an aromatic ring is fused with a non-aromatic ring. Bicyclic heterocyclyl encompasses ring systems wherein a benzene ring is fused to a 5- or a 6- membered ring containing 1, 2 or 3 ring heteroatoms or wherein a pyridine ring is fused to a 5- or a 6-membered ring containing 1, 2 or 3 ring heteroatoms. Bicyclic heterocyclic groups include, but are not limited to, indolyl, indazolyl, pyrazolo[1,5-a]pyridinyl, benzofuranyl, quinolinyl, quinoxalinyl, 1,3-benzodioxolyl, 2,3-dihydro-1,4-benzodioxinyl, 3,4-dihydro-2H- chromenyl, 1H-pyrazolo[4,3-c]pyridin-3-yl; 1H-pyrrolo[3,2-b]pyridin-3-yl; and 1H- pyrazolo[3,2-b]pyridin-3-yl. [0055] The term “heterocycloalkyl” as used herein refers to an aliphatic, partially unsaturated or fully saturated, 3- to 14-membered ring system, including single rings of 3 to 8 atoms and bi- and tricyclic ring systems. The heterocycloalkyl ring-systems include one to four heteroatoms independently selected from oxygen, nitrogen, and sulfur, wherein a nitrogen and sulfur heteroatom optionally can be oxidized and a nitrogen heteroatom optionally can be substituted. Representative heterocycloalkyl groups include, but are not limited to, pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, oxazolidinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, and tetrahydrofuryl. [0056] The term “hydroxyl” or “hydroxyl” as used herein is represented by the formula — OH. [0057] The term “ketone” as used herein is represented by the formula A¹C(O)A², where A¹ and A² can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. [0058] The term “azide” or “azido” as used herein is represented by the formula —N3. [0059] The term “nitro” as used herein is represented by the formula —NO2. [0060] The term “nitrile” or “cyano” as used herein is represented by the formula —CN. [0061] The term “silyl” as used herein is represented by the formula —SiA¹A²A³, where A¹, A², and A³ can be, independently, hydrogen or an alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. [0062] The term “sulfo-oxo” as used herein is represented by the formulas —S(O)A¹, — S(O)₂A¹, —OS(O)₂A¹, or —OS(O)₂OA¹, where A¹ can be hydrogen or an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. Attorney Docket No.21101.0480P1 Throughout this specification “S(O)” is a short hand notation for S=O. The term “sulfonyl” is used herein to refer to the sulfo-oxo group represented by the formula —S(O)2A¹, where A¹ can be hydrogen or an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. The term “sulfone” as used herein is represented by the formula A¹S(O)₂A², where A¹ and A² can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. The term “sulfoxide” as used herein is represented by the formula A¹S(O)A², where A¹ and A² can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. [0063] The term “thiol” as used herein is represented by the formula —SH. [0064] “R¹,” “R²,” “R³,” “Rⁿ,” where n is an integer, as used herein can, independently, possess one or more of the groups listed above. For example, if R¹ is a straight chain alkyl group, one of the hydrogen atoms of the alkyl group can optionally be substituted with a hydroxyl group, an alkoxy group, an alkyl group, a halide, and the like. Depending upon the groups that are selected, a first group can be incorporated within second group or, alternatively, the first group can be pendant (i.e., attached) to the second group. For example, with the phrase “an alkyl group comprising an amino group,” the amino group can be incorporated within the backbone of the alkyl group. Alternatively, the amino group can be attached to the backbone of the alkyl group. The nature of the group(s) that is (are) selected will determine if the first group is embedded or attached to the second group. [0065] As described herein, compounds of the invention may contain “optionally substituted” moieties. In general, the term “substituted,” whether preceded by the term “optionally” or not, means that one or more hydrogen of the designated moiety are replaced with a suitable substituent. Unless otherwise indicated, an “optionally substituted” group may have a suitable substituent at each substitutable position of the group, and when more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at every position. Combinations of substituents envisioned by this invention are preferably those that result in the formation of stable or chemically feasible compounds. In is also contemplated that, in certain aspects, unless expressly indicated to the contrary, individual substituents can be further optionally substituted (i.e., further substituted or unsubstituted). [0066] The term “stable,” as used herein, refers to compounds that are not substantially altered when subjected to conditions to allow for their production, detection, and, in certain aspects, their recovery, purification, and use for one or more of the purposes disclosed herein. Attorney Docket No.21101.0480P1 [0067] Suitable monovalent substituents on a substitutable carbon atom of an “optionally _{substituted” group are independently halogen; –(CH2)0–4R ; –(CH2)0–4OR ; -O(CH2)0-4Ro, – which may be} substituted with R°; –(CH2)0–4O(CH2)0–1Ph which may be substituted with R°; –CH=CHPh, which may be substituted with R°; –(CH2)0–4O(CH2)0–1-pyridyl which may be substituted _{with R°; –NO2; –CN; –N3; -(CH2)0–4N(R )2; –(CH2)0–4N(R )C(O)R ; –N(R )C(S)R ; – (CH2)0–4N(R )C(O)NR 2; -N(R )C(S)NR 2; –(CH2)0–4N(R )C(O)OR ; –N(R )N(R )C(O)R ; -N(R )N(R )C(O)NR 2; -N(R )N(R )C(O)OR ; –(CH2)0–4C(O)R ; –C(S)R ; –(CH2)0– 4C(O)OR ; –(CH2)0–4C(O)SR ; -(CH2)0–4C(O)OSiR 3; –(CH2)0–4OC(O)R ; –OC(O)(CH2)0– 4SR–, SC(S)SR°; –(CH2)0–4SC(O)R ; –(CH2)0–4C(O)NR 2; –C(S)NR 2; –C(S)SR°; -(CH2)0– 4OC(O)NR 2; -C(O)N(OR )R ; –C(O)C(O)R ; –C(O)CH2C(O)R ; –C(NOR )R ; -(CH2)0– 4SSR ; –(CH2)0–4S(O)2R ; –(CH2)0–4S(O)2OR ; –(CH2)0–4OS(O)2R ; –S(O)2NR 2; -(CH2)0– 4S(O)R ; -N(R )S(O)2NR 2; –N(R )S(O)2R ; –N(OR )R ; –C(NH)NR 2; –P(O)2R ; -P(O)R 2; -OP(O)R 2; –OP(O)(OR )2; SiR 3; –(C1–4 straight or branched alkylene)O–N(R )2; or –(C1–4 straight or branched alkylene)C(O)O–N(R )2, wherein each R may be substituted} as defined below and is independently hydrogen, C_1–6 aliphatic, –CH₂Ph, –O(CH₂)_0–1Ph, - CH₂-(5-6 membered heteroaryl ring), or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, _{notwithstanding the definition above, two independent occurrences of R , taken together with} their intervening atom(s), form a 3–12–membered saturated, partially unsaturated, or aryl mono– or bicyclic ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which may be substituted as defined below. _{[0068] Suitable monovalent substituents on R (or the ring formed by taking two independent occurrences of R together with their intervening atoms), are independently halogen, – (CH2)0–2R , –(haloR ), –(CH2)0–2OH, –(CH2)0–2OR , –(CH2)0–2CH(OR )2; -O(haloR ), –CN, –N3, –(CH2)0–2C(O)R , –(CH2)0–2C(O)OH, –(CH2)0–2C(O)OR , –(CH2)0–2SR , –(CH2)0–2SH, –(CH2)0–2NH2, –(CH2)0–2NHR , –(CH2)0–2NR 2, –NO2, –SiR 3, –OSiR 3, -C(O)SR , –(C1–4 straight or branched alkylene)C(O)OR , or –SSR wherein each R is unsubstituted or where} preceded by “halo” is substituted only with one or more halogens, and is independently selected from C_1–4 aliphatic, –CH₂Ph, –O(CH₂)_0–1Ph, or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, Attorney Docket No.21101.0480P1 _{oxygen, or sulfur. Suitable divalent substituents on a saturated carbon atom of R include =O} and =S. [0069] Suitable divalent substituents on a saturated carbon atom of an “optionally substituted” group include the following: =O, =S, =NNR^*2, =NNHC(O)R^*, =NNHC(O)OR^*, =NNHS(O)2R^*, =NR^*, =NOR^*, –O(C(R^*2))2–3O–, or –S(C(R^*2))2–3S–, wherein each independent occurrence of R^* is selected from hydrogen, C1–6 aliphatic which may be substituted as defined below, or an unsubstituted 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents that are bound to vicinal substitutable carbons of an “optionally substituted” group include: –O(CR^* ₂)_2–3O–, wherein each independent occurrence of R^* is selected from hydrogen, C_1–6 aliphatic which may be substituted as defined below, or an unsubstituted 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. _{[0070] Suitable substituents on the aliphatic group of R* include halogen, –R , -(haloR ), -OH, –OR , –O(haloR ), –CN, –C(O)OH, –C(O)OR , –NH2, –NHR , –NR 2, or –NO2, wherein each R is unsubstituted or where preceded by “halo” is substituted only with one or} more halogens, and is independently C1–4 aliphatic, –CH2Ph, –O(CH2)0–1Ph, or a 5–6– membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. [0071] Suitable substituents on a substitutable nitrogen of an “optionally substituted” group include –R^†, –NR^† ₂, –C(O)R^†, –C(O)OR^†, –C(O)C(O)R^†, –C(O)CH₂C(O)R^†, –S(O)₂R^†, -S(O)₂NR^† ₂, –C(S)NR^† ₂, –C(NH)NR^† ₂, or –N(R^†)S(O)₂R^†; wherein each R^† is independently hydrogen, C_1–6 aliphatic which may be substituted as defined below, unsubstituted –OPh, or an unsubstituted 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R^†, taken together with their intervening atom(s) form an unsubstituted 3–12–membered saturated, partially unsaturated, or aryl mono– or bicyclic ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. _{[0072] Suitable substituents on the aliphatic group of R† are independently halogen, –R , -(haloR ), –OH, –OR , –O(haloR ), –CN, –C(O)OH, –C(O)OR , –NH2, –NHR , –NR 2, or –NO2, wherein each R is unsubstituted or where preceded by “halo” is substituted only with} Attorney Docket No.21101.0480P1 one or more halogens, and is independently C1–4 aliphatic, –CH2Ph, –O(CH2)0–1Ph, or a 5–6– membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. [0073] The term “leaving group” refers to an atom (or a group of atoms) with electron withdrawing ability that can be displaced as a stable species, taking with it the bonding electrons. Examples of suitable leaving groups include halides and sulfonate esters, including, but not limited to, triflate, mesylate, tosylate, and brosylate. [0074] The terms “hydrolysable group” and “hydrolysable moiety” refer to a functional group capable of undergoing hydrolysis, e.g., under basic or acidic conditions. Examples of hydrolysable residues include, without limitation, acid halides, activated carboxylic acids, and various protecting groups known in the art (see, for example, “Protective Groups in Organic Synthesis,” T. W. Greene, P. G. M. Wuts, Wiley-Interscience, 1999). [0075] The term “organic residue” defines a carbon-containing residue, i.e., a residue comprising at least one carbon atom, and includes but is not limited to the carbon-containing groups, residues, or radicals defined hereinabove. Organic residues can contain various heteroatoms, or be bonded to another molecule through a heteroatom, including oxygen, nitrogen, sulfur, phosphorus, or the like. Examples of organic residues include but are not limited alkyl or substituted alkyls, alkoxy or substituted alkoxy, mono or di-substituted amino, amide groups, etc. Organic residues can preferably comprise 1 to 18 carbon atoms, 1 to 15, carbon atoms, 1 to 12 carbon atoms, 1 to 8 carbon atoms, 1 to 6 carbon atoms, or 1 to 4 carbon atoms. In a further aspect, an organic residue can comprise 2 to 18 carbon atoms, 2 to 15, carbon atoms, 2 to 12 carbon atoms, 2 to 8 carbon atoms, 2 to 4 carbon atoms, or 2 to 4 carbon atoms. [0076] A very close synonym of the term “residue” is the term “radical,” which as used in the specification and concluding claims, refers to a fragment, group, or substructure of a molecule described herein, regardless of how the molecule is prepared. For example, a 2,4- thiazolidinedione radical in a particular compound has the structure: , regardless of whether thiazolidinedione is used to prepare the compound. In some embodiments the radical (for example an alkyl) can be further modified (i.e., substituted Attorney Docket No.21101.0480P1 alkyl) by having bonded thereto one or more “substituent radicals.” The number of atoms in a given radical is not critical to the present invention unless it is indicated to the contrary elsewhere herein. [0077] “Organic radicals,” as the term is defined and used herein, contain one or more carbon atoms. An organic radical can have, for example, 1-26 carbon atoms, 1-18 carbon atoms, 1- 12 carbon atoms, 1-8 carbon atoms, 1-6 carbon atoms, or 1-4 carbon atoms. In a further aspect, an organic radical can have 2-26 carbon atoms, 2-18 carbon atoms, 2-12 carbon atoms, 2-8 carbon atoms, 2-6 carbon atoms, or 2-4 carbon atoms. Organic radicals often have hydrogen bound to at least some of the carbon atoms of the organic radical. One example, of an organic radical that comprises no inorganic atoms is a 5, 6, 7, 8-tetrahydro-2-naphthyl radical. In some embodiments, an organic radical can contain 1-10 inorganic heteroatoms bound thereto or therein, including halogens, oxygen, sulfur, nitrogen, phosphorus, and the like. Examples of organic radicals include but are not limited to an alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, mono-substituted amino, di-substituted amino, acyloxy, cyano, carboxy, carboalkoxy, alkylcarboxamide, substituted alkylcarboxamide, dialkylcarboxamide, substituted dialkylcarboxamide, alkylsulfonyl, alkylsulfinyl, thioalkyl, thiohaloalkyl, alkoxy, substituted alkoxy, haloalkyl, haloalkoxy, aryl, substituted aryl, heteroaryl, heterocyclic, or substituted heterocyclic radicals, wherein the terms are defined elsewhere herein. A few non-limiting examples of organic radicals that include heteroatoms include alkoxy radicals, trifluoromethoxy radicals, acetoxy radicals, dimethylamino radicals and the like. [0078] Compounds described herein can contain one or more double bonds and, thus, potentially give rise to cis/trans (E/Z) isomers, as well as other conformational isomers. Unless stated to the contrary, the invention includes all such possible isomers, as well as mixtures of such isomers. [0079] Unless stated to the contrary, a formula with chemical bonds shown only as solid lines and not as wedges or dashed lines contemplates each possible isomer, e.g., each enantiomer and diastereomer, and a mixture of isomers, such as a racemic or scalemic mixture. Compounds described herein can contain one or more asymmetric centers and, thus, potentially give rise to diastereomers and optical isomers. Unless stated to the contrary, the present invention includes all such possible diastereomers as well as their racemic mixtures, their substantially pure resolved enantiomers, all possible geometric isomers, and pharmaceutically acceptable salts thereof. Mixtures of stereoisomers, as well as isolated specific stereoisomers, are also included. During the course of the synthetic procedures used Attorney Docket No.21101.0480P1 to prepare such compounds, or in using racemization or epimerization procedures known to those skilled in the art, the products of such procedures can be a mixture of stereoisomers. [0080] Many organic compounds exist in optically active forms having the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes d and l or (+) and (-) are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are non- superimposable mirror images of one another. A specific stereoisomer can also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric mixture. A 50:50 mixture of enantiomers is referred to as a racemic mixture. Many of the compounds described herein can have one or more chiral centers and therefore can exist in different enantiomeric forms. If desired, a chiral carbon can be designated with an asterisk (*). When bonds to the chiral carbon are depicted as straight lines in the disclosed formulas, it is understood that both the (R) and (S) configurations of the chiral carbon, and hence both enantiomers and mixtures thereof, are embraced within the formula. As is used in the art, when it is desired to specify the absolute configuration about a chiral carbon, one of the bonds to the chiral carbon can be depicted as a wedge (bonds to atoms above the plane) and the other can be depicted as a series or wedge of short parallel lines is (bonds to atoms below the plane). The Cahn-Ingold-Prelog system can be used to assign the (R) or (S) configuration to a chiral carbon. [0081] When the disclosed compounds contain one chiral center, the compounds exist in two enantiomeric forms. Unless specifically stated to the contrary, a disclosed compound includes both enantiomers and mixtures of enantiomers, such as the specific 50:50 mixture referred to as a racemic mixture. The enantiomers can be resolved by methods known to those skilled in the art, such as formation of diastereoisomeric salts which may be separated, for example, by crystallization (see, CRC Handbook of Optical Resolutions via Diastereomeric Salt Formation by David Kozma (CRC Press, 2001)); formation of diastereoisomeric derivatives or complexes which may be separated, for example, by crystallization, gas-liquid or liquid chromatography; selective reaction of one enantiomer with an enantiomer-specific reagent, for example enzymatic esterification; or gas-liquid or liquid chromatography in a chiral environment, for example on a chiral support for example silica with a bound chiral ligand or in the presence of a chiral solvent. It will be appreciated Attorney Docket No.21101.0480P1 that where the desired enantiomer is converted into another chemical entity by one of the separation procedures described above, a further step can liberate the desired enantiomeric form. Alternatively, specific enantiomers can be synthesized by asymmetric synthesis using optically active reagents, substrates, catalysts or solvents, or by converting one enantiomer into the other by asymmetric transformation. [0082] Designation of a specific absolute configuration at a chiral carbon in a disclosed compound is understood to mean that the designated enantiomeric form of the compounds can be provided in enantiomeric excess (e.e.). Enantiomeric excess, as used herein, is the presence of a particular enantiomer at greater than 50%, for example, greater than 60%, greater than 70%, greater than 75%, greater than 80%, greater than 85%, greater than 90%, greater than 95%, greater than 98%, or greater than 99%. In one aspect, the designated enantiomer is substantially free from the other enantiomer. For example, the “R” forms of the compounds can be substantially free from the “S” forms of the compounds and are, thus, in enantiomeric excess of the “S” forms. Conversely, “S” forms of the compounds can be substantially free of “R” forms of the compounds and are, thus, in enantiomeric excess of the “R” forms. [0083] When a disclosed compound has two or more chiral carbons, it can have more than two optical isomers and can exist in diastereoisomeric forms. For example, when there are two chiral carbons, the compound can have up to four optical isomers and two pairs of enantiomers ((S,S)/(R,R) and (R,S)/(S,R)). The pairs of enantiomers (e.g., (S,S)/(R,R)) are mirror image stereoisomers of one another. The stereoisomers that are not mirror-images (e.g., (S,S) and (R,S)) are diastereomers. The diastereoisomeric pairs can be separated by methods known to those skilled in the art, for example chromatography or crystallization and the individual enantiomers within each pair may be separated as described above. Unless otherwise specifically excluded, a disclosed compound includes each diastereoisomer of such compounds and mixtures thereof. [0084] The compounds according to this disclosure may form prodrugs at hydroxyl or amino functionalities using alkoxy, amino acids, etc., groups as the prodrug forming moieties. For instance, the hydroxymethyl position may form mono-, di-, or triphosphates and again these phosphates can form prodrugs. Preparations of such prodrug derivatives are discussed in various literature sources (examples are: Alexander et al., J. Med. Chem.1988, 31, 318; Aligas-Martin et al., PCT WO 2000/041531, p.30). The nitrogen function converted in preparing these derivatives is one (or more) of the nitrogen atoms of a compound of the disclosure. Attorney Docket No.21101.0480P1 [0085] “Derivatives” of the compounds disclosed herein are pharmaceutically acceptable salts, prodrugs, deuterated forms, radio-actively labeled forms, isomers, solvates and combinations thereof. The “combinations” mentioned in this context refer to derivatives falling within at least two of the groups: pharmaceutically acceptable salts, prodrugs, deuterated forms, radio-actively labeled forms, isomers, and solvates. Examples of radio- actively labeled forms include compounds labeled with tritium, phosphorous-32, iodine-129, carbon-11, fluorine-18, and the like. [0086] Compounds described herein comprise atoms in both their natural isotopic abundance and in non-natural abundance. The disclosed compounds can be isotopically-labeled or isotopically-substituted compounds identical to those described, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number typically found in nature. Examples of isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine and chlorine, such as ²H, ³H, ¹³C, ¹⁴C, ¹⁵N, ¹⁸O, ¹⁷O, ³⁵S, ¹⁸F and ³⁶Cl, respectively. Compounds further comprise prodrugs thereof, and pharmaceutically acceptable salts of said compounds or of said prodrugs which contain the aforementioned isotopes and/or other isotopes of other atoms are within the scope of this invention. Certain isotopically-labeled compounds of the present invention, for example those into which radioactive isotopes such as ³H and ¹⁴C are incorporated, are useful in drug and/or substrate tissue distribution assays. Tritiated, i.e., ³H, and carbon-14, i.e., ¹⁴C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium, i.e., ²H, can afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and, hence, may be preferred in some circumstances. Isotopically labeled compounds of the present invention and prodrugs thereof can generally be prepared by carrying out the procedures below, by substituting a readily available isotopically labeled reagent for a non- isotopically labeled reagent. [0087] The compounds described in the invention can be present as a solvate. In some cases, the solvent used to prepare the solvate is an aqueous solution, and the solvate is then often referred to as a hydrate. The compounds can be present as a hydrate, which can be obtained, for example, by crystallization from a solvent or from aqueous solution. In this connection, one, two, three or any arbitrary number of solvent or water molecules can combine with the compounds according to the invention to form solvates and hydrates. Unless stated to the contrary, the invention includes all such possible solvates. Attorney Docket No.21101.0480P1 [0088] The term “co-crystal” means a physical association of two or more molecules which owe their stability through non-covalent interaction. One or more components of this molecular complex provide a stable framework in the crystalline lattice. In certain instances, the guest molecules are incorporated in the crystalline lattice as anhydrates or solvates, see e.g. “Crystal Engineering of the Composition of Pharmaceutical Phases. Do Pharmaceutical Co-crystals Represent a New Path to Improved Medicines?” Almarasson, O., et. al., The Royal Society of Chemistry, 1889-1896, 2004. Examples of co-crystals include p- toluenesulfonic acid and benzenesulfonic acid. [0089] It is also appreciated that certain compounds described herein can be present as an equilibrium of tautomers. For example, ketones with an -hydrogen can exist in an equilibrium of the keto form and the enol form. [0090] Likewise, amides with an N-hydrogen can exist in an equilibrium of the amide form and the imidic acid form. As another example, pyrazoles can exist in two tautomeric forms, N¹-unsubstituted, 3-A³ and N¹-unsubstituted, 5-A³ as shown below. [0091] As a further example, gadusol and gadusol-like compounds can exist in two tautomeric forms, as shown below. Attorney Docket No.21101.0480P1 [0092] Unless stated to the contrary, the invention includes all such possible tautomers. [0093] It is known that chemical substances form solids, which are present in different states of order which are termed polymorphic forms or modifications. The different modifications of a polymorphic substance can differ greatly in their physical properties. The compounds according to the invention can be present in different polymorphic forms, with it being possible for particular modifications to be metastable. Unless stated to the contrary, the invention includes all such possible polymorphic forms. [0094] In some aspects, a structure of a compound can be represented by a formula: , which is understood to be equivalent to a formula: , wherein n is typically an integer. That is, Rⁿ is understood to represent five independent substituents, R^n(a), R^n(b), R^n(c), , R^n(e). By “independent substituents,” it is meant that each R substituent can be independently defined. For example, if in one instance R^n(a) is halogen, then R^n(b) is not necessarily halogen in that instance. [0095] Certain materials, compounds, compositions, and components disclosed herein can be obtained commercially or readily synthesized using techniques generally known to those of skill in the art. For example, the starting materials and reagents used in preparing the disclosed compounds and compositions are either available from commercial suppliers such as Aldrich Chemical Co., (Milwaukee, Wis.), Acros Organics (Morris Plains, N.J.), Strem Chemicals (Newburyport, MA), Fisher Scientific (Pittsburgh, Pa.), or Sigma (St. Louis, Mo.) or are prepared by methods known to those skilled in the art following procedures set forth in references such as Fieser and Fieser’s Reagents for Organic Synthesis, Volumes 1-17 (John Wiley and Sons, 1991); Rodd’s Chemistry of Carbon Compounds, Volumes 1-5 and supplemental volumes (Elsevier Science Publishers, 1989); Organic Reactions, Volumes 1-40 (John Wiley and Sons, 1991); March’s Advanced Organic Chemistry, (John Wiley and Sons, Attorney Docket No.21101.0480P1 4th Edition); and Larock’s Comprehensive Organic Transformations (VCH Publishers Inc., 1989). [0096] Unless otherwise expressly stated, it is in no way intended that any method set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not actually recite an order to be followed by its steps or it is not otherwise specifically stated in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including: matters of logic with respect to arrangement of steps or operational flow; plain meaning derived from grammatical organization or punctuation; and the number or type of embodiments described in the specification. [0097] Disclosed are the components to be used to prepare the compositions of the invention as well as the compositions themselves to be used within the methods disclosed herein. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds cannot be explicitly disclosed, each is specifically contemplated and described herein. For example, if a particular compound is disclosed and discussed and a number of modifications that can be made to a number of molecules including the compounds are discussed, specifically contemplated is each and every combination and permutation of the compound and the modifications that are possible unless specifically indicated to the contrary. Thus, if a class of molecules A, B, and C are disclosed as well as a class of molecules D, E, and F and an example of a combination molecule, A-D is disclosed, then even if each is not individually recited each is individually and collectively contemplated meaning combinations, A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F are considered disclosed. Likewise, any subset or combination of these is also disclosed. Thus, for example, the sub-group of A-E, B-F, and C- E would be considered disclosed. This concept applies to all aspects of this application including, but not limited to, steps in methods of making and using the compositions of the invention. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific embodiment or combination of embodiments of the methods of the invention. [0098] It is understood that the compounds and compositions disclosed herein have certain functions. Disclosed herein are certain structural requirements for performing the disclosed functions, and it is understood that there are a variety of structures that can perform the same Attorney Docket No.21101.0480P1 function that are related to the disclosed structures, and that these structures will typically achieve the same result. METHODS OF MAKING [0099] In one aspect, disclosed are methods for preparing gadusol, derivatives of gadusol, and/or useful as intermediates towards the preparation of gadusol. [00100] In one aspect, gadusol and gadusol derivatives can be prepared as shown below. SCHEME 1. [00101] Generally, Compound 1.1 can be converted to Compound 1.2 by esterification. Compound 1.2 can be converted to Compound 1.3 by selective protection of two of the ring’s hydroxyl groups. Compound 1.3 can be converted to Compound 1.4 by alkylation of the remaining ring hydroxyl group. Compound 1.4 can be converted to Compound 1.5 by reduction of the ester to a primary hydroxyl group. Compound 1.5 can then be converted to Attorney Docket No.21101.0480P1 Compound 1.6 by epoxidation. Compound 1.6 can be converted to Compound 1.7 by ring opening reation with either acid or base. Compound 1.7 can then be converted to Compound 1.8 by protection of the hydroxyl groups resulting from the ring opening reaction. Compound 1.8 can then be converted to Compound 1.9 by deprotection of the original ring hydroxyl groups. Compound 1.9 can then be converted to Compound 1.10 by oxidation of the two hydroxyl groups to the diketone, which tautomerizes to the 3-hydroxycyclohex-2-en-1-one system. Compound 1.10 can then be converted to Compound 1.11 by deprotection. [00102] Compounds are represented in generic form, with substituents as noted in compound descriptions elsewhere herein. A more specific example is set forth below. SCHEME 2. [00103] Compound 2.1 (i.e., shikimic acid) was converted to Compound 2.2 by esterification with methanol in the presence of catalytic acid. It is contemplated that other alcohols can be used. Compound 2.2 was reacted with tert-butyldimethylsilyl chloride (TBSCl) in the presence of imidazole in dimethylformamide (DMF) to provide Compound 2.3 by selective protection of two of the ring’s hydroxyl groups. It is contemplated that other hydroxyl protecting agents (e.g., TMSCl) can be used. [00104] Compound 2.3 was alkylated with trimethyloxonium tetrafluoroborate to provide Compound 2.4. It is contemplated that other alkylating agents (e.g., CH₃CH₂Cl) can be used. Compound 2.4 was reduced with diisobutylaluminium hydride (DIBALH) to Attorney Docket No.21101.0480P1 provide Compound 2.5. It is contemplated that other alkylaluminium reducing agents can also be used. Compound 2.5 can then be coverted to Compound 2.6 by epoxidation with meta-chloroperoxybenzoic acid (mCPBA) or dimethyldioxirane (DMDO) or tert-butyl hydroperoxide (TBHP) in the presence of vanadyl acetylacetonate (VO(acac)₂). It is contemplated that other epoxidation agents can also be used. [00105] Compound 2.6 was converted to Compound 2.7 by ring opening reation. Sterochemistry of the resultant trans hydroxyls can be selected by use of acid (S_N1-like reation) or base (S_N2-like reaction). Compound 2.7 was then converted to Compound 2.8 by acetylation of the hydroxyl groups resulting from the ring opening reaction. Compound 2.8 was then deprotected with tetra-n-butylammonium fluoride to provide Compound 2.9. Oxidation of Compound 1.9 with Dess-Martin periodinane provided Compound 2.10 and its 3-hydroxycyclohex-2-en-1-one system. Compound 2.10 was then deprotected with strong base (e.g., sodium methoxide) to yield Compound 1.11. 1. ESTER REDUCTION METHOD [00106] In various aspects, disclosed are methods of making comprising an ester reduction reaction. [00107] In one aspect, the method comprises reducing a compound having a structure: to obtain a compound having a structure: , wherein R¹ is C1-C8 alkyl, wherein R² is C1-C8 alkyl, and wherein PG¹ is a hydroxyl protecting group. [00108] In one aspect, R¹ can be C1-C8 alkyl, C1-C4 alkyl, C1-C2 alkyl, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, i-butyl, or t-butyl. [00109] In one aspect, R² can be C1-C8 alkyl, C1-C4 alkyl, C1-C2 alkyl, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, i-butyl, or t-butyl. Attorney Docket No.21101.0480P1 [00110] In a further aspect, the method further comprises epoxidizing the compound having a structure: , to obtain a compound having a structure: . [00111] In a further aspect, the method further comprises treating the compound having a structure: with acid or base, to obtain a compound having a structure: . [00112] In a further aspect, the method further comprises protecting the compound having a structure: to obtain a compound having a structure: , wherein PG² is a hydroxyl protecting group that is different from PG¹. Attorney Docket No.21101.0480P1 [00113] In one aspect, PG¹ is a protecting group selected from acetyl (Ac), pivaloyl (Piv), methoxymethyl (MOM), 2-methoxyethoxymethyl ether (MEM), benzyloxymethyl (BOM), tetrahydropyranyl (THP), trimethylsilyl (TMS), triethylsilyl (TES), tert- butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), and trimethylsilylethoxymethyl (SEM), or a pharmaceutically acceptable salt thereof. [00114] In one aspect, PG2 is a protecting group selected from acetyl (Ac), pivaloyl (Piv), methoxymethyl (MOM), 2-methoxyethoxymethyl ether (MEM), benzyloxymethyl (BOM), tetrahydropyranyl (THP), trimethylsilyl (TMS), triethylsilyl (TES), tert- butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), and trimethylsilylethoxymethyl (SEM), or a pharmaceutically acceptable salt thereof. [00115] In a further aspect, the method further comprises deprotecting the compound having a structure: to obtain a compound having a structure: . [00116] In a further aspect, the method further comprises oxidizing the compound having a structure: to obtain a compound having a structure: . [00117] In a further aspect, the method further comprises deprotecting the compound having a structure: Attorney Docket No.21101.0480P1 to obtain a compound having a structure: . [00118] In various aspects, R¹ is methyl, R² is methyl, PG¹ is TBS, and/or PG² is Ac. [00119] In one aspect, the compound having a structure: [00120] In a further aspect, R² is methyl, and PG¹ is TBS. [00121] In one aspect, the compound having a structure: was obtained by alkylation of a compound having a structure: . [00122] In one aspect, the compound having a structure: was obtained by protection of a compound having a structure: Attorney Docket No.21101.0480P1 . [00123] In one aspect, the compound having a structure: was obtained by esterification of a compound having a structure: . [00124] In one aspect, the compound having the structure: _. [00125] Also discosed are the products produced by the disclosed methods. 2. OXIDATION METHOD [00126] In one aspect, disclosed are methods comprising oxidizing a compound having a structure: to obtain a compound having a structure: , wherein R² is C1-C8 alkyl, and wherein PG² is a hydroxyl protecting group. Attorney Docket No.21101.0480P1 [00127] In a further aspect, the method further comprises deprotecting the compound having a structure: to obtain a compound having a structure: . [00128] In a further aspect, the compound having a structure: . [00129] In a further aspect, R² is methyl. [00130] In a further aspect, the compound having a structure: was obtained by deprotection of a compound having a structure: , wherein PG¹ is a hydroxyl protecting group different from PG². [00131] In a further aspect, the compound having a structure: was obtained by protection of a compound having a structure: Attorney Docket No.21101.0480P1 . [00132] In a further aspect, the compound having a structure: was obtained by treatment of a compound having a structure: [00133] In a further aspect, the compound having a structure: was obtained by epoxidizing a compound having a structure: . [00134] In a further aspect, the compound having a structure: was obtained by reduction of a compound having a structure: , Attorney Docket No.21101.0480P1 wherein R1 is C1-C8 alkyl. [00135] In a further aspect, the compound having a structure: was obtained by alkylation of a compound having a structure: . [00136] In one aspect, R¹ can be C1-C8 alkyl, C1-C4 alkyl, C1-C2 alkyl, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, i-butyl, or t-butyl. [00137] In one aspect, R² can be C1-C8 alkyl, C1-C4 alkyl, C1-C2 alkyl, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, i-butyl, or t-butyl. [00138] In various aspects, R¹ is methyl, R² is methyl, PG² is Ac, and/or PG¹ is TBS. [00139] Also discosed are the products produced by the disclosed methods. [00140] In a further aspect, gadusol and gadusol derivatives can be prepared as shown below.

Attorney Docket No.21101.0480P1 [00141] Generally, Compound 3.1 can be converted to Compound 3.2 by esterification. Compound 3.2 can be converted to Compound 3.3 by selective protection of two of the ring’s hydroxyl groups. Compound 3.3 can be converted to Compound 3.4 by alkylation of the remaining ring hydroxyl group. Compound 3.4 can be converted to Compound 3.5 by reduction of the ester to a primary hydroxyl group. Compound 3.5 can then be converted to Compound 3.6 by epoxidation. Compound 3.6 can be converted to Compound 3.7 by protrection of the primary hydroxyl group. Compound 3.7 can then be converted to Compound 3.8 by deprotection of the original ring hydroxyl groups. Compound 3.8 can then be converted to Compound 3.9 by oxidation of the two hydroxyl groups to the diketone, which tautomerizes to the 3-hydroxycyclohex-2-en-1-one system. Compound 3.9 can then be converted to Compound 3.10 by treatment with base. [00142] Compounds are represented in generic form, with substituents as noted in compound descriptions elsewhere herein. A more specific example is set forth below. Attorney Docket No.21101.0480P1 [00143] Referring to Scheme 4, Compound 5 (i.e., shikimic acid) was converted to Compound 6 by esterification with methanol in the presence of catalytic acid. It is contemplated that other alcohols can be used. Compound 6 was reacted with tert- butyldimethylsilyl chloride (TBSCl) in the presence of imidazole in dimethylformamide (DMF) to provide Compound 7 by selective protection of two of the ring’s hydroxyl groups. It is contemplated that other hydroxyl protecting agents (e.g., TMSCl) can be used. [00144] Compound 7 was alkylated with trimethyloxonium tetrafluoroborate to provide Compound 4. It is contemplated that other alkylating agents (e.g., CH3CH2Cl) can be used. Compound 4 was reduced with diisobutylaluminium hydride (DIBALH) to provide Compound 3. It is contemplated that other alkylaluminium reducing agents can also be used. [00145] Compound 3 was then converted to Compound 8a by treatment with tert-butyl hydroperoxide (TBHP) in the presence of vanadyl acetylacetonate (VO(acac)2). Alternatively, Compound 3 can be converted to Compound 8b, an epoxide with the opposite stereochemistry, by treatment with meta-chloroperoxybenzoic acid (mCPBA). [00146] The primary hydroxyl group of Compound 8a was protected with benzyl chloride to afford Compound 9. It is contemplated the other protecting reagents can be used; preferably, the resultant protecting group is different from that used to protect the ring hydroxyl groups. The ring hydroxyl groups of Compound 9 were then selectively deprotected with tetra-n-butylammonium fluoride (TBAF) to afford Compound 11. It is contemplated the other deprotecting reagents can be used, preferably so long as it does not simultaneously deprotect the benzyl group protecting the primary hydroxyl. Attorney Docket No.21101.0480P1 [00147] Compound 11 was then oxidized with 2-Iodoxybenzoic acid (IBX) to afford Compound 12. It is contemplated the other oxidizing reagents can be used. Treatment of Compound 12 with sodium hydroxide achieved simultaneous deprotection and epoxide ring opening with base (S_N2-like reaction) to afford Compound 1 with the resultant trans hydroxyls. 3. PROTECTION-FIRST METHOD [00148] In various aspects, disclosed are methods of making comprising a protection- first reaction. In one aspect, the method comprises protecting a compound having a structure: , wherein R² is C1-C8 alkyl, and wherein PG¹ is a hydroxyl protecting group, to obtain a compound having a structure: wherein PG³ is a hydroxyl protecting group that is different from PG¹. [00149] In a further aspect, the emethod further comprises deprotecting the compound having a structure: to obtain a compound having a structure: . [00150] In a further aspect, the method further comprises oxidizing the compound having a structure: Attorney Docket No.21101.0480P1 , to obtain a compound having a structure: . [00151] In a further aspect, the method further comprises treating the compound having a structure: with base to obtain a compound having a structure: . [00152] In a further aspect, R² is methyl. In a further aspect, PG¹ is TBS. In a further aspect, PG³ is Bz. [00153] In a further aspect, the compound has a structure: wherein the compound having a structure: Attorney Docket No.21101.0480P1 [00154] In a further aspect, R² is methyl, PG¹ is TBS, and PG³ is Bz. [00155] In a further aspect, the compound has a structure: [00156] In a further aspect, the compound has a structure: [00157] In a further aspect, the compound has a structure: 4. ALTERNATIVE OXIDATION METHOD [00158] In various aspects, disclosed are methods of making comprising an alternative Oxidation method. In one aspect, the method comprises oxidizing a compound having a structure: , to obtain a compound having a structure: , wherein R² is C1-C8 alkyl, and wherein PG³ is a hydroxyl protecting group. [00159] In a further aspect, the method further comprises treating the compound having a structure: Attorney Docket No.21101.0480P1 with base to obtain a compound having a structure: . [00160] In a further aspect, the compound having a structure: wherein the compound having a structure: . [00161] In a further aspect, the compound having a structure: . [00162] In a further aspect, R² is methyl. In a further aspect, PG³ is Bz. C. COMPOUNDS [00163] In one aspect, disclosed are compounds useful as derivatives of Gadusol and/or useful as intermediates towards the preparation of Gadusol [00164] In a further aspect, the compound can be selected from: Attorney Docket No.21101.0480P1 , , wherein R¹ is C1-C8 alkyl, R² is C1-C8 alkyl, PG¹ is a hydroxyl protecting group, PG² is a hydroxyl protecting group that is different from PG¹, and the compound is not gadusol. [00165] In one aspect, R¹ can be C1-C8 alkyl, C1-C4 alkyl, C1-C2 alkyl, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, i-butyl, or t-butyl. [00166] In one aspect, R² can be C1-C8 alkyl, C1-C4 alkyl, C1-C2 alkyl, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, i-butyl, or t-butyl. [00167] In a further aspect, R¹ is methyl, R² is methyl, PG¹ is TBS, and/or PG² is Ac. [00168] In a further aspect, the compound can be: _, Attorney Docket No.21101.0480P1 [00169] In a further aspect, R¹ is methyl, R² is methyl, PG¹ is TBS, and/or PG² is Ac. In a further aspect, R¹ is methyl, wherein R² is methyl, wherein PG¹ is TBS, and wherein PG² is Ac. [00170] In a further aspect, a compound can be selected from: wherein R² is C1-C8 alkyl, wherein PG¹ is a hydroxyl protecting group, wherein PG³ is a hydroxyl protecting group that is different from PG¹, and wherein the compound is not gadusol. Attorney Docket No.21101.0480P1 [00171] In a further aspect, R² is methyl. In a further aspect, PG¹ is TBS. In a further aspect, PG² is Ac. In a further aspect, PG³ is Bz. [00172] In a further aspect, a compound has a structure: wherein the compound is not gadusol. [00173] In a further aspect, R² is methyl. In a further aspect, PG¹ is TBS. In a further aspect, PG³ is Bz. In a further aspect, R² is methyl, wherein PG¹ is TBS, and wherein PG³ is Bz. [00174] It is contemplated that each disclosed derivative can be optionally further substituted. It is also contemplated that any one or more derivative can be optionally omitted from the invention. It is understood that a disclosed compound can be provided by the disclosed methods. It is also understood that the disclosed compounds can be employed in the disclosed methods of using. [00175] It is understood that pharmaceutically acceptable derivatives of the disclosed compounds can be used also in connection with the disclosed methods. The pharmaceutically acceptable derivatives of the compounds can include any suitable derivative, such as pharmaceutically acceptable salts as discussed below, isomers, radiolabeled analogs, tautomers, and the like. D. EXAMPLES [00176] The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how the compounds, compositions, articles, devices and/or methods claimed herein are made and evaluated, and are intended to be purely exemplary of the invention and are not intended to limit the scope of what the inventors regard as their invention. Efforts have been made to ensure accuracy with respect to Attorney Docket No.21101.0480P1 numbers (e.g., amounts, temperature, etc.), but some errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, temperature is in °C or is at ambient temperature, and pressure is at or near atmospheric. [00177] The Examples are provided herein to illustrate the invention, and should not be construed as limiting the invention in any way. Examples are provided herein to illustrate the invention and should not be construed as limiting the invention in any way. 1. (3R,4S,5R)-3,4,5-TRIHYDROXYCYCLOHEX-1-ENE-1-CARBOXYLIC ACID METHYL ESTER (2.2). [00178] (-) shikimic acid (2.1, 25 g, 144 mmol) was suspended in MeOH (500 mL). Dowex-H⁺ resin (30 g) was then added and the solution was refluxed for 15 h. The mixture was filtered and the filtrate was concentrated and then precipitated from AcOEt to afford 2.2 (25.7 g, 96%) as a white solid. 2. 3R, 4S, 5R)-3,5-BIS{[(TERT-BUTYL)DIMETHYLSILYL]OXY}-4- HYDROXYCYCLOHEX-1-ENE-1-CARBOXYLIC ACID METHYL ESTER (2.3). [00179] Imidazole (18.79 g, 276 mmol, 2.69 equiv) and DMAP (6.5 g, 53 mmol, 0.5 equiv) were added to a solution of 2.2 (19.98 g, 106 mmol, 1.0 equiv) in DMF (212 mL) at 0°C. ^tBuMe₂Si (35.24 g, 234 mmol) was then added in five parts over 30 mins. The solution _{was stirred for 3 h at 0 and at 25 for 15 h. The solution was then diluted with AcOEt} (500 mL) and washed with 3 × 100 mL sat. aq. NH₄Cl and brine, dried with Na₂SO₄, and Attorney Docket No.21101.0480P1 concentrated. The resultant mixture was purified by FC (AcOEt/hexane 2:8): 2.3 (36.3 g, 82%). Viscous oil that solidified upon standing. 3. METHYL (3R,4S,5R)-3,5-BIS((TERT-BUTYLDIMETHYLSILYL)OXY)-4- METHOXYCYCLOHEX-1-ENE-1-CARBOXYLATE (2.4). [00180] A solution of 2.3 (49.18g, 133.1 mmol, 1.0 equiv.) in dry dichloromethane _{(380 mL) was cooled to 0 and Me3O+BF4- (25.6, 173 mmol, 1.2 equiv.) and proton sponge} (37.1g, 173 mmol, 1.2 equiv.) were added sequentially. The stirring mixture was allowed to warm to room temperature overnight and the heterogenous mixture was filtered with a medium porosity glass frit. The filter cake was washed thoroughly with 3 × 30mL dichloromethane and the eluent condensed in vacuuo. The crude oil was taken up in hexane and passed through a pad of celite eluting with 200mL of 10% EtOAc/Hexane. The eluent was condensed, affording 2.4 as a colorless viscous oil that solidified upon standing. (53.31g, 93%) 4. ((3R,4S,5R)-3,5-BIS((TERT-BUTYLDIMETHYLSILYL)OXY)-4- METHOXYCYCLOHEX-1-EN-1-YL)METHANOL (2.5). [00181] Diisobutyl aluminum hydride (25 wt% in toluene, 13.05mL, 19.6 mmol, 2.2 equiv) was added dropwise to a solution of 2.4 (3.84 g, 8.9 mmol, 1.0 equiv) in DCM (29.7 _{mL) under an N2 atmosphere, and the solution was stirred for 4 hr at -78 . Upon completion,} 10mL of methanol and 150mL saturated Rochelle’s salt solution was then added and the solution was stirred for 15h at room temperature. The solution was then added to a separatory funnel, organic phase separated, and aqueous fraction washed with 3 × 30mL DCM. The combined organic fractions were then washed with brine, dried over Na₂SO₄, and concentrated. The resultant mixture was purified by FC (AcOEt/hexane 2:8): 2.5 (2.66 g, 73.3%). Viscous oil. 5. ((3R,4S,5S)-3,5-BIS((TERT-BUTYLDIMETHYLSILYL)OXY)-4-METHOXY-7- OXABICYCLO[4.1.0]HEPTAN-1-YL)METHANOL (2.6). [00182] MCPBA: A few crystals of BHT were added to a solution of 2.5 (2.01 g, 4.9 _{mmol) in DCM. Then, mCPBA was added in three portions over 30 mins at 0 and allowed} to warm to room temperature over 15h with stirring. The resultant solution was filtered and the filtrate was washed with 3 × 50 mL saturated sodium bicarbonate, brine, dried with Na₂SO₄, and concentrated. The mixture was purified by FC (AcOEt/hexane 2:8): 2.6 (1.8 g, 87%). Viscous oil as a 10:1 diastereomeric mixture. Attorney Docket No.21101.0480P1 6. (1R,2S,3R,4S,5R)-3,5-BIS((TERT-BUTYLDIMETHYLSILYL)OXY)-1- (HYDROXYMETHYL)-4-METHOXYCYCLOHEXANE-1,2-DIOL (2.7). [00183] From 1R, 6R epoxide: To a dioxane solution of 2.6 (1.04g, 2.48 mmol, 1M), was added 10mL of 1M HCl. The solution was stirred 24h at 90 °C and then cooled to room temperature. The solution was then extracted with 3 × 10mL EtOAc and the combined organic fractions washed with saturated NaHCO3, brine, and dried over Na2SO4. The solution was concentrated and purified by FC (50% EtOAC:hexane) to afford 2.7 (802mg, 73%) as a viscous oil. From 1S, 6S epoxide: To a dioxane solution of 2.6 (1.22g, 2.91 mmol, 1M), was added 10mL of 5% NaOH solution. The solution was stirred 24h at 90 °C and then cooled to room temperature. The solution was then extracted with 3 × 10mL EtOAc and the combined organic fractions washed with saturated 1M HCl, brine, and dried over Na₂SO₄. The solution was concentrated and purified by FC (50% EtOAC:hexane) to afford 2.7 (1.06g, 84%) as a viscous oil. 7. (1R,2S,3S,4S,5R)-1-(ACETOXYMETHYL)-3,5-BIS((TERT- BUTYLDIMETHYLSILYL)OXY)-4-METHOXYCYCLOHEXANE-1,2-DIYL DIACETATE (2.8). [00184] A 0.5M solution of 2.7 (1.5g, 3.43 mmol, 1.0 equiv) in dry acetonitrile was cooled to 0°C, and Ac2O (390 L, 4.12 mmol, 1.2 equiv) and pyridine (332 L, 4.12 mmol, 1.2 equiv) were added. The solution was allowed to warm to room temperature overnight and diluted with 50mL water. The solution was then extracted with 3 × 10mL EtOAc, and the combined extracts were washed with 3 × 10mL 1M HCl, brine, and dried over Na2SO4. The solution of 2.8 was then concentrated and carried on without purification. 8. (1R,2S,3S,4S,5R)-1-(ACETOXYMETHYL)-3,5-BIS((TERT- BUTYLDIMETHYLSILYL)OXY)-4-METHOXYCYCLOHEXANE-1,2-DIYL DIACETATE (2.9). [00185] A solution of 2.8 (2.54g, 4.51 mmol) in dry THF (6mL) was cooled to 0°C and was then added 9.5mL of a 1M solution of TBAF in THF (9.47mmol, 2.1 equiv). The solution was stirred for 1h at 0°C and 1h at room temperature, and the solution was condensed and immediately purified by flash chromatography (50% EtOAc:hexane) to afford 2.9 as a viscous oil. (1.29g, 86%). 9. (1R,2S)-1-(ACETOXYMETHYL)-3-HYDROXY-4-METHOXY-5-OXOCYCLOHEX-3- ENE-1,2-DIYL DIACETATE (2.10). Attorney Docket No.21101.0480P1 [00186] To a solution of 2.9 (1.5g, 4.49 mmol, 1.0 equiv) in dichloromethane was added Dess–Martin periodinane (DMP) (4.0g, 9.43 mmol, 2.1 equiv) in a single portion, and 1 drop of DI water was added. The solution was stirred at room temperature for 18h, and the heterogeneous mixture was filtered. The filtrate was then condensed, and the crude mixture was purified by flash chromatography (10% MeOH:DCM) to afford the product 2.9 as a white solid. (1.38g, 93%) 10. (4R,5R)-3,4,5-TRIHYDROXY-5-(HYDROXYMETHYL)-2-METHOXYCYCLOHEX-2- EN-1-ONE (2.11) [00187] NaOMe was added to a solution of 2.10 (500mg, 1.51 mmol) in anhydrous MeOH to reach a pH of 9-10. The solution was then stirred for 4h at room temp. The solution was acidified to a pH of 3-4 by the addition of Dowex-H⁺, and the resin filtered off. The filtrate was then concentrated in vacuo and the resulting resin dissolved in 10mL of DI water and lyophilized to afford gadusol 2.11 (310mg, quant.) as a white powder. Attorney Docket No.21101.0480P1 [00188] (-) Shikimic acid (1, 25 g, 144 mmol) was combined with MeOH (500 mL) and Dowex-H⁺ cation resin (30 g) and refluxed for 15 h. The mixture was filtered once cooled to room temperature. The filtrate was concentrated and then recrystallized from AcOEt to make 2 (25.7 g, 96%). White solid.¹H-NMR (CD₃CN): 6.77 (m, =CH); 4.36 (s, CH); 3.98 (dd, CH); 3.76 (s, Me); 3.65 (dd, CH); 3.39 (br. s, OH); 2.72 (d, 1 H); 2.65 (d, 1H). Data matches reported values. 12. (3R,4S,5R)-3,5-BIS{[(TERT-BUTYL)DIMETHYLSILYL]OXY}-4- HYDROXYCYCLOHEX-1-ENE-1-CARBOXYLIC ACID METHYL ESTER (XX) [00189] Imidazole (18.79 g, 276 mmol) and DMAP (6.5 g, 53 mmol) were added to a _{solution of 2 (19.98 g, 106 mmol) in DMF (212 mL) at 0 . tBuMe2Si (35.24g, 234 mmol) was added in five parts over 30 mins. The solution was stirred for 3 h at 0 and at 25 for} 15 h. It was then diluted with AcOEt (500 mL) and washed with sat. aq. NH4Cl and brine, dried with Na2SO4, and concentrated. The resultant mixture was purified by FC (AcOEt/hexane 2:8): 3 (36.3 g, 95%). Viscous oil that crystallized upon standing.¹H-NMR (CDCl3): 6.67 (m, =CH); 4.55 (s, CH); 4.22 (dd, CH); 3.78 (s, Me); 3.72 (dd, CH); 2.61 (s, OH); 2.30 (m, 1 H); 2.24 (m, 1 H); 0.87 (s, 1 Me 3CSi); 0.80 (s, 1 Me 3CSi); 0.09 (s, 1 MeSi); 0.08 (s, 1 MeSi); 0.02 (s, 1 MeSi); 0.01 (s, 1 MeSi). Electrospray ionization Mass Spectroscopy (ESI-MS): 439.6 ([M + Na]⁺). Data matches reported values. 13. METHYL(3R,4S,5R)-3,5-BIS((TERT-BUTYLDIMETHYLSILYL)OXY)-4- METHOXYCYCLOHEX-1-ENE-1-CARBOXYLATE (4). [00190] A solution of 7 (49.18g, 133.1 mmol, 1.0 equiv.) in dry dichloromethane (380 mL) was cooled to 0°C and Me₃O⁺BF₄- (25.6, 173 mmol, 1.2 equiv.) and proton sponge (37.1g, 173 mmol, 1.2 equiv.) were added sequentially. The stirring mixture was allowed to warm to room temperature overnight and the heterogenous mixture was filtered with a Attorney Docket No.21101.0480P1 medium porosity glass frit. The filter cake was washed thoroughly with 3 × 30mL dichloromethane and the eluent condensed in vacuuo. The crude oil was taken up in hexane and passed through a pad of celite eluting with 200mL of 10% EtOAc/Hexane. The eluent was condensed, affording a colorless viscous oil that solidified upon standing: 4 (53.31g, 93%).¹H-NMR (CDCl₃): 6.70 (m, =CH); 4.48 (s, CH); 3.96 (dd, CH); 3.76 (s, MeO); 3.59 (dd, CH); 3.39 (s, MeO); 2.55 (m, 1 H); 2.41 (m, 1 H); 0.96 (s, 1 Me₃CSi); 0.87 (s, 1 Me₃CSi); 0.15 (s, 1 MeSi); 0.14 (s, 1 MeSi); 0.10 (s, 1 MeSi); 0.09 (s, 1 MeSi). ESI-MS: 453.2473 ([M + Na]⁺). Data matches reported values. 14. ((3R,4S,5R)-3,5-BIS((TERT-BUTYLDIMETHYLSILYL)OXY)-4- METHOXYCYCLOHEX-1-EN-1-YL)METHANOL (3). [00191] Diisobutyl aluminum hydride was added dropwise to a solution of 4 (3.84 g, 8.9 mmol) in DCM (29.7 mL) under an N2 atmosphere. The solution was stirred for 4 hr at - _{78 . Saturated Rochelle’s salt (50 mL) was then added and the reaction was stirred for 15 h} at room temperature. The solution was then washed with brine, dried with Na2SO4, and concentrated. The resultant mixture was purified by FC (AcOEt/hexane 2:8): 5 (2.66 g, ^{73.3%). Viscous oil. 1H-NMR (CDCl} ₃ ^{): 5.59 (m, =CH); 4.55 (s, CH); 4.18 (dd, CH); 4.02 (s,} MeO); 3.50 (s, MeO); 3.23 (dd, CH); 2.41 (m, 1H); 1.93 (m, 1H); 1.46 (br. s, OH); 0.96 (s, 1 Me₃CSi); 0.87 (s, 1 Me₃CSi); 0.15 (s, 1 MeSi); 0.14 (s, 1 MeSi); 0.10 (s, 1 MeSi); 0.09 (s, 1 MeSi). ESI-MS: 425.2522 ([M + Na]⁺). 15. ((3R,4S,5S)-3,5-BIS((TERT-BUTYLDIMETHYLSILYL)OXY)-4-METHOXY-7- OXABICYCLO[4.1.0]HEPTAN-1-YL)METHANOL (8B) [00192] A few crystals of BHT were added to a solution of 5 (2.01 g, 4.9 mmol) in DCM. Then mCPBA (0.665 g, 295 mmol) at 77% by weight was added in three portions over _{30 mins at 0 for 6 hours. The heterogenous resultant solution was filtered and the filtrate} Attorney Docket No.21101.0480P1 was washed with saturated sodium thiosulfate, sodium bicarbonate and brine. The extracts were then extracted with DCM (3 × 50mL), combined extracts were dried over Na2SO4, and concentrated. The mixture was purified by FC (hexane/EtOAc, 0% to 60%): 6 (1.8 g, 87%). Viscous oil.¹H-NMR (CDCl₃): 3.95 (dd, 1H), 3.72 (dt, 1H), 3.41 (s, 3H), 3.55 (d, 1H), 3.22 (dd, 1H), 3.15 (d, 1H), 1.74 (m, 2H), 0.99 (s, 18H), 0.19 (s, 12H). ESI-MS: 419.2262 ([M + H]⁺). 16. ((1R,3R,4S,5S,6R)-3,5-BIS((TERT-BUTYLDIMETHYLSILYL)OXY)-4-METHOXY-7- OXABICYCLO[4.1.0]HEPTAN-1-YL)METHANOL (8A). [00193] Under N2, 5 (2.0g, 4.9 mmol, 1.0 equiv) was dissolved in dry degassed toluene. To this solution was then added VO(acac)₂ (19.5 mg, .074 mmol, 0.015 equiv) was added and stirred until dissolved. To this blue solution was then added 5M TBHP in decane (6.4 mL, 6.37 mmol, 1.3 equiv) in five portions over 30 min. The dark red solution was stirred until complete by TLC. The solution was then dried by rotary evaporation to afford an orange oil. This orange oil was dissolved in Et₂O and filtered through a plug of silica to remove the colored byproducts and condensed by rotary evaporation to afford analytically pure material.¹H-NMR (CDCl3): 3.96 (dd, 1H), 3.72 (m, 2H), 3.55 (d, 1H), 3.42 (s, 3H), 3.24 (dd, 1H), 3.15 (s, 1H), 1.73 (m, 2H), 0.98 (s, 18H), 0.20 (s, 12H). ESI-MS: 419.2231 ([M + H]⁺). 17. ((3R,4S,5S)-3,5-BIS((TERT-BUTYLDIMETHYLSILYL)OXY)-4-METHOXY-7- OXABICYCLO[4.1.0]HEPTAN-1-YL)METHYL BENZOATE (9). [00194] Required epoxide (1.0 equiv.), NEt3 (1.3 equiv), and DMAP (0.1 equiv) were dissolved in dry DCM and cooled in an ice/water bath for 10 min. Benzoyl chloride (1.1 equiv) was then added slowly and the solution was stirred until completion by TLC. Upon completion, sat’d NaHCO3 was added and the solution stirred for 1h at rt. The resultant Attorney Docket No.21101.0480P1 solution was transferred to a separatory funnel and phases separated. The aqueous fraction was extracted with DCM, and the combined organic fractions were washed with sat’d NaHCO₃, water, and brine. Dried over Na₂SO₄ and concentrated. Quantitative yield.¹H- NMR (CDCl₃): 8.06 (d, 2H), 7.68 (d, 1H), 7.54 (dd, 2H), 4.35 (dd, 2H), 3.95 (dd, 1H), 3.74 (dd, 2H), 3.40 (s, 3H), 3.25 (dd, 1H), 3.15 (d,1H), 1.65 (m, 2H), 0.98 (s, 18H), 0.22 (s, 12H). ESI-MS: 445.2731 ([M + Na]⁺). 18. ((3R,4S,5S)-3,5-DIHYDROXY-4-METHOXY-7-OXABICYCLO[4.1.0]HEPTAN-1- YL)METHYL BENZOATE (11) [00195] Protected epoxide (1.0 equiv) was dissolved in dry THF and cooled in an ice/water bath. To the cooled solution TBAF (1M in THF, 1.1 equiv) was added and the solution stirred for 3h at this temperature. An additional 1.1 equiv of TBAF was then added and the solution stirred overnight. Upon completion, the solution was concentrated by rotary evaporation and the resultant oil was dissolved in EtOAc and transferred to a separatory funnel. The organic solution was washed with water, brine, and dried over Na₂SO₄ and concentrated. The product is suitable for carry on to the next step, however analytical samples can be prepared by crystallization from a saturated acetone solution at -40°C. Quant. yield. ¹H-NMR (CDCl₃): 8.08 (d, 2H), 7.66 (d, 1H), 7.50 (dd, 2H), 4.35 (dd, 2H), 3.99 (dd, 1H), 3.77 (dt, 1H), 3.40 (s, 3H), 3.26 (dd, 1H), 3.15 (d, 1H), 1.66 (m, 2H). ESI-MS: 317.1010 ([M + Na]⁺). 19. (3-HYDROXY-4-METHOXY-5-OXO-7-OXABICYCLO[4.1.0]HEPT-3-EN-1- YL)METHYL BENZOATE (12) [00196] Requisite diol 11 (1.0 equiv) and IBX (4 equiv) were suspended in dry acetone and heated to 55°C for 6h with vigorous stirring. The resulting heterogeneous solution was cooled to rt and solids filtered off, rinsing the filter cake with acetone. The eluent was Attorney Docket No.21101.0480P1 concentrated and purified by FC (acetone/EtOAc, 5% to 20%) to afford the product as an off- white solid (1.8 g, 72%) (CDCl3): 8.08 (d, 2H), 7.66 (d, 1H), 7.50 (dd, 2H), 5.2 (br s, 1H), 3.27 (dd, 2H), 3.31 (s, 3H), 3.22 (s, 1H), 2.45 (dd, 2H). ESI-MS: 290.0785 ([M – H]-). 20. (5R,6R)-3,5,6-TRIHYDROXY-5-(HYDROXYMETHYL)-2-METHOXYCYCLOHEX-2- EN-1-ONE. [00197] To a 5% solution of NaOH (10mL), was added 12 and the solution was stirred at rt for 6h with vigorous stirring. The solution was then cooled to rt and was added H⁺ ion- exchange resin to a pH of 3. The solution was then cooled in an ice/water bath to precipitate benzoic acid and the solution was filtered to remove the resin and benzoic acid. The solution was then dried by lyophilization. The solids were then purified by NP chromatography with 95% EtOH to afford gadusol as a white solid (72%). Spectra matches known products. [00198] It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the scope or spirit of the invention. Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.

Claims

Attorney Docket No.21101.0480P1 CLAIMS What is claimed is: 1. A method comprising reducing a compound having a structure: to obtain a compound having a structure: , wherein R¹ is C1-C8 alkyl, wherein R² is C1-C8 alkyl, and wherein PG¹ is a hydroxyl protecting group. 2. The method of claim 1, further comprising epoxidizing the compound having a structure: , to obtain a compound having a structure: . 3. The method of claim 2, further comprising treating the compound having a structure: with acid or base, to obtain a compound having a structure: Attorney Docket No.21101.0480P1 . 4. The method of claim 3, further comprising protecting the compound having a structure: to obtain a compound having a structure: , wherein PG² is a hydroxyl protecting group that is different from PG¹. 5. The method of claim 4, further comprising deprotecting the compound having a structure: to obtain a compound having a structure: . 6. The method of claim 5, further comprising oxidizing the compound having a structure: to obtain a compound having a structure: Attorney Docket No.21101.0480P1 . 7. The method of claim 6, further comprising deprotecting the compound having a structure: to obtain a compound having a structure: . 8. The method of claim 1, wherein R¹ is methyl. 9. The method of claim 1, wherein R² is methyl. 10. The method of claim 1, wherein PG¹ is TBS. 11. The method of claim 4, wherein PG² is Ac. 12. The method of claim 1, wherein the compound having a structure: 13. The method of claim 12, wherein R² is methyl, and PG¹ is TBS. 14. The method of claim 1, wherein the compound having a structure: was obtained by alkylation of a compound having a structure: Attorney Docket No.21101.0480P1 . 15. The method of claim 14, wherein the compound having a structure: was obtained by protection of a compound having a structure: . 16. The method of claim 15, wherein the compound having a structure: . was obtained by esterification of a compound having a structure: _. 17. The method of claim 16, wherein the compound having the structure: _. 18. A product produced by the method of any of claim 1-17. 19. A compound selected from: Attorney Docket No.21101.0480P1 wherein R1 is C1-C8 alkyl, wherein R² is C1-C8 alkyl, wherein PG¹ is a hydroxyl protecting group, wherein PG² is a hydroxyl protecting group that is different from PG¹, and wherein the compound is not gadusol. 20. The compound of claim 19, wherein R¹ is methyl. 21. The compound of claim 19, wherein R² is methyl. 22. The compound of claim 19, wherein PG¹ is TBS. 23. The compound of claim 19, wherein PG² is Ac. 24. The compound of claim 19, having a structure: Attorney Docket No.21101.0480P1 , 25. The compound of claim 24, wherein R¹ is methyl. 26. The compound of claim 24, wherein R² is methyl. 27. The compound of claim 24, wherein PG¹ is TBS. 28. The compound of claim 24, wherein PG² is Ac. 29. The compound of claim 24, wherein R¹ is methyl, wherein R² is methyl, wherein PG¹ is TBS, and wherein PG² is Ac. 30. A method comprising oxidizing a compound having a structure: to obtain a compound having a structure: , wherein R² is C1-C8 alkyl, and wherein PG² is a hydroxyl protecting group. 31. The method of claim 30, further comprising deprotecting the compound having a structure: to obtain a compound having a structure: Attorney Docket No.21101.0480P1 . 32. The method of claim 30, wherein the compound having a structure: 33. The method of claim 32, wherein R² is methyl. 34. The method of claim 30, wherein the compound having a structure: was obtained by deprotection of a compound having a structure: , wherein PG¹ is a hydroxyl protecting group different from PG². 35. The method of claim 34, wherein the compound having a structure: was obtained by protection of a compound having a structure: . 36. The method of claim 35, wherein the compound having a structure: Attorney Docket No.21101.0480P1 was obtained by treatment of a compound having a structure: with acid or base. 37. The method of claim 30, wherein the compound having a structure: was obtained by epoxidizing a compound having a structure: . 38. The method of claim 37, wherein the compound having a structure: was obtained by reduction of a compound having a structure: , wherein R1 is C1-C8 alkyl. 39. The method of claim 38, wherein the compound having a structure: Attorney Docket No.21101.0480P1 was obtained by alkylation of a compound having a structure: . 40. The method of claim 38, wherein R¹ is methyl. 41. The method of claim 30, wherein R² is methyl. 42. The method of claim 30, wherein PG² is Ac. 43. The method of claim 34, wherein PG¹ is TBS. 44. A product produced by the method of any of claim 30-43. 45. A method comprising protecting a compound having a structure: , wherein R² is C1-C8 alkyl, and wherein PG¹ is a hydroxyl protecting group, to obtain a compound having a structure: wherein PG³ is a hydroxyl protecting group that is different from PG¹. 46. The method of claim 45, further comprising deprotecting the compound having a structure: Attorney Docket No.21101.0480P1 to obtain a compound having a structure: . 47. The method of claim 46, further comprising oxidizing the compound having a structure: , to obtain a compound having a structure: . 48. The method of claim 47, further comprising treating the compound having a structure: with base to obtain a compound having a structure: . 49. The method of claim 45, wherein R² is methyl. 51. The method of claim 45, wherein PG¹ is TBS. 52. The method of claim 48, wherein PG³ is Bz. 56. The method of claim 45, wherein the compound having a structure: Attorney Docket No.21101.0480P1 wherein the compound having a structure: . 57. The method of claim 56, wherein R² is methyl, PG¹ is TBS, and PG³ is Bz. 58. The method of claim 46, wherein the compound having a structure: 58. The method of claim 47, wherein the compound having a structure: 58. The method of claim 48, wherein the compound having a structure: 59. A product produced by the method of any of claims 45-58. 60. A compound selected from: Attorney Docket No.21101.0480P1 wherein R² is C1-C8 alkyl, wherein PG¹ is a hydroxyl protecting group, wherein PG³ is a hydroxyl protecting group that is different from PG¹, and wherein the compound is not gadusol. 61. The compound of claim 60, wherein R² is methyl. 62. The compound of claim 60, wherein PG¹ is TBS. 63. The compound of claim 60, wherein PG² is Ac. 64. The compound of claim 60, wherein PG³ is Bz. 65. The compound of claim 60, having a structure: wherein the compound is not gadusol. 66. The compound of claim 65, wherein R² is methyl. 67. The compound of claim 65, wherein PG¹ is TBS. 68. The compound of claim 65, wherein PG³ is Bz. 69. The compound of claim 65, wherein R² is methyl, wherein PG¹ is TBS, and wherein PG³ is Bz. 70. A method comprising oxidizing a compound having a structure: Attorney Docket No.21101.0480P1 , to obtain a compound having a structure: , wherein R² is C1-C8 alkyl, and wherein PG³ is a hydroxyl protecting group. 71. The method of claim 70, further comprising treating the compound having a structure: with base to obtain a compound having a structure: . 72. The method of claim 70, wherein the compound having a structure: wherein the compound having a structure: . 73. The method of claim 71, wherein the compound having a structure: Attorney Docket No.21101.0480P1 74. The method of claim 70, wherein R² is methyl. 75. The method of claim 70, wherein PG³ is Bz. 76. A product produced by the method of any of claims 70-75.