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WO2007099392A2 - Synthèse convergente de motifs structuraux d'hydrate de carbone - Google Patents

Synthèse convergente de motifs structuraux d'hydrate de carbone Download PDF

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Publication number
WO2007099392A2
WO2007099392A2 PCT/IB2006/003357 IB2006003357W WO2007099392A2 WO 2007099392 A2 WO2007099392 A2 WO 2007099392A2 IB 2006003357 W IB2006003357 W IB 2006003357W WO 2007099392 A2 WO2007099392 A2 WO 2007099392A2
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Prior art keywords
substituted
alkyl
occurrence
group
independently
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WO2007099392A3 (fr
Inventor
Peter Seeberger
Alexander Adibekian
Mattheus S. M. Timmer
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Eidgenoessische Technische Hochschule Zurich ETHZ
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Eidgenoessische Technische Hochschule Zurich ETHZ
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Anticipated expiration legal-status Critical
Publication of WO2007099392A3 publication Critical patent/WO2007099392A3/fr
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives

Definitions

  • proline-catalized aldol reactions fashioned precursors to be used in Mukaiyama-type aldol reactions to synthesize partially protected glucose, mannose and allose monosaccharides. See e.g., A.B. Northrup, D.W.C. MacMillan Science 2004, 305, 1752-1755; D. Enders, C. Grondal Angew. Chem. Int. Ed. 2005, 44, 1210-1212.
  • the yields and selectivities reported for these transformations were highly dependent upon the specific protective groups.
  • One aspect of the present invention relates to a method for the preparation of carbohydrate building blocks by cyclization of a linear or branched open chain carbohydrate derivative, obtained by combining two 3 C fragments and cyclization of the linear or branched open chain carbohydrate to form a hexopyranose of the general formulas depicted below:
  • A represents acetimidoyl, substituted acetimidoyl, halogen, trichloroacetimidoyl, thiocarbamoyl, sulfoxide, -OR', -SR', or -SeR';
  • R' is selected independently for each occurrence from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, and substituted aryl;
  • X 2 , X 3 , X 4 and X 5 are independently selected from the group consisting of H, -O-, -CN 5 -NH-, -NO 2 , and N 3 ;
  • X 6 represents independently for each occurrence, -CH 2 O-, -CH 2 NH-, -CH 3 , -CH 2 NO 2 , -CH 2 N 3 , -COO-, -CONH-, -CN, or -COS-;
  • B, C, D, E, and F are selected independently for each occurrence, from the group consisting of H, protecting groups, carbohydrates and substituted carbohydrates;
  • X is independently for each occurrence selected from the group consisting of O,
  • R is independently for each occurrence selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkoxide, substituted alkoxide, carbonyl, substituted carbonyl, carboxide, substituted carboxide, orthoester, substituted orthoester, amine, substituted amine amide, substituted amide, imine, substituted imine, carbamate, substituted carbamate, sulfide, substituted sulfide, sulfoxide, substituted sulfoxide, sulfonate, substituted sulfonate, sulfate, substituted sulfate, silyl, substituted silyl, borane, substituted borane, phosphane, substituted phosphane, halogen, metal, and substituted
  • Another aspect of the present invention relates to a method of preparing carbohydrate building blocks, comprising the formation of a linear or branched open chain carbohydrate by combining two C2 fragments and cyclization of the linear or branched open chain carbohydrate to form a furanose carbohydrate building block as depicted below: condensation followed
  • A represents acetimidoyl, substituted acetimidoyl, halogen, trichloroacetimidoyl, thiocarbamoyl, sulfoxide, -OR', -SR', or -SeR';
  • R' is selected independently for each occurrence from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, and substituted aryl;
  • X 2 , and X 3 are independently selected from the group consisting of H, -O-, -CN, -NH-, -NO 2 , and -N 3 ;
  • B, C, and E are selected independently for each occurrence, from the group consisting of H, protecting groups, carbohydrates and substituted carbohydrates;
  • X is independently for each occurrence selected from the group consisting of O, NH, NR, S, and Se;
  • R is independently for each occurrence selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkoxide, substituted alkoxide, carbonyl, substituted carbonyl, carboxide, substituted carboxide, orthoester, substituted orthoester, amine, substituted amine amide, substituted amide, imine, substituted imine, carbamate, substituted carbamate, sulfide, substituted sulfide, sulfoxide, substituted sulfoxide, sulfonate, substituted sulfonate, sulfate, substituted sulfate, silyl, substituted silyl, borane, substituted borane, phosphane, substituted phosphane, halogen, metal, and substituted
  • Another aspect of the present invention relates to a method for the preparation of carbohydrate building blocks comprising the formation of a linear or branched open chain carbohydrate by combining a C2 and a C3 fragment and cyclization of the linear or branched open chain carbohydrate to form a furanose carbohydrate building block as depicted below:
  • A represents acetimidoyl, substituted acetimidoyl, halogen, trichloroacetimidoyl, thiocarbamoyl, sulfoxide, -OR', -SR', or -SeR';
  • R' is selected independently for each occurrence from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, and substituted aryl;
  • X 2 and X 3 are independently selected from the group consisting of H, -O-, -CN, -NH-, -NO 2 , and -N 3 ;
  • X 6 represents independently for each occurrence, -CH 2 O-, -CH 2 NH-, -CH 3 , -CH 2 NO 2 , -CH 2 N 3 , -COO-, -CONH-, -CN or -COS-;
  • B, C, E, and F are selected independently for each occurrence, from the group consisting of H, protecting groups, carbohydrates and substituted carbohydrates;
  • X is independently for each occurrence selected from the group consisting of O, NH, NR, S, and Se;
  • R is independently for each occurrence selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkoxide, substituted alkoxide, carbonyl, substituted carbonyl, carboxide, substituted carboxide, orthoester, substituted orthoester, amine, substituted amine amide, substituted amide, imine, substituted imine, carbamate, substituted carbamate, sulfide, substituted sulfide, sulfoxide, substituted sulfoxide, sulfonate, substituted sulfonate, sulfate, substituted sulfate, silyl, substituted silyl, borane, substituted borane, phosphane, substituted phosphane, halogen, metal, and substituted
  • Another aspect of the present invention relates to a method for the preparation of carbohydrate building blocks comprising the formation of a linear or branched open chain carbohydrate by combining a C2 and a C3 fragment and cyclization of the linear or branched open chain carbohydrate to form a furanose carbohydrate building block as depicted below: condensation Hn ⁇ R
  • A represents acetimidoyl, substituted acetimidoyl, halogen, trichloroacetimidoyl, thiocarbamoyl, sulfoxide, -OR', -SR', or -SeR';
  • R' is selected independently for each occurrence from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, and substituted aryl;
  • X 2 , X 3 , and X 5 are independently selected from the group consisting of H, -O-, -CN, -NH-, -NO 2 , and -N 3 ;
  • X 6 represents independently for each occurrence, -CH 2 O-, -CH 2 NH-, -CH 3 , -CH 2 NO 2 , -CH 2 N 3 , -COO-, -CONH-, -CN or -COS-;
  • B, C, E, and F are selected independently for each occurrence, from the group consisting of H, protecting groups, carbohydrates and substituted carbohydrates;
  • X is independently for each occurrence selected from the group consisting of O, NH, NR, S, and Se;
  • R is independently for each occurrence selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkoxide, substituted alkoxide, carbonyl, substituted carbonyl, carboxide, substituted carboxide, orthoester, substituted orthoester, amine, substituted amine amide, substituted amide, imine, substituted imine, carbamate, substituted carbamate, sulfide, substituted sulfide, sulfoxide, substituted sulfoxide, sulfonate, substituted sulfonate, sulfate, substituted sulfate, silyl, substituted silyl, borane
  • Another aspect of the present invention relates to a method for the preparation of carbohydrate building blocks comprising the formation of a linear or branched open chain carbohydrate by combining two C3 fragments and cyclization of the linear or branched open chain carbohydrate to form a hexafuranose carbohydrate building block as depicted below: condensation H0 ⁇ ,B
  • A represents acetimidoyl, substituted acetimidoyl, halogen, trichloroacetimidoyl, thiocarbamoyl, sulfoxide, -OR', -SR', or -SeR';
  • R' is selected independently for each occurrence from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, and substituted aryl;
  • X 2 , X 3 , and X 5 are independently selected from the group consisting of H, -O-, -CN, -NH-, -NO 2 , and -N 3 ;
  • X 6 represents independently for each occurrence, -CH 2 O-, -CH 2 NH-, -CH 3 , -CH 2 NO 2 , -CH 2 N 3 , -COO-, -CONH-, -CN or -COS-;
  • B, C, D, E, and F are selected independently for each occurrence, from the group consisting of H, protecting groups, carbohydrates or substituted carbohydrates;
  • X is independently for each occurrence selected from the group consisting of O,
  • R is independently for each occurrence selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkoxide, substituted alkoxide, carbonyl, substituted carbonyl, carboxide, substituted carboxide, orthoester, substituted orthoester, amine, substituted amine amide, substituted amide, imine, substituted imine, carbamate, substituted carbamate, sulfide, substituted sulfide, sulfoxide, substituted sulfoxide, sulfonate, substituted sulfonate, sulfate, substituted sulfate, silyl, substituted silyl, borane, substituted borane, phosphane, substituted phosphane, halogen, metal, and substituted
  • Another aspect of the present invention relates to a method for the preparation of carbohydrate building blocks comprising the formation of a linear or branched open chain carbohydrate by combining a C2 and a C4 fragment and cyclization of the linear or branched open chain carbohydrate to form a hexafuranose carbohydrate building block as depicted below:
  • A represents acetimidoyl, substituted acetimidoyl, halogen, trichloroacetimidoyl, thiocarbamoyl, sulfoxide, -OR', -SR', or -SeR';
  • R' is selected independently for each occurrence from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, or substituted aryl;
  • X 2 , X 3 , X 4 and X 5 are independently selected from the group consisting of H, -O-, -CN, -NH-, -NO 2 , or -N 3 ;
  • X 6 represents independently for each occurrence, -CH 2 O-, -CH 2 NH-, -CH 3 , -CH 2 NO 2 , -CH 2 N 3 , -COO-, -CONH-, -CN, or -COS-;
  • B, C, D, E, and F are selected independently for each occurrence, from the group consisting of H, protecting groups, carbohydrates and substituted carbohydrates;
  • X is independently for each occurrence selected from the group consisting of O, NH, NR, S, and Se;
  • R is independently for each occurrence selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkoxide, substituted alkoxide, carbonyl, substituted carbonyl, carboxide, substituted carboxide, orthoester, substituted orthoester, amine, substituted amine amide, substituted amide, imine, substituted imine, carbamate, substituted carbamate, sulfide, substituted sulfide, sulfoxide, substituted sulfoxide, sulfonate, substituted sulfonate, sulfate, substituted sulfate, silyl, substituted silyl, borane, substituted borane, phosphane, substituted phosphane, halogen, metal, and substituted
  • Another aspect of the present invention relates to a method for the preparation of carbohydrate building blocks comprising the formation of a linear or branched open chain carbohydrate by combining a C2 and a C4 fragment and cyclization of the linear or branched open chain carbohydrate to form a hexopyranose carbohydrate building block as depicted below:
  • A represents acetimidoyl, substituted acetimidoyl, halogen, trichloroacetimidoyl, thiocarbamoyl, sulfoxide, -OR', -SR', or -SeR';
  • R' is selected independently for each occurrence from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, and substituted aryl;
  • X 2 , X 3 , and X 4 are independently selected from the group consisting of H, -O-, -CN, -NH-, -NO 2 , and -N 3 ;
  • X 6 represents independently for each occurrence, -CH 2 O-, -CH 2 NH-, -CH 3 , -CH 2 NO 2 , -CH 2 N 3 , -COO-, -CONH-, -CN or -COS-;
  • B, C, D, E, and F are selected independently for each occurrence, from the group consisting of H, protecting groups, carbohydrates and substituted carbohydrates;
  • X is independently for each occurrence selected from the group consisting of O, NH, NR, S, and Se;
  • R is independently for each occurrence selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkoxide, substituted alkoxide, carbonyl, substituted carbonyl, carboxide, substituted carboxide, orthoester, substituted orthoester, amine, substituted amine amide, substituted amide, imine, substituted imine, carbamate, substituted carbamate, sulfide, substituted sulfide, sulfoxide, substituted sulfoxide, sulfonate, substituted sulfonate, sulfate, substituted sulfate, silyl, substituted silyl, borane, substituted borane, phosphane, substituted phosphane, halogen, metal, and substituted
  • Another aspect of the present invention relates to a method for the preparation of carbohydrate building blocks comprising the formation of a linear or branched open chain carbohydrate by combining a C2 and a C4 fragment and cyclization of the linear or branched open chain carbohydrate to form a hexopyranose carbohydrate building block as depicted below:
  • A represents acetimidoyl, substituted acetimidoyl, halogen, trichloroacetimidoyl, thiocarbamoyl, sulfoxide, -OR', -SR', or -SeR';
  • R' is selected independently for each occurrence from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, and substituted aryl;
  • X 2 , X 3 , X 4 and X 5 are independently selected from the group consisting of H, -O-,
  • X 6 represents independently for each occurrence, -CH 2 O-, -CH 2 NH-, -CH 3 , -CH 2 NO 2 , -CH 2 N 3 , -COO-, -CONH-, -CN or -COS-;
  • B, C, D, E 5 and F are selected independently for each occurrence, from the group consisting of H, protecting groups, carbohydrates or substituted carbohydrates;
  • X is independently for each occurrence selected from the group consisting of O, NH, NR, S, and Se;
  • R is independently for each occurrence selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkoxide, substituted alkoxide, carbonyl, substituted carbonyl, carboxide, substituted carboxide, orthoester, substituted orthoester, amine, substituted amine amide, substituted amide, imine, substituted imine, carbamate, substituted carbamate, sulfide, substituted sulfide, sulfoxide, substituted sulfoxide, sulfonate, substituted sulfonate, sulfate, substituted sulfate, silyl, substituted silyl, borane
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein said condensation is an aldol condensation.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein said condensation comprises a Lewis acid.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein said condensation comprises BF 3 OEt 2 or MgBr 2 -OEt.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein said condensation comprises MgBr 2 OEt.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein said one or more steps comprises one or more reductions, protections or deprotections.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein said cyclization comprises N-chlorosuccinimide (NCS), N-bromosuccinimide (NBS), N-iodosuccinimide (NIS), bromine, iodine, or pyridinium tribromide.
  • NCS N-chlorosuccinimide
  • NBS N-bromosuccinimide
  • bromine iodine
  • pyridinium tribromide pyridinium tribromide
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein A is -SR'; and R 1 is alkyl.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein A is -SEt.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein X 2 is -O-.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein X 2 is -O-; and B is H.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein X 2 is -O-; and B is Ac, Bn, TBDMS, TMS, Fmoc, Piv, Tr, or Lev.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein X 3 is -O-.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein X 3 is -O-; and C is H.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein X 3 is -O-; and C is Ac, Bn, TBDMS, TMS, Fmoc, Piv, Tr, or Lev.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein X 4 is -O-.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein X 4 is -O-; and D is H.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein X 4 is -O-; and D is Ac, Bn, TBDMS, TMS, Fmoc, Piv, Tr, or Lev.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein X 5 is -O-.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein X 5 is -O-; and E is H.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein X 5 is -O-; and E is Ac, Bn, TBDMS, TMS, Fmoc, Piv, Tr, or Lev.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein X 6 is -CH 2 O-.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein X 6 is -CH 2 O-; and F is H.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein X 6 is -CH 2 O-; and F is Ac, Bn, TBDMS, TMS, Fmoc, Piv, Tr, or Lev.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein B, C, D, or F is allose, altrose, arabinose, erythrose, erythrulose, fructose, fucosamine, fucose, galactosamine, galactose, glucosamine, glucosaminitol, glucose, glyceraldehyde, 2,3-dihydroxypropanal, glycerol, propane-l,2,3-triol, glycerone, 1,3-dihydroxypropanone, gulose, idose, lyxose, mannosamine, mannose, psicose, quinovose, quinovosamine, rhamnitol, rhamnosamine, rhamnose, ribose, ribulose, sialic acid, sorbose, tagatose, talose, tartaric acid, erythr
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein Y 1 is -C(XR) 2 H.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein Y 1 is -C(SR) 2 H; and R is alkyl.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein Y 1 is -C(SEt) 2 H.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein Y 4 is -C(X)XR.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein Y 4 is -C(H)OR.
  • a further aspect of the present invention relates to the aforementioned methods and any of the attendant definitions, wherein Y 4 is -C(H)OR; and R is silyl, carbonyl or alkyl.
  • Another aspect of the present invention relates to a method for the preparation of carbohydrate building blocks comprising the formation of a linear or branched open chain carbohydrate by combining a Cl and a C5 fragment and cyclization of the linear or branched open chain carbohydrate to form a hexopyranose carbohydrate building block as depicted below:
  • A represents acetimidoyl, substituted acetimidoyl, halogen, tricliloroacetimidoyl, thiocarbamoyl, sulfoxide, -OR', -SR', or -SeR';
  • R' is selected independently for each occurrence from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, and substituted aryl;
  • X 2 , X 3 , and X 4 are independently selected from the group consisting of H, -0-, -CN, -NH-, -NO 2 , or N 3 ;
  • X 6 represents independently for each occurrence, -CH 2 O-, -CH 2 NH-, -CH 3 , -CH 2 NO 2 , -CH 2 N 3 , -COO-, -CONH-, -CN or -COS-;
  • B, C, D, E, and F are selected independently for each occurrence, from the group consisting of H, protecting groups, carbohydrates and substituted carbohydrates;
  • Y 3 is selected from the group consisting of C(X)R 2 , C(X)(XR) 2 , C(R) 4 , C(R) 3 (XR), CR 2 (XR) 2 , C(XR) 4 , C(R) 3 N 3 , RCN, and C(R) 3 NO 2 ;
  • X is independently for each occurrence selected from the group consisting of O, NH, NR, S, and Se;
  • R is independently for each occurrence selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkoxide, substituted alkoxide, carbonyl, substituted carbonyl, carboxide, substituted carboxide, orthoester, substituted orthoester, amine, substituted amine amide, substituted amide, imine, substituted imine, carbamate, substituted carbamate, sulfide, substituted sulfide, sulfoxide, substituted sulfoxide, sulfonate, substituted sulfonate, sulfate, substituted sulfate, silyl, substituted silyl, borane, substituted borane, phosphane, substituted phosphane, halogen, metal, and substituted
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said condensation is an aldol condensation.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said condensation comprises a Lewis acid.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said condensation comprises BF 3 OEt 2 or MgBr 2 -OEt.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said condensation comprises MgBr 2 OEt.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said one or more steps comprises one or more reductions, protections or deprotections.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said cyclization comprises N-chlorosuccinimide (NCS), N-bromosuccinimide (NBS), N-iodosuccinimide (NIS), bromine, iodine, or pyridinium tribromide.
  • NCS N-chlorosuccinimide
  • NBS N-bromosuccinimide
  • NMS N-iodosuccinimide
  • bromine iodine
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said cyclization comprises N-iodosuccinimide (NIS).
  • NIS N-iodosuccinimide
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein A is -SR 1 ; and R 1 is alkyl.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein A is -SEt.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 2 is -O-.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 2 is -O-; and B is H.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 2 is -O-; and B is Ac, Bn, TBDMS, TMS, Fmoc, Piv, Tr, or Lev.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 3 is -O-.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 3 is -O-; and C is H.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 3 is -O-; and C is Ac, Bn, TBDMS, TMS, Fmoc, Piv, Tr, or Lev.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 4 is -O-.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 4 is -O- ; and D is H.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 4 is -O-; and D is Ac, Bn, TBDMS, TMS, Fmoc, Piv, Tr, or Lev.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 6 is -CH 2 O-.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 6 is -CH 2 O-; and F is H.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 6 is -CH 2 O-; and F is Ac, Bn, TBDMS, TMS, Fmoc, Piv, Tr, or Lev.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein B, C, D, or F is allose, altrose, arabinose, erythrose, erythrulose, fructose, fucosamine, fucose, galactosamine, galactose, glucosamine, glucosaminitol, glucose, glyceraldehyde, 2,3-dihydroxypropanal, glycerol, propane-l,2,3-triol, glycerone, 1,3-dihydroxypropanone, gulose, idose, lyxose, mannosamine, mannose, psicose, quinovose, quinovosamine, rhamnitol, rhamnosamine, rhamnose, ribose, ribulose, sialic acid, sorbose, tagatose, talose, tartaric acid, erythr
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein Y 1 is -C(XR) 2 H.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein Y 1 is -C(SR) 2 H; and R is alkyl.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein Y 1 is -C(SEt) 2 H.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein Y 3 is RCN.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein Y 3 is RCN; and R is silyl.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein Y 3 is TMSCN.
  • Another aspect of the present invention relates to a method for the preparation of carbohydrate building blocks comprising the formation of a linear or branched open chain carbohydrate by combining a Cl and a C5 fragment and cyclization of the linear or branched open chain carbohydrate to form a hexopyranose carbohydrate building block as depicted below:
  • A represents acetimidoyl, substituted acetimidoyl, halogen, trichloroacetimidoyl, thiocarbamoyl, sulfoxide, -OR', -SR', or -SeR';
  • R' is selected independently for each occurrence from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, and substituted aryl;
  • X 2 , X 3 , X 4 and X 5 are independently selected from the group consisting of H, -O-,
  • X 6 represents independently for each occurrence, -CH 2 O-, -CH 2 NH-, -CH 3 , -CH 2 NO 2 , -CH 2 N 3 , -COO-, -CONH-, -CN or -COS-;
  • B, C, D, E, and F are selected independently for each occurrence, from the group consisting of H, protecting groups, carbohydrates or substituted carbohydrates;
  • Y 1 is selected from the group consisting OfC(X)R 2 , C(X)(XR) 2 , C(R) 4 , C(R) 3 (XR), CR 2 (XR) 2 , C(XR) 4 , C(R) 3 N 3 , RCN, or C(R) 3 NO 2 ;
  • X is independently for each occurrence selected from the group consisting of O, NH, NR, S, and Se;
  • R is independently for each occurrence selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkoxide, substituted alkoxide, carbonyl, substituted carbonyl, carboxide, substituted carboxide, orthoester, substituted orthoester, amine, substituted amine amide, substituted amide, imine, substituted imine, carbamate, substituted carbamate, sulfide, substituted sulfide, sulfoxide, substituted sulfoxide, sulfonate, substituted sulfonate, sulfate, substituted sulfate, silyl, substituted silyl, borane, substituted borane, phosphane, substituted phosphane, halogen, metal, or substituted
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said condensation is an aldol condensation.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said condensation comprises a Lewis acid.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said condensation comprises BF 3 OEt 2 or MgBr 2 -OEt.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said condensation comprises MgBr 2 OEt.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said one or more steps comprises one or more reductions, protections or deprotections.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said cyclization comprises N-chlorosuccinimide (NCS), N-bromosuccinimide (NBS), N-iodosuccinimide (NIS), bromine, iodine, or pyridinium tribromide.
  • NCS N-chlorosuccinimide
  • NBS N-bromosuccinimide
  • bromine iodine
  • pyridinium tribromide pyridinium tribromide
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein A is -SR'; and R' is alkyl.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein A is -SEt.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 2 is -O-.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 2 is -O- ; and B is H.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 2 is -O-; and B is Ac, Bn, TBDMS, TMS, Fmoc, Piv, Tr, or Lev.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 3 is -O-.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 3 is -O-; and C is H.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 3 is -O-; and C is Ac, Bn, TBDMS, TMS, Fmoc, Piv, Tr, or Lev.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 4 is -O-.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 4 is -O-; and D is H.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 4 is -O-; and D is Ac, Bn, TBDMS, TMS, Fmoc, Piv, Tr, or Lev.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 5 is -O-.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 5 is -O-; and E is H.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 5 is -O-; and E is Ac, Bn, TBDMS, TMS, Fmoc, Piv, Tr, or Lev.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 6 is -CH 2 O-.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 6 is -CH 2 O-; and F is H.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 6 is -CH 2 O-; and F is Ac, Bn, TBDMS, TMS, Fmoc, Piv, Tr, or Lev.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein B, C, D, or F is allose, altrose, arabinose, erythrose, erythrulose, fructose, fucosamine, fucose, galactosamine, galactose, glucosamine, glucosaminitol, glucose, glyceraldehyde, 2,3-dihydroxypropanal, glycerol, propane-l,2,3-triol, glycerone, 1-,3-dihydroxypropanone, gulose, idose, lyxose, mannosamine, mannose, psicose, quinovose, quinovosamine, rhamnitol, rhamnosamine, rhamnose, ribose, ribulose, sialic acid, sorbose, tagatose, talose, tartaric acid, eryth
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein Y 1 is C(X)R 2 .
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein Y 4 is -C(X)XR.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein Y 4 is -C(H)OR.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein Y 4 is -C(H)OR; and R is silyl, carbonyl or alkyl.
  • Another aspect of the present invention relates to a method for the preparation of carbohydrate building blocks comprising the formation of a linear or branched open chain carbohydrate by combining a C4 and a C2 fragment and cyclization of the linear or branched open chain carbohydrate to form a hexafuranose carbohydrate building block as depicted below:
  • A represents acetimidoyl, substituted acetimidoyl, halogen, trichloroacetimidoyl, thiocarbamoyl, sulfoxide, -OR', -SR', or -SeR';
  • R' is selected independently for each occurrence from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, and substituted aryl;
  • X 2 , and X 3 are independently selected from the group consisting of H, -0-, -CN, -NH-, -NO 2 , and N 3 ;
  • B and C are selected independently for each occurrence, from the group consisting of H, protecting groups, carbohydrates or substituted carbohydrates;
  • X is independently for each occurrence selected from the group consisting of O, NH, NR, S, and Se;
  • R is independently for each occurrence selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkoxide, substituted alkoxide, carbonyl, substituted carbonyl, carboxide, subsituted carboxide, orthoester, subsituted orthoester, amine, substituted amine amide, substituted amide, imine, substituted imine, carbamate, substituted carbamate, sulfide, substituted sulfide, sulfoxide, substituted sulfoxide, sulfonate, substituted sulfonate, sulfate, substituted sulfate, silyl, substituted silyl, borane, substituted borane, phosphane, substituted phosphane, halogen
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said condensation is an aldol condensation.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said condensation comprises a Lewis acid.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said condensation comprises BF 3 OEt 2 or MgBr 2 -OEt.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said condensation comprises MgBr 2 OEt.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said cyclization comprises acid.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein said cyclization comprises trifluoroacetic acid (TFA).
  • TFA trifluoroacetic acid
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein A is -SR'; and R' is alkyl.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein A is -SEt.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 2 is -0-.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 2 is -0-; and B is H.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 2 is -O-; and B is Ac, Bn, TBDMS, TMS, Fmoc, Piv, Tr, or Lev.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 3 is -O-.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 3 is -O-; and C is H.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein X 3 is -O-; and C is Ac, Bn, TBDMS, TMS, Fmoc, Piv, Tr, or Lev.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein B or C is allose, altrose, arabinose, erythrose, erythrulose, fructose, fucosamine, fucose, galactosamine, galactose, glucosamine, glucosaminitol, glucose, glyceraldehyde, 2,3-dihydroxypropanal, glycerol, propane-1,2,3- triol, glycerone, 1,3-dihydroxypropanone, gulose, idose, lyxose, mannosamine, mannose, psicose, quinovose, quinovosamine, rhamnitol, rhamnosamine, rhamnose, ribose, ribulose, sialic acid, sorbose, tagatose, talose, tartaric acid, erythraric/threaric
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein Y 1 is -C(XR) 2 H.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein Yi is -C(SR) 2 H; and R is alkyl.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein Y 1 is -C(SEt) 2 H.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein Y 4 is -CR 3 ; and R is hydrogen or alkyl.
  • a further aspect of the present invention relates to the aforementioned method and any of the attendant definitions, wherein Y 4 is -CH 3 .
  • FIGURES Figure IA depicts a retrosynthetic analysis of uronic acid thioglycosides.
  • Figure IB depicts the synthesis of differentially protected aldehyde dithioacetals from L-arabinose.
  • EtSH cone. aq. HCl, 10 min, 77%.
  • BnBr, TBAI catalog.
  • NaH DMF
  • DMF 0 0 C
  • 4 h. W-Bu 2 SnO, toluene, Dean-Stark trap, then BnBr, CsF, TBAI (cat.), DMF.
  • a typical carbohydrate building block used in oligosaccharide assembly is equipped with different protecting groups to mask the hydroxyl functions and/or amine functions, and an anomeric leaving group that can be activated to induce the formation of a glycosidic linkage.
  • These differentially protected and functionalized monosaccharides have traditionally been accessed from naturally occurring sugar starting materials through a series of protection-deprotection maneuvers in order to establish the desired protecting group pattern. This process typically requires between six and twenty transformations depending upon the sugar, the protecting group pattern and the anomeric leaving group.
  • the invention provides a improved universal method for the preparation of carbohydrate building blocks by cyclization of a linear or branched open chain carbohydrate, obtained by combining two fragments.
  • the reaction scheme for the synthesis of each building block is designed so as to specify the different protecting groups to mask hydroxyl and amine functions, thereby allowing selective deprotection of the hydroxyls elected for ensuing glycosylation and permanent protection of the remainder of hydroxyl and/or amine functions.
  • the anomeric leaving group is selected based on the eventual activation protocol of choice.
  • a reference to "A and/or B", when used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.
  • the phrase "at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements.
  • This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase "at least one" refers, whether related or unrelated to those elements specifically identified.
  • At least one of A and B can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc.
  • a “carbohydrate” (or, equivalently, a “sugar”) is a saccharide (including monosaccharides, oligosaccharides and polysaccharides) and/or a molecule (including oligomers or polymers) derived from one or more monosaccharides, e.g., by reduction of carbonyl groups, by oxidation of one or more terminal groups to carboxylic acids, by replacement of one or more hydroxy group(s) by a hydrogen atom, an amino group, a thiol group or similar heteroatomic groups, etc.
  • the term “carbohydrate” also includes derivatives of these compounds.
  • Non-limiting examples of carbohydrates include allose (“All”), altrose (“Alt”), arabinose (“Ara”), erythrose, erythrulose, fructose (“Fru”), fucosamine (“FucN”), fucose (“Fuc”), galactosamine (“GaIN”), galactose (“Gal”), glucosamine (“GIcN”), glucosaminitol (“GlcN-ol”), glucose (“GIc”), glyceraldehyde, 2,3- dihydroxypropanal, glycerol (“Gro”), propane- 1,2,3-triol, glycerone ("1,3- dihydroxyacetone”), 1,3-dihydroxypropanone, gulose (“GuI”), idose (“Ido”), lyxose (“Lyx”), mannosamine (“ManN”), mannose (“Man”), psicose (“Psi”), quinovose ("
  • the carbohydrate may be a pentose (i.e., having 5 carbons) or a hexose (i.e., having 6 carbons); and in certain instances, the carbohydrate may be an oligosaccharide comprising pentose and/or hexose units, e.g., including those described above.
  • a “monosaccharide,” is a carbohydrate or carbohydrate derivative that includes one saccharide unit.
  • a "disaccharide,” a “trisaccharide,” a “tetrasaccharide,” a “pentasaccharide,” etc. respectively has 2, 3, 4, 5, etc. saccharide units.
  • An “oligosaccharide,” as used herein, has 1-20 saccharide units, and the saccharide units may be joined in any suitable configuration, for example, through alpha or beta linkages, using any suitable hydroxy moiety, etc. The oligosaccharide may be linear, or branched in certain instances.
  • a “polysaccharide,” as used herein, typically has at least 4-20 saccharide units.
  • the polysaccharide may have at least 25 saccharide units, at least 50 saccharide units, at least 75 saccharide units, at least 100 saccharide units, etc.
  • the carbohydrate is mulitmeric, i.e., comprising more than one saccharide chain.
  • chemically protected form refers to a compound in which one or more reactive functional groups are protected from undesirable chemical reactions, that is, are in the form of a protected or protecting group (also known as a masked or masking group).
  • an aldehyde or ketone group may be protected as an acetal or ketal, respectively, in which the carbonyl group (C( ⁇ O)) is converted to a diether (C(OR) 2 ), by reaction with, for example, a primary alcohol.
  • the aldehyde or ketone group is readily regenerated by hydrolysis using a large excess of water in the presence of acid.
  • a carboxylic acid group may be protected as an ester or an amide, for example, as: a benzyl ester; a t-butyl ester; a methyl ester; or a methyl amide.
  • Lewis acid is art-recognized and refers to an atom, compound or complex capable of accepting a pair of electrons from another atom, compound or complex.
  • nucleophile is recognized in the art, and as used herein means a chemical moiety having a reactive pair of electrons.
  • Electrophilic moieties useful in the method of the present invention include halides and sulfonates.
  • electron-withdrawing group is recognized in the art, and denotes the tendency of a substituent to attract valence electrons from neighboring atoms, i.e., the substituent is electronegative with respect to neighboring atoms.
  • ⁇ Hammett sigma
  • Exemplary electron-withdrawing groups include nitro, ketone, aldehyde, sulfonyl, trifluoromethyl, cyano, chloride, and the like.
  • Exemplary electron-donating groups include amino, methoxy, and the like.
  • catalytic amount is recognized in the art and means a substoichionietric amount of a reagent relative to a reactant.
  • a catalytic amount means from 0.0001 to 90 mole percent reagent relative to a reactant, more preferably from 0.001 to 50 mole percent, still more preferably from 0.01 to 10 mole percent, and even more preferably from 0.1 to 5 mole percent reagent to reactant.
  • a “polar solvent” means a solvent which has a dielectric constant ( ⁇ ) of 2.9 or greater, such as DMF, THF, ethylene glycol dimethyl ether (DME), DMSO, acetone, acetonitrile, methanol, ethanol, isopropanol, n-propanol, t-butanol or 2-methoxyethyl ether.
  • Preferred solvents are DMF, DME, NMP, and acetonitrile.
  • a "polar, aprotic solvent” means a polar solvent as defined above which has no available hydrogens to exchange with the compounds of this invention during reaction, for example DMF, acetonitrile, diglyme, DMSO, or THF.
  • an “aprotic solvent” means a non-nucleophilic solvent having a boiling point range above ambient temperature, preferably from about 25°C to about 19O 0 C, more preferably from about 8O 0 C to about 16O 0 C, most preferably from about 8O 0 C to 15O 0 C, at atmospheric pressure.
  • solvents are acetonitrile, toluene, DMF, diglyme, THF or DMSO.
  • heteroatom is art-recognized and refers to an atom of any element other than carbon or hydrogen.
  • Illustrative heteroatoms include boron, nitrogen, oxygen, phosphorus, sulfur and selenium.
  • alkyl is art-recognized, and includes saturated aliphatic groups, including straight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl (alicyclic) groups, alkyl substituted cycloalkyl groups, and cycloalkyl substituted alkyl groups, hi certain embodiments, a straight chain or branched chain alkyl has about 80 or fewer carbon atoms in its backbone (e.g., C 1 -C 80 for straight chain, C 3 -C 80 for branched chain), and alternatively, about 30 or fewer.
  • cycloalkyls have from about 3 to about 10 carbon atoms in their ring structure, and alternatively about 5, 6 or 7 carbons in the ring structure.
  • fluoroalkyl denotes an alkyl where one or more hydrogens have been replaced with fluorines
  • perfluoroalkyl denotes an alkyl where all the hydrogens have been replaced with fluorines.
  • lower alkyl refers to an alkyl group, as defined above, but having from one to about ten carbons, alternatively from one to about six carbon atoms in its backbone structure.
  • lower alkenyl and “lower alkynyl” have similar chain lengths.
  • aralkyl is art-recognized and refers to an alkyl group substituted with an aryl group (e.g., an aromatic or heteroaromatic group).
  • alkenyl and alkynyl are art-recognized and refer to unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond respectively.
  • aryl is art-recognized and refers to 5-, 6- and 7-membered single-ring aromatic groups that may include from zero to four heteroatoms, for example, benzene, naphthalene, anthracene, pyrene, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine and pyrimidine, and the like.
  • aryl groups having heteroatoms in the ring structure may also be referred to as "aryl heterocycles" or “heteroaromatics.”
  • the aromatic ring may be substituted at one or more ring positions with such substituents as described herein, for example, halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, alkoxyl, amino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, silyl, alkylthio, sulfonyl, sulfonamido, ketone, aldehyde, ester, heterocyclyl, aromatic or heteroaromatic moieties, trifluoromethyl, cyano, or the like.
  • aryl also includes polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjoining rings (the rings are "fused rings") wherein at least one of the rings is aromatic, e.g., the other cyclic rings may be cycloalkyls, cycloalkenyls, cycloalkynyls, aryls and/or heterocyclyls.
  • ortho, meta and para are art-recognized and refer to 1,2-, 1,3- and 1,4- disubstituted benzenes, respectively.
  • 1,2-dimethylbenzene and ortho-dimethylbenzene are synonymous.
  • heterocyclyl refers to 3- to about 10-membered ring structures, alternatively 3- to about 7-membered rings, whose ring structures include one to four heteroatoms.
  • Heterocycles may also be polycycles.
  • Heterocyclyl groups include, for example, thiophene, thianthrene, furan, pyran, isobenzofuran, chromene, xanthene, phenoxanthene, pyrrole, imidazole, pyrazole, isothiazole, isoxazole, pyridine, pyrazine, pyrimidine, pyridazine, indolizine, isoindole, indole, indazole, purine, quinolizine, isoquinoline, quinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, pteridine, carbazole, carboline, phenanthridine, acridine, pyrimidine, phenanthroline, phenazine, phenarsazine, phenothiazine, furazan, phenoxazine, pyrrolidine, o
  • the heterocyclic ring may be substituted at one or more positions with such substituents as described above, as for example, halogen, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, amino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, silyl, alkylthio, sulfonyl, ketone, aldehyde, ester, a heterocyclyl, an aromatic or heteroaromatic moiety, trifluoromethyl, cyano, or the like.
  • substituents as described above, as for example, halogen, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, amino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, si
  • polycyclyl or “polycyclic group” are art-recognized and refer to two or more rings ⁇ e.g., cycloalkyls, cycloalkenyls, cycloalkynyls, aryls and/or heterocyclyls) in which two or more carbons are common to two adjoining rings, e.g., the rings are "fused rings". Rings that are joined through non-adjacent atoms are termed "bridged" rings.
  • Each of the rings of the polycycle may be substituted with such substituents as described above, as for example, halogen, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, amino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, silyl, alkylthio, sulfonyl, ketone, aldehyde, ester, a heterocyclyl, an aromatic or heteroaromatic moiety, trifluoromethyl, cyano, or the like.
  • substituents as described above, as for example, halogen, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, amino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, silyl,
  • carrier is art-recognized and refers to an aromatic or non-aromatic ring in which each atom of the ring is carbon.
  • ring atom refers to a backbone atom that makes up the ring. Such ring atoms are selected from C, N, O or S and are bound to 2 or 3 other such ring atoms (3 in the case of certain ring atoms in a bicyclic ring system).
  • ring atom does not include hydrogen.
  • nitro is art-recognized and refers to -NO 2 ;
  • halogen is art- recognized and refers to -F, -Cl, -Br or -I;
  • sulfhydryl is art-recognized and refers to -SH;
  • hydroxyl means -OH;
  • sulfonyl is art-recognized and refers to -SO 2 " .
  • Halide designates the corresponding anion of the halogens
  • pseudohalide has the definition set forth on page 560 of "Advanced Inorganic Chemistry” by Cotton and Wilkinson, that is, for example, monovalent anionic groups sufficiently electronegative to exhibit a positive Hammett sigma value at least equaling that of a halide (e.g., CN, OCN, SCN, SeCN, TeCN, N 3 , and C(CN) 3 ).
  • a halide e.g., CN, OCN, SCN, SeCN, TeCN, N 3 , and C(CN) 3 .
  • amine and “amino” are art-recognized and refer to both unsubstituted and substituted amines, e.g., a moiety that may be represented by the general formulas:
  • R51 R52 wherein R50, R51, R52 and R53 each independently represent a hydrogen, an alkyl, an alkenyl, -(CH 2 ) m -R61, or R50 and R51 or R52, taken together with the N atom to which they are attached complete a heterocycle having from 4 to 8 atoms in the ring structure;
  • R61 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle; and
  • m is zero or an integer in the range of 1 to 8.
  • R50 and R51 (and optionally R52) each independently represent a hydrogen, an alkyl, an alkenyl, or -(CH 2 ) m -R61.
  • alkylamine includes an amine group, as defined above, having a substituted or unsubstituted alkyl attached thereto, i.e., at least one of R50 and R51 is an alkyl group.
  • acylamino is art-recognized and refers to a moiety that may be represented by the general formula:
  • R50 is as defined above
  • R54 represents a hydrogen, an alkyl, an alkenyl or -(CH 2 ) m -R61, where m and R61 are as defined above.
  • amino is art recognized as an amino-substituted carbonyl and includes a moiety that may be represented by the general formula:
  • alkylthio refers to an alkyl group, as defined above, having a sulfur radical attached thereto.
  • the "alkylthio" moiety is represented by one of -S-alkyl, -S-alkenyl, -S-alkynyl, and -S-(CH 2 ) m -R61, wherein m and R61 are defined above.
  • Representative alkylthio groups include methylthio, ethyl thio, and the like.
  • X50 is a bond or represents an oxygen or a sulfur
  • R55 and R56 represents a hydrogen, an alkyl, an alkenyl, -(CH 2 ) m -R61or a pharmaceutically acceptable salt
  • R56 represents a hydrogen, an alkyl, an alkenyl or -(CH 2 ) m -R61, where m and R61 are defined above.
  • X50 is an oxygen and R55 or R56 is not hydrogen
  • the formula represents an "ester”.
  • X50 is an oxygen
  • R55 is as defined above, the moiety is referred to herein as a carboxyl group, and particularyl when R55 is a hydrogen, the formula represents a "carboxylic acid".
  • X50 is an oxygen, and R56 is hydrogen
  • the formula represents a "formate".
  • the oxygen atom of the above formula is replaced by sulfur
  • the formula represents a "thiolcarbonyl” group.
  • X50 is a sulfur and R55 or R56 is not hydrogen
  • the formula represents a "thiolester.”
  • X50 is a sulfur and R55 is hydrogen
  • the formula represents a "thiolcarboxylic acid.”
  • X50 is a sulfur and R56 is hydrogen
  • the formula represents a "thiolformate.”
  • X50 is a bond, and R55 is not hydrogen
  • the above formula represents a "ketone” group.
  • X50 is a bond, and R55 is hydrogen
  • the above formula represents an "aldehyde” group.
  • oxime and "oxime ether” are art-recognized and refer to moieties that may be represented by the general formula:
  • R75 is hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, or -(CH 2 ) m -R61.
  • the moiety is an "oxime” when R is H; and it is an "oxime ether” when R is alkyl, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, or -(CH 2 ) m -R61.
  • alkoxyl or "alkoxy” are art-recognized and refer to an alkyl group, as defined above, having an oxygen radical attached thereto.
  • Representative alkoxyl groups include methoxy, ethoxy, propyloxy, tert-butoxy and the like.
  • An "ether” is two hydrocarbons covalently linked by an oxygen. Accordingly, the substituent of an alkyl that renders that alkyl an ether is or resembles an alkoxyl, such as may be represented by one of -O-alkyl, -O-alkenyl, -0-alkynyl, -O-(CH 2 ) m -R61, where m and R61 are described above.
  • R57 is an electron pair, hydrogen, alkyl, cycloalkyl, or aryl.
  • sulfate is art recognized and includes a moiety that may be represented by the general formula:
  • R57 is as defined above.
  • R50 O in which R50 and R56 are as defined above.
  • sulfamoyl is art-recognized and refers to a moiety that may be represented by the general formula:
  • sulfonyl is art-recognized and refers to a moiety that may be represented by the general formula:
  • R58 is one of the following: hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl.
  • sulfoxido is art-recognized and refers to a moiety that may be represented by the general formula: in which R58 is defined above.
  • Analogous substitutions may be made to alkenyl and alkynyl groups to produce, for example, aminoalkenyls, aminoalkynyls, amidoalkenyls, amidoalkynyls, iminoalkenyls, iminoalkynyls, thioalkenyls, thioalkynyls, carbonyl-substituted alkenyls or alkynyls.
  • selenoalkyl is art-recognized and refers to an alkyl group having a substituted seleno group attached thereto.
  • exemplary "selenoethers" which may be substituted on the alkyl are selected from one of -Se-alkyl, -Se-alkenyl, -Se-alkynyl, and -Se-(CH 2 ) m -R61, m and R61 being defined above.
  • triflyl, tosyl, mesyl, and nonaflyl are art-recognized and refer to trifluoromethanesulfonyl, p-toluenesulfonyl, methanesulfonyl, and nonafluorobutanesulfonyl groups, respectively.
  • trifiate, tosylate, mesylate, and nonaflate are art-recognized and refer to trifluoromethanesulfonate ester, /?-toluenesulfonate ester, methanesulfonate ester, and nonafluorobutanesulfonate ester functional groups and molecules that contain said groups, respectively.
  • each expression e.g., alkyl, m, n, and the like, when it occurs more than once in any structure, is intended to be independent of its definition elsewhere in the same structure.
  • Me, Et, Ph, Tf, Nf, Ts, and Ms represent methyl, ethyl, phenyl, trifluoromethanesulfonyl, nonafluorobutanesulfonyl, p-toluenesulfonyl and methanesulfonyl, respectively.
  • a more comprehensive list of the abbreviations utilized by organic chemists of ordinary skill in the art appears in the first issue of each volume of the Journal of Organic Chemistry; this list is typically presented in a table entitled Standard List of Abbreviations .
  • compositions of the present invention may exist in particular geometric or stereoisomeric forms.
  • polymers of the present invention may also be optically active.
  • the present invention contemplates all such compounds, including cis- and trans-isomers, R- and S-enantiomers, diastereomers, (D)-isomers, (L)- isomers, the racemic mixtures thereof, and other mixtures thereof, as falling within the scope of the invention.
  • Additional asymmetric carbon atoms may be present in a substituent such as an alkyl group.
  • AU such isomers, as well as mixtures thereof, are intended to be included in this invention.
  • a particular enantiomer of compound of the present invention may be prepared by asymmetric synthesis, or by derivation with a chiral auxiliary, where the resulting diastereonieric mixture is separated and the auxiliary group cleaved to provide the pure desired enantiomers.
  • the molecule contains a basic functional group, such as amino, or an acidic functional group, such as carboxyl, diastereomeric salts are formed with an appropriate optically-active acid or base, followed by resolution of the diastereomers thus formed by fractional crystallization or chromatographic means well known in the art, and subsequent recovery of the pure enantiomers.
  • substitution or “substituted with” includes 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., which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, or other reaction.
  • substituted is also contemplated to include all permissible substituents of organic compounds.
  • the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic substituents of organic compounds.
  • Illustrative substituents include, for example, those described herein above.
  • the permissible substituents may be one or more and the same or different for appropriate organic compounds.
  • the heteroatoms such as nitrogen may have hydrogen substituents and/or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms. This invention is not intended to be limited in any manner by the permissible substituents of organic compounds.
  • a convergent route to orthogonally protected D-glucuronic and L-iduronic acid thioglycoside building blocks, commonly used in heparin oligosaccharide assembly, is described.
  • the approach relies on a selective Mukaiyama aldol reaction between a silyl enol ether and a dithioacetal-containing aldehyde.
  • NIS promoted cyclization results in the differentially protected pyranose uronic acid thioglycosides as competent glycosylating agents. Rapid access to sufficient quantities of these key intermediates feeds the growing need for monosaccharide building blocks for use in the assembly of bioactive oligosaccharides.
  • the approach relies on a selective Mukaiyama aldol reaction between a silyl enol ether and a dithioacetal-containing aldehyde. NIS promoted cyclization results in the differentially protected pyranose uronic acid thioglycosides as competent glycosylating agents. Rapid access to sufficient quantities of these key intermediates feeds the growing need for monosaccharide building blocks for use in the assembly of bioactive oligosaccharides.
  • Retrosynthetic analysis of uronic acids A ( Figure IA) reveals that the fully protected uronic acid thioglycosides could be obtained via cyclization of linear hexoses B.
  • the open chain hexoses can be formed in turn via a Mukaiyama aldol reaction of an appropriately protected ketene acetal C with a dithioacetal-cntaining aldehyde D.
  • L-Arabinose di(ethylthio)acetal L-Arabinose (50 g, 330 mmol) was added to a vigorously stirred mixture of ethane thiol (50 mL) and cone. aq. HCl (50 mL). After the exothermic reaction starts, the slightly pink solution was cooled (0° C) and stirring was continued for 10 min upon which the product crystalizes. The suspension was filtered and the residue was washed with cold water (3 x 50 mL), dried by suction, washed with ether (3 x 50 mL) and dried again.
  • the resulting white powder could be used without further purification or recrystallized from ethyl acetate to obtain L-arabinose di(ethylthio)acetal 2 (65 g, 254 mmol, 77%) as white platelets.
  • Method A BF 3 » Et 2 0 (1.5 equiv.) was added to a solution of the silyl enol ether 10 (1.5 equiv.) and the aldehyde 8 (1.0 equiv.) in CH 2 Cl 2 (5 niL/mmol) at 0°C. After stirring for 15 min, the reaction mixture was quenched with sat. aq. NH 4 Cl and diluted with CH 2 Cl 2 . The organic layer was separated and washed with sat. aq. NaHCO 3 and brine, dried (MgSO 4 ) and filtered. After concentration and purification of the residue by column chromatography (hexanes ⁇ hexanes/CH 2 Cl 2 , 1/3, v/v), the pure aldol products 11, 14 and 17 were obtained as colorless oils.
  • Method B The silyl enol ether 10 (1.5 equiv.) was added to a suspension of MgBr 2 ⁇ Et 2 O (3 equiv.) in toluene (5 mL/mmol) at -78°C. After stirring for 30 min, the aldehyde 8 (1.0 equiv.) was added and the mixture was stirred for another 2 h at the same temperature. The solution was then warmed up to room temperature and stirring was continued until the starting material was completely consumed (TLC analyses). After quenching with sat. aq. NH 4 Cl, the reaction mixture was extracted three times with EtOAc, the combined organic layers were washed with brine, dried (MgSO 4 ) and filtered. After concentration and purification of the residue by column chromatography (hexanes ⁇ hexanes/CH 2 Cl 2 , 1/3, v/v), the pure aldol product 11 was obtained as a colorless oil.
  • 2,3-di-0-benzyl uronic acid di(ethylthio)acetals 11, 14 and 17 Aldehyde 8 (0.30 g, 0.75 mmol) and enol ether 10 were subjected to method A to give glucuronate 11: (0.14 g, 0.23 mmol, 31%), iduronate 14: (0.14 g, 0.23 mmol, 31%) and altruronate 17: (0.13 g, 0.22 mmol, 29%). Aldehyde 8 (40 mg, 0.10 mmol) and enol ether 10 were subjected to method B to give glucuronate 11: (61 mg, 0.10 mmol, quant.).
  • FmocCl (2 equiv.) was added to a solution of the alcohol (1 equiv.) in pyridine (1 mL/mmol) and the mixture was stirred for 2 h at room temperature. The mixture was concentrated and traces of solvent were removed by coevaporation with toluene. Column chromatography (hexanes/CH 2 Cl 2 , 1/1, v/v) of the residue gave the homogeneous ester as a colorless oil. The residue was dissolved in THF (5 mL/mmol) and HF .pyridine (1 mL) was added. After stirring for 16 h, the reaction mixture was diluted with ether and quenched with sat.
  • Di(ethylthio)acetal 20 (0.10 mmol, 56 mg) was subjected to the general procedure for the Fmoc protection and cyclization of example 2 to give ethyl thioglycoside 22 (48 mg, 79 ⁇ mol, 79%).
  • Methyl (ethyl 2-0-acetyl-3-0-benzyl-4-0-fluoren-9-ylmethyIoxycarbonyl-l- thio- ⁇ / ⁇ -L-idopyranoside)uronate 25.
  • Di(ethylthio)acetal 23 (0.10 mmol, 56 mg) was subjected to the general procedure for the Fmoc protection and cyclization of example 2 to give ethyl thioglycoside 25 (46 mg, 76 ⁇ mol, 76%).
  • Alcohol 27 (14.8 g, 34.2 mmol) was dissolved in DMF (100 mL) and cooled to 0 °C.
  • Sodium hydride 1.5 g, 60 % in oil, 37.62 mmol
  • benzyl bromide 4.5 mL, 37.62 mmol
  • TBAI TBAI
  • Acetonide 31 (21.8 g, 46.3 mmol) was dissolved in 50 % AcOH in H 2 O (500 mL). The mixture was allowed to stir at 50 °C for 3 h. The solvent was removed in vacuo and the residue was coevaporated with toluene twice.
  • ester 38 (1.19 g, 84 %) as a colorless oil.
  • Methyl (ethyl 3-0-benzyl-4-0-levulinoyl-2-0-pivaloyl-l-thio-L- idopyranoside)uronate (40).
  • Levulinic acid 36 mg, 0.31 mmol
  • 4-DMAP 38 mg, 0.31 mmol
  • the mixture was cooled to 0 °C and N, ⁇ T-diisopropyl carbodiimide (49 ⁇ L, 0.31 mmol) was added. After 10 min alcohol 39 (111 mg, 0.26 mmol) in CH 2 Cl 2 (2 mL) was added dropwise.
  • a solution of NaIO 4 (6.34 g, 30 mmol, 1.4 equiv.) in H 2 O (25 mL) was added dropwise to a cooled (0°C) and stirred solution of diol 41 (6.34 g, 21.4 mmol) in THF (75 mL). The ice bath was removed and the suspension stirred for 10 min before being quenched by the addition of cone. aq. sodium bicarbonate (100 mL) and extracted with ethyl acetate (2 x 100 mL).
  • aqueous solution was extracted with ether (2 x 100 mL), acidified with 1 M aq. HCl to pH 2, and extracted with ethyl acetate (3 x 100 mL).
  • the combined organic extracts were dried (MgSO 4 ), filtered and concentrated.
  • KOH (3.42 g, 56.1 mmol, 2.8 equiv.) was dissolved in a mixture of ether (15 mL), diethylene glycol monomethyl ether (30 mL) and H 2 O (15 mL).

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Abstract

L'invention concerne un procédé de préparation de motifs structuraux d'hydrate de carbone obtenus en combinant deux fragments de carbone pour former un hydrate de carbone à chaine ouverte linéaire ou ramifiée protégé. L'hydrate de carbone à chaine ouverte linéaire ou ramifiée protégé est ensuite cyclisé pour former un motif structural d'hydrate de carbone.
PCT/IB2006/003357 2005-09-27 2006-09-27 Synthèse convergente de motifs structuraux d'hydrate de carbone Ceased WO2007099392A2 (fr)

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8420607B2 (en) 2006-06-30 2013-04-16 University Of Georgia Research Foundation, Inc. Anthrax carbohydrates, synthesis and uses thereof
US8933239B1 (en) 2013-07-16 2015-01-13 Dow Global Technologies Llc Bis(aryl)acetal compounds
US8962779B2 (en) 2013-07-16 2015-02-24 Dow Global Technologies Llc Method of forming polyaryl polymers
US9063420B2 (en) 2013-07-16 2015-06-23 Rohm And Haas Electronic Materials Llc Photoresist composition, coated substrate, and method of forming electronic device
US9310366B2 (en) 2006-06-30 2016-04-12 University Of Georgia Research Foundation, Inc. Anthrax carbohydrates, synthesis and uses thereof
US9410016B2 (en) 2013-07-16 2016-08-09 Dow Global Technologies Llc Aromatic polyacetals and articles comprising them
CN106810519A (zh) * 2015-12-02 2017-06-09 中国科学院大连化学物理研究所 一种催化羟醛缩合反应的方法
CN108752399A (zh) * 2018-07-19 2018-11-06 南京艾普特生物医药有限公司 一种异丙基-β-D-硫代半乳糖苷的合成方法
KR102092786B1 (ko) * 2019-10-17 2020-03-24 국방과학연구소 작용기가 보호된 다이아지도글라이옥심 및 그의 합성 방법
US11008358B2 (en) * 2015-03-25 2021-05-18 President And Fellows Of Harvard College Synthesis of desosamines

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
ALOUI, M. ET AL.: "Stereoselective 1,2-cis-Glycosylation of 2-O-allyl-protected thioglycosides" CHEM. EUR. J., vol. 8, 2002, page 2608, XP002513580 *
DAVIES, S.G. ET AL.: "The asymmetric synthesis of D-galactose via an iterative syn-glycolate aldol strategy" SYNLETT, 2002, pages 1637-1640, XP002513582 *
HANESSIAN, S.: "Preparative Carbohydrate Chemistry" 1997, MARCEL DEKKER , XP002513583 Chapter 28, pages 615-636 *
KOFOED, JACOB ET AL: "Prebiotic carbohydrate synthesis: zinc-proline catalyzes direct aqueous aldol reactions of .alpha.-hydroxy aldehydes and ketones" ORGANIC & BIOMOLECULAR CHEMISTRY , 3(10), 1850-1855 CODEN: OBCRAK; ISSN: 1477-0520, 2005, XP002513581 *
NORTHRUP, A.B. AND MACMILLAN, W.C.: "Two-step synthesis of carbohydrates by selective aldol reactions" SCIENCE, vol. 305, 2004, pages 1752-1755, XP002513579 cited in the application *
SCHMIDT R R ET AL: "O-(ALPHA-D-GLUCOPYRANOSYL)TRICHLOROACETIM IDATE AS A GLUCOSYL DONOR" JOURNAL OF CARBOHYDRATE CHEMISTRY, NEW YORK, NY, US, vol. 4, no. 2, 1 January 1985 (1985-01-01), pages 141-169, XP009059325 ISSN: 0732-8303 *

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8420607B2 (en) 2006-06-30 2013-04-16 University Of Georgia Research Foundation, Inc. Anthrax carbohydrates, synthesis and uses thereof
US9310366B2 (en) 2006-06-30 2016-04-12 University Of Georgia Research Foundation, Inc. Anthrax carbohydrates, synthesis and uses thereof
US8933239B1 (en) 2013-07-16 2015-01-13 Dow Global Technologies Llc Bis(aryl)acetal compounds
US8962779B2 (en) 2013-07-16 2015-02-24 Dow Global Technologies Llc Method of forming polyaryl polymers
US9063420B2 (en) 2013-07-16 2015-06-23 Rohm And Haas Electronic Materials Llc Photoresist composition, coated substrate, and method of forming electronic device
US9410016B2 (en) 2013-07-16 2016-08-09 Dow Global Technologies Llc Aromatic polyacetals and articles comprising them
US11008358B2 (en) * 2015-03-25 2021-05-18 President And Fellows Of Harvard College Synthesis of desosamines
CN106810519A (zh) * 2015-12-02 2017-06-09 中国科学院大连化学物理研究所 一种催化羟醛缩合反应的方法
CN108752399A (zh) * 2018-07-19 2018-11-06 南京艾普特生物医药有限公司 一种异丙基-β-D-硫代半乳糖苷的合成方法
CN108752399B (zh) * 2018-07-19 2021-02-26 南京艾普特生物医药有限公司 一种异丙基-β-D-硫代半乳糖苷的合成方法
KR102092786B1 (ko) * 2019-10-17 2020-03-24 국방과학연구소 작용기가 보호된 다이아지도글라이옥심 및 그의 합성 방법

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