Synthetic Studies on Sialoglycoconjugates 15: Synthesis of Ganglioside GM3 Analogs Containing A Variety Of Lipophilic Parts

ABSTRACT

Several ganglioside GM₃ analogs, containing a variety of lipophilic parts in place of the ceramide moiety have been synthesized. Glycosylation of (2S, 3R, 4E)-2-azido-3-0-benzoyl-4-octa-decen-l, 3-diol (2) with 0-(methyl 5-acetamido-4, 7, 8, 9-tetra-0-acetyl-3, 5-dideoxy-o-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-(2, 4-di-0-acetyl-6-0-benzoyl-ß-D-galactopyranosyl)-(l→4)-3-(1)-acetyl-2, 6-di-0-benzoyl-α-D-glucopyranosyl trichloroacetimidate (1) gave the 8-glycoside (5), which was converted, via selective reduction of the azide group, introduction of acyl groups, 0-deacylation, and de-esterification, into the desired compounds (10-12). On the other hand, coupling of 1 with 3-benzyloxycarbonyl-amino-1-propanol (3) or (2RS)-3-benzyloxycarbonylamino-2-0-benzoyl-1, 2-propanediol (4) gave the corresponding ß-glycosides 13 and 14, respectively. These were converted by N-debenzyloxycarbonylation, coupling with 2-tetradecylhexadecanoic acid, 0-deacylation, and hydrolysis of the methyl ester group, into the end products (17 and 18).     

Synthetic Studies on Sialoglycoconjugates 27: Synthesis of Sialyl-α(2→6)-Lewis X

ABSTRACT

Synthesis of a positional isomer of sialyl Lewis X with regard to the substitution of the terminal galactose residue of the pentasaccharide by N-acetylneuraminic acid is described. Dimethyl(methylthio)sulfonium triflate-promoted coupling of 2-(trimethylsilyl)ethyl O-(2,3,4-tri-O-benzyl-α-L-fucopyranosyl)-(1→3)-O-(2-acetamido-6-O-benzyl-2-deoxy-ß-D-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-benzyl-ß-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-ß-D-glucopyranoside (1) with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→6)-2,4-di-O-benzoyl-3-O-benzyl-1-thio-ß-D-galactopyranoside (2) gave the desired hexasaccharide 3. Compound 3 was converted into the α-trichloro-acetimidate 6, via reductive removal of the benzyl groups, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, and treatment with trichloro-acetonitrile, which, on coupling with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (7), gave the ß-glycoside 8. Finally, 8 was transformed, via selective reduction of the azide group, coupling with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group, into the title ganglioside 11 in good yield.     

Synthetic Studies on Sialoglycoconjugates 7: Synthesis of N-Acetylneuraminic Acid Derivatives and Analogs

ABSTRACT

Various types of the O-protected derivatives and the 9-bromo analogs of methyl [2-(trimethylsilyl)ethyl 5-acetamido-3, 5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid]onate were synthesized from methyl [2-(trimetnyl-silyl)ethyl 5-acetamido-4, 7-di-O-acetyl-3, 5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid]onate (1) or methyl [2-(trimethylsilyl)ethyl 5-acetamido-8, 9-di-O-isopropylidene-D-glycero-α-D-galacto-2-nonulopyranosidlonate (3).     

Synthetic Studies on Sialoglycoconjugates 16: α-Predominant Glycoside Synthesis of N-Acetylneuraminic Acid With the Primary Hydroxyl Group in Carbohydrates Using Dimethyl(Methylthio)Sulfonium Triflate as a Glycosyl Promoter

ABSTRACT

Coupling of the primary hydroxyl group in the suitably protected 2-(trimethylsilyl)ethyl glycosides of D-glucopyranose (3), N-acetyl-D-glucosamine (7), N-acetyl-D-galactosamine (9), D-lactose (10), and N-acetylneuraminic acid (11), with methyl (methyl 5-acetamido-4, 7,8, 9-tetra-O-acetyl-3, 5-dideoxy-2-thio-D-glycero-α-D-galacto-2-nonulopyranosid)onate (12) as the glycosyl donor in acetonitrile in the presence of dimethyl(methylthio)sulfonium triflate (DMTST) as a glycosyl promoter and molecular sieves 3A, gave predominantly the corresponding α-glycosides 13, 15, 17, 25, and 29 of N-acetylneuraminic acid in 43-71% yields, respectively, together with the ß-glycosides (13-24%).     

Syntheses of 3-Deoxy-3-Fluoroglucosamine Derivatives

ABSTRACT

Methyl

2-acetamido-4,6-di-0-acetyl-2,3-dideoxy-3-fluoro-α-D-glucopyranoside (5) and methyl 2-diallylamino-2,3,6-trideoxy-3,6-difluoro-4-0-methanesulfonyl-α-D-glucopyranoside (10) were prepared from methyl 4,6-0-benzylidene-α-D-glucopyranoside. Fluorination at C-3 was carried out by ring opening of an aziridinium ion. Two fluorinating reagents were used depending on the starting material.     

Synthetic Studies on Sialoglycoconjugates 23: Total Synthesis of Sialyl-α(2↠6)-Lactotetraosylceramide and Sialyl-α(2↠6)-Neolactotetraosylceramide

ABSTRACT

The first total syntheses of sialyl-α(2→6)-lactotetraosylceramide (29, IV⁶NeuAcLc₄Cer) and sialyl-α(2→6)-neolatotetraosylceramide (33, IV⁶NeuAcnLc₄Cer) are described. Methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→6)-2,4-di-O-benzoyl-3-O-benzyl-1-thio-ß-D-galactopyranoside (11), the key glycosyl donor was prepared, via glycosylation of 2-(trimethylsilyl)ethyl 3-O-benzyl-ß-D-galactopyranoside (2) with the methyl α-thioglycoside 3 of N-acetylneuraminic acid, benzoylation, replacement of the 2-(trimethylsilyl)ethyl group by acetyl, and introduction of the methylthio group with (methylthio)trimethylsilane. Each coupling of 2-(trimethylsilyl)ethyl O-(2-acetamido-4,6-O-benzylidene-2-deoxy-ß-D-glucopyranosyl)-(1→3′)-per-O-benzyl-ß-lactoside (12) or 2-(trimethylsilyl)ethyl O-(2-acetamido-3-O-acetyl-6-O-benzyl-2-deozy-ß-D-glucopyranosyl)-(1→3′)-per-O-benzyl-ß-D-lactoside (14) prepared from 12 by O-acetylation and reductive opening of the benzylidene acetal, with 11 gave the pentasaccharides 16 and 20 in good yields. Compounds 16 and 20 were converted into the corresponding α-trichloroacetimidates 19 and 24 which, on coupling with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (25), gave the ß-glycosides 26 and 30, respectively. Finally, 26 and 30 were transformed, via selective reduction of the azide group, condensation with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group, into 29 and 33, respectively.     

Synthetic Studies on Sialoglycoconjugates 91: Total Synthesis of Gangliosides GD1C and GT1A

Abstract

A first total synthesis of gangliosides GD1c and GT1a containing Neu5Acα(2→8) Neu5Acα(2→3)Gal residue in their non-reducing terminal is described. Condensation of methyl O-[methyl 5-acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylono-1¹,9-lactone) -4,7- di-O-acetyl-3,5-dideoxy-D-glycero-α-D-galcto-2-nonulopyranosyranosylanate]-(2→3)-2,4,6-tri-O-benzoyl-1-thio-β-D-gala-ctopyranoside (1) with 2-(trimethylsilyl)ethyl O-(2-acetamido-4,6-O-benzylidene-2-deoxy-β-D-galactopyranosyl)- (1→4) -O -(2,3,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (2) or 2-(trimethylsilyl)ethyl O-(2-acetamido-6-O-benzyl-2-deoxy-β-D-galactopyranosyl)-(1→4)-(9-[methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)]-O-(2,6-di-O-benzyl-β-D-galactopyranosyl) - (1→4) - 2,3,6-tri-O-benzyl-β-D-glucopyranoside (3) in the presence of dimethyl(methylthio)sulfonium triflate (DMTST) gave the corresponding hexa-and heptasaccharide derivatives 4 and 5, respectively. These oligosaccharides were converted into the α-trichloroacetimidates 10 and 11 via reductive removal of the benzyl groups and/or benzylidene group, O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group and treatment with trichloroacetonitrile, which, on coupling with 2-azidosphingosine derivatives 12 or 13, gave the β-glycosides 14 and 15, respectively. Finally, 14 and 15 were transformed, via selective reduction of the azido group, coupling with octadecanoic acid and removal of all protecting groups, into the title gangliosides GD1c 18 and GT1a 19.     

Synthesis of a Single Repeat Unit of Type VIII Group B Streptococcus Capsular Polysaccharide 1

Abstract

We have synthesized a single repeat unit of type VIII Group B Streptococcus capsular polysaccharide, the structure of which is {L-Rhap(β1→4)-D-Glcp(β1→4)[Neu5Ac(α2→3)]-D-Galp(β→4)}_n. The synthesis presented three significant synthetic challenges namely: the L-Rhap(β→4)-D-Glcp bond, the Neu5Ac(α2→3)-D-Galp bond and 3,4-D-Galp branching. The L-Rhap bond was constructed in 60% yield (α:β 1:1.2) using 4-O-acetyl-2,3-di-O-benzoyl-α-L-rhamnopyranosyl bromide 6 as donor, silver silicate as promotor and 6-O-benzyl-2,3-di-O-benzoyl-1-thio-β-D-glucopyranoside as acceptor to yield disaccharide 18. The Neu5Ac(α2→3) linkage was synthesized in 66% yield using methyl [phenyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-nonulopyranosid]onate as donor and triol 2-(trimethylsilyl) ethyl 6-O-benzyl-β-D-galactopyranoside as acceptor to give disaccharide 21. The 3,4-D-Galp branching was achieved by regioselective glycosylation of disaccharide diol 21 by disaccharide 18 in 28% yield to give protected tetrasaccharide 22. Tetrasaccharide 22 was deprotected to give as its 2-(trimethylsilyl)ethyl glycoside the title compound 1a. In addition the 2-(trimethylsilyl)ethyl group was cleaved and the tetrasaccharide coupled by glycosylation (via tetrasaccharide trichloroacetimidate) to a linker suitable for conjugation.

     

Synthetic Studies on Sialoglycoconjugates 7: Synthesis of N-Acetylneuraminic Acid Derivatives and Analogs

Abstract

Various types of the O-protected derivatives and the 9-bromo analogs of methyl [2-(trimethylsilyl)ethyl 5-acetamido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid]onate were synthesized from methyl [2-(trimethyl-silyl)ethyl 5-acetamido-4,7-di-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid]onate (1) or methyl [2-(trimethylsilyl)ethyl 5-acetamido-8,9-di-O-isopropylidene-D-glycero-α-D-galacto-2-nonulopyranosid]onate (3).     

Studies on the Thioglycosides of N-Acetylneuraminic Acid 7: Synthesis of S-(α-Sialyl)-(2↠6)-β-D-Hexopyranosyl and -(2↠6)-β-D-Lactosyl Ceramides and their Biological Activity

ABSTRACT

The coupling of the sodium salt of methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3, 5-dideoxy-2-thio-D-glycero-α-D-galacto-2-nonulopyranosonate (17) with 2-(trimethylsilyl)ethyl 2,3,4-tri-O-acetyl-6-bromo-6-deoxy-β-D-galactopyranoside (5), glucopyranoside (10), and 2-(trimethylsilyl)ethyl 2,3,6,2′,3′,4′-hexa-O-acetyl-6′-bromo-6′-deoxy-β-D-lactoside (16), gave the corresponding α-thioglycosides 18, 21, and 24 of the 2-thio-N-acetyl-neuraminic acid derivative in good yields, which were converted, via selective removal of the 2-(trimethylsilyl)ethyl group, trichloroacetimidation, and coupling with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (27), into the ß-glycosides 28, 32, and 36, respectively.

Compounds 28, 32, and 36 were transformed, via selective reduction of the azide group, coupling with octadecanoic acid, O-deacetylation, and de-esterification, into the title compounds 31, 35, and 39, which showed potent inhibitory effect for sialidases from influenza and other viruses.     

Synthetic Studies on Sialoglycoconjugates 22: Total Synthesis of Tumor-Associated Ganglioside,Sialyl Lewis X1

ABSTRACT

The first total synthesis of tumor-associated glycolipid antigen, sialyl Lewis X is described. Glycosylation of 2-(trimethylsilyl)ethyl O-(2-acetamido-4,6-O-benzylidene-2-deoxy-β-D-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (1) with methyl 2,3,4-tri-O-benzyl-1-thio-β-L-fuco-pyranoside (4) gave the α-glycoside (5), which was converted by reductive ring-opening of the benzylidene acetal into the glycosyl acceptor (6). Dimethyl(methylthio)sulfonium triflate-promoted coupling of 6 with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-2,4,6-tri-O-benzoyl-1-thio-β-D-galactopyranoside (7) afforded the desired hexasaccharide 8 in good yield. Compound 8 was converted into the α-trichloroacetimidate 11, via reductive removal of the benzyl groups, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, and treatment with trichloroacetonitrile, which, on coupling with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octa-decene-1,3-diol (12), gave the β-glycoside 13. Finally, 13 was transformed, via selective reduction of the azide group, condensation with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group, into the title compound 16.     

An effective synthesis of α-glycosides of -acetylneuraminic acid derivatives by use of 2-deoxy-2β-halo-3β-hydroxy-4,7,8,9-tetra- -acetyl- -acetylneuraminic acid methyl ester

Condensation of a new glycosyl donor, methyl 5-acetamido-4, 7,8,9-tetra- -acetyl-2,3-dibromo-2,3,5-trideoxy-β- -2-nonulopyranosonate with various acceptors such as methyl 2,3,4-tri- -benzyl-α- -glucopyranoside, cholesterol, methyl 2,4,6-tri- -bonzyl-α- -galactopyranoside, and nethyl 5-acetamido-4,7,9-tri- -acetyl-2,6-anhydro-3,5-dideoxy- -non-2-enopyranosonate gave only the corresponding β-glycosides. The 3α-bromo group of the glycoaides obtained above was reduced with tributylstannane to the corresponding glycosids, which were deprotected to give the free glycoaides in high yields.     

Synthesis of Methyl 2-O-, 3-O-, 4-O-, 6-O-, 2,3-Di-O- and 4,6-Di-O-β-D-Galactopyranosyl-β-D-glucopyranoside

Abstract

Synthesis of methyl O-β-D-galactopyranosyl-(1→2)-β-D-glucopyranoside 1, methyl O-β-D-galactopyranosyl-(1→3)-β-D-glucopyranoside 2, methyl O-β-D-galactopyranosyl-(1→4)-β-D-glucopyranoside 3, methyl O-β-D-galactopyranosyl-(1→6)-β-D-glucopyranoside 4, methyl O-β-D-galactopyranosyl-(1→4)-[O-β-D-galactopyranosyl-(1→6)]-β-D-glucopyranoside 5, and methyl O-β-D-galactopyranosyl-(1→2)-[O-β-D-galactopyranosyl-(1→3)]-β-D-glucopyranoside 6, using 2,3,4,6 tetra-O-acetyl-α-D-galactopyranosyl trichloroacetimidate or 2,3,4,6 tetra-O-acetyl-α-D-galactopyranosyl bromide as a glycosyl donor and selectively protected derivatives of methyl O-β-D-glucopyranoside as glycosyl acceptors are described.     

Synthesis Of Ligands Related To The O-Specific Antigen Of Shigella Dysenteriae Type 1.

Abstract

Stereoselective α-D-galactosylation at the position 3 of 4,6-O-substituted derivatives of methyl 2-acetamido-2-deoxy-α-D-glucopyranoside is described. Glycosyl chlorides derived from 3,4,6-tri-O-acetyl-2-O-benzyl- and 2-O-(4-methoxybenzyl)-D-galactopyranose have been used as glycosyl donors. Methyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-3-O-(3,4,6-tri-O-acetyl-α-D-galactopyranosyl)-α-D-glucopyranoside (27) and methyl 2-acetamido-4,6-di-O-benzyl-2-deoxy-3-O-(3,4,6-tri-O-acetyl-α-D-galactopyranosyl)-α-D-glucopyranoside (31) have been prepared.     

Synthetic Studies on Sialoglycoconjugates 44: Synthesis of KDN-Gangliosides Gm4 and GM3

Abstract

Ganglioside GM₄ and GM₃ analogs, containing 3-deoxy-D-glycero-D-galacto-2-nonulopyranosonic acid (KDN) in place of N-acetylneuraminic acid, have been synthesized. KDN, prepared by the condensation of oxalacetic acid with D-mannose, was converted into methyl (phenyl 4,5,7,8,9-penta-O-acetyl-3-deoxy-2-thio-D-glycero-D-galacto-2-nonulopyranosid)onate (2) via methyl esterification, O-acetylation and replacement of the anomeric acetoxy group with phenyl thio. Glycosylation of 2 with 2-(trimethylsilyl)ethyl 6-O-benzoyl-β-D-galactopyranoside (3) or 2-(trimethylsilyl)ethyl O-(6-O-benzoyl-β-D-galactopyranosyl)-(1→4)-2,6-di-O-benzoyl-β-D-glucopyranoside (4) was performed, using N-iodosuccinimide-trimethylsilyl trifluoromethanesulfonate as the glycosyl promoter, to give 2-(trimethylsilyl)ethyl O-(methyl 4,5,7,8,9-penta-O-acetyl-3-deoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-6-O-benzoyl-β-D-galacto-pyranoside (5) and 2-(trimethylsilyl)ethyl O-(methyl 4,5,7,8,9-penta-O-acetyl-3-deoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-(6-O-benzoyl-β-D-galactopyrano-syl)-(l→4)-(2,6-di-O-benzoyl-β-D-glucopyranoside (9), respectively. Compounds 5 and 9 were converted via O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group and subsequent imidate formation, into the corresponding trichloroacetimidates 8 and 12, respectively. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-l,3-diol (13) with 8 and 12 in the presence of boron trifluoride etherate afforded the expected β-glycosides 14 and 17, which were transformed via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation and de-esterification, into the target gangliosides 16 and 19 in high yields.     

Synthetic Studies on Sialoglycoconjugates 90: Total Synthesis of Sulfated Glucuronyl Paraglobosides

ABSTRACT

3-O-Sulfo glucuronyl paragloboside derivatives (pentasaccharides) have been synthesized. The important intermediate designed for a facile sulfation in the last step and effective, stereocontrolled glycosidation, methyl (4-O-acetyl-2-O-benzoyl-3-O-levulinoyl-α-D-glucopyranosyl trichloroacetimidate)uronate (8) was prepared from methyl [2-(trimethylsilyl)ethyl β-D-glucopyranosid]uronate (3) via selective 4-O-acetylation, 2-O-benzoylation, 3-O-levulinoylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation. The glycosylation of 8 with 2-(trimethylsilyl)ethyl 2,4,6-tri-O-benzyl-β-D-galactopyranoside (9) using trimethylsilyl trifluoromethanesulfonate gave 2-(trimethylsilyl)ethyl O-(methyl 4-O-acetyl-2-O-benzoyl-3-O-levulinoyl-β-D-glucopyranosyluronate)-(1→3)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (10), which was transformed via removal of the benzyl group, benzoylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation into the disaccharide donor 13. On the other hand, 2-(trimethylsilyl)ethyl O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (20) as the acceptor was prepared from 2-(trimethylsilyl)ethyl 3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside (14) via O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, imidate formation, coupling with 2-(trimethylsilyl)ethyl O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (18), removal of the O-acetyl and N-phthaloyl group followed by N-acetylation. Condensation of 13 with 20 using trimethylsilyl trifluoromethanesulfonate afforded the desired pentasaccharide 21, which was transformed by removal of the benzyl group, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation into the pentasaccharide donor 24. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (25) with 24 gave the desired β-glycoside 26, which was transformed into the four target compounds, via reduction of the azido group, coupling with octadecanoic acid or tetracosanoic acid, selective removal of the levulinoyl group, O-sulfation, hydrolysis of the methyl ester group and O-deacylation.     

Synthetic Studies on Sialoglycoconjugates 95: Total Synthesis of Sulfated Glucuronyl Lactosaminyl Paraglobosides

ABSTRACT

3-O-Sulfo glucuronyl neolactohexanosyl ceramide derivatives (heptasaccharides) have been synthesized. Condensation of 2-(trimethylsilyl)ethyl 2,4,6-tri-O-benzyl-β-D-galactopyranoside (2) with 4-O-acetyl-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl trichloroacetimidate (1) gave the desired β-glycoside 3, which was converted into 2-(trimethylsilyl)ethyl O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl)-(1→3)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (4) via removal of the O-acetyl and N-phthaloyl groups, followed by N-acetylation. Glycosylation of 4 with O-(methyl 4-O-acetyl-2-O-benzoyl-3-O-levulinoyl-β-D-glucopyranosyluronate)-(1→3)-2,4,6-tri-O-benzoyl-α-D-galactopyranosyl trichloroacetimidate (5) using trimethylsilyl trifluoromethanesulfonate gave the target tetrasaccharide 6, which was transformed via removal of the benzyl group, O-benzoylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation into the tetrasaccharide donor 9. Glycosylation of 2-(trimethylsilyl)ethyl O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (10) with the imidate donor 9 using trimethylsilyl trifluoromethanesulfonate gave the desired heptasaccharide 11, which was transformed into the heptasaccharide imidate donor 14. Glycosylation of (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (15) with 14 gave β-glycoside 16, which was transformed into the four target compounds, via reduction of the azido group, coupling with octadecanoic acid or tetracosanoic acid, selective removal of the levulinoyl group, O-sulfation, hydrolysis of the methyl ester group and O-deacylation.     

Application of Phenyl 1-Selenoglycosides in the Synthesis of a Cell-Wall Tetrameric Fragment of Proteus Vulgaris Strain 5/43

Abstract

DAST-assisted rearrangement of 3-O-allyl-4-O-benzyl-α-l-rhamnopyranosyl azide followed by treatment of the generated fluorides with ethanethiol and BF₃·OEt₂ gave glycosyl donor ethyl 3-O-allyl-2-azido-4-O-benzyl-2,6-dideoxy-1-thio-α/β-l-glucopyranoside. Stereoselective glycosylation of methyl 4,6-O-benzylidene-2-deoxy-2-phthalimido-β-D-glucopyranoside with ethyl 3-O-allyl-2-azido-4-O-benzyl-2,6-dideoxy-1-thio-α/β-l-glucopyranoside, under the agency of NIS/TfOH afforded methyl 3-O-(3-O-allyl-2-azido-4-O-benzyl-2,6-dideoxy-α-l-glucopyranosyl)-4,6-O-benzyli-dene-2-deoxy-2-phthalimido-β-D-glucopyranoside. Removal of the allyl function of the latter dimer, followed by condensation with properly protected 2-azido-2-deoxy-glucosyl donors, in the presence of suitable promoters, yielded selectively methyl 3-O-(3-O-[6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-α-D-glucopyranosyl]-2-azido-4-O-benzyl-2,6-dideoxy-α-l-glucopyranosyl)-4,6-O-benzylidene-2-deoxy-2-phthalimido-β-D-glucopyranoside. Deacetylation and subsequent glycosylation of the free HO-6 with phenyl 2,3,4,6-tetra-O-benzoyl-1-seleno-β-D-glucopyranoside in the presence of NIS/TfOH furnished a fully protected tetrasaccharide. Deprotection then gave methyl 3-O-(3-O-[6-O-{β-D-glucopyranosyl}-2-acetamido-2-deoxy-β-D-glucopyranosyl)-2-acetamido-2,6-dideoxy-α-L-glucopyranosyl)-2-acetamido-2-deoxy-β-D-glucopyranoside.     

Chemoenzymatic Synthesis of Ganglioside Gm4 Analogs as Potential Immunosuppressive Agents

ABSTRACT

An efficient, chemoenzymatic synthesis of ganglioside GM4 analogs having a potent immunosuppressive activity is described. One-step and highly regìoselective 6-O-acetylation of long-chain alkyl, 2-(trimethysilyl)ethyl and phenyl 1-thio β-D-galactopyranosides was performed by using vinyl acetate and lipase PS. The resulting 6-O-acetates (70-93%) were sialylated with methyl (phenyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-2-nonulopyranosid)onate promoted by N-iodosuccinimide (NIS) and trifluoromethanesulfonic acid (TfOH). The 2-(trimethylsilyl)ethyl glycoside derivative was converted to the imidate which was then coupled with dodecan-1-ol, hexadecan-1-ol, and 2-(tetradecyl)hexadecan-1-ol, respectively, to give the protected GM4 derivatives (90-96%). O-Deacylation and saponification of the methyl ester gave the target ganglioside GM4 analogs in high yields.     

Synthetic Studies on Sialoglycoconjugates 48: Total Synthesis of Gangliosides Gm1 and Gd1a

Abstract

A stereo controlled, facile total synthesis of gangliosides GM₁ and GD_1a, in connection with systematic synthesis of ganglio-series of ganglioside, is described. Glycosylation of 2-(trimethylsilyl) ethyl O-(2-acetamido-6-O-benzoyl-2-deoxy-(β-D-galactopyranosyl)-(l→4)-O-[(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacro-2–nonulopyranosylonate)-(2→3)]-O-2,6-di-O-benzyl-β-D-galacto-pyranosyl)-(l→40)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (4), with methyl 2,4,6-tri-O-benzoyl-3-O-benzyl-l-thio-β-D-galactopyranoside (8) or methyl O-(methyl 5-acetamido -4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacro-2-nonulopyranosylonate)-(2→3)-2,4,6-tri-O-benzoyl-l-thio-β-D-galactopyranoside (9) by use of N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid (TfOH) or dimethyl(methylthio)sulfonium triflate (DMTST) as a promoter, gave the corresponding [β-glycoside 10 and 18 in 66 and 62% yields, which were converted, via reductive removal of the benzyl groups, O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and subsequent imidate formation, into the α-trichloroacetimidates 13 and 21. Glycosylation of (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-l,3-diol (14) with 13 or 21 by use of trimethylsilyl trifluoromethanesulfonate gave the corresponding β-glycoside 15 and 22, which on channeling through selective reduction of die azido group, coupling of the thus formed amino group with octadecanoic acid, O-deacylation, and saponification of the methyl ester group, gave the tital gangliosides GM₁ and GD_1a.