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.     

Synthetic Studies on Sialoglycoconjugates 12: Total Synthesis of Sialyl Neolactotetraosyl Ceramide

Abstract

Sialoglycoconjugates such as glycoproteins and glycolipids are present as components of cell memberanes and play important roles^1,2 in biological systems. Sialyl neolactotetrasyl ceramide (IV³NeuAcnLc₄Cer), a complex type of ganglioside, was isolated as the major ganglioside of human erythrocytes³ and was shown to be a receptor of that this glycolipid induces granulocytic differentiation of human premyelocytic leukemia cell.     

Synthetic Studies on Sialoglycoconjugates 50: Total Synthesis of Ganglioside GD2

Abstract

As more and more biological functions^1-10 of gangliosides are being revealed, their facile, stereocontrolled synthesis is strongly required. We have developed^11-l4 an α-stereoselective glycosylation of sialic acids, α-sialyl-(2→8)-sialic acid and α-sialyl-(2→8)-α-sialyl-(2→8)-sialic acid, by using their 2-thioglycosides as the glycosyl donor and suitably protected acceptors, and dimethyl(methy1thio)sulfonium triflate (DMTST) or N-iodosuccinimide (NIS)-trifluoromethanesufonic acid (or TMS triflate) as the glycosyl promoter in acetonitrile. In this way, we have synthesized a variety of gangliosides¹⁵ and their analogs.¹⁶ Previously,¹³ we synthesized Ganglioside GD3 containing α-sialyl-(2-8)-sialic acid residue in the molecule, in connection with a novel approach for systematic synthesis of polysialo-glycoconjugates. As a part of our continuing studies on the synthesis and elucidation of the functions of gangliosides, we describe here a facile, stereocontrolled, total synthesis of ganglioside GD2. Ganglioside GD2, which was first isolated from human brain by R. Kuhn et al.,¹⁷ is well known as a human melanoma associated antigen.¹⁸     

Synthetic Studies on Sialoglycoconjugates 41: A Facile Total Synthesis of Ganglioside GM2

Abstract

A stereocontrolled, facile total synthesis of ganglioside GM2 is described. Coupling of 2- (trimethylsilyl)ethyl O-(2,6-di-O-benzyl-(β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (2), prepared from 2-(trimethylsilyl)ethyl β-lactoside (1) by selective 3′,4′-O-isopropylidenation, O-benzylation, and subsequent removal of the isopropylidene group, with methyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy -2-thio-D-glycero-D-galacto -2-nonulopyranosid)onate (4) using N-iodosuccini-midc (NIS), gave the trisaccharide (5), which on condensation with methyl 6-O-benzoyl -2-dcoxy-3,4-O-isopropylidene-2-phthalimido-l-thio-β-D-galactopyranoside (11), gave the protected ganglioside GM₂ oligosaccharide 12. Compound 12 was transformed, via O-deisopropylidenation, O-acetylation, removal of the phthaloyl group, N-acetylation, removal of the benzyl groups followed by (O-acetylation, selective removal of the 2-(rximethylsilyl)ethyl group, and subsequent imidate formation, into the final glycosyl donor 19. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-l,3-diol (20) with the α-trichloroacetimidate 19 gave the β-glycoside 21, which on channeling through selective reduction of the azide group, coupling of the amino group with octadecanoic acid, O-deacylation and saponification of the methyl ester group, gave the title ganglioside.     

Synthetic Studies on Sialoglycoconjugates 59: Total Synthesis of Tumor-Associated Ganglioside,Sialyl Le

Abstract

The first total synthesis of tumor-associated glycolipid antigen, sialyl Le^a, is described. Methylsulfenyl bromide-silver triflate-promoted coupling of 2-(trimethylsilyl)ethyl O-(2-acetamido-6-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 (2) 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 (3) afforded the pentasaccharide 4a and 5a in good yields. Glycosylation of 4a with methyl 2,3,4-tri-O-benzyl-1-thio-β-l-fucopyranoside (6) by use of N-iodosuccinimide (NIS) — trifluoromethanesulfonic acid (TfOH) as a promoter, gave the desired hexasaccharide 7. Compound 7 was converted into the α-trichloroacetimidate 10, via reductive removal of 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-octadecene-1, 3-diol (11), gave the β-glycoside 12. Finally, 12 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 15 in good yield.     

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.     

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.     

Synthetic Studies on Sialoglycoconjugates 54: Synthesis of I-Active Ganglioside Analog

Abstract

A stereocontrolled synthesis of I-active ganglioside analog is described. Glycosylation of 2-(trimethylsilyl)ethyl O-(2-O-benzyl-4,6-O-benzylidene-β-d-galactopyranosyl)-(1 → 4)-2,3,6-tri-O-benzyl-β-d-glucopyranoside (5) with methyl 4-O-acetyl-1,6-di-O-benzyl-2-deoxy-2-phthalimido-1-thio-β-d-glucopyranoside (10) by use of N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid (TfOH) gave the desired trisaccharide 11, which was transformed into trisaccharide acceptor 14 via removal of the phthaloyl group followed by N-acetylation, and debenzylidenation. Glycosylation of 14 with methyl 3-O-benzyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-1-thio-β-d-glucopyranoside (8) gave the biantennary compound 15, which was transformed into the acceptor 16. Dimethyl(methylthio)sulfonium triflate (DMTST)-promoted coupling of 16 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 (17) afforded the desired hexasaccharide 19. Coupling of the hexasaccharide acceptor 20, prepared from 19 by reductive ring-opening of benzylidene acetal, with 17 gave octasaccharide derivative 21. Compound 21 was transformed, via removal of the benzyl group followed by O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group and subsequent imidate formation, into the final glycosyl donor 24. Condensation of 24 with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (18) gave the β-glycoside 25, which on channeling through selective reduction of azido group, coupling of the amino group with octadecanoic acid, O-deacylation and saponification of the methyl ester group, gave the title compound 28.     

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.     

Synthetic Studies on Sialoglycoconjugates 8: Synthesis of 8-EPI-N-Acetylenuraminic Acid Derivatives

Abstract

Methyl [2-(trimethylsilyl)ethyl 5-acetamido-3,5-dideoxy-L-glycero-α-D-galacto-2-nonulopyranosid]onate (6) and its 8-epi-N-acetylneuraminic acid derivatives were synthesized from methyl [2-(trimethylsilyl)ethyl 5-acetamido-4,7-di-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulo-pyranosid]onate (1) and methyl [2-(trimethylsilyl)ethyl 5-acetamido-3,5-dideoxy-4,7-di-O-2-(trimethylsilyl)ethoxymethyl-D-glycero-α-D-galacto-2-nonulopyranosid]onate (2).     

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 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).     

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 40: Stereocontrolled Synthesis of Sialyl Lewis X Epitope and Its Ceramide Derivative

Abstract

Stereocontrolled synthesis of sialyl Le^x epitope and its ceramide derivative with regard to the introduction of galactose or β-D-galactosyl ceramide into the terminal N-acetylglucosamine residue of sialyl Le^x determinant is described. Königs-Knorr condensation of 2-(trimethylsilyl)ethyl 2, 4, 6-tri-O-benzyl-β-D-galactopyranoside (4) with 3, 4, 6-tri-O-acetyl-2-deoxy-2-phthalimido-D-glucopyranosyl bromide (5) gave the desired β-glycoside 6, which was converted into 2-(trimethylsilyl)ethyl O-(2-acetamido-4, 6-O-benzylidene-2-deoxy-β-D-glucopyranosyl)-(l→3)-2, 4, 6-tri-O-benzyl-β-D-galactopyranoside (8) via removal of the phthaloyl and O-acetyl groups, followed by N-acetylation and 4, 6-O-benzylidenation. Glycosylation of 8 with methyl 2, 3, 4-tri-O-benzyl-1-thio-β-L-fucopyranoside (9) gave the α-glycoside (10), which was transformed by reductive ring-opening of the benzyliderie acetal into the acceptor (11). Dimethyl(methylthio)sulfonium triflate (DMTST)-promoted coupling of 11 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-l-thio-β-D-galactopyra-noside (12) afforded the desired pentasaccharide (13), which was converted into the α-trichloroacetimidate 16 via reductive removal of the benzyl groups, then O-acetylation, removal of the 2-(trimethyIsilyl)ethyl group and treatment with trichloroacetonitrile. Condensation of 16 with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-l, 3-diol (18) gave the β-glycoside 19, which was transformed into the title compound 21, via reduction of the azido group, coupling with octadecanoic acid, O-deacylation and hydrolysis of the methyl ester group. On the other hand, O-deacylation of 13 and subsequent hydrolysis of the methyl ester group gave the pentasaccharide epitope 17.     

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 52: Synthesis of Sialyl Lewis X Analogs Containing Azidoalkyl Groups at the Reducing End

Abstract

Stereocontrolled synthesis of sialyl Le^x epitope analogs in which the terminal N-acetylglucosamine residue of sialyl Le^x determinant is replaced by a D-glucopyranose residue containing β-glycosidically linked azidoalkyl groups is described. Glycosylation of 2-(trimethylsilyl)ethyl O-(2,6-di-O-benzoyl-3,4-O-isopropylidene-β-D-galactopyra-nosyl)-(1→4)-2,6-di-O-benzoyl-β-D-glucopyranoside (2), prepared from 2-(trimethylsi-lyl)ethyl β-lactoside (1) by 3,4-O-isopropylidenation and selective-O-benzoylation, with methyl 2,3,4-tri-O-benzyl-l-thio-β-L-fucopyranoside (3) gave the desired a-glycoside 4, which was converted by O-deisopropylidenation into 7, and via O-debenzoylation, selective 2,6,6′-tri-O-benzoylation and O-deisopropylidenation into 8, respectively. N-Iodosuccinimide (NIS)-TfOH-promoted glycosylation of 7 or 8 with methyl (phenyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-2-nonulopyra-nosid)onate (9) afforded the desired tetrasaccharides 10 and 11.

Compound 11 was converted into the α-trichloroacetimidate 14 via reductive removal of the benzyl groups, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group and treatment with trichloroacetonitrile. Coupling of 14 with 2-azidoethanol, 8-azidooc-tanol, and 2-[2-(2-azidoethoxy)ethoxy]ethanol, gave the desired β-glycosides 15-17, respectively. O-Deacylation of 12, 15-17 and subsequent hydrolysis of the methyl ester group yielded the tide compounds.     

Synthetic Studies on Sialoglycoconjugates. 4: Synthesis of 5-Acetamido-3,5-Dideoxy-d-Galacto-2-Octulosonic Acid Derivatives and Analogs

Abstract

5-Acetamido-3.5-dideoxy-D-galacto-2-octulosonic acid derivatives and the α-2-thioanalog (14) were synthesized. Methyl [2-(trimethylsilyl)ethyl 5-acetamido-3,5-dideoxy-α-D-galacto-2-octulopyranosid]onate (8), prepared from methyl [2-(trimethylsilyl)ethyl 5-acetamido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid]onate (1) via 8,9-O-isopropylidenation, O-acetylation, O-deisopropylidenation, metaperiodate oxidation, and sodium borohydride reduction, was converted, by selective bromination, into the 8-bromo derivatives (9). Compound 12, derived from 8 via O-acetylation and boron trifluoride etherate treatment, was converted to the 2-chloro derivative (13), which underwent displacement with potassium thioacetate, to yield methyl 5-acetamido-4,7,8-tri-O-acetyl-2-S-acetyl-2-thio-α-D-galacto-2-octulopyranosonate (14).     

Synthetic Studies on Sialoglycoconjugates 18: Synthesis of 7-O-, 7,9-Di-O-, and 7,8,9-Tri-O-Acetyl-N-Acetyl-Neuraminic Acid Derivatives

ABSTRACT

7-O-, 7,9-Di-O-, and 7,8,9-tri-O-acetyl derivatives of N-acetyl-neuraminic acid were synthesized starting from benzyl [2-(trimethylsilyl)-ethyl 5-acetamido-3,5-dideoxy-8,9-O-isopropylidene-D-glycero-α-D-galacto-2-nonulopyranosid]onate (1).     

Synthetic Studies on Sialoglycoconjugates 14: Synthesis of Ganglioside GM3 Analogs Containing The Carbon 7 And 8 Sialic Acids

ABSTRACT

Ganglioside GM₃ analogs, containing 5-acetamido-3, 5-dideoxy-L-arabino-heptulosonic acid and 5-acetamido-3, 5-dideoxy-D-galacto-octulosonic acid have been synthesiyed. Glycosylation of 2-(trimethylsilyl)ethyl 0-(6-0-benzoyl-ß-D-galactopyranosyl)-(l→4)-2, 6-di-0-benzoyl-ß-D-glucopyranoside (5), with methyl (methyl 5-acetamido-4, 7-di-0-acetyl-3, 5-dideoxy-2-thio-ß-L-arabino-2-heptulo-pyranosid)onate (2) or with methyl (methyl 5-acetamido-4, 7, 8-tri-0-acetyl-3, 5-dideoxy-2-thio-α-D-galacto-2-octulopyranosid)onate (4), which were respectively prepared from the corresponding 2-S-acetyl derivatives (1 and 3) by selective 2-S-deacetylation and subsequent S-methylation, using dimethyl(methylthio)sulfonium triflate as a glycosyl promoter, gave 2-(trimethylsilyl)ethyl 0-(methyl 5-acet-amido-4, 7-di-0-acetyl-3, 5-dideoxy-ß-L-arabino-2-heptulopyranosyl-onate)-(2→3)-0-(6-0-benzoyl-ß-D-galactopyranosyl)-(1→4)-2, 6-di-0-benzoyl-ß-D-glucopyranoside (6) and 2-(trimethylsilyl)ethyl (0)-(methyl 5-acetamido-4, 7, 8-tri-0-acetyl-3, 5-dideoxy-α-D-galacto-2-octulopyranosylonate)-(2→3)-0-(6-0-benzoyl-ß-D-galactopyranosyl)-(l-4)-2, 6-di-0-benzoyl-ß-D-glucopyranoside (10), respectively. Compounds 6 and 10 were converted, via 0-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and subsequent imidate formation, into the corresponding trichloroacetimidates 9 and 13, respectively.

Glycosylation of (2S, 3R, 4E)-2-azido-3-0-benzoyl-4-octadecen1, 3-duik (14) with 9 or 13 affored the ß-glcosides (15 and 18), which were converted, via selective reduction of the azide group, coupling with octadecanoic acid, 0-deacylation, and deesterification, into the title compounds, respectively.     

Synthetic Studies on Erythrina Alkaloids: Formal Total Synthesis of (+)-3-Demethoxyerythratidinone

A formal asymmetric synthesis of (+)-3-demethoxyerythratidinone (1) is reported using the key intermediate 3 as the starting material, which is available from L-malic acid by a known method.