Surjit S. Rana

The selective acetylation of primary alcohols in the presence of secondary alcohols in carbohydrates

Abstract Treatment of primary-secondary sugar diols with ethyl acetate in the presence of Woelm neutral alumina produced selectively the corresponding primary monoacetates in good yield. No di-acetate was formed in a detectable amount.

Lysosomal-enzyme targeting: the phosphorylation of synthetic d-mannosyl saccharides by UDP-N-acetylglucosamine:lysosomal-enzyme N-acetylglucosaminephosphotransferase from rat-liver microsomes and fibroblasts

Phosphorylation of the D-mannose residues of lysosomal enzymes is essential for the uptake and intracellular transport of these enzymes to lysosomes. The GlcNAc-P-transferase which is involved in the phosphorylation reaction seems to recognize a signal, probably a protein conformation, common to many lysosomal enzymes. To evaluate the role of the carbohydrate portion of the enzyme in these phosphorylation reactions, the acceptor specificity of GlcNAc-P-transferase from rat-liver microsomes and fibroblasts was examined with the aid of synthetic D-mannosyl disaccharides and derivatives that are closely related to the high-mannose type of oligosaccharides. Four methyl D-mannobiosides were synthesized, and their structures were established by 13C-n.m.r. spectroscopy. Of all the D-mannosyl saccharides tested, alpha-D-Man-(1----2)-alpha-D-Man-(1----OMe) was found to be the best acceptor, thereby suggesting that oligosaccharide structure may also have a role to play in recognition by this enzyme.

Synthesis of p-nitrophenyl 2-acetamido-2-deoxy-4-O-β-d-galactopyranosyl- β-d-glucopyranoside, and p-nitrophenyl 6-O-(2-acetamido-2-deoxy-3-O- and -4-O-β-d-galactopyranosyl- β-d-glucopyranosyl)-α-d-mannopyranoside☆

Abstract A facile synthesis of p -nitrophenyl 2-acetamido-2-deoxy-4- O -β- d -galactopyranosyl- β- d -glucopyranoside was accomplished by saponification of the product obtained by reaction of 2-acetamido-3,6-di- O -acetyl-2-deoxy-4- O -(2,3,4,6-tetra- O -acetyl- β- d -galactopyranosyl)-α- d -glucopyranosyl chloride and Amberlyst A-26 p -nitrophenoxide. The reaction of p -nitrophenyl 2,3- O -isopropylidene-α- d -mannopyranoside ( 7 ) with the easily accessible 2-methyl-[4,6-di- O -acetyl-2-deoxy-3- O -(2,3,4,6-tetra- O - acetyl-β- d -galactopyranosyl)-α- d -glucopyrano]-[2,1- d ]-2-oxazoline proceeded readily, to give the protected trisaccharide derivative which, on deacetonation, followed by O -deacetylation, produced one of the title trisaccharides, namely, p -nitrophenyl 6- O -(2-acetamido-2-deoxy-3- O -β- d -galactopyranosyl-β- d -glucopyranosyl)-α- d -mannopyranoside. Synthesis of the other trisaccharide, p -nitrophenyl 6- O -(2-acetamido- 2-deoxy-4- O -β- d -galactopyranosyl-β- d -glucopyranosyl)-α- d -mannopyranoside was accomplished by a similar reaction-sequence when the corresponding 2-methyl-[3,6- di- O -acetyl-2-deoxy-4- O -(2,3,4,6-tetra- O -acetyl-β- d -galactopyranosyl)-α- d -glucopyrano]- [2,1- d ]-2-oxazoline ( 19 ) reacted with 7 . Preparation of oxazoline 19 was achieved via acetolysis of methyl 2-acetamido-2-deoxy-4- O -β- d -galactopyranosyl-α- d -glucopyranoside. The structures assigned to the final saccharides were supported by 1 H- and 13 C-n.m.r.-spectral data.

The chemical synthesis of O-α-l-fucopyranosyl-(1→2)-O-β-d-galactopyranosyl-(1→3)-O-[α-l-fucopyranosyl-(1→4)]-2- acetamido-2-deoxy-d-glucopyranose, the lewis b blood-group antigenic determinant

Abstract An approach has been developed for the rapid synthesis of benzyl 2-acetamido-2-deoxy-3- O -β- d -galactopyranosyl-β- d -glucopyranoside ( 5 ). Disaccharide 5 was per(trimethylsilyl)ated, to provide the fully protected trimethylsilyl (Me 3 Si) derivative which, on treatment with pyridine-acetic anhydride-acetic acid for 2 days, gave the disaccharide derivative having O -acetyl groups selectively at the primary positions and Me 3 Si groups at the secondary positions. The latter groups were readily cleaved by treatment with aqueous acetic acid in methanol, to afford benzyl 2-acetamido-6- O -acetyl-3- O -(6- O -acetyl-β- d -galactopyranosyl)-2-deoxy-β- d -glucopyranoside, which, on isopropylidenation, gave the desired, key intermediate 9 , having two hydroxyl groups free. Condensation of 9 with 2,3,4,-tri- O -benzyl-α- l -fucopyranosyl bromide, under catalysis by halide ion, afforded the tetrasaccharide derivative, from which the title tetrasaccharide was obtained by systematic removal of the protecting groups. The structure of the final product, and of various other intermediates, was established by 1 H- and 13 C-n.m.r. spectroscopy.

Synthesis of phenyl 2-acetamido-2-deoxy-3-O-α-l-fucopyranosyl-β-d-glucopyranoside and related compounds☆

Abstract The reaction of phenyl 2-acetamido-2-deoxy-4,6- O -( p -methoxybenzylidene)-β- d -glucopyranoside with 2,3,4-tri- O -benzyl-α- l -fucopyranosyl bromide under halide ion-catalyzed conditions proceeded readily, to give phenyl 2-acetamido-2-deoxy-4,6- O -( p -methoxybenzylidene)-3- O -(2,3,4-tri- O -benzyl-α- l -fucopyranosyl)-β- d -glucopyranoside ( 8 ). Mild treatment of 8 with acid, followed by hydrogenolysis, provided the disaccharide phenyl 2-acetamido-2-deoxy-3- O -α- l -fucopyranosyl-β- d -glucopyranoside. Starting from 6-(trifluoroacetamido)hexyl 2-acetamido-3,4,6-tri- O -acetyl-2-deoxy-β- d -glucopyranoside, the synthesis of 6-(trifluoroacetamido)hexyl 2-acetamido-2-deoxy-3- O -β- l -fucopyranosyl-β- d -glucopyranoside has been accomplished by a similar reaction-sequence. On acetolysis, methyl 2-acetamido-2-deoxy-3- O -α- l -fucopyranosyl-α- d -glucopyranoside gave 2-methyl-[4,6-di- O -acetyl-1,2-dideoxy-3- O -(2,3,4-tri- O -acetyl-α- l -fucopyranosyl)-α- d -glucopyrano]-[2, 1- d ]-2-oxazoline as the major product.

Synthesis of p-nitrophenyl 6-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-α-d-mannopyranoside☆

Abstract The reaction of p-nitrophenyl 2,3-O-isopropylidene-α- d -mannopyranoside and 2-methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-α- d -glucopyrano)-[2,1-d]-2-oxazoline gave a crystalline, 6-O-substituted disaccharide derivative which, on de-isopropylidenation followed by saponification, produced the disaccharide p-nitrophenyl 6-O-(2-acetamido-2-deoxy-β- d -glucopyranosyl)-α- d -mannopyranoside. Synthesis of methyl 6-O-(2-acetamido-2-deoxy-β- d -glucopyranosyl)-α- d -mannopyranoside was also accomplished by a similar reaction-sequence. The structures of these disaccharides have been established by 13C-n.m.r. spectroscopy.

Synthesis of 2-acetamido-2-deoxy-6-O-β-d-galactopyranosyl-d-galactopyranose and o-nitrophenyl 2-acetamido-2-deoxy-6-O-β-d-galactopyranosyl-α-d-galactopyranoside☆

Abstract Acetalation of o -nitrophenyl 2-acetamido-2-deoxy-α- d -galactopyranoside with p -methoxybenzaldehyde-zinc chloride complex afforded the 4,6- O -( p -methoxybenzylidene) derivative ( 1 ). Acetylation of 1 with pyridine-acetic anhydride gave the crystalline monoacetate ( 2 ), the acetal group of which was cleaved by brief treatment with hot, 80% aqueous acetic acid to furnish the diol ( 3 ). The 1 H-n.m.r. spectra of both 2 and 3 supported their overall structures. Glycosylation of 3 with 2,3,4,6-tetra- O -acetyl-α- d -galactopyranosyl bromide ( 5 ) in 1:1 nitromethane-benzene, in the presence of mercuric cyanide, afforded the disaccharide derivative ( 6 ). O -Deacetylation of 6 in methanolic sodium methoxide gave the title disaccharide ( 8 ). A similar glycosylation of benzyl 2-acetamido-3- O -acetyl-2-deoxy-α- d -galactopyranoside with bromide 5 , followed by O -deacetylation of the resulting intermediate, produced disaccharide 9 . The structures of 8 and 9 were confirmed by 13 C-n.m.r. spectroscopy. Hydrogenolysis of the benzyl aglycon of 9 gave the free disaccharide 2-acetamido-2-deoxy-6- O -β- d -galactopyranosyl- d -galactopyranose ( 13 ). The 13 C-n.m.r. spectrum of 13 is recorded, and discussed in conjunction with those of the β-(1→3)- and the β-(1→4)-linked isomers.

A practical synthesis of 2-acetamido-2-deoxy-3,4-di-O-β-d-galactopyranosyl-d-galactopyranose☆

Abstract Two different sugar derivatives having free hydroxyl groups have been employed for synthesis of the title trisaccharide. In one attempt, benzyl 2-acetamido-6-O-benzyl-2-deoxy-α- d -galactopyranoside (8) was treated with an excess of 2,3,4,6-tetra-O-acetyl-α- d -galactopyranosyl bromide (11), to give a mixture of products which, on fractionation, afforded benzyl 2-acetamido-6-O-benzyl-3,4-di-O-(2,3,4,6-tetra-O-acetyl-β- d -galactopyranosyl)- α- d -galactopyranoside (15) in 21% yield. However, in another, preferable approach, benzyl 2-acetamido-6-O-benzyl-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-β- d - galactopyranosyl)-α- d -galactopyranoside (13) was treated with 11, to produce 15 in 69% yield. Both 8 and 13 were conveniently prepared via reductive ring-opening of the respective 4,6-benzylidene acetals. O-Deacetylation of 15, followed by hydrogenolysis, provided the title trisaccharide. The structure of the final product, and of various other intermediates, was established by 1H- and 13C-n.m.r. spectroscopy.

A facile synthesis of 2-acetamido-2-deoxy-4-O-α-l-fucopyranosyl-3-O-β-d-galactopyranosyl-d-glucopyranose, the Lewis a blood-group antigenic determinant, and related compounds

Abstract A simple strategy was developed for the procurement of benzyl 2-acetamido-6- O -benzyl-2-deoxy-3- O -(2,3,4,6-tetra- O -acetyl-β- d -galactopyranosyl)-β- d -gluco-pyranoside ( 8 ). Reductive opening of the acetal ring of benzyl 2-acetamido-4,6- O -benzylidene-2-deoxy-3- O -(2,3,4,6-tetra- O -acetyl-β- d -galactopyranosyl)-β- d -gluco-pyranoside gave, exclusively, the desired, key intermediate 8 . Fucosylation of 8 with 2,3,4-tri- O -benzyl-α- l -fucopyranosyl bromide, under catalysis by bromide ion, afforded the trisaccharide derivative which, on O -deacetylation, followed by hydrogenolysis, produced the title trisaccharide. Starting from methyl 2-acetamido-4,6- O -benzylidene-2-deoxy-3- O -(2,3,4,6-tetra- O -acetyl-β- d -galactopyranosyl)-α- d -glucopyranoside, the synthesis of methyl 2-acetamido-2-deoxy-4- O -α- l -fucopyranosyl-3- O -β- d -galactopyranosyl-α- d -glucopyranoside was accomplished by a similar reaction-sequence. The synthesis of 2-acetamido-2-deoxy-4- O -α- l -fucopyranosyl- d -glucopyranose is also described. The structures of the final saccharides, and of various other intermediates, were established by 1 H- and 13 C-n.m.r. spectroscopy.

Synthesis of O-α-L-Fucopyranosyl-(1→2)-O-β-D-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-D-glucopyranose. The H-Blood Group Specific Trisaccharide

Abstract Different reaction conditions were investigated for the preparation of benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside (5). Compound 5 on reaction with 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl bromide afforded the 4-O-substituted 2-acetamido-2-deoxy-β-D-glucopyranosyl derivative which, on O-deacetylation, gave benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-β-D-galactopyranosyl-β-D-glucopyranoside (8). The trimethylsilyl (Me3Si) derivative of 8, on treatment with pyridineacetic anhydride-acetic acid for 2 days, gave the disaccharide derivative having an O-acetyl group selectively introduced at the primary position and Me3Si groups at the secondary positions. The latter groups were readily cleaved by treatment with aqueous acetic acid in methanol to afford benzyl 2-acetamido-4-O-(6-O-acetyl-β-D-galactopyranosyl)-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside, which on isopropylidenation gave the desired, key intermediate benzyl 2-acetamido-4-O-(6-O-acetyl-3,4-O-isopropylidene-β-D-gal...