Studies on dextranases. 3. Insolubilization of a bacterial dextranase

Ammonium hydroxide treatment of 1,6:2,3-dianhydro-4-O-benzyl-β-D-mannopyranose, followed by acetylation, gave 2-acetamido-3-O-acetyl-1,6-anhydro-4-O-benzyl-2-deoxy-β-D-glucopyranose which was catalytically reduced to give 2-acetamido-3-O-acetyl-1,6-anhydro-2-deoxy-β-D-glucopyranose (6), the starting material for the synthesis of (1→4)-linked disaccharides bearing a 2-acetamido-2-deoxy-D-glucopyranose reducing residue. Selective benzylation of 2-acetamido-1,6-anhydro-2-deoxy-β-D-glucopyranose gave a mixture of the 3,4-di-O-benzyl derivative and the two mono-O-benzyl derivatives, the 4-O-benzyl being preponderant. The latter derivative was acetylated, to give a compound identical with that just described. For the purpose of comparison, 2-acetamido-4-O-acetyl-1,6-anhydro-2-deoxy-β-D-glucopyranose has been prepared by selective acetylation of 2-acetamido-1,6-anhydro-2-deoxy-β-D-glucopyranose.Condensation between 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide and 6 gave, after acetolysis of the anhydro ring, the peracetylated derivative (17) of 2-acetamido-2-deoxy-4-O-β-D-glucopyranosyl-α-D-glucopyranose. A condensation of 6 with 3,4,6-tri-O-acetyl-2-deoxy-2-diphenoxyphosphorylamino-α-D-glucopyranosyl bromide likewise gave, after catalytic hydrogenation, acetylation, and acetolysis, the peracylated derivative (21) of di-N-acetylchitobiose.     

The stepwise synthesis of a methyl β-xylotetraoside related to branched xylans

3,4-Di-O-acetyl-2-O-benzyl-α-d-xylopyranosyl bromide (1) reacts with methyl 2,3-anhydro-α-d-ribopyranoside (2) to afford, in high yield, methyl 2,3-anhydro-4-O- (3,4-di-O-acetyl-2-O-benzyl-β-d-xylopyranosyl)-β-d-ribopyranoside (3). Deacetylation of 3 gave 4, which reacted with 2,3,4-tri-O-acetyl-α-d-xylopyranosyl bromide to give the branched tetrasaccharide derivative 5, which, in turn, was converted by a series or conventional reactions into methyl 4-O-[3,4-di-O-(β-d-xylopyranosyl)-β-d- xylopyranosyl]-β-d-xylopyranoside. The reaction of 1 with its hydrolysis product gave 3,4-di-O-acetyl-2-O-benzyl-α-d-xylopyranosyl 3,4-di-O-acetyl-2-O-benzyl-β-d-xylopyranoside, which was also isolated after the reaction of 1 with 2.     

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

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.     

Photochemical addition of 1,3-dioxolane and of 2-propanol to 1,2,4,6-tetra-O-acetyl-3-deoxy-α- and -β-D-erythro-hex-2-enopyranose

Photoirradiation of a solution of 1,2,4,6-tetra-O-acetyl-3-deoxy-β-D-erythro-hex-2-enopyranose (1) in 1:50 acetone-1,3-dioxolane with a high-pressure mercury-lamp, followed by chromatographic separation, gave 1,2,4,6-tetra-O-acetyl-3-deoxy-3-C-(1,3-dioxolan-2-yl)-β-D-glucopyranose (3) (44%) and-mannopyranose (4) (35%). Similar treatment of the α anomer (2) of 1 afforded 1,2,4,6-tetra-O-acetyl-3-deoxy-3-C-(1,3-dioxolan-2-yl)-α-D-glucopyranose (5) (38%), -mannopyranose (6) (31%), and -allopyranose (7) (21%).On the other hand, irradiation of 2 in 1:100 acetone-2-propanol gave 1,2,4,6-tetra-O-acetyl-3-deoxy-3-C-(1-hydroxy-1-methylethyl)-α-D-mannopyranose (8) (76%). Moreover, irradiation of 2 in 1:1 acetone-2-propanol yielded 1,4,6-tri-O-acetyl-3-deoxy-2,3-di-C-(1-hydroxy-1-methylethyl)-α-D-gluco- or -manno-pyranose 2,2¹,3¹-orthoacetate (10) (15%), in addition to 8 (44%).     

Synthesis of 2-acetamido-2-deoxy-3-O-β-d-mannopyranosyl-d-glucose

Condensation of 4,6-di-O-acetyl-2,3-O-carbonyl-α-d-mannopyranosyl bromide with benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-α-d-glucopyranoside (2) gave an α-d-linked disaccharide, further transformed by removal of the carbonyl and benzylidene groups and acetylation into the previously reported benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-α-d-mannopyranosyl)-α-d-glucopyranoside. Condensation of 3,4,6-tri-O-benzyl-1,2-O-(1-ethoxyethylidene)-α-d-glucopyranose or 2-O-acetyl-3,4,6-tri-O-benzyl-α-d-glucopyranosyl bromide with 2 gave benzyl 2-acetamido-3-O-(2-O-acetyl-3,4,6-tri-O-benzyl-β-d-glucopyranosyl)-4,6-O-benzylidene-2-deoxy-α-d-glucopyranoside. Removal of the acetyl group at O-2, followed by oxidation with acetic anhydride-dimethyl sulfoxide, gave the β-d-arabino-hexosid-2-ulose 14. Reduction with sodium borohydride, and removal of the protective groups, gave 2-acetamido-2-deoxy-3-O-β-d-mannopyranosyl-d-glucose, which was characterized as the heptaacetate. The anomeric configuration of the glycosidic linkage was ascertained by comparison with the α-d-linked analog.     

Use of 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-2,4,6-tri-O-acetyl-α-d-galactopyranosyl bromide as a glycosyl donor: Synthesis of p-nitrophenyl 3-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-β-d-galactopyranoside

Acetolysis of methyl 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-2,4,6-tri-O-acetyl-α-d-galactopyranoside afforded 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-1,2,4,6-tetra-O-acetyl-d-galactopyranose (2). Treatment of 2 in dichloromethane with hydrogen bromide in glacial acetic acid gave 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)- 2,4,6-tri-O-acetyl-α-d-galactopyranosyl bromide (3). The α configuration of 3 was indicated by its high, positive, specific rotation, and supported by its ¹H-n.m.r. spectrum. Reaction of 3 with Amberlyst A-26-p-nitrophenoxide resin in 1:4 dichloromethane-2-propanol furnished p-nitrophenyl 3-O-(2-acetamido-3,4,6- tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-2,4,6-tri-O-acetyl-β-d-galactopyranoside (7). Compound 7 was also obtained by the condensation (catalyzed by silver trifluoromethanesulfonate-2,4,6-trimethylpyridine) of 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl bromide with p-nitrophenyl 2,4,6-tri-O-acetyl-β-d-galactopyranoside, followed by the usual deacylation-peracetylation procedure. O-Deacetylation of 7 in methanolic sodium methoxide furnished the title disaccharide (8). The structure of 8 was established by ¹³C-n.m.r. spectroscopy.     

Synthesis of the tetrasaccharide repeating-unit of the O-specific polysaccharide from Salmonella senftenberg

The oligosaccharide β-d-Man-(1 → 4)-α-l-Rha (1 → 3)-d-Gal-(6 ← 1)-α-d-Glc, which is the repeating unit of the O-specific polysaccharide chain of the lipopolysaccharide from Salmonella senftenberg, was obtained by glycosylation of benzyl 2,4-di-O-benzyl-6-O-(2,3,4-tri-O-benzyl-6-O-p-nitrobenzoyl-α-d-glucopyranosyl)-β-d-galactopyranoside or benzyl 2-O-acetyl-6-O-(2,3,4-tri-O-benzyl-6-O-p-nitrobenzoyl-α-d-glucopyranosyl)-β-d-galactopyranoside with 3-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-β-d-mannopyranosyl)-β-l-rhamnopyranose 1,2-(methyl orthoacetate) followed by removal of protecting groups.     

Synthetic mucin fragments. Methyl 6-O-(2-acetamido-2-deoxy-β-D-glycopyranosyl)-β-D-galactopyranoside,methyl 3,4-di-O-(2-acetamido-2-deoxy-β-D-glycopyranosyl)-β-D-galactopyranoside,and methyl O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1 å 3)-O-β-D-galactopyranosyl-(1 å 3)-O-(2-acetamido-2-deoxy-β- D-glucopyranosyl)-(1 å 3)-β-D-galactopyranoside

Condensation of methyl 2,6-di-O-benzyl-β-d-galactopyranoside with 2-methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-d-glucopyrano)-[2,1,-d]-2-oxazoline (1) in 1,2-dichloroethane, in the presence of p-toluenesulfonic acid, afforded a trisaccharide derivative which, on deacetylation, gave methyl 3,4-di-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-2,6-di-O-benzyl-β-d- glactopyranoside (5). Hydrogenolysis of the benzyl groups of 5 furnished the title trisaccharide (6). A similar condensation of methyl 2,3-di-O-benzyl-β-d-galactopyranoside with 1 produced a partially-protected disacchraide derivative, which, on O-deacetylation followed by hydrogenolysis, gave methyl 6-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-β-d-glactopyranoside (10). Condensation of methyl 3-O-(2-acetamido-4,6-O-benzylidene-2-deoxy-β-d-glucopyranosyl)-2,4,6-tri-O-benzyl-β-d- galactopyranoside with 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-2,4,6-tri-O-acetyl-α-d-galactopyranosyl bromide in 1:1 benzene-nitromethane in the presence of powdered mercuric cyanide gave a fully-protected tetrasaccharide derivative, which was O-deacetylated and then subjected to catalytic hydrogenation to furnish methyl O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1→3)-O-β-d-galactopyranosyl-(1å3)-O-(2-acetamido-2-deoxy- β-d-glucopyranosyl)-(1å3)-β-d-galactopyranoside (15). The structures of 6, 10, and 15 were established by ¹³C-n.m.r. spectroscopy.     

Chemical Syntheses of 4-O-α and -β-D-galactopyranosyl-D-galactose and 3-O-α- and -β-D-galactopyranosyl-D-galactose

Reaction of 2,3-di-O-acetyl-1,6-anhydro-β-D-galactopyranose (2) with 2,3,4,6-tetra- O-acetyl-α-D-galactopyranosyl bromide in the presence of mercuric cyanide and subsequent acetolysis gave 1,2,3,6-tetra-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl)-α-D-galactopyranose (4, 40%) and 1,2,3,6-tetra-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-α-D-galactopyranose (5, 30%). Similarly, reaction of 2,4-di-O-acetyl-1,6-anhydro-β-D-galactopyranose (3) gave 1,2,4,6-tetra-O-acetyl-3-O-(2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl)-α-D-galactopyranose (6, 46%) and 1,2,4,6-tetra-O-acetyl-3-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-α-D-galactopyranose (7, 14%). The anomeric configurations of 4-7 were assigned by n.m.r. spectroscopy. Deacetylation of 4-7 afforded 4-O-α-D-galactopyranosyl-D-galactose (8), 4-O-β-D-galactopyranosyl-D-galactose (9), 3-O-α-D-galactopyranosyl-D-galactose (10), and 3-O-β-D-galactopyranosyl-D-galactose (11), respectively.     

The synthesis of O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1→4)-N-acetylnormuramoyl-l-α-aminobutanoyl-d-isoglutamine

Benzyl 2-acetamido-3-O-allyl-6-O-benzyl-2-deoxy-4-O-(3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl)- α-d-glucopyranoside (4) was obtained in high yield on using the silver triflate method in the absence of base. Compound 4 was converted in six steps into benzyl 2-acetamido-4-O-(2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-β-d-glucopyranosyl)-6-O-benzyl-3-O-(carboxymethyl)-2-deoxy-α-d- glucopyranoside, which was coupled with the benzyl ester of l-α-aminobutanoyl-d-isoglutamine and the product hydrogenolyzed to afford the title compound. O-Benzylation of benzyl 2-acetamido-4-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-3-O-allyl-6-O-benzyl-2-deoxy-α-d-glucopyranoside with benzyl bromide and barium hydroxide in N,N-dimethylformamide is strongly exhanced by sonication of the reaction mixture.     

A synthesis of psi-cytidine

2-O-Benzoyl-3,6-di-O-benzyl-4-O-(chloroacetyl)-, 4-O-acetyl-2-O-benzoyl-3,6-di-O-benzyl-, and 2-O-benzoyl-3,4,6-tri-O-benzyl-α-d-galactopyranosyl chloride were converted into the corresponding 2,2,2-trifluoroethanesulfonates, and these were treated with allyl 2-O-benzoyl-3,6-di-O-benzyl-α-d-galactopyranoside, to give allyl 2-O-benzoyl-4-O-[2-O-benzoyl-3,6-di-O-benzyl-4-O-(chloroacetyl)-β-d-galactopyranosyl]-3,6-di-O-benzyl- α-d-galactopyranoside (26; 41% yield), allyl 4-O-(4-O-acetyl-2-O-benzoyl-3,6-di-O-benzyl-β-d-galactopyranosyl)-2-O-benzoyl-3,6-di-O-benzyl- α-d-galactopyranoside (27; 62% yield), and allyl 2-O-benzoyl-4-O-(2-O-benzoyl-3,4,6-tri-O-benzyl-β-d-galactopyranosyl)-3,6-di-O-benzyl-α-d-galactopyranoside (28; 65% yield). All disaccharides were free from their α anomers. Disaccharides 26 and 27 were found to be base-sensitive, and were de-esterified by KCN in aqueous ethanol, and debenzylated with H₂-Pd. Attempts to produce (1→4)-β-d-galactopyranosides from the coupling of a number of fully esterified d-galactopyranosyl sulfonates to allyl 2,3,6-tri-O-benzoyl-α-d-galactopyranoside were unsuccessful.     

Ring-opening reactions of sucrose epoxides: Synthesis of 4′-derivatives of sucrose

The 2,1′-O-isopropylidene derivative (1) of 3-O-acetyl-4,6-O-isopropylidene-α-d-glucopyranosyl 6-O-acetyl-3,4-anhydro-β-d-lyxo-hexulofuranoside and 2,3,4-tri-O-acetyl-6-O-trityl-α-d-glucopyranosyl 3,4-anhydro-1,6-di-O-trityl-β-d-lyxo-hexulofuranoside have been synthesised and 1 has been converted into 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,6-di-O-acetyl-3,4-anhydro-β-d-lyxo-hexulofuranoside (2). The S_N2 reactions of 2 with azide and chloride nucleophiles gave the corresponding 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,3,6-tri-O-acetyl-4-azido-4-deoxy-β-d-fructofuranoside (6) and 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,3,6-tri-O-acetyl-4-chloro-4-deoxy-β-d-fructofuranoside (8), respectively. The azide 6 was catalytically hydrogenated and the resulting amine was isolated as 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 4-acetamido-1,3,6-tri-O-acetyl-4-deoxy-β-d-fructofuranoside. Treatment of 5 with hydrogen bromide in glacial acetic acid followed by conventional acetylation gave 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,3,6-tri-O-acetyl-4-bromo-4-deoxy-β-d-fructofuranoside. Similar S_N2 reactions with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,6-di-O-acetyl-3,4-anhydro-β-d-ribo-hexulofuranoside (12) resulted in a number of 4′-derivatives of α-d-glucopyranosyl β-d-sorbofuranoside. The regiospecific nucleophilic substitution at position 4′ in 2 and 12 has been explained on the basis of steric and polar factors.     

Synthese der “repeating unit” der O-spezifischen kette des lipopolysaccharides aus Aeromonas salmonicida

8-Methoxycarbonyloctyl 2-azido-4,6-O-benzylidene-2-deoxy-β-d-mannopyranoside reacted with 2,3,4-tri-O-acetyl-α-l-rhamnopyranosyl bromide to give a disaccharide from the which the glycosyl-acceptor 8-methoxycarbonyloctyl 2-azido-4,6-O-benzylidene-2-deoxy-3-O-(2,4,-di-O-acetyl-α-l-rhamnopyranosyl)-β-d-manno pyranoside (19) was obtained. This glycosyl-acceptor with 2,3,4,6-tetra-O-benzyl-α-d-glucopyranosyl chloride to give trisaccharide derivative 22 and with 2,3,6-tri-O-(α-²H₂)benzyl-4-O-(2,3,4,6-tetra-O-(α-²H₂)benzyl-α-d-glucopyranosyl)-α-d-glucopyranosyl chloride to give tetrasaccharide derivative 29. Deblocking of 22 yielded 8-methoxycarbonyloctyl O-(α-d-glucopyranosyl)-(1→3)-O-α-l-rhamnopyranosyl-(1→3)-2-acetamido-2-deoxy-β-d-mannopyranoside and deblocking of 29 8-methoxycarbonyloctyle O-α-d-glucopyranosyl-(1→4)-O-α-d-glucopyranosyl-(1→3)-O-α-l-rhamnopyranosyl- (1→3)-2-acetamido-2-deoxy-β-d-mannopyranoside. Both oligosaccharides represent the “repeating unit” of the O-specific chain of the lipopolysaccharide from Aeromonas salmonicida.     

Synthèse des 2-acé-tamido-2-désoxy-6-O-α-et β-D-xylopyranosyl-α-D-glucopyranose

2-Acetamido-2- deoxy-6-O-, -xylopyranosyl-O-D-glucopyranose has been synthesized in crystalline form by condensation of 2,3,4-tri-O-acetyl-α-D-xylopyranosyl chloride (1) with benzyl 2-acetamido-3,4-di-O-acetyl-2-deoxy-β-D-glucopyranoside (2), followed by O-deacetylation and catalytic hydrogenation. Condensation of 2 with 2,3,4-tri-O-chlorosulfonyl-β-D-xylopyranosyl chloride, followed by dechlorosulfonylation and acetylation, gave benzyl 2-acetamido-3,4-di-O-acetyl-2-deoxy-6-O-(2,3,4-tri-O-acetyl-α-D-xylopyranosyl)β-D-glucopyranoside in crystalline form. O-Deacetylation, followed by catalytic hydrogenation, gave 2-acetamido-2-deoxy-6-O-α-D-xylopyranosyl-α-D-glucopyranose in crystalline form.     

The synthesis and properties of benzylated oxazolines derived from 2-acetamido-2-deoxy-D-glucose

2-Methyl-(2-acetamido-3,4,6-tri-O-benzyl-1,2-dideoxy-α-D-glucopyrano)-[2,1-d]-2-oxazoline,2-methyl-(2-acetamido-6-O-acetyl-3,4-di-O-benzyl-1,2-dideoxy-α-D-glucopyrano)-[2,1-d]-2-oxazoline,and 2-methyl-(2-acetamido-4-O-acetyl-3,6-di-O-benzyl-1,2-dideoxy-α-D-glucopyrano)-[2,1-d]-2-oxazoline were synthesized from the allyl 2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-D-glucopyranosides, and from the 3,4-di-O-benzyl or 3,6-di-O-benzyl analogs, respectively, both the α and β anomer being used in each case. The preparation of allyl 2-acetamido-3,4,6-tri-O-benzyl- and 3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside is also described. Treatment of the tri-O-benzyl oxazoline with dibenzyl phosphate gave a pentabenzylglycosyl phosphate, from which all the benzyl groups were removed by catalytic hydrogenation, giving 2-acetamido-2-deoxy-α-D-glucopyranosyl phosphate. The corresponding β anomer was not detectable. Treatment of the 3,4-, or 3,6-, di-O-benzyl oxazoline with allyl 2-acetamido-3,4-di-O-benzyl-α-D-glucopyranoside readily gave disaccharide products from which the protecting groups were removed, to give the (1→6)-linked isomer of di-N-acetylchitobiose. Under both acidic and basic conditions, this isomer was less stable than the (1→4)-linked compound.Attempts to employ the 3,6-di-O-benzyl oxazoline for the formation of (1→4)-linked disaccharides, by treatment with either anomer of allyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-D-glucopyranoside, were not very successful, presumably owing to hindrance by the bulky benzyl groups.     

Syntheses of 3-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-α-d-galactopyranose (“lacto-N-biose II”) and 3,4-di-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-d-galactopyranose

3- O-(2-Acetamido-2-deoxy-β-d-glucopyranosyl)-α-d-galactopyranose (10, “Lacto-N-biose II”) was synthesized by treatment of benzyl 6-O-allyl-2,4-di-O-benzyl-β-d-galactopyranoside with 2-methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-d-glucopyrano)[2,1-d]-2-oxazoline (5), followed by selective O-deallylation, O-deacetylation, and catalytic hydrogenolysis. Condensation of 5 with benzyl 6-O-allyl-2-O-benzyl-α-d-galactopyranoside, followed by removal of the protecting groups, gave 10 and a new, branched trisaccharide, 3,4-di-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-d-galactopyranose (27).     

Syntheses of 2-acetamido-2-deoxy-4-O-α-D-glucopyranosyl-α-d-glucopyranose (n-acetylmaltosamine) and 2-acetamido-2-deoxy-4-O-β-d-glucopyranosyl-α-d-glucopyranose

Condensation of benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-glucopyranoside with 2,3,4,6-tetra-O-benzyl-1-O-(N-methyl)acetimidoyl-β-D-glucopyranose gave benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)-α-D-glucopyranoside which was catalytically hydrogenolysed to crystalline 2-acetamido-2-deoxy-4-O-α-D-glucopyranosyl-α-D-glucopyranose (N-acetylmaltosamine). In an alternative route, the aforementioned imidate was condensed with 2-acetamido-3-O-acetyl-1,6-anhydro-2-deoxy-β-D-glucopyranose, and the resulting disaccharide was catalytically hydrogenolysed, acetylated, and acetolysed to give 2-acetamido-1,3,6-tri-O-acetyl-2-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-α-D-glucopyranose Deacetylation gave N-acetylmaltosamine. The synthesis of 2-acetamido-2-deoxy-4-O-β-D-glucopyranosyl-α-D-glucopyranose involved condensation of benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-glucopyranoside with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide in the presence of mercuric bromide, followed by deacetylation and catalytic hydrogenolysis of the condensation product.     

O-Benzylated thio sugars. Derivatives of 2,3,6-tri-O-benzyl-1-thio-d-galactopyranose suitable for use in oligosaccharide synthesis

The 4-O-benzoyl (15a) 4-O-p-nitrobenzoyl (15b) derivatives of 2,3, 6-tri-O-benzyl-1-thio-d-galactopyranose were synthesized from allyl 2,6-di-O-benzyl-α-d-galactopyranoside (1). In the first stage of the synthesis the 3-position of 1 was benzylated by an indirect route, and also by the direct reaction (preferred) of benzyl bromide with the 3,4-O-dibutylstannylene intermediate 7. The product 6 was sequentially isomerized (allyl → 1-propenyl), acylated at the 4-position, and hydrolyzed. The free sultars 11a and 11b were converted into the thio sugars by a standard sequence involving formation of the glycosyl halides 13a and 13b and the reaction of these with appropriate sulfur nucleophiles. A third derivative (29) of 2,3,6-tri-O-benzyl-1-thio-d-galactopyranose, having a 4-O-allyl protecting group, was similarly made from the corresponding normal sugar 25. The key intermediate 22, precursor to 25, was prepared by two routes from methyl 2,3,6-tri-O-benzoyl-α-d-galactopyranoside (17).     

The synthesis of 5-O-(2-acetamido-2-deoxy-α-D-glucopyranosyl)-β-D-glucofuranose

Condensation of dimeric 3,4,6-tri-O-acetyl-2-deoxy-2-nitroso-α-D-glucopyranosyl chloride (1) with 1,2-O-isopropylidene-α-D-glucofuranurono-6,3-lactone (2) gave 1,2-O-isopropylidene-5-O-(3,4,6-tri-O-acetyl-2-deoxy-2-hydroxyimino-α-D-arabino-hexopyranosyl)-α-D-glucofuranurono-6,3-lactone (3). Benzoylation of the hydroxyimino group with benzoyl cyanide in acetonitrile gave 1,2-O-isopropylidene-5-O-(3,4,6-tri-O-acetyl-2-benzoyloxyimino-2-deoxy-α-D-arabino-hexopyranosyl)-α-D-glucofuranurono-6,3-lactone (4). Compound 4 was reduced with borane in tetrahydrofuran, yielding 5-O-(2-amino-2-deoxy-α-D-glucopyranosyl)-1,2-O-isopropylidene-α-D-glucofuranose (5), which was isolated as the crystalline N-acetyl derivative (6). After removal of the isopropylidene acetal, the pure, crystalline title compound (10) was obtained.     

Synthesis of benzyl and allyl ethers of D-glucopyranose

Starting from allyl 3-O-benzyl-4,6-O-benzylidene-α-D-glucopyranoside as a key intermediate, the following crystalline compounds were prepared: 2-O-allyl-3,4,6-tri-O-benzyl-D-glucopyranose (11) and its p-nitrobenzoate; 2,3,5-tri-O-benzyl-D-arabinofuranose (12) and the corresponding arabinitol; allyl 3,4,6-tri-O-benzyl-α-D-glucopyranoside (7); 3,4,6-tri-O-benzyl-D-glucopyranose (8); 2-O-allyl-3,4-di-O-benzyl-D-glucopyranose (17) and its bis(p-nitrobenzoate); and 3,4-di-O-benzyl-D-glucopyranose (19). The p-nitrobenzoates of compounds 11 and 17 are potential intermediates for the synthesis of the glycolipids of the cytoplasmic membranes of Streptococci.