Synthesis of 2-acetamido-2-deoxy-5-thio-d-glucopyranose

2-Acetamido-2-deoxy-5-thio-d-glucopyranose (12) has been synthesized from methyl 2-acetamido-2-deoxy-5,6-O-isopropylidene-β-d-glucofuranoside (1). Benzoylation of 1, followed by O-deisopropylidenation, gave methyl 2-acetamido-3-O-benzoyl-2-deoxy-β-d-glucofuranoside, which was converted, via selective benzoylation and mesylation, into methyl 2-acetamido-3,6-di-O-benzoyl-2-deoxy-5-O-mesyl-β-d-glucofuranoside (5). Treatment of 6, formed by the action of sodium methoxide in chloroform on 5, with thiourea gave methyl 2-acetamido-2,5,6-trideoxy-5,6-epithio-β-d-glucofuranoside (7), which was converted into the 5-thio compound 9 by cleavage of the epithio ring in 7 with potassium acetate. Alkaline treatment of 10, derived from 9 by hydrolysis, afforded the title compound. Evidence in support of the structures assigned to the new derivatives is presented.     

The synthesis of oligosaccharide-asparagine compounds. V. O- -D-mannopyranosyl-(1 leads to 6)-O-(2-acetamido-2-deoxy- -D-glucopyranosyl)-(1 leads to 4)-2-acetamido-N-(L-aspart-4-oyl)-2-deoxy- -D-glucopyranosylamine

O-α-d-Mannopyranosyl-(1→6)-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1→4)-2-acetamido-N-(l-aspart-4-oyl)-2-deoxy-β-d-glucopyranosylamine (12), used in the synthesis of glycopeptides and as a reference compound in the structure elucidation of glycoproteins, was synthesized via condensation of 2,3,4,6-tetra-O-acetyl-α-d-mannopyranosyl bromide with 2-acetamido-4-O-(2-acetamido-3-O-acetyl-2-deoxy-β-d-glucopyranosyl)-3,6-di-O-acetyl-2-deoxy-β-d-glucopyranosyl azide (5) to give the intermediate, trisaccharide azide 7. [Compound 5 was obtained from the known 2-acetamido-4-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-3,6-di-O-acetyl-2-deoxy-β-d-glucopyranosyl azide by de-O-acetylation, condensation with benzaldehyde, acetylation, and removal of the benzylidene group.] The trisaccharide azide 6 was then acetylated, and the acetate reduced in the presence of Adams' catalyst. The resulting amine was condensed with 1-benzyl N-(benzyloxycarbonyl)-l-aspartate, and the O-acetyl, N-(benzyloxycarbonyl), and benzyl protective groups were removed, to give the title compound.     

The linkage of 4-O-methyl-L-galactose in the sulphated polysaccharide of Aeodes ulvoidea

Methyl 2-acetamido-5,6-di-O-benzyl-2-deoxy-β-d-glucofuranoside (11) was obtained in six steps from the known methyl 3-O-allyl-2-benzamido-2-deoxy-5,6-O-isopropylidene-β-d-glucofuranoside. Mild acid hydrolysis, followed by benzylation gave the 5,6-dibenzyl ether. The benzamido group was exchanged for an acetamido group by strong alkaline hydrolysis, followed by N-acetylation, and the allyl group was isomerized into a 1-propenyl group that was hydrolyzed with mercuric chloride. Treatment of 11 with l-α-chloropropionic acid and with diazomethabe gave methyl 2-acetamido-5,6-di-O-benzyl-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-β-d-glucofuranoside which formed on mercaptolysis the internal ester 16, further converted into 2-acetamido-4-O-acetyl-5,6-di-O-benzyl-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-d-glucose diethyl dithioacetal (18) by alkaline treatment followed by esterification with diazomethane and acetylation. Attempts to remove the O-acetyl group of the corresponding dimethyl acetal 20 with sodium methoxide in mild conditions were not successful.     

Synthesis of a 2-acetamido-5-amino-2,5-dideoxy-d-xylopyranosyl derivative

2-Acetamido-5-amino-2,5-dideoxy-d-xylopyranosyl hydrogensulfite (11) has been synthesized from benzyl 2-(benzyloxycarbonylamino)-2-deoxy-5,6-O-isopro-pylidene-β-d-glucofuranoside (1). O-Deisopropylidenation of 1 gave the triol 2, which was converted, via oxidative cleavage at C-5-C-6 and subsequent reduction, into the related benzyl β-d-xylofuranoside derivative (3). Catalytic reduction of benzyl 2-(benzyloxycarbonylamino)-2-deoxy-5-O-tosyl-β-d-xylofuranoside, derived from 3 by selective tosylation, and subsequent N-acetylation, afforded benzyl 2-acetamido-2-deoxy-5-O-tosyl-β-d-xylofuranoside, which was treated with sodium azide to give the corresponding 5-azido derivative (6). (Tetrahydropyran-2-yl)ation of the product formed by hydrolysis of 6 gave 2-acetamido-5-azido-2,5-dideoxy-1,3- di-O-(tetrahydropyran-2-yl)-d-xylofuranose (9). Treatment of 2-acetamido-5-amino-2,5-dideoxy-1,3-di-O-(tetrahydropyran-2-yl)-d-xylofuranose, derived from 9 by reduction, with sulfur dioxide in water gave 11. Hydrogenation of 6 and subsequent acetylation yielded 3-acetamido-4,5-diacetoxy-1-acetyl-xylo-piperidine. Evidence in support of the structures assigned to the new derivatives is presented.     

Synthesis and biological activity of O-(N-acetyl-β-muramoyl-l-alanyl-d-isoglutamine)-(1→6)-2-acylamino-2-deoxy-d-glucoses

Benzoylation of benzyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-α-d-glucopyranoside, benzyl 2-deoxy-2-(dl-3-hydroxytetradecanoylamino)-4,6-O-isopropylidene-α-d-glucopyranoside, and benzyl 2-deoxy-4,6-O-isopropylidene-2-octadecanoylamino-β-d-glucopyranoside, with subsequent hydrolysis of the 4,6-O-isopropylidene group, gave the corresponding 3-O-benzoyl derivatives (4, 5, and 7). Hydrogenation of benzyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-α-d-glucopyranoside, followed by chlorination, gave a product that was treated with mercuric actate to yield 2-acetamido-1,4,6-tri-O-acetyl-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-β-d-glucopyranose (11). Treatment of 11 with ferric chloride afforded the oxazoline derivative, which was condensed with 4, 5, and 7 to give the (1→6)-β-linked disaccharide derivatives 13, 15, and 17. Hydrolysis of the methyl ester group in the compounds derived from 13, 15, and 17 by 4-O-acetylation gave the corresponding free acids, which were coupled with l-alanyl-d-isoglutamine benzyl ester, to yield the dipeptide derivatives 19–21 in excellent yields. Hydrolysis of 19–21, followed by hydrogenation, gave the respective O-(N-acetyl-β-muramoyl-l-alanyl-d-isoglutamine)-(1→6)-2-acylamino-2-deoxy-d-glucoses in good yields. The immunoadjuvant activity of these compounds was examined in guinea-pigs.     

Synthesis of 2,6-di(acylamino)-2,6-dideoxy-3-O-(d-2-propanoyl-l-alanyl-d-isoglutamine)-d-glucopyranoses

Five 2,6-di(acylamino)-2,6-dideoxy-3-O-(d-2-propanoyl-l-alanyl-d-isoglutamine)-d-glucopyranoses (lipophilic, muramoyl dipeptide analogs) were synthesized from benzyl 2-(benzyloxycarbonylamino)-3-O-(d-1-carboxyethyl)-2-deoxy-5,6-O-isopropylidene-β-dglucopyranoside (1). Methanesulfonylation of 3, derived from the methyl ester of 1 by O-deisopropylidenation, gave the 6-methanesulfonate (4). (Tetrahydropyran-2-yl)ation of 4 gave benzyl 2-(benzyloxycarbonylamino)-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-6-O-(methylsulfonyl)-5-O-(tetrahydropyran-2-yl)-β-d- glucofuranoside, which was treated with sodium azide to give the corresponding 6-azido derivative (6). Condensation of benzyl 6-amino-2-(benzyloxycarbonyl-amino)-2,6-dideoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-5-O-(tetrahydropyran-2-yl)-β-d-glucofuranoside, derived from 6 by reduction, with the activated esters of octanoic, hexadecanoic, and eicosanoic acid gave the corresponding 6-N-fatty acyl derivatives (8–10). Coupling of the 2-amino derivatives, obtained from compounds 8, 9, and 10 by catalytic reduction, with the activated esters of the fatty acids, gave the 2,6-(diacylamino)-2,6-dideoxy derivatives (11–15). Condensation of the acids, formed from 11–15 by de-esterification, with the benzyl ester of l-alanyl-d-isoglutamine, and subsequent hydrolysis, afforded benzyl 2,6-di(acylamino)-2,6-dideoxy-3-O-(d-2-propanoyl-l-alanyl-d-isoglutamine benzyl ester)-β-d-glucofuranosides. Hydrogenation of the dipeptide derivatives thus obtained gave the five lipophilic analogs of 6-amino-6-deoxymuramoyl dipeptide, respectively, in good yields.     

The attachment of poly(ribitol phosphate) to lipoteichoic acid carrier

2-Acetamido-3,4,6-tri-O-acetyl-1-N-[N-(benzyloxycarbonyl)-L-aspart-1-oyl-(L-leucyl-L-threonyl-N²-tosyl-L-lysine p-nitrobenzyl ester)-4-oyl]-2-deoxy-β-D-glucopyranosylamine (21) and 2-acetamido-3,4,6-tri-O-acetyl-1-N-[N-(benzyloxycarbonyl)-L-aspart-1-oyl-(L-leucyl-L-threonyl-N²-tosyl-L-lysine p-nitrobenzyl ester)-4-oyl]-2-deoxy-β-D-glucopyranosylamine (22), 2-acetamido-3,4,6-tri-O-acetyl-1-N-[N-(benzyloxycarbonyl)-L-aspart-1-oyl-(glycine ethyl ester)-4-oyl]-2-deoxy-β-D-glucopyranosylamine, and 2-acetamido-3,4,6-tri-O-acetyl-1-N-[N-(benzyloxycarbonyl)-L-aspart-1-oyl-(phenylalanine methyl ester)-4-oyl]-2-deoxy-β-D-glucopyranosylamine were synthesized by condensation of 2-acetamido-3,4,6-tri-O-acetyl-1-N-[N-(benzyloxycarbonyl)-L-aspart-4-oyl]-2-deoxy-β-D-glucopyranosylamine with the appropriate protected amino acids and tri- and tetra-peptides. The amino acid sequences of 21 and 22 correspond to the protected amino acid sequences 34–37 and 34–38 of ribonuclease B that are adjacent to the carbohydrate-protein linkage.     

Glycosidation at C-4 of 2-acetamido-2-deoxy-D-glucopyranose derivatives by koenigs-knorr type condensations

The condensation of 2,3,4,6-tetra-O-benzyl-D-glucopyranosyl bromide and 2,3,4,6-tetra-O-benzyl-D-mannopyranosyl chloride with benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-glucopyranoside (1), under Koenigs-Knorr conditions, gave the fully benzylated derivatives of benzyl 2-acetamido-2-deoxy-4-O-α-D-glucopyranosyl-α-D-glucopyranoside, benzyl 2-acetamido-2-deoxy-4-O-β-D-glucopyranosyl-α-D-glucopyranoside, and benzyl 2-acetamido-2-deoxy-4-O-α-D-mannopyranosyl-α-D-glucopyranoside. Three further compounds, namely, benzyl 2-acetamido-3-O-benzyl-2-deoxy-6-O-(2,3,4,6-tetra-O-benzyl-D-glucopyranosyl)-α-D-glucopyranoside, benzyl 2-acetamido-3-O-benzyl-2-deoxy-6-O-(2,3,4,6-tetra-O-benzyl-D)-mannopyranosyl)-α-D-glucopyranoside, and benzyl 2-acetamido-3-O-benzyl-2-deoxy-4,6-di-O-(2,3,4,6-tetra-O-benzyl-D-mannopyranosyl)-α-D-glucopyranoside, were formed by reaction of the respective glycosyl halide with benzyl 2-acetamido-3-O-benzyl-2-deoxy-α-D-glucopyranoside present as contaminant in 1.     

The relationship of molecular weight, and sulfate content and distribution to anticoagulant activity of heparin preparations

The crystalline intermediate 2-acetamido-6-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-3,4-di-O-acetyl-2-deoxy-β-D-glucopyranosyl azide (5), obtained by condensation of 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl bromide with either 2-acetamido-3,4-di-O-acetyl-2-deoxy-β-D-glucopyranosyl azide or its 6-O-triphenylmethyl derivative, was reduced in the presence of Adams' catalyst to give a disaccharide amine. Condensation with 1-benzyl N-(benzyloxycarbonyl)-L-aspartate afforded crystalline 2-acetamido-6-O-(2-acetamido-3,4 6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-3,4-di-O-acetyl-1-N-[1-benzyl N-(benzyloxycarbonyl)-L-aspart-4-oyl]-2-deoxy-β-D-glucopyranosylamine (9). Catalytic hydrogenation in the presence of palladium-on-charcoal was followed by saponification to give 2-acetamido-6-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-1-N-(L-aspart-4-oyl)-2-deoxy-β-D-glucopyranosylamine (11) in crystalline form. From the mother liquors of the reduction of 5, a further crystalline product was isolated, to which was assigned a bisglycosylamine structure (12).     

Preparation of glycosides of 2-deoxy-2-methylamino-D-mannose, 2-deoxy-2-methylamino-D-glucose,and 2-deoxy-2-methylamino-D-galactose: observations on N-methylation of amides

Benzyl 2-[(benzyloxycarbonyl)methylamino]-2-deoxy-α-D-mannopyranoside (10) and its furanose isomer (9), the derived N-methyloxazolidinones 11 and 6, benzyl 2-[(benzyloxycarbonyl)methylamino]-2-deoxy-β-D-glucofuranoside (15) and methyl 2-deoxy-2-methylacetamido-β-D-galactofuranoside (20), were prepared from appropriate diethyl dithioacetals. They were considered the most suitable starting materials for synthesis of O-methyl-2-deoxy-2-methylamino-hexoses because of their ease of preparation and the presence of suitable blocking groups. Oxazolidinones were prepared from N-benzyloxycarbonyl derivatives of 2-amino-2-deoxy-D-mannose by using methanolic sodium methoxide. Their use in preparation of 2-deoxy-2-methyl-amino derivatives is discussed. The Kuhn reagent was used in these syntheses for N-methylating amides. However, certain amides containing comparatively bulky substituents in the vicinity of the NH group are resistant to methylation.     

Chemical modification of the carbohydrate moiety in N-acetylmuramoyl-l-alanyl-d-isoglutamine,and the immunoadjuvant activity

Five carbohydrate analogs of N-acetylmuramoyl-l-alanyl-d-isoglutamine have been synthesized from benzyl 2-acetamido-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-α-d-glucopyranoside (1) and the corresponding 6-O-benzoyl derivative (2). Chlorination of 1 and 2 with triphenylphosphine in carbon tetrachloride gave the 4,6-dichloro compound 3 and the 6-O-benzoyl-4-chloro compound (4), which were treated with tributyltin hydride, to yield benzyl 2-acetamido-2,4,6-trideoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-α-d-xylo-hexopyranoside (6) and benzyl 2-acetamido-6-O-benzoyl-2,4-dideoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-α-d-xylo-hexopyranoside (7), respectively. Methanesulfonylation of 8, derived from 7 by debenzoylation, gave the 6-methanesulfonate, which underwent displacement with azide ion to afford benzyl 2-acetamido-6-azido-2,4,6-trideoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-α-d-xylo-hexopyranoside (10). Hydrolysis of the methyl ester group in compounds 3, 5 (debenzoylated 4), 6, 8, and 10 gave the corresponding free acids, which were coupled with l-alanyl-d-isoglutamine benzyl ester, to yield the dipeptide derivatives in excellent yields. Hydrogenation of the dipeptide derivatives thus obtained gave the five carbohydrate analogs of N-acetylmuramoyl-l-alanyl-d-isoglutamine, respectively, in good yields. The immunoadjuvant activity of the N-acetylmuramoyl-dipeptide analogs was examined.     

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.     

2-β-d-ribofuranosylbenzoxazole from 2,5-anhydro-d-allonoimidate,and 1,3-dimethyl-8-β-d-ribofuranosylxanthine from 2,5-anhydro-d-allono-thioimidates and -dithioates

The ability of imidates, thioimidates, and dithioates to react with o-aminophenol (2) and 5,6-diamino-1,3-dimethyluracil (6) was studied, using non-saccharide model compounds, as well as saccharide derivatives. All of the model compounds gave 2-methylbenzoxazole, but only ethyl dithioacetate gave a purine derivative with 6. Methyl 2,5-anhydro-d-allonoimidate hydrochloride reacted with 2 to yield 2-β-d-ribofuranosylbenzoxazole, but failed to react with compound 6. On reaction with compound 6 such fully acylated thioimidates as ethyl and benzyl 2,5-anhydrotri-O-benzoyl- or tri-O-p-toluoyl-d-allonothiomidate hydrochloride yielded amidines that underwent aromatization of the furanose ring. Such monoacylated thioimidates as ethyl or benzyl 2,5-anhydro-6-O-benzoyl--d-allonothioimidate hydrochloride yielded, with compound 6, 8-(5-O-benzoyl-β-d-ribofuranosyl)-1,3-dimethylxanthine, without aromatization. Such dithioates as benzyl 2,5-anhydro-6-O-benzoyl-d-allonodithioate and ethyl 2,5-anhydrotri-O-benzoyl-d-allonodithioate were obtained by treating the corresponding thioimidate with H₂S in pyridine. With compound 6, the first yielded 8-(5-O-benzoyl-β-d-ribofuranosyl)-1,3-dimethylxanthine, which afforded the free C-nucleoside 1,3-dimethyl-8-β-d-ribofuranosylxanthine on treatment with methanolic ammonia.     

Synthesis of glycopeptides containing the amino acid sequence 17-23 of bovine pancreatic deoyxribonuclease

2-Acetamino-3,4,6-tri-O-acetly-1-N-[N-(benzyloxycarbonly-l-seryl)-l-aspart-1-oyl-(p-nitrobenzyl ester)-4-oyl]-2-deoxy-β-d-glucopyranosylamine,2-acetamido-3,4,6-tri,O-acetyl-1-N-[N-(benzyloxycarbonyl-l-seryl)-l-aspart-1-oyl-(l-alanine methyl ester)-4-oyl]-2-deoxy-β-d-glucopyranosylamine, and 2-acetamido-3,4,6-tri-O-acetyl-1-N-[N-benzyloxycarbonyl)-l-aspart-1-oyl-(l-alanyl-l-threonyl-l-leucyl-l-alanyl-l-serine p-nitrobenzyl ester)-4-oyl]-2-deoxy-β-d-glucopyranosylamine (7), which span the amino acid sequence 17-23 of bovine pancreatic deoxyribonuclease A and contain a 2-acetamido-2-deoxy-d-glucose residue, were synthesized. On treatment with lithium hydroxide, the blocked glycohexapeptide 7 gave 2-acetamido-1-N-[N-(benzyloxycarbonyl)-l-aspart-1-oyl-(l-alanyl-l-threonyl-l-leucyl-l-alanyl-l-serine)-4-oyl]-2 deoxy-β-d-glucopyranosylamine.     

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 2,4-diacetamido-2,4,6-trideoxy-L-altrose, -L-idose, and -L-talose from benzyl 6-deoxy-3,4-O-isopropylidene-beta-L-galactopyranoside

Acetylation of benzyl 6-deoxy-3,4O-isopropylidene-β-L-galactopyranoside gave benzyl 2-O-acetyl-6-deoxy-3,4-O-isopropylidene-β-L-galactopyranoside (1). Removal of the isopropylidene group afforded benzyl 2-O-acetyl-6-deoxy-β-L-galactopyranoside (2), which was converted into benzyl 2-O-acetyl-6-deoxy-3,4-di-O-(methyl-sulfonyl)-β-L-galactopyranoside (3). Benzyl 2,3-anhydro-6-deoxy-4-O-(methyl-sulfonyl)-β-L-gulopyranoside (4) was obtained from 3 by treatment with alkali. Reaction of 4 with sodium azide in N,N-dimethylformamide gave a mixture of two isomeric benzyl 2,4-diazido-2,4,6-trideoxy hexoses, the syrupy diazido derivative 5 and the crystalline benzyl 2,4-diazido-2,4,6-trideoxy-β-L-idopyranoside (6). Acetylation of 6 afforded a compound whose n.m.r. spectrum was completely first order and in agreement with the structure of benzyl 3-O-acetyl-2,4-diazido-2,4,6-trideoxy-β-L-idopyranoside (7). Lithium aluminium hydride reduction of 5, followed by acetylation, afforded a crystalline product (8), shown by n.m.r. spectroscopy to be benzyl 2,4-diacetamido-3-O-acetyl-2,4,6-trideoxy-β-L-altropyranoside. Similar treatment of the diazido derivative 6 afforded benzyl 2,4-diacetamido-3-O-acetyl-2,4,6-trideoxy-β-L-idopyranoside (9). Compounds 8 and 9 could also be obtained from 4 by treatment of the crude diazido mixture with lithium aluminium hydride, with subsequent N-acetylation. The syrupy benzyl 2,4-diacetamido-2,4,6-trideoxy-β-L-altropyranoside (10) and the crystalline benzyl 2,4-diacetamido-2,4,6-trideoxy-β-L-idopyranoside (11) thus obtained were then O-acetylated to give 8 and 9 respectively. Benzyl 2,4-diacetamido-2,4,6-trideoxy-β-L-talopyranoside (15) was obtained from 11 by treatment with methanesulfonyl chloride and subsequent solvolysis. Compound 15 was O-acetylated to yield benzyl 2,4-diacetamido-3-O-acetyl-2,4,6-trideoxy-β-L-talopyranoside (16). the n.m.r. spectrum of which was in full agreement with the assigned structure. The mass spectra of compounds 8–11, 15, and 16 were also in agreement with their proposed structures. Removal of the benzyl groups from 10, 11 and 15 afforded the corresponding 2,4-diacetamido-2,4,6-trideoxyhexoses 12, 13, and 17, having the L-altro, L-ido, and L-talo configurations, respectively.     

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).     

Synthesis of 5-O-β-D-galactofuranosyl-D-galactofuranose

Conversion of benzyl αβ-D-galactofuranoside into the 5,6-O-[α-(dimethyl-amino)benzylidene] derivative, followed by acetylation of HO-2 and HO-3, and selective ring opening or the acetal, gave benzyl 2,3-di-O-acetyl-6-O-benzoyl-αβ-D-galactofuranoside(4). The title disaccharide was synthesised from4 by reaction with 3,4,6-tri-O-acetyl-α-D-galactofuranose 1,2-(methyl orthoacetate) followed by removal of protecting groups     

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.     

Sucrochemistry : Part X. 1′,4,6′-tri-O-mesylsucrose penta-acetate: A comparison of the reactivity at the 4 and 1′ positions

The 1′,4,6′-trisulphonate 2, obtained by mesylation of sucrose 2,3,3′,4′,6-penta-acetate (1), undergoes nucleophilic substitution with sodium benzoate in hexamethylphosphoric triamide at positions 1′,4, and 6′ to give 1,6-di-O-benzoyl-β-D-fructofuranosyl 4-O-benzoyl-α-D-galactopyranoside penta-acetate (3), and selectively at positions 4 and 6′ to give 6-O-benzoyl-1-O-mesyl-β-D-fructofuranosyl 4-O-benzoyl-α-D-galactopyranoside penta-acetate (4). The products 3 and 4 were identified from their ¹H-n.m.r. spectra and by O-deacylation to give β-D-fructofuranosyl α-D-galactopyranoside (5) and its 1-methanesulphonate 6, respectively. Treatment of the trisulphonate 2 with sodium azide gave analogous products, namely, 1,6-diazido-1,6-dideoxy-β-D-fructofuranosyl 4-azido-4-deoxy-α-D-galactopyranoside penta-acetate (8) and 6-azido-6-deoxy-1-O-mesyl-β-D-fructofuranosyl 4-azido-4-deoxy-α-D-galactopyranoside penta-acetate (7).