Joseph J. Barlow

Synthesis of p-nitrobenzyl and p-nitrophenyl 1-trioglycopyranosides☆☆☆

Reaction of 2,3,4-trio-O-acetyl-alpha-L-fucopyranosyl bromide (1) with thiourea (2), followed by reductive cleavage of the product, gave 2,3,4-tri-O-acetyl-1-thio-beta-L-fucopyranose (4). Reaction of 4 with p-nitrobenzyl bromide followed by O-deacylation yielded p-nitrobenzyl 1-thio-beta-L-fucopyranoside (6). Similar reaction conditions were used for the synthesis of p-nitrobenzyl 1-thio-beta-D-fucopyranoside (11) and 1-thio-alpha-D-mannopyranoside (16). A facile preparation of O-acylated p-nitrophenyl 1-thioglycopyranosides was achieved by condensing the appropriate glycosyl halide with sodium p-nitrobenzenethioxide in N,N-dimethylformamide.

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.

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.

Synthesis of p-nitrophenyl 2-acetamido-2-deoxy-O-β-Dgalactopyranosyl-β-D-glucopyranosides

Abstract Reaction of p -nitrophenyl 2-acetamido-2-deoxy-4,6- O -( p -methoxybenzylidene)-β- D -glucopyranoside ( 2 ) with 2,3,4,6-tetra- O -acetyl-α- D -galactopyranosyl bromide ( 3 ) under the usual conditions, followed by removal of the p -methoxybenzylidene group and O -deacylation, produced crystalline p -nitrophenyl 2-acetamido-2-deoxy-3- O -β- D -galactopyranosyl-β- D -glucopyranoside ( 6 ). Starting from p -nitrophenyl 2-acetamido 3,4-di- O -acetyl-2-deoxy-β- D -glucopyranoside, the synthesis of p -nitrophenyl 2-acetamido-2-deoxy-6-O-β- D -galactopyranosyl-β- D -glucopyranoside was also accomplished.

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 p-nitrophenyl 6-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-β-d-galactopyranoside and p-nitrophenyl O-β-d-galactopyranosyl-(1→3)-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1→6)-β-d-galactopyranoside

Abstract Condensation of 2-methyl-(3,4,6-tri- O -acetyl-1,2-dideoxy-α- d -glucopyrano)-[2′,1′:4,5]-2-oxazoline with p -nitrophenyl 2,3-di- O -acetyl-β- d -galactopyranoside ( 4 ), followed by saponification of the resulting disaccharide derivative, produced p -nitrophenyl 6- O -(2-acetamido-2-deoxy-β- d -glucopyranosyl)-β- d -galactopyranoside as a crystalline compound. Reaction of 2-methyl-[4,6-di- O -acetyl-1,2-dideoxy-3- O -(2,3,4,6-tetra- O -acetyl-β- d -galactopyranosyl)-α- d -glucopyrano]-[2′,1′:4,5]-2- oxazoline with 4 in a similar reaction-sequence provided the title trisaccharide compound.

Synthesis of p-nitrophenyl 2-acetamido-2-deoxy-3-O-β-D-galactopyranosyl-D-galactopyranosides

Abstract Reaction of 2,3,4,6-tetra- O -acetyl-α- D -galactopyranosyl bromide ( 5 ) with p -nitrophenyl 2-acetamido-2-deoxy-4,6- O -( p -methoxybenzylidene)-α- D -galactopyranoside ( 3 ) under the usual conditions, followed by removal of the p -methoxybenzylidene group and O -deacylation, gave crystalline p -nitrophenyl 2-acetamido-2- deoxy-3- O -β- D -galactopyranosyl-α- D -galactopyranoside ( 10 ). The synthesis of p -nitrophenyl 2-acetamido-2-deoxy-3- O -β- D -galactopyranosyl-β- D -galactopyranoside ( 11 ) has also been accomplished by a similar reaction-sequence.

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.

Rapid procedures for determination of endo-N-acetyl-α-d-galactosaminidase in clostridium perfringens, and of the substrate specificity of exo-β-d-galactosidases☆☆☆

Abstract Culture fluid of Clostridium perfringens hydrolyzed the synthetic, chromogenic substrates, β-Gal-(1→3)-α-GalNAc-1→OPh and, β-Gal-(1→3)-α-GalNAc-1→OC 6 H 4 -NO 2 - o or -p to β-Gal-(1→3)-GalNAc and the aglycon. Such assays facilitated the characterization and purification of this endo- N-acetyl-α - d -galactosaminidase activity. This activity was purified 1200-fold by fractionation with ammonium sulfate and chromatography on columns of Sephadex-G200, DEAE-Sephadex, and hydroxylapatite. The final preparation showed activity over a broad range of pH, with an optimum at 9.0, but less-pure material had two pH optima, 4.0 and 9.0. Another assay method, which employed the synthetic, chromogenic substrates β-Gal-(1→3)-β-GlcNAc-1→-OC 6 H 4 NO 2 - p , β-Gal-(1→4)-β-GlcNAc-1→OC 6 H 4 NO 2 - p , and β-Gal-(1→6)-β-GlcNAc-1-OC 6 H 4 NO 2 - p , was developed for the rapid identification of the linkage specificity of exo-β- d -galactosidases from any source via a coupled reaction with N -acetyl-β- d -hexosaminidase.

Synthesis of O-α-l-fucopyranosyl-(1→2)-O-β-d-galactopyranosyl-(1→4)-d-glucopyranose (2′-O-α-l-fucopyranosyl-lactose)

Abstract Selective benzoylation of 2,3:5,6:3′,4′-tri- O -isopropylidenelactose dimethyl acetal ( 1 ) with benzoyl chloride in dichloromethane afforded the 6′- O -benzoyl derivative ( 2 ). The constitution of 2 was inferred from its n.m.r. spectrum, and confirmed by methylation and subsequent hydrolysis to 2- O -methyl- d -galactose and d -glucose. Glycosidation of 2 (catalyzed by bromide ion) with 2,3,4-tri- O -benzyl-α- l -fucopyranosyl bromide gave the 2′- O -linked, fully protected trisaccharide ( 9 ). O -Debenzoylation of 9 , followed by deacetalation, furnished the tri- O -benzyl trisaccharide ( 11 ). Subsequent hydrogenolysis of the benzyl groups of 11 afforded the title trisaccharide. The acetal 1 was converted into a monoacetate and a dibenzoate, and a simple synthesis of 2′- O -methyl-lactose, starting from 1 , is also described.