Concerning the Problem of Stereospecific Glycosylation. Synthesis and Methanolysis of some 2-O-Benzylated D-Galactopyranosyl and D-Galactofuranosyl Halides

Abstract

Acetolysis of 1,6-anhydro-2,3,4-tri-O-benzyl-β-D-galactopyranose (3) followed by de-O-acetylation and p-nitrobenzoylation gave 2,3,4-tri-O-benzyl-1,6-di-O-p-nitrobenzoyl-β-D-galactopyranose (4) which was converted into 2,3,4-tri-O-benzyl-6-O-p-nitrobenzoyl-α-D-galactopyranosyl bromide (5). Benzylation of methyl 4,6-O-benzylidene-α-D-galactopyranoside (6) gave the 2,3-dibenzyl ether (7) which was hydrolyzed to 2,3-di-O-benzyl-D-galactose (8). p-Nitrobenzoylation of 8 furnished 2,3-di-O-benzyl-1,5,6-tri-O-p-nitrobenzoyl-β-D-galactofuranose (9) and an isomer, presumably a β-pyranose derivative (10). Compound 9 was converted into 2,3-di-O-benzyl-5,6-di-O-p;-nitrobenzoyl-β-D-galactofuranosyl bromide (11) and chloride (12). The new halides 5, 11, and 12 as well as known 2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl bromide (1) and chloride (2) were subjected to methanolysis in dichloromethane solution in the presence of methanol alone and in the presence of tetrabutylammonium bromide, mercuric cyanide, and silver tetrafluoroborate, respectively, and the ratios of anomeric glycosides produced were examined by n.m.r. spectroscopy. Factors influencing stereoselectivity in these reactions are discussed. The new methyl α- and β-glycosides derived from 5 (13 and 14) and the methyl α-glycoside (15) produced from 11 and 12 were isolated, and methyl 2,3,5,6-tetra-O-benzyl-α-D-galactofuranoside (16) was prepared for the first time.