Acetal migration during glycosylations catalyzed by mercuric cyanide: Synthesis of p-nitrophenyl 6- O-β- d-galactopyranosyl-β- d-galactopyranoside

Abstract

Isopropylidenation of p-nitrophenyl β- d-galactopyranoside under kinetic control afforded the 4,6-acetal ( 2). The structure of 2 was established by 1H- and 13C-n.m.r. spectroscopy, and confirmed by methylation, and hydrolysis to 2,3-di- O-methyl- d-galactose. Selective benzoylation of 2 with benzoyl chloride in pyridine afforded the 3- O-benzoyl derivative 3. Isomerization of 3 in a phase-transfer type of reaction gave a mixture of 3 and its 2- O-benzoyl isomer 4. Glycosidation of 4 (catalyzed by mercuric cyanide) with 2,3,4,6-tetra- O-acetyl-α- d-galactopyranosyl bromide ( 7) gave a crystalline disaccharide derivative ( 8). O-Deacylation of 8 furnished the disaccharide acetal ( 9). The 13C-n.m.r. spectrum of 9 revealed the presence of a 3,4-acetal, indicating that neither 9 nor 8 was a (1→3)-linked disaccharide derivative. Deacetylation of 9 afforded p-nitrophenyl 6- O-β- d-galactopyranosyl-β- d-galactopyranoside ( 10). The (1→6) linkage in 10 was established by permethylation, and hydrolysis to 2,3,4-tri- O-methyl- d-galactose. Compound 10 was converted into the crystalline 2-benzoate ( 11) of its 3,4,2′,3′,4′,6′-hexaacetate, and 11 afforded the amorphous 2,3,4,2′,3′,4′,6′-heptaacetate. The disaccharide 10 was also synthesized by condensation of the bromide 7 with p-nitrophenyl 2,3-di- O-acetyl-β- d-galactopyranoside ( 6), followed by O-deacetylation; compound 6 was obtained from 2 by way of the crystalline 4,6-acetal 2,3-diacetate.