Chemical synthesis of the trisaccharide unit of the species-specific phenolic glycolipid from Mycobacterium leprae

Abstract

O-(3,6-di- O-methyl-β- d-glucopyranosyl)-(1→4)- O-(2,3-di- O-methyl-α- l-rhamnopyranosyl)-(1→2)-3- O-methyl- l- rhamnopyranose, the haptenic trisaccharide of the Mycobacterium leprae-specific phenolic glycolipid I (PGL-I) antigen, and related trisaccharides, were synthesized by allylation of O-2 of benzyl 4- O-benzyl-α- l-rhamnopyranoside using phase-transfer catalysis, methylation of the product, deallylation, and coupling to O-(2,4-di- O-acetyl-3,6-di- O-methyl-β- d-glucopyranosyl)-(1→4)-2,3-di- O-methyl- l-rhamnopyranosyl bromide or related disaccharides. Anomeric mixtures of the trisaccharide derivatives were separated by preparative t.l.c., deacetylated, and hydrogenolyzed, to give the pure trisaccharides. It had already been demonstrated that only those trisaccharides containing an intact, terminal 3,6-di- O-methyl-β- d-glucopyranosyl unit are effective in inhibiting the specific binding between PGL-I and unit-PGL-I immunoglobulin M antibodies in human lepromatous leprosy sera.