Synthesis of a hexasaccharide, the repeating unit of O-deacetylated GXM of C. neoformans serotype A

Abstract

β- d-Glc pA-(1→2)-α- d-Man p-(1→3)-[β- d-Xyl p-(1→2)]-α- d-Man p-(1→3)[-β- d-Xyl p-(1→2)]-α- d-Man p, the repeating unit of the exopolysaccharide from Cryptococcus neoformans serovar A, was synthesized as its allyl glycoside. Thus, 3-O-selective acetylation of allyl 4,6- O-benzylidene-α- d-mannopyranoside afforded 2, and subsequent glycosylation of 2 with 2,3,4-tri- O-benzoyl- d-xylopyranosyl trichloroacetimidate furnished the β-(1→2)-linked disaccharide 4. Debenzylidenation followed by benzoylation gave allyl 2,3,4-tri- O-benzoyl-β- d-xylopyranosyl-(1→2)-3- O-acetyl-4,6-di- O-benzoyl-α- d-mannopyranoside ( 5), and selective 3-O-deacetylation gave the disaccharide acceptor 6. Coupling of 6 with 2- O-acetyl-3,4,6-tri- O-benzoyl-α- d-mannopyranosyl trichloroacetimidate yielded the trisaccharide 8, and subsequent deallylation and trichloroacetimidation gave 2,3,4-tri- O-benzoyl-β- d-xylopyranosyl-(1→2)-[2- O-acetyl-3,4,6-tri- O-benzoyl-α- d-mannopyranosyl-(1→3)]-4,6-di- O-benzoyl-α- d-mannopyranosyl trichloroacetimidate ( 9). Condensation of the trisaccharide donor 9 with the disaccharide acceptor 6 gave the pentasaccharide 10 whose 2-O-deacetylation gave the acceptor 11. Glycosylation of 11 with methyl 2,3,4-tri- O-acetyl-α- d-glucopyranosyluronate trichloroacetimidate and subsequent deprotection gave the target hexasaccharide.