Synthesis of a hexasaccharide fragment of the O-deacetylated GXM of C. neoformans serotype B

Abstract

β- d-Xyl p-(1 → 4)-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 fragment of the exopolysaccharide from Cryptococcus neoformans serovar B, was synthesized as its methyl glycoside. Thus, acetylation of allyl 3- O-benzoyl-4,6- O-benzylidene-α- d-mannopyranoside ( 1) followed by debenzylidenation and selective 6-O-benzoylation afforded allyl 2- O-acetyl-3,6-di- O-benzoyl-α- d-mannopyranoside ( 4). Glycosylation of 4 with 2,3,4-tri- O-benzoyl- d-xylopyranosyl trichloroacetimidate ( 5) furnished the β-(1 → 4)-linked disaccharide 6. Deallylation followed by trichloroacetimidate formation gave the disaccharide donor 8, and subsequent coupling with allyl 2,3,4-tri- O-benzoyl-β- d-xylopyranosyl-(1 → 2)-4,6-di- O-benzoyl-α- d-mannopyranoside ( 9), produced the tetrasaccharide 10. Reiteration of deallylation and trichloroacetimidate formation from 10 yielded the tetrasaccharide donor 12. The downstream disaccharide acceptor 18 was obtained by condensation of 5 with methyl 3- O-acetyl-4,6- O-benzylidene-α- d-mannopyranoside, followed by debenzylidenation, benzoylation, and selective 3-O-deacetylation. Coupling of 18 with 12 afforded the hexasaccharide 19, and subsequent deprotection gave the hexasaccharide glycoside 20. Selective 2″-O-deacetylation of 19 gave the hexasaccharide acceptor 21. Condensation of 21 with glucopyranosyluronate imidate 22 did not produce the expected heptasaccharide glycoside; instead, a transacetylation product 19 was obtained. Meanwhile, there was no reaction between 21 and the bromide donor 23.