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

β-d-Xylp-(1 → 4)-α-d-Manp-(1 → 3)-[β-d-Xylp-(1 → 2)]-α-d-Manp-(1 → 3)-[β-d-Xylp-(1 → 2)]-α-d-Manp, 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.