新型隐球菌B血清型O-脱乙酰化葡糖醛酸木糖甘露聚糖七糖重复单元的简便合成

Facile synthesis of the heptasaccharide repeating unit of O-deacetylated GXM of C. neoformans serotype B.

作者信息

Zhao Wei, Kong Fanzuo

机构信息

Research Center for Eco-Environmental Sciences, Academia Sinica, PO Box 2871, Beijing 100085, PR China.

出版信息

Bioorg Med Chem. 2005 Jan 3;13(1):121-30. doi: 10.1016/j.bmc.2004.09.049.

DOI:10.1016/j.bmc.2004.09.049

PMID:15582457

Abstract

A heptasaccharide, beta-D-Xylp-(1-->2)-alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->2)]-alpha-D-Manp-(1-->3)-[beta-D-GlcpA-(1-->2)][beta-D-Xylp-(1-->4)]-alpha-D-Manp, the repeating unit of the exopolysaccharide from Cryptococcus neoformans serovar B, was synthesized as its methyl glycoside. Thus 2,3,4-tri-O-benzoyl-beta-D-xylopyranosyl-(1-->2)-3,4,6-tri-O-benzoyl-alpha-d-mannopyranosyl trichloroacetimidate (7) and allyl 2,3,4-tri-O-benzoyl-beta-D-xylopyranosyl-(1-->2)-4,6-di-O-benzoyl-alpha-D-mannopyranoside (8), readily obtained from the corresponding monosaccharide derivatives via simple transformation, were coupled to give a (1-->3)-linked tetrasaccharide 9. Deallylation of 9 followed by trichloroacetimidate formation produced the tetrasaccharide donor 11. Condensation of methyl 2,3,4-tri-O-benzoyl-beta-d-xylopyranosyl-(1-->4)-2-O-acetyl-6-O-benzoyl-alpha-D-mannopyranoside (18) with 11 followed by selective deacetylation yielded hexasaccharide acceptor 20. Coupling of 20 with methyl 2,3,4-tri-O-acetyl-alpha-D-glucopyranosyluronate bromide (21) and subsequent deprotection furnished the target heptaoside. A hexasaccharide fragment, alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->2)]-alpha-D-Manp-(1-->3)-[beta-D-GlcpA-(1-->2)][beta-D-Xylp-(1-->4)]-alpha-D-Manp, was also similarly synthesized as its methyl glycoside.

摘要

一种七糖，即β-D-木糖基-(1→2)-α-D-甘露糖基-(1→3)-[β-D-木糖基-(1→2)]-α-D-甘露糖基-(1→3)-[β-D-葡萄糖醛酸基-(1→2)][β-D-木糖基-(1→4)]-α-D-甘露糖，作为新型隐球菌B血清型胞外多糖的重复单元，被合成为其甲基糖苷。因此，通过简单转化从相应的单糖衍生物容易获得的2,3,4-三-O-苯甲酰基-β-D-吡喃木糖基-(1→2)-3,4,6-三-O-苯甲酰基-α-D-甘露糖基三氯乙酰胺(7)和烯丙基2,3,4-三-O-苯甲酰基-β-D-吡喃木糖基-(1→2)-4,6-二-O-苯甲酰基-α-D-甘露糖苷(8)进行偶联，得到一个(1→3)-连接的四糖9。9脱苯甲酰基后形成三氯乙酰胺，得到四糖供体11。2,3,4-三-O-苯甲酰基-β-D-吡喃木糖基-(1→4)-2-O-乙酰基-6-O-苯甲酰基-α-D-甘露糖苷(18)与11缩合，随后进行选择性脱乙酰化，得到六糖受体20。20与甲基2,3,4-三-O-乙酰基-α-D-葡萄糖醛酸溴化物(21)偶联，随后脱保护，得到目标七糖苷。一个六糖片段，即α-D-甘露糖基-(1→3)-[β-D-木糖基-(1→2)]-α-D-甘露糖基-(1→3)-[β-D-葡萄糖醛酸基-(1→2)][β-D-木糖基-(1→4)]-α-D-甘露糖，也同样被合成为其甲基糖苷。