霍氏毕赤酵母（汉逊酵母）NRRL Y - 2448细胞外磷酸化甘露聚糖中磷酸化二糖成分的合成

The synthesis of phosphorylated disaccharide components of the extracellular phosphomannan of Pichia (Hansenula) holstii NRRL Y-2448.

作者信息

Fairweather Jon K, Karoli Tomislav, Ferro Vito

机构信息

Drug Design Group, Progen Industries Ltd, 2806 Ipswich Road, Darra, Queensland 4076, Australia.

出版信息

Bioorg Med Chem. 2004 Dec 1;12(23):6063-75. doi: 10.1016/j.bmc.2004.09.005.

DOI:10.1016/j.bmc.2004.09.005

PMID:15519152

Abstract

Methods for the stereoselective synthesis of alpha-(1-->2)- and alpha-(1-->3)-linked 6(II)-O-phosphomannobiosides were developed. Two strategies were successfully employed: a D-mannosyl acceptor was coupled with a phosphorylated D-mannosyl trichloroacetimidate donor, or alternatively with a differentially 6-O-protected D-mannosyl trichloroacetimidate donor which, after glycosylation, was selectively deprotected and phosphorylated. Two target phosphomannobiosides intended for use in SAR studies of the antiangiogenic drug candidate PI-88, 2-O-(6-O-phospho-alpha-D-mannopyranosyl)-D-mannopyranose and methyl 3-O-(6-O-phospho-alpha-D-mannopyranosyl)-alpha-D-mannopyranoside, were synthesized. The former is a minor component of the side-chain repeating unit of the extracellular phosphomannan of Pichia (Hansenula) holstii NRRL Y-2448, whilst the latter represents a nonreducing end fragment of the phosphomannan.

摘要

开发了立体选择性合成α-(1→2)-和α-(1→3)-连接的6(II)-O-磷酸甘露二糖的方法。成功采用了两种策略：将D-甘露糖基受体与磷酸化的D-甘露糖基三氯乙酰亚胺酯供体偶联，或者与经不同6-O-保护的D-甘露糖基三氯乙酰亚胺酯供体偶联，该供体在糖基化后进行选择性脱保护和磷酸化。合成了两种用于抗血管生成候选药物PI-88的构效关系研究的目标磷酸甘露二糖，即2-O-(6-O-磷酸-α-D-甘露吡喃糖基)-D-甘露吡喃糖和3-O-(6-O-磷酸-α-D-甘露吡喃糖基)-α-D-甘露吡喃糖苷甲酯。前者是霍氏毕赤酵母（汉逊酵母）NRRL Y-2448细胞外磷酸甘露聚糖侧链重复单元的次要成分，而后者代表磷酸甘露聚糖的非还原端片段。