与PI-88相关的6(V)-硫酸化甘露五糖类似物的合成。

Synthesis of a 6(V)-sulfated mannopentasaccharide analogue related to PI-88.

作者信息

Gu Guofeng, Wei Guohua, Du Yuguo

机构信息

Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, PO Box 2871, Beijing 100085, China.

出版信息

Carbohydr Res. 2004 Apr 28;339(6):1155-62. doi: 10.1016/j.carres.2004.01.020.

DOI:10.1016/j.carres.2004.01.020

PMID:15063205

Abstract

An efficient and convergent synthesis of a regioselectively 6(V)-sulfated mannopentasaccharide derivative 1c, octyl 6-O-sulfo-alpha-D-mannopyranosyl-(1-->3)-alpha-D-mannopyranosyl-(1-->3)-alpha-d-mannopyranosyl-(1-->3)-alpha-D-mannopyranosyl-(1-->2)-alpha-D-mannopyranoside, was achieved by a '3 + 2' strategy. The target was designed to mimic the promising anticancer agent PI-88 and was obtained from the building blocks, octyl 3,4,6-tri-O-benzoyl-alpha-D-mannopyranoside, allyl 2,4,6-tri-O-benzoyl-3-O-(4-methoxybenzyl)-alpha-D-mannopyranoside, and 6-O-acetyl-2,3,4-tri-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate (11), under TMSOTf-catalyzed glycosylation conditions. Compound 1c displays a mild anti-angiogenic activity based on a chorioallantoic membrane (CAM) model study.

摘要

通过“3 + 2”策略实现了区域选择性6(V)-硫酸化甘露五糖衍生物1c（辛基6-O-磺基-α-D-甘露吡喃糖基-(1→3)-α-D-甘露吡喃糖基-(1→3)-α-D-甘露吡喃糖基-(1→3)-α-D-甘露吡喃糖基-(1→2)-α-D-甘露吡喃糖苷）的高效收敛合成。该目标化合物的设计旨在模拟有前景的抗癌药物PI-88，并在三甲基硅基三氟甲磺酸酯（TMSOTf）催化的糖基化条件下，由构建块辛基3,4,6-三-O-苯甲酰基-α-D-甘露吡喃糖苷、烯丙基2,4,6-三-O-苯甲酰基-3-O-(4-甲氧基苄基)-α-D-甘露吡喃糖苷和6-O-乙酰基-2,3,4-三-O-苯甲酰基-α-D-甘露吡喃糖基三氯乙酰亚胺酯（11）制得。基于鸡胚绒毛尿囊膜（CAM）模型研究，化合物1c表现出温和的抗血管生成活性。