一种源自乳糖的新型唾液酸化路易斯X模拟物的合成与生物学评价

Synthesis and biological evaluation of a new sialyl Lewis X mimetic derived from lactose.

作者信息

Chervin Stephanie M, Lowe John B, Koreeda Masato

机构信息

Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1055, USA.

出版信息

J Org Chem. 2002 Aug 9;67(16):5654-62. doi: 10.1021/jo025579t.

DOI:10.1021/jo025579t

PMID:12153264

Abstract

A sialyl Lewis X (sLe(x)) mimetic compound, 2-(trimethylsilyl)ethyl 3-O-carboxymethyl-beta-D-galactopyranosyl-(1-->4)-[alpha-L-fucosyl-(1-->6)]-beta-D-glucopyranoside (2a), has been synthesized in 14 steps from D-lactose. This synthesis features the use of the activated glycosylating donor, lactosyl iodide, in a Koenigs-Knorr sequence, the regioselective derivatization at the C-3 position of the galactose moiety, and the stereoselective construction of a fucose-alpha(1-->6)-lactose linkage. The mimetic was tested for its ability to inhibit human polymorphonuclear leukocyte (hPMNL) adhesion to immobilized recombinant human E-selectin under shear stress conditions.

摘要

一种唾液酸化路易斯X（sLe(x)）模拟化合物，2-(三甲基硅基)乙基3-O-羧甲基-β-D-吡喃半乳糖基-(1→4)-[α-L-岩藻糖基-(1→6)]-β-D-吡喃葡萄糖苷（2a），已由D-乳糖经14步合成。该合成方法的特点包括在柯尼希斯-克诺尔反应序列中使用活化的糖基化供体乳糖基碘，在半乳糖部分的C-3位进行区域选择性衍生化，以及立体选择性构建岩藻糖-α(1→6)-乳糖连接。测试了该模拟物在剪切应力条件下抑制人多形核白细胞（hPMNL）与固定化重组人E-选择素粘附的能力。