唾液酸化路易斯 X 衍生物的全合成用于癌症的诊断。

Total synthesis of a sialyl Lewis(x) derivative for the diagnosis of cancer.

机构信息

Institut Parisien de Chimie Moléculaire, CNRS UMR 7201, Université Pierre et Marie Curie-Paris 6, 4 Place Jussieu, 75005 Paris, France; ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

出版信息

Carbohydr Res. 2014 Jan 13;383:89-96. doi: 10.1016/j.carres.2013.11.012. Epub 2013 Nov 23.

DOI:10.1016/j.carres.2013.11.012

PMID:24333940

Abstract

The total synthesis of aminoethyl glycoside of sialyl Lewis(x) (sLe(x)) is described. A galactose donor was condensed with a diol of glucosamine to afford regioselectively a β1,4 linked disaccharide, which was further stereoselectively fucosylated to provide a protected Lewis(x) trisaccharide. After chemical modification, the trisaccharide was sialylated to give regio- and stereoselectively an azidoethyl glycoside of sLe(x). Finally, deprotection and azide reduction afforded the target compound. This compound will be coupled with protein and then be used to conduct further preclinical studies for the diagnosis of cancer.

摘要

本文描述了唾液酸化 Lewis(x)（sLe(x)）氨基乙基糖苷的全合成。半乳糖供体与葡糖胺二醇缩合，以高区域选择性方式得到β1,4 连接的二糖，然后立体选择性地进行岩藻糖基化，得到保护的 Lewis(x)三糖。经过化学修饰，三糖进行唾液酸化，以高区域和立体选择性方式得到 sLe(x)的叠氮乙基糖苷。最后，脱保护和叠氮还原得到目标化合物。该化合物将与蛋白质偶联，然后用于进一步进行癌症诊断的临床前研究。