厦门霉素A的全合成及立体化学修正

Total synthesis and stereochemical revision of xiamenmycin A.

作者信息

Jiao Xiaozhen, Yao Yangyang, Yang Beibei, Liu Xiaoyu, Li Xiaoyu, Yang Hongguang, Li Li, Xu Jun, Xu Minjuan, Xie Ping

机构信息

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Beijing Key Laboratory of Active Substances Discovery and Drugability Evaluation, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China.

Institute of Oceanology and State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai 200240, PR China.

出版信息

Org Biomol Chem. 2016 Feb 7;14(5):1805-13. doi: 10.1039/c5ob02476e.

DOI:10.1039/c5ob02476e

PMID:26757679

Abstract

The relative and absolute configurations of xiamenmycin A, a benzopyran compound isolated from Streptomyces xiamenensis 318 with a highly potent anti-fibrotic activity, have been characterized through the total synthesis. The key steps include the construction of the 3-chromanol moiety via Sharpless epoxidation followed by regio- and diastereo-selective cyclization and introduction of the threonine moiety at a later stage via Pd-catalysed aminocarbonylation in a one-pot procedure. The stereochemical assignment of natural xiamenmycin A has been accordingly revised to be 2R, 3S, 3'S, 4'R.

摘要

从厦门链霉菌318中分离得到的具有高效抗纤维化活性的苯并吡喃化合物厦门霉素A的相对和绝对构型已通过全合成得以确定。关键步骤包括通过夏普莱斯环氧化反应构建3-色满醇部分，随后进行区域和非对映选择性环化，并在后期通过钯催化的氨基羰基化一锅法引入苏氨酸部分。天然厦门霉素A的立体化学归属因此修订为2R, 3S, 3'S, 4'R。