3-氨基茚满-1-酮的立体选择性合成及其随后纳入HIV-1蛋白酶抑制剂

Stereoselective synthesis of 3-aminoindan-1-ones and subsequent incorporation into HIV-1 protease inhibitors.

作者信息

Arefalk Anna, Wannberg Johan, Larhed Mats, Hallberg Anders

机构信息

Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, BMC, P.O. Box-574, SE-751 23 Uppsala, Sweden.

出版信息

J Org Chem. 2006 Feb 3;71(3):1265-8. doi: 10.1021/jo0521504.

DOI:10.1021/jo0521504

PMID:16438552

Abstract

A new method for the stereoselective synthesis of 3-aminoindan-1-ones from triflates of salicylic sulfinyl imines and ethylene glycol vinyl ether has been developed. The reaction sequence starts with a regioselective Heck reaction followed by stereoselective Lewis acid mediated annulation. Acidic cleavage of the sulfinamides produced pure (R)- and (S)-3-aminoindan-1-ones, which were successfully isolated and incorporated into active HIV-1 protease inhibitors.

摘要

已开发出一种从亚磺酰亚胺水杨酸酯的三氟甲磺酸酯和乙二醇乙烯基醚立体选择性合成3-氨基茚满-1-酮的新方法。反应序列始于区域选择性Heck反应，随后是立体选择性路易斯酸介导的环化反应。亚磺酰胺的酸解产生了纯的（R）-和（S）-3-氨基茚满-1-酮，它们被成功分离并用于活性HIV-1蛋白酶抑制剂中。