通过(S)-3,3'-二氟联萘酚催化的不对称甲基烯丙基化反应对11-β-羟基类固醇脱氢酶-1抑制剂进行对映选择性合成。

An Enantioselective Synthesis of an 11-β-HSD-1 Inhibitor via an Asymmetric Methallylation Catalyzed by (S)-3,3'-F2-BINOL.

作者信息

Zhang Yongda, Wu Jiang-Ping, Li Guisheng, Fandrick Keith R, Gao Joe, Tan Zhulin, Johnson Joe, Li Wenjie, Sanyal Sanjit, Wang Jun, Sun Xiufeng, Lorenz Jon C, Rodriguez Sonia, Reeves Jonathan T, Grinberg Nelu, Lee Heewon, Yee Nathan, Lu Bruce Z, Senanayake Chris H

机构信息

Chemical Development, Boehringer Ingelheim Pharmaceuticals Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.

出版信息

J Org Chem. 2016 Mar 18;81(6):2665-9. doi: 10.1021/acs.joc.6b00189. Epub 2016 Mar 2.

DOI:10.1021/acs.joc.6b00189

PMID:26909738

Abstract

An efficient asymmetric synthesis of 11-β-HSD inhibitor 1 has been accomplished in five linear steps and 53% overall yield, starting from the readily available 3-chloro-1-phenylpropan-1-one. The key feature of the synthesis includes an asymmetric methallylation of 3-chloro-1-phenylpropan-1-one catalyzed by the highly effective organocatalyst (S)-3,3'-F2-BINOL under solvent-free and metal-free conditions.

摘要

以易于获得的3-氯-1-苯基丙-1-酮为起始原料，通过五个线性步骤，以53%的总收率完成了11-β-HSD抑制剂1的高效不对称合成。该合成的关键特征包括在无溶剂和无金属条件下，由高效有机催化剂(S)-3,3'-F2-BINOL催化3-氯-1-苯基丙-1-酮的不对称甲基烯丙基化反应。