Asymmetric Synthesis of a Glucagon Receptor Antagonist via Friedel–Crafts Alkylation of Indole with Chiral α-Phenyl Benzyl Cation

…, D Steinhuebel, SW Krska, FW Hartner…

Index: Chung, John Y. L.; Steinhuebel, Dietrich; Krska, Shane W.; Hartner, Fred W.; Cai, Chaoxian; Rosen, Jonathan; Mancheno, Danny E.; Pei, Tao; Dimichele, Lisa; Ball, Richard G.; Chen, Cheng-Yi; Tan, Lushi; Alorati, Antony D.; Brewer, Sarah E.; Scott, Jeremy P. Organic Process Research and Development, 2012 , vol. 16, # 11 p. 1832 - 1845

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Citation Number: 7

Abstract

Development of a practical asymmetric synthesis of a glucagon receptor antagonist drug candidate for the treatment of type 2 diabetes is described. The antagonist consists of a 1, 1, 2, 2-tetrasubstituted ethane core substituted with a propyl and three aryl groups including a fluoro-indole. The key steps to construct the ethane core and the two stereogenic centers involved a ketone arylation, an asymmetric hydrogenation via dynamic kinetic resolution, ...