化学
蛋白激酶B
组合化学
激酶
立体化学
生物化学
磷酸化
作者
Chong Han,Scott Savage,Mohammad H. Al‐Sayah,Herbert Yajima,Travis Remarchuk,Reinhard Reents,Beat Wirz,Hans Iding,Stephan Bachmann,Serena Fantasia,Michelangelo Scalone,André Hell,Pirmin C. Hidber,Francis Gosselin
出处
期刊:Organic Letters
[American Chemical Society]
日期:2017-08-31
卷期号:19 (18): 4806-4809
被引量:36
标识
DOI:10.1021/acs.orglett.7b02228
摘要
A highly efficient asymmetric synthesis of the Akt kinase inhibitor ipatasertib (1) is reported. The bicyclic pyrimidine 2 starting material was prepared via a nitrilase biocatalytic resolution, halogen-metal exchange/anionic cyclization, and a highly diastereoselective biocatalytic ketone reduction as key steps. The route also features a halide activated, Ru-catalyzed asymmetric hydrogenation of a vinylogous carbamic acid to produce α-aryl-β-amino acid 3 in high yield and enantioselectivity. The API was assembled in a convergent manner through a late-stage amidation/deprotection/monohydrochloride salt formation sequence.
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