op1c00255_si_001.pdf (1.38 MB)
Application of Biocatalytic Reductive Amination for the Synthesis of a Key Intermediate to a CDK 2/4/6 Inhibitor
journal contribution
posted on 2021-09-03, 10:43 authored by Shengquan Duan, Daniel W. Widlicka, Michael P. Burns, Rajesh Kumar, Ian Hotham, Jean-Nicolas Desrosiers, Paul Bowles, Kris N. Jones, Lindsay D. Nicholson, Michele T. Buetti-Weekly, Lu Han, Jeremy Steflik, Eric Hansen, Cheryl M. Hayward, Holly Strohmeyer, Sébastien Monfette, Scott C. Sutton, Christopher MorrisBiocatalytic reductive amination
catalyzed by engineered imine
reductase (RedAms) is a new and powerful tool for the synthesis of
substituted chiral amines. Herein, we describe a streamlined synthesis
of compound 3, a key intermediate to a CDK 2/4/6 inhibitor 1, relying on the enzymatic reductive amination of a hydroxyketone
to introduce the chiral secondary amine with high diastereoselectivity.
The improved synthesis of the hydroxyketone precursor by a titanium-catalyzed
reductive cyclization and the process development for two SNAr reactions en route to 3 are also presented.
