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Synthesis of Vibegron Enabled by a Ketoreductase Rationally Designed for High pH Dynamic Kinetic Reduction |
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| Authors: | Dr. Feng Xu Dr. Birgit Kosjek Dr. Fabien L. Cabirol Dr. Haibin Chen Richard Desmond Dr. Jeonghan Park Anupam P. Gohel Dr. Steven J. Collier Dr. Derek J. Smith Dr. Zhuqing Liu Dr. Jacob M. Janey Dr. John Y. L. Chung Dr. Oscar Alvizo |
| Affiliation: | 1. Department of Process Research and Development, MRL, Merck & Co., Inc., Rahway, NJ, USA;2. Codexis, Inc., Redwood City, CA, USA |
| Abstract: | Described here is an efficient stereoselective synthesis of vibegron enabled by an enzymatic dynamic kinetic reduction that proceeds in a high‐pH environment. To overcome enzyme performance limitations under these conditions, a ketoreductase was evolved by a computationally and structurally aided strategy to increase cofactor stability through tighter binding. |
| Keywords: | biocatalysis directed evolution enzymes ketoreductases total synthesis |