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- W4250827124 abstract "This chapter describes the synthesis of vibegron enabled by a ketoreductase rationally designed for high-pH dynamic kinetic reduction. It discusses procedure for preparing dynamic kinetic ketone reduction of tert-Butyl and its analytical method. The asymmetric synthesis of Vibegron offers succinct, atom-efficient chemistry with minimal functional group manipulations. The key enabling feature is a dynamic kinetic biocatalytic ketone reduction, setting the challenging C1',C2 stereocentres in excellent selectivity. A robust and efficient route was developed to simultaneously install the chiral centres of the tricyclic headpiece of a GPR40 agonist. The chapter establishes an intramolecular enolate alkylation from a trans-alcohol which could be accessed from the ketone precursor 1 via dynamic kinetic reduction. Detailed investigation of the kinetic and thermodynamic mechanisms was essential to inform the directed evolution strategy and develop the final enzymatic process." @default.
- W4250827124 created "2022-05-12" @default.
- W4250827124 creator A5051075913 @default.
- W4250827124 date "2020-08-21" @default.
- W4250827124 modified "2023-10-05" @default.
- W4250827124 title "Reductive Methods" @default.
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- W4250827124 doi "https://doi.org/10.1002/9781119487043.ch7" @default.
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