American Chemical Society

Amination of a Green Solvent via Immobilized Biocatalysis for the Synthesis of Nemtabrutinib

Posted on 2023-05-26 - 12:20
Enzymes are capable of unique and selective transformations that can enable efficient chemical production. While many industrial processes have been developed using free enzymes in aqueous solutions, immobilizing enzymes on a solid support can offer considerable advantages, including improved reaction efficiency, enzyme stability, the ability to perform reactions in non-aqueous media, and simplified separation of the product from the enzyme. Herein, we describe the development of a biocatalytic transaminase reaction of Cyrene (2) utilizing an immobilized, evolved transaminase enzyme in an organic solvent to provide amine intermediate 3a en route to Bruton’s tyrosine kinase (BTK) inhibitor nemtabrutinib. Enzyme immobilization is critical to facile isolation of the water-soluble product. Improved reaction kinetics and diastereoselectivity were achieved by bridging directed enzyme evolution with the selection of an optimal reaction solvent and solid support for immobilization, enabling a unified solvent system and direct isolation of 3a as a crystalline salt with dr > 50:1.


3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
AAPG Bulletin
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Select your citation style and then place your mouse over the citation text to select it.


need help?