Asymmetric Reductive Amination of Structurally Diverse Ketones with an Engineered Amine Dehydrogenase

26 March 2025, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Chemical catalysis with an open-boundary catalytic architecture can confer a broad substrate scope but is typically accompanied with non-ideal enantioselectivity. Enzymatic catalysis with a closed-boundary catalytic architecture promises the achievement of quantitative enantioselectivity but generally at the cost of a narrow substrate scope. Herein an engineered amine dehydrogenase has been developed as an exemplary catalytic system for addressing this substrate scope-enantioselectivity dilemma. Asymmetric reductive amination with essentially quantitative enantioselectivity has been demonstrated for structurally diverse, both aromatic and alkyl ketones. Reciprocal conformational adaptation, with complementary matching of conformational flexibility and sterics on both the enzyme and substrate sides, is proposed as an effective working mechanism for ensuring the efficient occurrence of catalysis. The synthetic features showcased herein support the combination of a closed-boundary catalytic architecture and reciprocal conformational adaptation as a generic pathway to simultaneously, a broad substrate scope and quantitative enantioselectivity.

Keywords

Chemical Catalysis
Enzymatic Catalysis
Reciprocal Conformational Adaptation
Amine Dehydrogenase
Asymmetric Reductive Amination

Supplementary materials

Title
Description
Actions
Title
Supporting Information
Description
Supporting Information for "Asymmetric Reductive Amination of Structurally Diverse Ketones with an Engineered Amine Dehydrogenase"
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.