Biocatalytic Cleavage of para-Acetoxy Benzyl Ethers: Application to Protecting Group Chemistry

IF 11.3 1区化学 Q1 CHEMISTRY, PHYSICAL

ACS Catalysis Pub Date : 2024-12-16 DOI:10.1021/acscatal.4c04257

Ben Ashley, Chiara Demingo, Henriette Rozeboom, Niccoló Bianciardi, Tomás Dunleavy, Jacob-Jan Haaksma, Yiming Guo, Marco W. Fraaije

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Abstract

Aryl ethers are ubiquitous protecting groups of alcohols and amines in organic chemistry. This is owed to the simplicity of their appendage to molecules and the robust protection afforded. However, aryl ethers and amines can be challenging to cleave, often requiring harsh and unselective reductive conditions. We report the structure-based engineering of a promiscuous, ether-cleaving vanillyl alcohol oxidase-type biocatalyst for activity on a wide range of para-hydroxy benzyl ethers. Two superior quadruple mutants are identified with improved kinetics and substrate scope. One evolved variant and two predecessors are crystallized, and their structures resolved to 2.8–1.5 Å, revealing a significant increase in the volume and flexibility of the active site cavity. To illustrate the potential usefulness of the engineered biocatalysts, one is later coupled with another biocatalyst in a cascade reaction to catalyze the selective cleavage of an uncommon aryl ether protecting group, para-acyloxy benzyl ethers, in good yield and under mild conditions.

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来源期刊

ACS Catalysis CHEMISTRY, PHYSICAL-

CiteScore

20.80

自引率

6.20%

发文量

1253

审稿时长

1.5 months

期刊介绍： ACS Catalysis is an esteemed journal that publishes original research in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. It offers broad coverage across diverse areas such as life sciences, organometallics and synthesis, photochemistry and electrochemistry, drug discovery and synthesis, materials science, environmental protection, polymer discovery and synthesis, and energy and fuels. The scope of the journal is to showcase innovative work in various aspects of catalysis. This includes new reactions and novel synthetic approaches utilizing known catalysts, the discovery or modification of new catalysts, elucidation of catalytic mechanisms through cutting-edge investigations, practical enhancements of existing processes, as well as conceptual advances in the field. Contributions to ACS Catalysis can encompass both experimental and theoretical research focused on catalytic molecules, macromolecules, and materials that exhibit catalytic turnover.