Stereospecific Enzymatic Conversion of Boronic Acids to Amines

Hanley, Deirdre; Li, Zi-Qi; Gao, Shilong; Virgil, Scott C.; Arnold, Frances H.; Alfonzo, Edwin

doi:10.1021/jacs.4c04190

Stereospecific Enzymatic Conversion of Boronic Acids to Amines

Journal Article · Wed Jul 03 00:00:00 EDT 2024 · Journal of the American Chemical Society

DOI:https://doi.org/10.1021/jacs.4c04190· OSTI ID:2395946

Hanley, Deirdre ^[1]; Li, Zi-Qi ^[2]; ^[2]; Virgil, Scott C. ^[2]; ^[2]; Alfonzo, Edwin ^[2]

California Institute of Technology (CalTech), Pasadena, CA (United States); California Institute of Technology
California Institute of Technology (CalTech), Pasadena, CA (United States)

Boronic acids and esters are highly regarded for their safety, unique reactivity, and versatility in synthesizing a wide range of small molecules, bioconjugates, and materials. They are not exploited in biocatalytic synthesis, however, because enzymes that can make, break, or modify carbon–boron bonds are rare. We wish to combine the advantages of boronic acids and esters for molecular assembly with biocatalysis, which offers the potential for unsurpassed selectivity and efficiency. Here, we introduce an engineered protoglobin nitrene transferase that catalyzes the new-to-nature amination of boronic acids using hydroxylamine. Initially targeting aryl boronic acids, we show that the engineered enzyme can produce a wide array of anilines with high yields and total turnover numbers (up to 99% yield and >4000 TTN), with water and boric acid as the only byproducts. We also demonstrate that the enzyme is effective with bench-stable boronic esters, which hydrolyze in situ to their corresponding boronic acids. Exploring the enzyme’s capacity for enantioselective catalysis, we found that a racemic alkyl boronic ester affords an enantioenriched alkyl amine, a transformation not achieved with chemocatalysts. The formation of an exclusively unrearranged product during the amination of a boronic ester radical clock and the reaction’s stereospecificity support a two-electron process akin to a 1,2-metallate shift mechanism. Here, the developed transformation enables new biocatalytic routes for synthesizing chiral amines.

View Accepted Manuscript (DOE)

Research Organization:: California Institute of Technology (CalTech), Pasadena, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: SC0021141

OSTI ID:: 2395946

Journal Information:: Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Journal Issue: 28 Vol. 146; ISSN 0002-7863

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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