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Aldehyde and Ketone Synthesis by P450‐Catalyzed Oxidative Deamination of Alkyl Azides
Author(s) -
Giovani Simone,
Alwaseem Hanan,
Fasan Rudi
Publication year - 2016
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201600487
Subject(s) - chemistry , chemoselectivity , oxidative deamination , azide , deamination , alkyl , heme , biocatalysis , combinatorial chemistry , ketone , reactivity (psychology) , catalysis , organic chemistry , reaction mechanism , enzyme , medicine , alternative medicine , pathology
Heme‐containing proteins have recently attracted increasing attention for their ability to promote synthetically valuable transformations not found in nature. Following the recent discovery that engineered variants of myoglobin can catalyze the direct conversion of organic azides into aldehydes, we investigated the azide oxidative deamination reactivity of a variety of hemoproteins featuring different heme coordination environments. Our studies show that although several heme‐containing enzymes possess basal activity in this reaction, an engineered variant of the bacterial cytochrome P450 CYP102A1 constitutes a particularly efficient biocatalyst for promoting this transformation, and it exhibits a broad substrate scope along with high catalytic activity (up to 11 300 turnovers), excellent chemoselectivity, and enhanced reactivity toward secondary alkyl azides to yield ketones. Mechanistic studies and Michaelis–Menten analyses provided insight into the mechanism of the reaction and the impact of active‐site mutations on the catalytic properties of the P450. Altogether, these studies demonstrate that engineered P450 variants represent promising biocatalysts for the synthesis of aryl aldehydes and ketones through the oxidative deamination of alkyl azides under mild reaction conditions.