Aldehyde and Ketone Synthesis by P450‐Catalyzed Oxidative Deamination of Alkyl Azides. Issue 16 (26th July 2016)

• Record Type: Journal Article
• Authors: Giovani, Simone; Alwaseem, Hanan; Fasan, Rudi
• Is Part Of: ChemCatChem. Volume 8:Issue 16(2016)
• Page Start: 2609
• Page End: 2613
• Publication Date: 2016-07-26
• Subjects: aldehydes -- azides -- cytochrome P450 -- oxidative deamination -- protein engineering; Catalysis -- Periodicals; 541.39505
• DOI: 10.1002/cctc.201600487
• Languages: English
• ISSNs: 1867-3880

Abstract

Abstract: 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. Abstract : Move azide : An engineered variant of CYP102A1 efficiently catalyzes the oxidative deamination of primary alkyl azides to yield aldehydes and exhibits a broad substrate scope along with high catalytic activity and excellent chemoselectivity. The enhanced reactivity of this enzyme also enables the conversion of selected secondary alkyl azides into ketones.