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Enantioselective Aminohydroxylation of Styrenyl Olefins Catalyzed by an Engineered Hemoprotein
Author(s) -
Cho Inha,
Prier Christopher K.,
Jia ZhiJun,
Zhang Ruijie K.,
Görbe Tamás,
Arnold Frances H.
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201812968
Subject(s) - enantioselective synthesis , chemistry , biocatalysis , reagent , catalysis , hemeprotein , directed evolution , active site , selectivity , organic chemistry , combinatorial chemistry , amino acid , cytochrome , enzyme , heme , biochemistry , reaction mechanism , mutant , gene
Chiral 1,2‐amino alcohols are widely represented in biologically active compounds from neurotransmitters to antivirals. While many synthetic methods have been developed for accessing amino alcohols, the direct aminohydroxylation of alkenes to unprotected, enantioenriched amino alcohols remains a challenge. Using directed evolution, we have engineered a hemoprotein biocatalyst based on a thermostable cytochrome c that directly transforms alkenes to amino alcohols with high enantioselectivity (up to 2500 TTN and 90 % ee ) under anaerobic conditions with O ‐pivaloylhydroxylamine as an aminating reagent. The reaction is proposed to proceed via a reactive iron‐nitrogen species generated in the enzyme active site, enabling tuning of the catalyst's activity and selectivity by protein engineering.