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Asymmetric Enzymatic Synthesis of Allylic Amines: A Sigmatropic Rearrangement Strategy
Author(s) -
Prier Christopher K.,
Hyster Todd K.,
Farwell Christopher C.,
Huang Audrey,
Arnold Frances H.
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201601056
Subject(s) - allylic rearrangement , sigmatropic reaction , enantioselective synthesis , nitrene , chemistry , stereochemistry , chemical biology , biocatalysis , enzyme , combinatorial chemistry , catalysis , organic chemistry , biochemistry , reaction mechanism
Abstract Sigmatropic rearrangements, while rare in biology, offer opportunities for the efficient and selective synthesis of complex chemical motifs. A “P411” serine‐ligated variant of cytochrome P450 BM3 has been engineered to initiate a sulfimidation/[2,3]‐sigmatropic rearrangement sequence in whole E. coli cells, a non‐natural function for any enzyme, providing access to enantioenriched, protected allylic amines. Five mutations in the enzyme substantially enhance its activity toward this new function, demonstrating the evolvability of the catalyst toward challenging nitrene transfer reactions. The evolved catalyst additionally performs the highly enantioselective imidation of non‐allylic sulfides.