Asymmetric Enzymatic Synthesis of Allylic Amines: A Sigmatropic Rearrangement Strategy
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.
Additional Information
© 2016 Wiley-VCH Verlag GmbH & Co. Received: February 1, 2016. First published: 11 March 2016. Our research is supported by the National Science Foundation, Division of Molecular and Cellular Biosciences (grant MCB-1513007). C.K.P. thanks the Resnick Sustainability Institute for a postdoctoral fellowship. T.H.K. and C.C.F. were supported by a Ruth L. Kirschstein National Research Service Award (F32GM108143) and an NSF Graduate Research Fellowship, respectively. We thank Dr. Scott Virgil and the Center for Catalysis and Chemical Synthesis at Caltech for assistance with chiral chromatography.Attached Files
Accepted Version - nihms763326.pdf
Supplemental Material - anie201601056-sup-0001-misc_information.pdf
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Additional details
- Alternative title
- Asymmetric Enzymatic Synthesis of Allylic Amines:A Sigmatropic Rearrangement Strategy
- PMCID
- PMC4818679
- Eprint ID
- 65407
- DOI
- 10.1002/anie.201601056
- Resolver ID
- CaltechAUTHORS:20160317-072334231
- NSF
- MCB-1513007
- Ruth L. Kirschstein National Research Service Awards
- F32GM108143
- Resnick Sustainability Institute
- NSF Graduate Research Fellowship
- Created
-
2016-03-17Created from EPrint's datestamp field
- Updated
-
2022-05-05Created from EPrint's last_modified field
- Caltech groups
- Resnick Sustainability Institute