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Title: Protoglobin‐Catalyzed Formation of cis ‐Trifluoromethyl‐Substituted Cyclopropanes by Carbene Transfer
Abstract

Trifluoromethyl‐substituted cyclopropanes (CF3‐CPAs) constitute an important class of compounds for drug discovery. While several methods have been developed for synthesis oftrans‐CF3‐CPAs, stereoselective production of correspondingcis‐diastereomers remains a formidable challenge. We report a biocatalyst for diastereo‐ and enantio‐selective synthesis ofcis‐CF3‐CPAs with activity on a variety of alkenes. We found that an engineered protoglobin fromAeropyrnum pernix(ApePgb) can catalyze this unusual reaction at preparative scale with low‐to‐excellent yield (6–55 %) and enantioselectivity (17–99 % ee), depending on the substrate. Computational studies revealed that the steric environment in the active site of the protoglobin forced iron‐carbenoid and substrates to adopt a pro‐cisnear‐attack conformation. This work demonstrates the capability of enzyme catalysts to tackle challenging chemistry problems and provides a powerful means to expand the structural diversity of CF3‐CPAs for drug discovery.

 
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NSF-PAR ID:
10386296
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Angewandte Chemie
Volume:
135
Issue:
4
ISSN:
0044-8249
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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