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Abstract In this work, we report the regiospecific and stereoselective synthesis of novel pyrrolo thioxoimidazolidinones with promising biological activities due to the inherent pharmaceutical properties of thioxoimidazolidinone core. The reaction of different thioxoimidazolidinones withtrans‐4‐ethoxy‐1,1,1‐trifluorobut‐3‐en‐2‐one (ETFBO) yields bicyclic 1,3‐diaza heterocycles bearing the trifluoromethyl (CF3) moiety. Our investigation involved both depth experimental analysis and theoretical calculations to fathom out the mode of reaction of this building block and elucidate the underlying mechanism operating for the observed reactions. Remarkably, this unusual mechanism retained the ethanol moiety from the building block in the final products, deviating from conventional nucleophilic reactions reported in the literature.
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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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- Award ID(s):
- 2016137
- PAR ID:
- 10391584
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 62
- Issue:
- 4
- ISSN:
- 1433-7851
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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