| Autor: |
Schaus, Lucas, Das, Anuvab, Knight, Anders M., Jimenez‐Osés, Gonzalo, Houk, K. N., Garcia‐Borràs, Marc, Arnold, Frances H., Huang, Xiongyi |
| Předmět: |
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| Zdroj: |
Angewandte Chemie International Edition; 1/23/2023, Vol. 62 Issue 4, p1-5, 5p |
| Abstrakt: |
Trifluoromethyl‐substituted cyclopropanes (CF3‐CPAs) constitute an important class of compounds for drug discovery. While several methods have been developed for synthesis of trans‐CF3‐CPAs, stereoselective production of corresponding cis‐diastereomers remains a formidable challenge. We report a biocatalyst for diastereo‐ and enantio‐selective synthesis of cis‐CF3‐CPAs with activity on a variety of alkenes. We found that an engineered protoglobin from Aeropyrnum 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‐cis near‐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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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