Biocatalytic Strategy for Highly Diastereo‐ and Enantioselective Synthesis of 2,3‐Dihydrobenzofuran‐Based Tricyclic Scaffolds
-
- David A. Vargas
- Department of Chemistry University of Rochester 120 Trustee Road Rochester NY 14627 USA
-
- Rahul L. Khade
- Department of Chemistry and Chemical Biology Stevens Institute of Technology Hoboken NJ 07030 USA
-
- Yong Zhang
- Department of Chemistry and Chemical Biology Stevens Institute of Technology Hoboken NJ 07030 USA
-
- Rudi Fasan
- Department of Chemistry University of Rochester 120 Trustee Road Rochester NY 14627 USA
書誌事項
- 公開日
- 2019-06-24
- 権利情報
-
- http://onlinelibrary.wiley.com/termsAndConditions#am
- http://onlinelibrary.wiley.com/termsAndConditions#vor
- DOI
-
- 10.1002/anie.201903455
- 公開者
- Wiley
この論文をさがす
説明
<jats:title>Abstract</jats:title><jats:p>2,3‐Dihydrobenzofurans are key pharmacophores in many natural and synthetic bioactive molecules. A biocatalytic strategy is reported here for the highly diastereo‐ and enantioselective construction of stereochemically rich 2,3‐dihydrobenzofurans in high enantiopurity (>99.9% de and ee), high yields, and on a preparative scale via benzofuran cyclopropanation with engineered myoglobins. Computational and structure‐reactivity studies provide insights into the mechanism of this reaction, enabling the elaboration of a stereochemical model that can rationalize the high stereoselectivity of the biocatalyst. This information was leveraged to implement a highly stereoselective route to a drug molecule and a tricyclic scaffold featuring five stereogenic centers via a single‐enzyme transformation. This work expands the biocatalytic toolbox for asymmetric C–C bond transformations and should prove useful for further development of metalloprotein catalysts for abiotic carbene transfer reactions.</jats:p>
収録刊行物
-
- Angewandte Chemie International Edition
-
Angewandte Chemie International Edition 58 (30), 10148-10152, 2019-06-24
Wiley
