Premium
Hemoprotein‐Catalyzed Cyclopropanation En Route to the Chiral Cyclopropanol Fragment of Grazoprevir
Author(s) -
Kim Taejin,
Kassim Amude M.,
Botejue Ajit,
Zhang Chen,
Forte Jared,
Rozzell David,
Huffman Mark A.,
Devine Paul N.,
McIntosh John A.
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800652
Subject(s) - cyclopropanation , ketone , chemistry , catalysis , biocatalysis , organic chemistry , combinatorial chemistry , stereochemistry , reaction mechanism
Reactions that were once the exclusive province of synthetic catalysts can increasingly be addressed using biocatalysis. Through discovery of unnatural enzyme reactions, biochemists have significantly expanded the reach of enzymatic catalysis to include carbene transfer chemistries including olefin cyclopropanation. Here we describe hemoprotein cyclopropanation catalysts derived from thermophilic bacterial globins that react with diazoacetone and an unactivated olefin substrate to furnish a cyclopropyl ketone, a previously unreported reaction for enzyme catalysts. We further demonstrate that the resulting cyclopropyl ketone can be converted to a key cyclopropanol intermediate that occurs en route to the anti‐hepatitis C drug grazoprevir.