Publication Date:
2019
Description:
〈p〉A major challenge in carbon-hydrogen (C-H) bond functionalization is to have the catalyst control precisely where a reaction takes place. In this study, we report engineered cytochrome P450 enzymes that perform unprecedented enantioselective C-H amidation reactions and control the site selectivity to divergently construct β-, -, and -lactams, completely overruling the inherent reactivities of the C-H bonds. The enzymes, expressed in 〈i〉Escherichia coli〈/i〉 cells, accomplish this abiological carbon-nitrogen bond formation via reactive iron-bound carbonyl nitrenes generated from nature-inspired acyl-protected hydroxamate precursors. This transformation is exceptionally efficient (up to 1,020,000 total turnovers) and selective (up to 25:1 regioselectivity and 97%, please refer to compound 2v enantiomeric excess), and can be performed easily on preparative scale.〈/p〉
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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