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Chemoselective, Enzymatic C-H Bond Amination Catalyzed by a Cytochrome P450 Containing an Ir(Me)-PIX Cofactor
- Source :
- Journal of the American Chemical Society. 139(5)
- Publication Year :
- 2017
-
Abstract
- Cytochrome P450 enzymes have been engineered to catalyze abiological C-H bond amination reactions, but the yields of these reactions have been limited by low chemoselectivity for the amination of C-H bonds over competing reduction of the azide substrate to a sulfonamide. Here we report that P450s derived from a thermophilic organism and containing an iridium porphyrin cofactor (Ir(Me)-PIX) in place of the heme catalyze enantioselective intramolecular C-H bond amination reactions of sulfonyl azides. These reactions occur with chemoselectivity for insertion of the nitrene units into C-H bonds over reduction of the azides to the sulfonamides that is higher and with substrate scope that is broader than those of enzymes containing iron porphyrins. The products from C-H amination are formed in up to 98% yield and ∼300 TON. In one case, the enantiomeric excess reaches 95:5 er, and the reactions can occur with divergent site selectivity. The chemoselectivity for C-H bond amination is greater than 20:1 in all cases. Variants of the Ir(Me)-PIX CYP119 displaying these properties were identified rapidly by evaluating CYP119 mutants containing Ir(Me)-PIX in cell lysates, rather than as purified enzymes. This study sets the stage to discover suitable enzymes to catalyze challenging C-H amination reactions.
- Subjects :
- chemistry.chemical_classification
Sulfonyl
010405 organic chemistry
Nitrene
General Chemistry
010402 general chemistry
01 natural sciences
Biochemistry
Medicinal chemistry
Catalysis
0104 chemical sciences
Sulfonamide
chemistry.chemical_compound
Colloid and Surface Chemistry
chemistry
Intramolecular force
Organic chemistry
Azide
Chemoselectivity
Amination
Thermophilic organism
Subjects
Details
- ISSN :
- 15205126
- Volume :
- 139
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Journal of the American Chemical Society
- Accession number :
- edsair.doi.dedup.....09d9baad273ce25ff887f92d0a414159