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Title: Site-Selective Functionalization of (sp3)C-H Bonds Catalyzed by Artificial Metalloenzymes Containing an Iridium-Porphyrin Cofactor

Journal Article · · Angewandte Chemie
 [1];  [1];  [1];  [2]; ORCiD logo [1]
  1. Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Chemical Sciences Division
  2. Univ. of California, Berkeley, CA (United States). Dept. of Chemical and Biomolecular Engineering; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division

The selective functionalization of one C-H bond over others in nearly identical steric and electronic environments can facilitate the construction of complex molecules. We report site-selective functionalizations of C-H bonds, differentiated solely by remote substituents, catalyzed by artificial metalloenzymes (ArMs) that are generated from the combination of an evolvable P450 scaffold and an iridium-porphyrin cofactor. The generated systems catalyze the insertion of carbenes into the C-H bonds of a range of phthalan derivatives containing substituents that render the two methylene positions in each phthalan inequivalent. These reactions occur with site-selectivity ratios of up to 17.8:1 and, in most cases, with pairs of enzyme mutants that preferentially form each of the two constitutional isomers. This study demonstrates the potential of abiotic reactions catalyzed by metalloenzymes to functionalize C-H bonds with site selectivity that is difficult to achieve with small-molecule catalysts.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22), Chemical Sciences, Geosciences & Biosciences Division (SC-22.1)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1608274
Alternate ID(s):
OSTI ID: 1558123
Journal Information:
Angewandte Chemie, Vol. 131, Issue 39; ISSN 0044-8249
Publisher:
German Chemical SocietyCopyright Statement
Country of Publication:
United States
Language:
English

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Figures / Tables (8)