Year: 2019
Type: article
Abstract: One-pot reactions that combine non-enzymatic and biocatalytic transformations represent an emerging strategy in chemical synthesis. Some of the most powerful chemoenzymatic methodologies, although uncommon, are those that form a carbon-carbon (C-C) bond and a stereocenter at one of the reacting carbons, thereby streamlining traditional retrosynthetic disconnections. Here we report the one-pot, chemoenzymatic conversion of amides to enantioenriched alcohols. This transformation combines a nickel-catalyzed Suzuki-Miyaura coupling of amides in aqueous medium with an asymmetric, biocatalytic reduction to provide diarylmethanol derivatives in high yields and enantiomeric excesses. The synthetic utility of this platform is underscored by the formal syntheses of both antipodes of the pharmaceutical orphenadrine, which rely on ketoreductase enzymes that instill complementary stereoselectivities. We provide an explanation for the origins of stereoselectivity based on an analysis of the enzyme binding pockets.
Source: Communications Chemistry
Authors: Jacob E. Dander, Maude Giroud, Sophie Racine, Evan R. Darzi, Oscar Alvizo, David Entwistle, Neil K. Garg
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,170
Funders: National Science Foundation, U.S. Department of Health and Human Services, California Institute of Technology, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Institutes of Health, University of California, Los Angeles, National Institute of General Medical Sciences, National Center for Research Resources, Division of Chemistry
Awards: Acquisition of Upgraded NMR Instrumentation for Chemistry Research, Education and Training, G1661892572, G401885085, Methodology towards the synthesis of complex stereochemically dense natural products, Graduate Research Fellowship Program (GRFP), Time-of-Flight Mass Spectrometer for Synthesis Supporting Biomedical Research, G7435049567, G7456503222, G8056187709, G910930967, New Directions in Cross-Couplings Catalyzed by Non-Precious Metals
OpenAlex ID: W2964052229