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Title: Cooperative asymmetric reactions combining photocatalysis and enzymatic catalysis

Abstract

Living organisms rely on simultaneous reactions catalysed by mutually compatible and selective enzymes to synthesize complex natural products and other metabolites. To combine the advantages of these biological systems with the reactivity of artificial chemical catalysts, chemists have devised sequential, concurrent, and cooperative chemoenzymatic reactions that combine enzymatic and artificial catalysts. Cooperative chemoenzymatic reactions consist of interconnected processes that generate products in yields and selectivities that cannot be obtained when the two reactions are carried out sequentially with their respective substrates. However, such reactions are difficult to develop because chemical and enzymatic catalysts generally operate in different media at different temperatures and can deactivate each other. Owing to these constraints, the vast majority of cooperative chemoenzymatic processes that have been reported over the past 30 years can be divided into just two categories: chemoenzymatic dynamic kinetic resolutions of racemic alcohols and amines, and enzymatic reactions requiring the simultaneous regeneration of a cofactor. New approaches to the development of chemoenzymatic reactions are needed to enable valuable chemical transformations beyond this scope. Here in this paper we report a class of cooperative chemoenzymatic reaction that combines photocatalysts that isomerize alkenes with ene-reductases that reduce carbon–carbon double bonds to generate valuable enantioenriched products.more » This method enables the stereoconvergent reduction of E/Zmixtures of alkenes or reduction of the unreactive stereoisomers of alkenes in yields and enantiomeric excesses that match those obtained from the reduction of the pure, more reactive isomers. The system affords a range of enantioenriched precursors to biologically active compounds. More generally, these results show that the compatibility between photocatalysts and enzymes enables chemoenzymatic processes beyond cofactor regeneration and provides a general strategy for converting stereoselective enzymatic reactions into stereoconvergent ones.« less

Authors:
 [1];  [2];  [3];  [1]
  1. Univ. of California, Berkeley, CA (United States). Dept. of Chemistry
  2. Univ. of Illinois, Urbana-Champaign, IL (United States). Dept. of Chemical and Biomolecular Engineering
  3. Univ. of Illinois, Urbana-Champaign, IL (United States). Dept. of Chemical and Biomolecular Engineering, and Dept. of Chemistry, and Dept. of Biochemistry, and Dept. of of Bioengineering, and Carl R. Woese Inst. for Genomic Biology
Publication Date:
Research Org.:
Univ. of Illinois at Urbana-Champaign, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1470980
Grant/Contract Number:  
SC0018420
Resource Type:
Accepted Manuscript
Journal Name:
Nature (London)
Additional Journal Information:
Journal Name: Nature (London); Journal Volume: 560; Journal Issue: 7718; Journal ID: ISSN 0028-0836
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Litman, Zachary C., Wang, Yajie, Zhao, Huimin, and Hartwig, John F. Cooperative asymmetric reactions combining photocatalysis and enzymatic catalysis. United States: N. p., 2018. Web. doi:10.1038/s41586-018-0413-7.
Litman, Zachary C., Wang, Yajie, Zhao, Huimin, & Hartwig, John F. Cooperative asymmetric reactions combining photocatalysis and enzymatic catalysis. United States. doi:10.1038/s41586-018-0413-7.
Litman, Zachary C., Wang, Yajie, Zhao, Huimin, and Hartwig, John F. Thu . "Cooperative asymmetric reactions combining photocatalysis and enzymatic catalysis". United States. doi:10.1038/s41586-018-0413-7. https://www.osti.gov/servlets/purl/1470980.
@article{osti_1470980,
title = {Cooperative asymmetric reactions combining photocatalysis and enzymatic catalysis},
author = {Litman, Zachary C. and Wang, Yajie and Zhao, Huimin and Hartwig, John F.},
abstractNote = {Living organisms rely on simultaneous reactions catalysed by mutually compatible and selective enzymes to synthesize complex natural products and other metabolites. To combine the advantages of these biological systems with the reactivity of artificial chemical catalysts, chemists have devised sequential, concurrent, and cooperative chemoenzymatic reactions that combine enzymatic and artificial catalysts. Cooperative chemoenzymatic reactions consist of interconnected processes that generate products in yields and selectivities that cannot be obtained when the two reactions are carried out sequentially with their respective substrates. However, such reactions are difficult to develop because chemical and enzymatic catalysts generally operate in different media at different temperatures and can deactivate each other. Owing to these constraints, the vast majority of cooperative chemoenzymatic processes that have been reported over the past 30 years can be divided into just two categories: chemoenzymatic dynamic kinetic resolutions of racemic alcohols and amines, and enzymatic reactions requiring the simultaneous regeneration of a cofactor. New approaches to the development of chemoenzymatic reactions are needed to enable valuable chemical transformations beyond this scope. Here in this paper we report a class of cooperative chemoenzymatic reaction that combines photocatalysts that isomerize alkenes with ene-reductases that reduce carbon–carbon double bonds to generate valuable enantioenriched products. This method enables the stereoconvergent reduction of E/Zmixtures of alkenes or reduction of the unreactive stereoisomers of alkenes in yields and enantiomeric excesses that match those obtained from the reduction of the pure, more reactive isomers. The system affords a range of enantioenriched precursors to biologically active compounds. More generally, these results show that the compatibility between photocatalysts and enzymes enables chemoenzymatic processes beyond cofactor regeneration and provides a general strategy for converting stereoselective enzymatic reactions into stereoconvergent ones.},
doi = {10.1038/s41586-018-0413-7},
journal = {Nature (London)},
number = 7718,
volume = 560,
place = {United States},
year = {2018},
month = {8}
}

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