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Photoexcitation of flavoenzymes enables a stereoselective radical cyclization
by
Gao, Xin
, Joyce, Leo A.
, Sandoval, Braddock A.
, Hyster, Todd K.
, Scholes, Gregory D.
, Biegasiewicz, Kyle F.
, Oblinsky, Daniel G.
, Garfinkle, Samuel E.
, Kim, Ji Hye
, Cooper, Simon J.
in
BASIC BIOLOGICAL SCIENCES
/ Biocatalysis - radiation effects
/ Catalysis
/ Chemical reactions
/ Chemical synthesis
/ Chemistry
/ Coenzymes
/ Coordination compounds
/ Cyclization
/ Electron transfer
/ Enzyme Activation
/ Enzymes
/ Flavin
/ FMN Reductase - chemistry
/ FMN Reductase - radiation effects
/ Lactams - chemical synthesis
/ Light
/ Organic chemistry
/ Photoexcitation
/ Reagents
/ Reductases
/ Stereochemistry
/ Stereoisomerism
/ Stereoselectivity
/ Substrates
2019
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Photoexcitation of flavoenzymes enables a stereoselective radical cyclization
by
Gao, Xin
, Joyce, Leo A.
, Sandoval, Braddock A.
, Hyster, Todd K.
, Scholes, Gregory D.
, Biegasiewicz, Kyle F.
, Oblinsky, Daniel G.
, Garfinkle, Samuel E.
, Kim, Ji Hye
, Cooper, Simon J.
in
BASIC BIOLOGICAL SCIENCES
/ Biocatalysis - radiation effects
/ Catalysis
/ Chemical reactions
/ Chemical synthesis
/ Chemistry
/ Coenzymes
/ Coordination compounds
/ Cyclization
/ Electron transfer
/ Enzyme Activation
/ Enzymes
/ Flavin
/ FMN Reductase - chemistry
/ FMN Reductase - radiation effects
/ Lactams - chemical synthesis
/ Light
/ Organic chemistry
/ Photoexcitation
/ Reagents
/ Reductases
/ Stereochemistry
/ Stereoisomerism
/ Stereoselectivity
/ Substrates
2019
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Photoexcitation of flavoenzymes enables a stereoselective radical cyclization
by
Gao, Xin
, Joyce, Leo A.
, Sandoval, Braddock A.
, Hyster, Todd K.
, Scholes, Gregory D.
, Biegasiewicz, Kyle F.
, Oblinsky, Daniel G.
, Garfinkle, Samuel E.
, Kim, Ji Hye
, Cooper, Simon J.
in
BASIC BIOLOGICAL SCIENCES
/ Biocatalysis - radiation effects
/ Catalysis
/ Chemical reactions
/ Chemical synthesis
/ Chemistry
/ Coenzymes
/ Coordination compounds
/ Cyclization
/ Electron transfer
/ Enzyme Activation
/ Enzymes
/ Flavin
/ FMN Reductase - chemistry
/ FMN Reductase - radiation effects
/ Lactams - chemical synthesis
/ Light
/ Organic chemistry
/ Photoexcitation
/ Reagents
/ Reductases
/ Stereochemistry
/ Stereoisomerism
/ Stereoselectivity
/ Substrates
2019
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Photoexcitation of flavoenzymes enables a stereoselective radical cyclization
Journal Article
Photoexcitation of flavoenzymes enables a stereoselective radical cyclization
2019
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Overview
Photoexcitation is a common strategy for initiating radical reactions in chemical synthesis. We found that photoexcitation of flavin-dependent “ene”-reductases changes their catalytic function, enabling these enzymes to promote an asymmetric radical cyclization. This reactivity enables the construction of five-, six-, seven-, and eight-membered lactams with stereochemical preference conferred by the enzyme active site. After formation of a prochiral radical, the enzyme guides the delivery of a hydrogen atom from flavin—a challenging feat for small-molecule chemical reagents. The initial electron transfer occurs through direct excitation of an electron donor-acceptor complex that forms between the substrate and the reduced flavin cofactor within the enzyme active site. Photoexcitation of promiscuous flavoenzymes has thus furnished a previously unknown biocatalytic reaction.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science,American Association for the Advancement of Science (AAAS)
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