Details

Autor(en) / Beteiligte

• Biegasiewicz, Kyle F.
• Cooper, Simon J.
• Gao, Xin
• Oblinsky, Daniel G.
• Kim, Ji Hye
• Garfinkle, Samuel E.
• Joyce, Leo A.
• Sandoval, Braddock A.
• Scholes, Gregory D.
• Hyster, Todd K.

Titel

Photoexcitation of flavoenzymes enables a stereoselective radical cyclization

Ist Teil von

• Science (American Association for the Advancement of Science), 2019-06, Vol.364 (6446)

Ort / Verlag

United States: AAAS

Erscheinungsjahr

2019

Link zum Volltext

Quelle

American Association for the Advancement of Science

Beschreibungen/Notizen

• 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. As a result, photoexcitation of promiscuous flavoenzymes has thus furnished a previously unknown biocatalytic reaction.