Enzymatic Assembly of Diverse Lactone Structures: An Intramolecular C–H Functionalization Strategy

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(2), P. 1580 - 1587

Published: Jan. 2, 2024

Lactones are cyclic esters with extensive applications in materials science, medicinal chemistry, and the food perfume industries. Nature's strategy for synthesis of many lactones found natural products always relies on a single type retrosynthetic strategy, C–O bond disconnection. Here, we describe set laboratory-engineered enzymes that use new-to-nature C–C bond-forming to assemble diverse lactone structures. These engineered "carbene transferases" catalyze intramolecular carbene insertions into benzylic or allylic C–H bonds, which allow different ring sizes scaffolds from simple starting materials. Starting serine-ligated cytochrome P450 variant previously other carbene-transfer activities, directed evolution generated P411-LAS-5247, exhibits high activity constructing five-membered ε-lactone, lactam, ketone (up 5600 total turnovers (TTN) >99% enantiomeric excess (ee)). Further engineering led variants P411-LAS-5249 P411-LAS-5264, deliver six-membered δ-lactones seven-membered ε-lactones, respectively, overcoming thermodynamically unfavorable strain associated these compared γ-lactones. This new was further extended complex based fused, bridged, spiro rings. The enzymatic platform developed here complements biosynthetic strategies assembly expands structural diversity accessible through functionalization.

Language: Английский

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Accelerating the implementation of biocatalysis in industry

Applied Microbiology and Biotechnology, Journal Year: 2019, Volume and Issue: 103(12), P. 4733 - 4739

Published: May 2, 2019

Language: Английский

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Scalable biocatalytic C–H oxyfunctionalization reactions

Chemical Society Reviews, Journal Year: 2020, Volume and Issue: 49(22), P. 8137 - 8155

Published: Jan. 1, 2020

Biocatalytic methods for selective C–H oxyfunctionalization reactions are rapidly emerging and hold significant potential to streamline complex molecule synthesis. This review highlights key advances in this area developed within the past decade.

Language: Английский

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Photochemical oxidation of benzylic primary and secondary alcohols utilizing air as the oxidant

Green Chemistry, Journal Year: 2019, Volume and Issue: 22(2), P. 471 - 477

Published: Dec. 11, 2019

A mild and green photochemical protocol for the oxidation of alcohols to aldehydes ketones was developed.

Language: Английский

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S-adenosylhomocysteine as a methyl transfer catalyst in biocatalytic methylation reactions

Nature Catalysis, Journal Year: 2019, Volume and Issue: 2(8), P. 696 - 701

Published: June 17, 2019

Language: Английский

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