cercosporin-photocatalyzed-4-1-4-2-annulations-azoalkenes-under-mild

Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions

The interest on nitrogen-containing heterocycles has expanded rapidly in the synthetic community since they are important motifs for new drugs. ...

Jiangnan University

Diaryl ketones are important building blocks for synthesizing pharmaceuticals and are generally regarded as "difficult-to-reduce" ketones due to the large steric hindrance of their two bulky aromatic side chains. Alcohol dehydrogenase from Kluyveromyces polyspora ( KpADH) has been identified as a robust biocatalyst due to its high conversion of diaryl ketone substrate (4-chlorophenyl)(pyridine-2-yl)ketone (CPMK) with a moderate R-selectivity of 82% ee. To modulate the stereoselectivity of KpADH, a "polarity scanning" strategy was proposed, in which six key residues inside and at the entrance of the substrate binding pocket were identified. After iterative combinatorial mutagenesis, variants Mu-R2 and Mu-S5 with enhanced (99.2% ee, R) and inverted (97.8% ee, S) stereoselectivity were obtained. The crystal structures of KpADH and two mutants in complex with NADPH were resolved to elucidate the evolution of enantioselective inversion. Based on MD simulation, Mu-R2-CPMK and Mu-S5-CPMK were more favorable in the formation of prereaction states. Interestingly, a quadrilateral plane formed by α-carbons of four residues (N136, V161, C237, and G214) was identified at the entrance of the substrate binding pocket of Mu-S5; this plane acts as a "polar gate" for substrates. Due to the discrepancy in charge characteristics between chlorophenyl and pyridine substituents, the pro- S orientation of CPMK is defined when it passes through the "polar gate" in Mu-S5, whereas the similar plane in wild-type is blocked by several aromatic residues. Our result paves the way for engineering stereocomplementary ADH toward bulky diaryl ketones and provides structural insight into the mechanism of stereoselective inversion.

Structural Insight into Enantioselective Inversion of an Alcohol Dehydrogenase Reveals a "Polar Gate" in Stereorecognition of Diaryl Ketones.

Naturally occurring perylenequinonoid pigments (PQPs) have attracted considerable attention owing to their excellent properties of photosensitization. They have been widely investigated as an aspect of photophysics and photobiology. However, their applications in photocatalysis are yet to be explored. We report here that sunlight along with 1 mol% cercosporin, which is one of the perylenequinonoid pigments, catalyzes the direct C-H bond arylation of (het)arenes by a photoredox process with good regioselectivity and broad functional group compatibility. Furthermore, a gram-scale reaction with great conversions of substrates was achieved even by a cercosporin-containing supernatant without organic solvent extraction and purification after liquid fermentation. Thus we set up a bridge between microbial fermentation and organic photocatalysis for chemical reactions in a sustainable, environmentally friendly manner.

Perylenequinonoid-catalyzed photoredox activation for the direct arylation of (het)arenes with sunlight.

We reported a new method that visible light along with cercosporin, one of the naturally occurring perylenequinonoid pigments with excellent properties of photosensitization, photocatalyzed sp (C-H) activation for the synthesis of pyrrolo[3,4-c]quinolones through the annulation of anilines and maleimides under mild conditions.

Article	Year
Structural Insight into Enantioselective Inversion of an Alcohol Dehydrogenase Reveals a "Polar Gate" in Stereorecognition of Diaryl Ketones. Journal of the American Chemical Society\| PubMed ID: 30247889	2018
Perylenequinonoid-catalyzed photoredox activation for the direct arylation of (het)arenes with sunlight. Organic & biomolecular chemistry\| PubMed ID: 30984953	2019
Cercosporin-photocatalyzed sp (C-H) activation for the synthesis of pyrrolo[3,4-c]quinolones. Organic & biomolecular chemistry\| PubMed ID: 31580376	2019

Yijian Rao

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