Concise Asymmetric Total Syntheses of (+)-Dihydropleurotinic Acid and (−)-Pleurotin, Enabling Rapid Late-Stage Diversification
Year: 2024
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide (−)-Pleurotin ( 1 ) and (+)-dihydropleurotinic acid ( 2 ) are benzoquinone meroterpenoids isolated from fungal sources with powerful antitumor and antibiotic activities. Concise asymmetric total syntheses of the stereochemically pure (+)-dihydropleurotinic acid ( 2 ) and (−)-pleurotin ( 1 ) from the chiral pool ( R )-Roche ester-derived vinyl bromide 7 have been achieved in 12 and 13 longest linear steps, respectively. The key transformations feature a Michael addition/alkylation cascade reaction to forge three contiguous stereocenters matched with the natural products, a PtO 2 -catalyzed stereoselective reduction of olefin to generate the correct stereocenter at C3, a palladium-catalyzed Negishi cross-coupling between triflate and zinc reagent to introduce the redox-sensitive para-quinone moiety, and a hydroboration/copper-catalyzed carboxylation sequence to incorporate the vital carboxyl group. Thus, the highly efficient and scalable preparation of pleurotin’s pentacyclic skeleton enables the late-stage diversification, affording otherwise unavailable pleurotin analogs with significantly improved antiproliferative activities against the thioredoxin reductase (TrxR) overexpressed human breast cancer cell lines relative to the natural product pleurotin ( 1 ).
Source: JACS Au
Authors: Bin Huang, Jing Pang, Nan Cao, Ya-Shuang Dai, Ya-Qiu Long
Institution: Soochow University
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,500
OpenAlex ID: W4404235241