Biocatalytic Kinetic Resolution to Access Enantiomerically Enriched Dihydropyrimidinone/Thiones through Recognition of a Remote Stereocentre

• Published in: European Journal of Organic Chemistry
• Main Authors: Zanin, Lucas Lima, Brito Matos, Thiago Kelvin, Leitão, Andrei, Ellena, Javier, Porto, André Luiz Meleiro
• Other Authors: Fundação de Amparo à Pesquisa do Estado de São Paulo
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2022
• Subjects: Organic Chemistry; Physical and Theoretical Chemistry; Antarc*; Antarctica
• Online Access: http://dx.doi.org/10.1002/ejoc.202200331; https://onlinelibrary.wiley.com/doi/pdf/10.1002/ejoc.202200331; https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ejoc.202200331

Abstract The Biginelli synthesis is a classic tricomponent reaction known to result in polyfunctionalized dihydropyrimidinone (DHPM) derivatives. Herein, we described a chemo‐enzymatic strategy for obtaining enantiomerically enriched hydroxy‐DHPMs. These compounds were previously esterified with butyric or acetic anhydride and were later submitted to hydrolysis reactions catalysed by lipase B from Candida antarctica . Although the stereogenic centre is far from the reaction site (4–5 bonds), moderate to excellent enantiomeric excess values were obtained (up to 99 %). Docking studies were performed in parallel to elucidate the binding modes of some molecules with the CALB active site, and were able to provide information on the enantiospecificity of these compounds in the hydrolysis reaction.