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

Author(s)

Zanin, Lucas Lima ; Brito Matos, Thiago Kelvin ; Leitao, Andrei ; Ellena, Javier ; Meleiro Porto, Andre Luiz

• Document type: Journal article
• Source: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY; v. N/A, p. 9-pg., 2022-06-20.

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. (AU)

• FAPESP's process: 19/07654-2 - Biginelli reaction (synthesis and chemoenzymatic resolution) and biotransformation of steroids by microorganisms
• Grantee: Andre Luiz Meleiro Porto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/15904-6 - Characterization of cysteine protease inhibitors with antineoplastic activity by in silico and cell-based assays coupled with chemical analyses
• Grantee: Andrei Leitão
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/20155-7 - Biocatalytic reactions of aminolysis and kinetic resolution by lipases and biodegradation of agrochemicals by microorganisms
• Grantee: Andre Luiz Meleiro Porto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/15850-0 - X-ray diffraction as a tool in potential drug development
• Grantee: Eduardo Ernesto Castellano
• Support Opportunities: Research Projects - Thematic Grants