Enzyme-Catalyzed Dynamic Kinetic Resolution for the Asymmetric Synthesis of 2,3-Dihydrobenzofuran Esters and Evaluation of Their Anti-inflammatory Activity

Org Lett. 2024 Dec 20;26(50):11056-11061. doi: 10.1021/acs.orglett.4c04242. Epub 2024 Dec 11.

Abstract

Utilizing enzymes as biocatalysts, an alternative strategy has been developed for the highly enantioselective synthesis of chiral 2,3-dihydrobenzofuran (2,3-DHB) esters via the dynamic kinetic resolution of 2,3-dihydro-3-benzofuranols, which are generated from an intramolecular Aldol reaction. This protocol provides easy access to a series of 2,3-DHB ester derivatives, prodrugs, and allows for functional group transformations. Biological evaluation also indicates that some of the products exhibit potent anti-inflammatory activity.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents* / chemical synthesis
  • Anti-Inflammatory Agents* / chemistry
  • Anti-Inflammatory Agents* / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Benzofurans* / chemical synthesis
  • Benzofurans* / chemistry
  • Benzofurans* / pharmacology
  • Biocatalysis
  • Catalysis
  • Esters* / chemistry
  • Esters* / pharmacology
  • Kinetics
  • Molecular Structure
  • Stereoisomerism

Substances

  • Benzofurans
  • Esters
  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal