Enzymatic kinetic resolution of an intermediate alcohol of the drug Tegoprazan using lipase from Thermomyces lanuginosus

Abstract

An enzymatic approach for the synthesis of intermediate alcohol of the drug tegoprazan in 99% ee at 20 °C in hexane has been developed utilizing commercially available immobilized Thermomyces lanuginosus lipase (TL lipase) as a biocatalyst and vinyl acetate as a acyl donor. This method involves the enantioselective esterification of (RS)-5,7-difluorochroman-4-ol with vinyl acetate using TL Lipase. This enzymatic approach provides the (S)-chiral alcohol in 44% yield with 99% enantiomeric excess (ee) and the (R)-acetate in 43% yield and >99% ee. It is a sustainable approach for the synthesis of enantiopure tegoprazan intermediate, contributing to the advancement of green chemistry. The recovered TL lipase was reused in 13 subsequent runs without loss of activity.

GRAPHICAL ABSTRACT

Keywords:

• Chemo-enzymatic approach
• lipases
• biocatalysts
• tegoprazan
• green synthesis

Additional information

Funding

PD thanks to CSIR, New Delhi, India for the financial assistance (HCP-0023); PR and LB thanks to the Department of Science and Technology (DST-SERB) India grant no: EEQ/2020/000455. IICT/Pubs./2023/269.