J Org Chem. 2026 Jun 25. doi: 10.1021/acs.joc.6c00980. Online ahead of print.

ABSTRACT

A chemo-enzymatic approach to enantiopure (S)-linezolid 1 is presented. The key chiral intermediate, (R)-alcohol 4, was obtained via CRL lipase-catalyzed kinetic resolution of (RS)-4, affording an enantiopure (R)-alcohol 4 with 98.5% ee_s (enantiomeric excess of substrate) and an (S)-ester with 97.1% ee_p (enantiomeric excess of product). The key intermediate (R)-4 undergoes cyclization, followed by azide substitution, reductive acylation, and coupling with morpholine, affording enantiopure (S)-1 in ≥ 99% ee and 23% overall yield over six steps. This route offers an efficient biocatalytic strategy to access linezolid with high selectivity.

PMID:42343745 | DOI:10.1021/acs.joc.6c00980