Kinetic Resolution of Cyclic β-Amino Esters with Lipase B from Candida antarctica on Magnetic Nanoparticles

Abstract

The biocatalytic kinetic resolution of three racemic cyclic β‑amino esters (±)-ethyl cis‑2‑aminocyclopent‑3‑enecarboxylate (±)-1a, (±)-ethyl cis‑2‑aminocyclohex‑3‑enecarboxylate (±)-1b, and (±)-ethyl trans‑6‑aminocyclohex‑3‑enecarboxylate (±)-1c was investigated using lipase B from Candida antarctica immobilized on magnetic nanoparticles with three different acylating agents (E, C, M). Among the substrates examined, (±)-1a underwent a highly enantioselective N‑acylation, displaying the characteristic profile of a classical kinetic resolution with conversions ~50% and excellent enantiomeric excess of the (R)-amide product (ee_(R)-2aE > 99.9%). The reaction showed notable robustness across a wide substrate concentration range, highlighting its potential for larger‑scale preparation of enantiomerically pure compounds. In contrast, substrates (±)-1b and (±)-1c were not resolved at preparative scale due to the low selectivity of the biocatalyst in kinetic resolution (for (±)-1b) or insufficient chromatographic separation of the corresponding racemic amide (±)-2cE). The three novel racemic amides [(±)-2a–cE] and enantiopure (R)-2aE and (S)-1a were isolated and properly characterized.