J Agric Food Chem. 2026 Jul 7. doi: 10.1021/acs.jafc.5c17439. Online ahead of print.

ABSTRACT

(R)-N-(2,6-dimethylphenyl) aminopropionic acid methyl ester ((R)-DMPM) is a key chiral intermediate for the fungicide N-(2,6-Dimethylphenyl)-N-(methoxyacetyl)-alanine methyl ester ((R)-Metalaxyl). The biological function of the (R)-Metalaxyl is heavily dependent on its R-configuration, however, conventional chemical or single-esterase esterification for (R)-DMPM production induces severe racemization, dramatically compromising the optical purity and the efficacy of (R)-metalaxyl. In this study, a novel dual-enzyme cascade immobilized on polystyrene resin, combining the esterase PAE from Pseudochrobactrum asaccharolyticum WZZ003 for stereoselective hydrolysis of the substate (R,S)-(DMPM) to produce (S)-DMPM and (R)-MAP-acid, and the Novozym 435 for transmethylation of (R)-MAP-acid to produce (R)-DMPM, was applied. After a systematic optimization of dual-enzyme catalysis, the highest optical purity of (R)-DMPM ever reported with an e.e._p of 99.1% and an E value of 900 was obtained under the 49.2% conversion of (R,S)-DMPM and 96.2% of esterification yield conditions. The results overcome the limitations of racemization and provides a green, high-yield route for the industrial production of (R)-DMPM.

PMID:42411293 | DOI:10.1021/acs.jafc.5c17439