Biosynthesis of [S]-naproxen starch ester by Carica papaya lipase in intermittent opening reaction mode

ABSTRACT

In order to brought S-naproxen into small intestine, an optically pure [S]-naproxen starch ester was produced by lipase through enantio-selective trans-esterification of racemic naproxen methyl ester with pretreatment starch in solvent system. With carefully selection of the reaction medium [isooctane], lipase [Carica Papaya Lipase, CPL] and the reaction mode [intermittent opening], a high conversion rate [48.6%] and enantiomeric excess of product [99.6%] was obtained. The slow release macromolecular [S]-Naproxen had been synthesized to improve the efficacy of racemic naproxen and overcome its side effects. The enanitomeric ratio of CPL [E=52.5] was higher than CRL [E=22] and greatly influenced by the byproduct methyl alcohol. The intermittent opening reaction mode was the effective way to remove the inhibition of methyl alcohol and to improve the enantio-selectivity of CPL. S-naproxen starch was confirmed by HPLC and [1]H NMR. This method may also apply to preparation the other optically pure 2-phenylpropionic acid derivatives. S-naproxen starch was a new optically pure derivatives possessing emulsifying and slow release properties would be widely applied to the food, pharmaceutical and biomedical industries