Lipase-catalysed two-step desymmetrization of 2-methylmalonic dipyrazolide for preparation of optically pure enantiomer in organic solvents

2017-09-14T15:26:36Z (GMT) by Ching-Hsiang Hsu Shau-Wei Tsai
<p>A lipase-catalysed two-step butanolytic desymmetrization process for the preparation of pyrazolidyl butyl (<i>S</i>)-2-methylmalonate from 2-methylmalonic dipyrazolide was developed. The best reaction condition of using lipase PS-D in anhydrous <i>n</i>-hexane at 55 °C was first selected, leading to high yield and enantiomeric excess for the remained (<i>S</i>)-enantiomer. The kinetic analysis by considering the competitive inhibition from butanol was then carried out for obtaining the stereoselectivity of <i>E</i><sub>1</sub> = 11.2 for the first desymmetrization and enantiomeric ratio of <i>E</i><sub>3</sub><i>E</i><sub>2</sub><sup>−1</sup>=11.8 for the subsequent kinetic resolution. The thermodynamic analysis furthermore revealed that the enzyme stereodiscrimination was enthalpy-driven for the desymmetrization step, but changed as entropy-driven for the kinetic resolution step.</p>