The Preparation Of Chinal β-hydroxy Acids By Enzyme

Chiralβ-hydroxy acids are important drug intermediates which can be used for synthesizing various anti-inflammatory and antiseptic drugs. Chiral p-hydroxy acid is also the monomer of the polyhydroxyalkanoate (PHA) which is a kind of biodegradable plastic. Optically pure P-hydroxy-β-phenyl propionic acid andβ-hydroxy caproic acid were prepared using enzyme as a biocatalyst in this paper.In the process of preparation, the racemates of ethyl P-hydroxy-β-phenylpropionate and ethyl P-hydroxy caproate were synthesized firstly. They were synthesized according to Reformatsky reaction which protected by nitrogen at room temperature using zinc power as a catalyst which had been activated previously. The benzaldehyde and butyl aldehyde reacted with ethyl bromoacetate respectively. Secondly, optical pure (S)-β-hydroxy-β-phenyl propionic acid and (S)-β-hydroxy caproic acid were prepared using porcine pancreas lipase (PPL) as a catalyst in pure water system. The conditions of these reactions were all at the temperature of 35℃, pH 7.5. This method took full advantage of the stereoselectivity of lipase. Lipase that used in catalytic reactions is stereospecific and efficient. The mild reaction conditions can avoid many side effects. In addition, it has less pollution to the environment than other chemical catalysts. Lipase is a kind of "green" catalysts.The catalytic conversion and optical purity of (S)-β-hydroxy-β-phenyl propionic acid were also discussed under different conditions, such as the kinds of lipase, solvent, temperature and pH. Experimental results showed that PPL is the ideal lipase in the resolution of optically pure (S)-β-hydroxy-β-phenyl propionic acid considering resolution efficiency and cost-saving. The catalytic conversion and the product's enantiomeric excess (ee) were relatively better when they reacted in pure water phase, at the temperature of 35℃and pH 7.5. Therefore, under the condition of PPL-catalyzed resolution of ethylβ-hydroxyl-β-phenylpropionate, the best experimental conditions were at the temperature of 35℃and pH 7.5. The conversion of 31.48% and the ee of 77.83% could be obtained in the resolution ofβ-hydroxy-β-phenyl propionic acid.