Study On Enantioselective Esterification Of Aryl Propionic Acid Enantiomers Catalyzed By Lipase In Non-aqueous Solvent

In this paper,the tendency of enantiomer excess of substrate?ee_s?in chiral resolutions catalyzed by lipase was studied.The ee_s showed a tendency of decreasing after arriving the max value,the reason of it was analyzed and then two methods to enhance the max ee_s value(ee_s,max)were obtained and mathematical equations of ee_s were established.Leaded by equations,chiral resolutions for 4 kinds of aryl propionic acids?2-phenylpropionic acid,2-?4-methylphenyl?propionic acid,ibuprofen and loxoprofen?were operated.It was proved that methods of enhancing ee_s,max were efficient and equations were useful for these reactions.The study in this paper show a possibility on obtaining high optical purity aryl propionic acids by lipase catalyzed esterification.Primary work and results as follows.1.In process of chiral resolutions catalyzed by lipase,the reason of ee_s decreasing was the strong inhibition to reaction rate of fast reaction enantiomer.When its rate and concentration ratio was less than slow reaction enantiomer,ee_s decreased.After study furthermore,ee_s,max,max could enhanced by increasing reacted alcohol concentration and control water concentration.2.For esterification catalyzed by lipase in this paper,the ideal mathematical equations of ee_s,max was established.3.Lipase and organic solvent type were chosen.Influence of reaction temperature,enantiomer initial concentration,n-hexanol initial concentration and enzyme loading on enzyme activity and enantioselectivity were studied.4.Esterification of 4 kinds of aryl propionic acids catalyzed by lipase were studied.Leaded by mathematical equations of ee_s,max,reaction conditions were calculated for a desired ee_s and got it in experiment.Esterification of 200 mmol/L n-hexanol with 100 mmol/L2-phenylpropionic acid catalyzed by lipase Novozym435 in n-hexane at 50°C yielded 89.20%of the value of ee_s?desired ee_s=91.3%?.Esterification of 1500 mmol/L n-hexanol with 1000mmol/L 2-?4-methylphenyl?propionic acid catalyzed by lipase Novozym435 in n-hexane at80°C yielded 97.84%of the value of ee_s?desired ee_s=97.7%?.Esterification of 800 mmol/L n-hexanol with 600 mmol/L ibuprofen catalyzed by lipase Novozym40086 in methyl tert-butyl ether at 70°C yielded 93.78%of the value of ee_s?desired ee_s=95.6%?.Esterification of 500mmol/L n-hexanol with 300 mmol/L loxoprofen catalyzed by lipase Novozym40086 in methyl tert-butyl ether at 79°C yielded 98.64%of the value of ee_s?desired ee_s=97.2%?.