Kinetic Resolution Of (R, S)-2-octanol By Esterification Reactions With Mycelium-bound Lipase From Rhizopus Chinensis

(R)-2-octanol and (S)-2-octanol are important optically active alcohols and used as chiral intermediates for the preparation of chiral natural products and related compounds such as many pharmaceuticals. Compared with the traditional chemical method, utilization of enzymes is of great value both in academy and practical application, because of the mild reaction condition, high enantioselectivity, less side reactions and environment pollution of enzyme-catalyzed reaction. Mycelium-bound Lipase from Rhizopus chinensis (RCL) was的determinded as biocatalyst for resolution of (R, S)-2-octanol in this research.The catalytic reaction system and the separation of products (R)-2-octanol, (S)-2-octanol were also systematically studied.At first, by contrasting the capabilities of different lipases for resolution of (R, S)-2-octanol in the organic media, RCL was obtained as the biocatalyst for its high catalytic activity and high enantioselectivity.In this dissertation, the optimum preparation of RCL and catalytic reaction of resolution of (R, S)-2-octanol was determined. It is as follows:memorial pH value 6~7, organic media isooctane, rotation speeds 150 rpm, temperature 40℃.In order to improve the resolution of (R, S)-2-octanol catalytic efficiency catalyzed by RCL, acyl donor n- octanoic acid and water activity 0.11 was determinded during the study. At the same time, the catalytic activity and enantioselectivity were different extent improved by adding low concentration (≤0.5 mg/mL) no-nion surfactant such as Trion X-100 and Span-80.More valuable discovery was that by adding 3 ? molecular sieves to the reaction system which in order to absorb the water which come from the catalytic reaction, the initial velocity of production of (R)-ester was improved to 54.9μmol/g·h which increased by 7.3 times, compared that without 3 ? molecular sieves. Meantime, the ideal enantiomeric excess of product octan-2-yl octanoate (eep 95.9%) was also got. Compared with other commercial lipases, higher enantiomeric ratio (E) from resolution of (R, S)-2-octanol catalyzed by RCL was obtained. It is showed great application prospect.Because of the difference of boiling points from two products, the vacuum distillation which was utilized to separate the 2-octanol and octan-2-yl octanoate showed good result. At last the process of separation was determined. The mass recovery of (S)-2-octanol was 65.5 % and the ee value was 97.1 %. The mass recovery of (R)-2-octanol was 68.5 % and the ee value was 95.2 %.According to the mechanism of enzymatic esterification during the resolution of (R, S)-2-octanol in nonaqueous media, the kinetic model of this enzymatic resolution was established. There was no noTable difference between measured data and predicted values by cross-validation, suggesting that this model could describe the resolution process of (R, S)-2-octanol catalyzed by RCL successfully.In this research, RCL was determinded as the good biocatalyst for resolution of (R, S)-2-octanol. And the key factor which could effectively improve the resolution of (R, S)-2-octanol catalytic efficiency was also found. The process of products separation and the kinetic model of this enzymatic resolution could be valuable toward the industrial scale-up.