微生物酶不对称水解合成S(+)-布洛芬的研究 Ⅱ.反应条件和产物提取

SYNTHESIS OF S(+)-2-(4-ISOBUTYLPHENYL) PROPIONIC ACID BY ASYMMETRIC HYDROLYSIS OF MICROBIAL ENZYME II. REACTION CONDITIONS AND PRODUCT EXTRACTION

皮状丝孢酵母具有较强不对称水解底物专一性.在试验的五种布洛芬消旋酯中,水解甲酯和异丙酯生成s(+)-布洛芬ee可达97%,乙酯为93%以上;而水解活性以乙酯最强,转化率高于30%.不对称水解最适pH6.5—7.0;温度在28—37℃范围内拆分能力无明显差别.该酵母的水解酶为胞内酶,将酵母细胞制成两酮干粉进行水解可提高立体专一性.产物S(+)-布洛芬可借助于酸碱反应和有机溶剂提取得到,同时回收未水解的酯.

Trichosporon cutaneum 158 exhibited higher sterospecificity to hydro-lyze substrate ibuprofen ester. Among the five chosen substrate, asymmetric hydrolysis of methyl ester or isopropyl ester formed S(+)-ibuprofen of 97% ee. Whileethyl ester not only gave ee 93% but also showed the highest hydrolytic activity.The optimum pH range for asymmetric hydrolysis was 6.5-7.0. Ability of resolu-sion was stabler in the range of temperature 28-37℃. This yeast produced intra-cellular enzyme. Hydrolysis can be carried out by powered cells treated by iced-acetone to improve the specificity of resolution. The product S(+)-ibuprofen canbe got with acid-base reaction and organic solvent extraction, unreacted esters canbe recovered simutaneously.