桃仁醇腈酶促不对称合成含硅(R)-酮氰醇

Asymmetric synthesis of silicon containing (R)-ketone cyanhydrin catalyzed by (R)-hydroxynitrile lyase from peach seed meal

采用气相色谱手性分析,研究桃仁(R)-醇腈酶催化2-三甲基硅-2-乙酮与丙酮氰醇,在水和有机溶剂双相中不对称合成(R)-2-三甲基硅-2-羟基-丙腈.分析酶添加量、底物浓度、有机溶剂、两相体积比、水相pH值、反应温度及底物结构对桃仁醇腈酶促反应的影响.结果表明,桃仁醇腈酶催化2-三甲基硅-2-乙酮与丙酮氰醇不对称合成的优化反应条件为酶添加量0.6g左右,底物2-三甲基硅-2-乙酮浓度14mmol/L,有机溶剂为异丙醚,水相与有机相体积比1.5∶10,水相pH=5.0,反应温度30℃.在优化反应条件下,反应转化率和产物的对映体过剩值均达99%以上.为探讨底物中硅原子对桃仁醇腈酶促不对称合成的影响,对比研究了桃仁醇腈酶催化碳结构类似物3,3-二甲基-2-丁酮的不对称转化.发现底物2-三甲基硅-2-乙酮中的硅原子对桃仁醇腈酶催化反应有重要影响,桃仁醇腈酶催化2-三甲基硅-2-乙酮反应在底物转化率和产物光学纯度等方面均显著优于其碳结构类似物3,3-二甲基-2-丁酮的相应值.

Due to the specific characteristics of silicon atom,organosilicon compounds have attracted growing interest for some years.In the present study,the asymmetric synthesis of optically active （R）-2-trimethylsilyl-2-hydroxyl-ethylcyanide via enantioselective transcyanation of acetyltrimethylsilane with acetone cyanohydrin（donor of HCN） catalyzed by （R）- hydroxynitrile lyase from defatted peach seed meal in an aqueous/organic biphasic system was successfully carried out.The conversion of acetyltrimethylsilane and enantiomeric excess of （R）-2-trimethylsilyl-2-hydroxyl-ethylcyanide were determined by gas chromatography on a β-cyclodextrin chiral column. The influences of enzyme amount,substrate concentration,organic solvent,the volume ratio of aqueous to organic phase,buffer pH,reaction temperature and substrate structure on the reaction were investigated systematically.Under the optimum conditions including an enzyme amount of 0.6 g,a concentration of acetyltrimethylsilane of 14 mmol/L,an organic solvent of diisopropyl rther,a volume ratio of aqueous to organic phase of 1.5∶10,a buffer pH of 5.0 and a reaction temperature of 30 ℃,both acetyltrimethylsilane conversion and enantiomeric excess of the product were above 99%. Comparative study demonstrates that silicon atom in acetyltrimethylsilane has a great effect on the reaction and both the substrate conversion and the product enantiomeric excess of the transcyanation of acetyltrimethylsilane are much higher than those of its carbon counterpart 3,3-dimethyl-2-butanone.