脂肪酶催化合成对映纯硫杂环戊烷动力学模型  

Kinetic Model of Dynamic Covalent Kinetic Resolution for Synthesis of Enantiopure Oxathiolane Catalyzed by Lipase

作　　者：唐慧 王繁业[1] TANG Hui;WANG Fanye(School of Chemical Engineering,Qingdao University of Science and Technology,Qingdao 266042,China)

机构地区：[1]青岛科技大学化工学院,山东青岛266042

出　　处：《青岛大学学报（工程技术版）》2021年第1期61-68,共8页Journal of Qingdao University(Engineering & Technology Edition)

基　　金：国家自然科学基金资助项目(21546004,21576145);山东省重点研发计划资助项目(2019GSF107027,2019GNC106028,2019GSF107033)。

摘　　要：为有效提高医药中间体对映纯1,3-氧杂硫杂环戊烷(P_(R))的产率,本研究对动态动力学拆分,制备P_(R),并建立其动力学模型。采用一锅法合成对映纯((R)-5乙酰氧基-1,3-氧杂噻喃-2-基)乙基苯甲酸酯(P_(R)),其中,催化剂为固定化丝孢酵母脂肪酶(Trichosporonlaibachii CBS 5791),底物为2-(苯基甲氧基)乙醛(A),1,4-二硫-2,5-二醇(B)和乙酸苯酯(D)。研究结果表明,其转化率可以达到99.6%,产率为97.3%,对映体过量百分率(enantiomeric excess,ee%)为96.5%,所建立的反应体系动力学模型,很好地拟合了实验数据,表明可逆半硫代乙缩醛转化反应动力学遵从幂律方程,而酶催化内酯化反应为带产物抑制的序列机制。该研究可高效合成P_(R),最大限度地提高了生产效率。In order to effectively improve the yield of enantiomeric 1,3-oxathiolane(P_(R))of pharmaceutical intermediates,dynamic covalent kinetic resolution was performed in this study to prepare P R and establish its kinetic model.Using one-pot process,enantiopure((R)-5-acetoxy-1,3-oxathiolan-2-yl)ethyl benzoate(P_(R))was synthesized with 99.6%conversion,97.3%yield and 96.5%ee.,and it was performed using an enzyme called Trichosporonlaibachii CBS 5791,with substrates of 2-(phenylmethoxy)acetaldehyde(A),1,4-dithiophene-2,5-diol(B),and phenyl acetate(D).A kinetic model for the resolution was developed for the first time,which fits the experimental data very well.The transformation may follow a power law,and the enzymatic lactonization may follow a sequential mechanism with product inhibition.P R can be synthesized efficiently by the one-pot method,and the mechanism of the reaction is revealed by the kinetic model established.

关 键 词：动力学模型 脂肪酶 半硫缩醛转化 1 3-氧硫杂环戊烷 酶促对映选择性合成 

分 类 号：TQ463[化学工程—制药化工]