酶法动态动力学拆分制备R-(-)-乙酰基邻氯扁桃酸.pdf

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化工进展
2014年第33卷第9期
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研究开发
酶法动态动力学拆分制备R()广乙酰基邻氯扁桃酸
沈萨萨,姜灵2,陆杰,于洪巍2
('江南大学化学与材料工程学院,江苏无锡214122:2浙江大学化学工程与生物工程学系,浙江杭州310028)
摘要:采用假单胞茵脂肪酶 Pseudomonas sp.ECU1011催化乙跳基邻氟扁桃酸进行不对称水解,利用突变后的扁
桃酸消旋酶(V29)对拆分后的产物S-(-)邻氯扁桃酸进行消旋,消旋后的邻氟扁桃酸经过酰化重新被利用到水解
反应中,实现了酶法动态动力学拆分制备R-(-)-乙酰基邻氯扁桃酸。通过对拆分反应、拆分混合物的分离回收以
及消旋反应的工艺优化,最终获得光学纯度e>99.9%的R()乙酰基邻氯扁桃酸,其收率达80%。本研究建立的
R-(-)-乙酰基邻氟扁桃酸的动态动力学拆分エ艺,对其エ业化应用具有重要的指导意义
关键词:酶法动态动力学拆分;脂肪酶 Pseudomonas sp.ECU1011;扁桃酸消旋酶;乙酰基邻氯扁桃酸;邻氯扁
桃酸
中图分类号:TQ463;Q819文献标志码:A文章编号:1000-6613(2014)09-2425-07
DOI:10.39695issn.1000-6613.2014.09.032
R-c)-acetyl-o-mandelic acid preparation via enzymatic dynamic kinetic
resolution
SHEN Sasa, JIANG Ling LU Jie, YU Ho
onge
(School of Chemical and Material Engineering, Jiangnan University, wuxi 214122, Jiangsu, China; School of
Chemical and Biological Engineering, Zhejiang University, Hangzhou 310028, Zhejiang, China)
Abstract: In this study, asymmetric hydrolysis of acetyl chloromandelic acid was catalyzed b
Pseudomonas sp. ECU1011, and the S-(-)-chloromandelic acid in the resolution mixture was then
racemerized using the mutated mandelate racemase and fed back into the hydrolysis reaction after
acylation realizing enzymatic dynamic kinetic resolution for preparation of R--acety
chloromandelic acid. Firstly, the conditions for enzymatic resolution, separation of resolution mixture
and enzymatic racemization were optimized. Subsequently, dynamic kinetic resolution of acety
chloromandelic acid was conducted under the optimal conditions, obtaining optically pure R-()-acetyl
chloromandelic acid with final yield of 80%. The conditions for enzymatic resolution, chloromandelic
acid recycling and racemization were optimized in this study, leading to preliminary establishment of
the dynamic kinetic resolution process for R-)-acetyl chloromandelic acid preparation, with guiding
significance for future industrial applications
Key words: enzymatic dynamic kinetic resolution Pseudomonas sp. ECU1011 lipase; mandelate
racemase; R-()-acetyl-o-mandelic acid; chloromandelic acid
邻氯扁桃酸是一种重要的精细化学品,在医药收稿日期:201401.02修改稿日期:201401,2
化学品领域具有广泛应用。其中,R-(-)-邻氯扁桃酸
基金项目:国家自然科学基金(21176102、21176215、GZ935)、江
苏省自然科学基金(BK20131100)、江苏省环保科研课题基金
是合成新型血小板聚集抑制剂氯叱格雷的重要中间
(2012004)及浙江省自然科学基金杰出青年基金(21076181)项目。
体1]。随着氯吡格雷、邻氯扁桃酸及其衍生物用途第二作者。沈萨(1985-),女,硕土+E-mailsasashen(@163.com
物合成等
的进一步开发,R-(-)-邻氯扁桃酸的需求量日益增 lujie(@jiangna
a..cne