酶催化外消旋体的动态动力学拆分反应研究进展

外消旋体的动态动力学拆分（DKR）是制备手性化合物的重要方法之一,过去多用化学催化剂进行反应,近年来生物催化剂的引入大大提高了DKR的效率和收率。系统地介绍了DKR的原理及酶催化外消旋体的动力学拆分反应的最新进展。     

化学-酶催化动态动力学拆分工艺中多相催化剂的研究进展

利用外消旋体进行化学-酶催化动态动力学拆分是制备单一手性化合物的有效手段之一。论述了近几年用于动态动力学拆分工艺中的固定化脂肪酶和固相外消旋化多相催化剂的研究进展,介绍了过渡金属配合物、酸性β-沸石和酸性树脂等固相外旋消化催化剂与固定化脂肪酶配伍,用于化学-酶催化动态动力学拆分工艺的催化效果。     

动态动力学拆分制备手性化合物的研究进展

综述了固体酸、固体碱和金属配合物在动态动力学拆分制备光学纯手性化合物进行外消旋化的催化机理,讨论了均相外消旋催化剂和多相外消旋催化剂在动态动力学拆分工艺中的应用,重点介绍了过渡金属配合物催化剂和生物酶配伍进行动态动力学拆分制备手性化合物的研究进展和发展趋势。     

金属催化和生物催化在对映体拆分中的联合应用

随着对单一对映体化合物需求的日益增长，外消旋体向单一对映体的转化(去外消旋化过程)成为研究的主要方面之一，最近在去外消旋化过程中的生物催化和金属催化的联合作用被证明是非常有效的。动态动力学拆分和循环去外消旋化已经对这方面的研究有很大的推动作用。     

有机相中脂肪酶催化转酯化反应动力学拆分左旋帕罗醇

研究了在有机相中脂肪酶催化转酯化反应动力学拆分左旋帕罗醇,考察了酶种类、溶剂、酰基供体、温度、底物与酰基供体摩尔比等因素对反应的影响。结果表明:以Novozym 435为催化剂,在30℃下,以乙腈为反应溶剂,乙酸乙烯酯为酰基供体,底物浓度40mmol/L及其与酰基供体摩尔比为1:8时,反应8h后,底物转化率为48.1%,ee_s为53.3%,E值为6.20。     

金属-酶协同催化动态动力学拆分反应研究进展

金属催化和酶催化在很长时间被认为是两个不同的领域,动态动力学拆分反应是金属-酶协同催化的成功应用。如何有效地协同金属催化的消旋化与酶催化的动力学拆分是其中的关键问题。本文对金属-酶协同催化动态动力学拆分醇和胺类化合物进行了综述,重点介绍了动态动力学拆分中常用的金属催化剂,各种金属与酶的协同,并对其前景进行了展望,指出提高酶在反应体系中的稳定性是未来的发展方向。     

酶催化卤化和去卤化反应

通过研究微生物降解卤素化合物发现了不同种类的去卤化酶,这些酶可以在好氧或厌氧条件下通过不同的作用机理脱去卤原子催化降解卤素化合物。到目前,通过生物法得到将近4000多种卤素化合物,早期仅分离并获得了催化卤化反应的卤过氧化物酶,近来,在研究细菌卤化代谢物的生物合成时发现了以FADH2为辅基的卤化酶。这种新型的卤化酶在卤化代谢物的生物合成中起催化作用。     

脂肪酶催化拆分环戊烯酮动力学研究

考察了４种不同来源的脂肪酶对环戊烯酮的拆分活性;从中选择ＰｓｅｕｄｏｍｏｎａｓＣｅｐａｃｉａＬｉｐａｓｅ为实验用酶,考察了影响酶拆分反应动力学的几种因素,结果表明酶拆分的最适温度为４０℃,ｐＨ值为７．０;反应过程存在严重的底物抑制,反应最终得到质量分数为４６．５％单一旋光纯的（Ｒ）－环戊烯酮。     

桃醛的外消旋物的分离研究进展

桃醛是一种重要的内酯香料,可广泛应用于日化香精和食用香精。桃醛是手性香料,其R-异构体具有独特的商业价值,而关于外消旋体的拆分报道较少,文中简单介绍了由化学合成得到的桃醛外消旋体的化学拆分、酶动力学拆分和色谱拆分法,期望对以后桃醛的外消旋体的拆分研究给予帮助。     

动态动力学拆分在手性药物合成中的应用

动态动力学拆分是合成手性化合物最方便和最有效的方法之一,该方法的主要特征是用酶催化拆分和金属催化原位外消旋化未反应的底物,克服了经典动力学拆分最高产率只有50%的缺陷,理论上可以达到100%的收率。本文概述了动态动力学拆分技术在手性药物合成中的应用。     

酰基供体对动态动力学拆分1-四氢萘胺的影响

采用新型消旋催化剂耦合Novozym 435成功构建1-四氢萘胺的动态动力学拆分体系用于制备光学纯(R)-1-四氢萘胺。该反应存在着自催化酰胺化反应,会降低反应的对映体选择性。从改变酰基供体结构的角度出发来抑制这种自催化酰胺化反应,考察了不同酸部以及不同醇部的酰基供体对1-四氢萘胺动态动力学拆分反应的影响,发现随着酰基供体结构变得复杂,1-四氢萘胺动态动力学拆分反应结果也相应变得越好,当采用戊酸对氯苯酯作为酰基供体时,动态动力学拆分反应结果就可达到最佳,即转化率>99%,光学纯度eeP>99%。     

动态动力学拆分方法在不对称催化中的应用与进展

不对称催化在有机合成中具有广阔的应用前景。传统的动力学拆分方法的缺点是最大产率仅为 5 0 %。而采用动态动力学拆分方法 ,所有外消旋底物都能转化成单一的对映体 ,产率为 10 0 %。主要论述了酶催化的动力学拆分、金属催化的外消旋作用及两者相结合的动态动力学拆分方法的原理和应用     

Process intensification with biocatalysts: dynamic kinetic resolution and fluorous phase switch with continuous extraction

Kinetic resolution of racemates with the help of enzymes has become a widely adopted method for the synthesis of chiral intermediates and compounds with biological activity. However, the inherent limitation to 50% yield of any one stereoisomer restricts the use of this method in industrial practice, when only one of the stereoisomers is required. The yield can theoretically be improved to 100% through either a chemical reaction, which inverts the stereochemistry at the optical active center, or through racemization of the unwanted isomer, followed by additional enzymatic resolution. The combination of the racemization of the slower reacting stereoisomer with kinetic resolution in a one-pot reaction is termed dynamic resolution. We describe the dynamic resolution of secondary alcohols through enzymatic stereoselective transesterification and heterogeneously catalyzed racemization of the alcohol over several zirconia-containing catalysts. In order to facilitate the separation of the products, we used a fluorous phase-switching technique coupled with fluorous extraction. The continuous extraction in a membrane contactor allows for facile recovery of the fluorous tagged species in a scaleable operation. The unoptimized scheme offers over 90% conversion with ca. 75% enantiomeric excess (e.e.).     

Lipase‐catalyzed dynamic kinetic resolution of (R,S)‐fenoprofen thioester in isooctane

A lipase‐catalyzed enantioselective hydrolysis process under in situ racemization of the remaining (R)‐thioetser substrate with trioctylamine as the catalyst was developed for the production of (S)‐fenoprofen from (R,S)‐fenoprofen 2,2,2‐trifluoroethyl thioester in isooctane. Detailed investigations of trioctylamine concentration on the enzyme activation and the kinetic behavior of the thioester in racemization and enzymatic reactions were conducted, in which good agreement between the experimental data and theoretical results was observed. © 2002 Society of Chemical Industry     

水解动力学拆分合成手性环氧氯丙烷用催化剂研究

水解动力学拆分是目前合成手性环氧氯丙烷的有效方法。salen催化剂的应用使得该反应得到的手性环氧氯丙烷产率高且具有高光学纯度,因此,关于salen催化剂的研究得到广泛关注。综述了合适salen催化剂的研究发现和完善过程,提出了引入价廉、具有高催化活性和高重复利用性的催化剂仍是当前乃至今后该领域研究工作的重点。     

酶法动态动力学拆分制备R-(-)-乙酰基邻氯扁桃酸

采用假单胞菌脂肪酶Pseudomonas sp. ECU1011催化乙酰基邻氯扁桃酸进行不对称水解,利用突变后的扁桃酸消旋酶(V29I)对拆分后的产物S-(-)-邻氯扁桃酸进行消旋,消旋后的邻氯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ee>99.9%的R-(-)-乙酰基邻氯扁桃酸,其收率达80%。本研究建立的R-(-)-乙酰基邻氯扁桃酸的动态动力学拆分工艺,对其工业化应用具有重要的指导意义。     

Enzymatic kinetic resolution of secondary alcohols by esterification with FA under vacuum

Kinetic resolution of some chiral secondary alcohols [2-octanol, 1-phenylethanol, and 1-(2-naphthyl)ethanol] with high enantioselectivity (E>300) was achieved by direct esterification with FFA catalyzed by immobilized Candida antarctica B lipase. The reaction equilibrium was shifted toward the synthetic side by the removal of the water formed under vacuum. Esterification of rac-2-octanol at an alcohol/FFA molar ratio of 2∶1 was used as a model reaction. The chain length of FFA and their structure influenced the reaction rate but did not have a measureable effect on E. The best acyl donor was decanoic acid: >47% conversion at 4 h with virtually perfect E. Temperature did not affect E in the range studied (15–45°C), but temperatures at the higher end afforded improved reaction rates. The reaction rates and E were compared for three different acyl donors. The initial reaction rate increased in the following order: ethyl laurate < lauric acid < vinyl acetate. E was high (E>300) for all acyl donors. Racemic 1-phenylethanol and 1-(2-naphthyl)ethanol were also resolved by direct esterification with decanoic acid in short times (3 and 4 h, respectively) with E>300 and excellent conversions. Preparative-scale kinetic resolution of 2-octanol was also performed.