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。     

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。     

酶催化的动态动力学拆分和去消旋化反应的研究进展

最近,在外消旋化合物的动态动力学拆分以及去消旋化反应方面,新型催化剂的发现以及反应条件的优化都得到了很大的发展。一些特殊功能团使得它们的化合物可以发生动态动力学拆分或是去消旋反应,如仲醇、α-氨基酸、胺及羧酸。在催化反应过程中,一般都是对映体选择性酶与化学试剂的相结合,化学试剂一般常用于催化非活性对映体发生去消旋反应或是回收去消旋化过程中的中间体。在一些动态动力学拆分中,消旋酶还可以催化对映异构体之间发生互变。     

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。     

脂肪酶催化动力学拆分大分子手性化合物的研究进展

脂肪酶已广泛用于制备手性化合物的动力学拆分中,但大多数酶催化拆分外消旋化合物,特别是大分子手性化合物的对映选择性不很理想。目前,提高脂肪酶对映选择性的研究主要在改造脂肪酶蛋白结构、优化体系的反应条件、改善反应过程以及对映选择性抑制等方面进行。本文主要介绍了几种改善脂肪酶催化动力学拆分大分子手性化合物对映选择性的合理方法。     

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。     

Penicillium expansum脂肪酶选择性拆分外消旋萘普生

为了实现固定化扩展青霉TS414(Penicillium expansum TS414)脂肪酶在有机相中对外消旋萘普生的高效拆分,实验考察了水分、温度、有机溶剂、酶浓度、醇结构和醇浓度对酶促拆分反应的影响,确立了优化的酯化反应条件为：异辛烷为溶剂,外消旋萘普生2.15 mmol/L,正丙醇34.3 mmol/L,固定化酶量12 g/L,水0.05%(j), 40℃恒温摇床中200 r/min反应100 h. 在此条件下,酯化拆分反应的转化率为48.3%. 结果表明,固定化Penicillium expansum脂肪酶是一种较为理想的用于外消旋萘普生拆分的工具酶.     

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     

脂肪酶转酯化和水解反应拆分薄荷醇的研究进展

在拆分薄荷醇的研究中,脂肪酶因具有化学、区域和立体选择性以及来源广泛,价廉、操作简单而得到普遍应用。本文从脂肪酶拆分薄荷醇的转酯化、水解反应的工艺和影响因素等方面,分析了脂肪酶动力学拆分过程的转酯化和水解反应的催化路径和特点,指出脂肪酶拆分薄荷醇的最佳路径和工艺选择。综述了近10年来脂肪酶拆分消旋体薄荷醇的研究进展,特别综述了具有工业化前景的脂肪酶催化拆分和单元操作工艺的研究进展。同时展望了未来脂肪酶拆分薄荷醇的研究方向。     

手性反应控制进展

现在越来越多的方法应用到用酶高效催化手性非外消旋化合物的对映性选择反应中来.对于不对称性合成反应或者动力学拆分的替代反应有动态动力学拆分、去消旋化和对映会聚转化等.另外,人们对影响反应生成的立体化学产物的参数(如溶剂、底物设计、固定化、定向进化等)有了进一步的了解.     

架起化学-酶催化之间的桥梁：构建策略及催化应用

化学-酶级联催化结合了化学催化的广泛反应性与生物催化的高选择性，是不对称合成高附加值手性化合物的有效途径。然而，化学催化剂和酶之间以及它们反应条件之间的不相容性极大地限制了这一领域的发展。因此设计可行的方法解决这些问题，实现两种催化范畴的兼容和优势互补，将使化学-酶级联催化反应得到更广泛的应用。综述了近年来克服化学催化与酶催化不相容性所采取的一些策略以及相关的研究进展，如时间分隔、空间分隔和集成催化剂等，并介绍了化学-酶级联催化在手性化合物动态动力学拆分及手性药物合成方面的应用，最后展望了该领域未来的局限性和发展趋势。     

Bridging gap between chemo- and biocatalysis: strategies and applications

The chemoenzymatic cascade catalysis combines the broad reactivity of chemical catalysis with the high selectivity of biocatalysis, and is an effective way to asymmetrically synthesize high value-added chiral compounds. However, the incompatibilities between the chemo- and biocatalysts as well as between their respective reaction conditions greatly restricted the development of this field. The design of feasible approaches to solve these problems can achieve the compatibility and complementary advantages of the two catalytic categories, thus making the chemoenzymatic cascade catalytic reactions more widely applied. In this review, the recent progress in developing strategies to overcome the incompatibility between chemical catalysis and enzymatic catalysis, such as temporal separation, spatial separation and integrated catalysts, is reviewed. The applications of chemoenzymatic cascade catalysis in dynamic kinetic resolution of chiral compounds and synthesis of chiral drugs are also introduced. Finally, the future limitations and the development trends of this field are prospected.     

Heterogeneous Catalysts for Racemization and Dynamic Kinetic Resolution of Amines and Secondary Alcohols

This paper gives an overview of the available heterogeneous catalysts for racemization of chirally stable secondary alcohols and amines, and of the combination of these catalysts with immobilized enzymes in dynamic kinetic resolution (DKR) for production of enantiopure esters or amides. For the one-pot DKR process, compatibility of enzyme and heterogeneous catalyst is a major issue, and in some cases the combination fails because of (mutual) deactivation. Heterogeneous catalysts of various types, such as zeolites or oxides effect alcohol racemization; they function either via acid catalysis and carbenium chemistry, or via a redox pathway via the ketone. Dynamic kinetic resolution of aliphatic alcohols using a heterogeneous catalyst in mild conditions is however an open challenge. Heterogeneous amine racemization catalysts invariably operate using a redox mechanism via the imine. In this case, the scope encompasses benzylic and aliphatic amines. The practicality of the approach is illustrated with the production of enantiopure N-acylated homoserine lactones, which are signalling compounds in microbial communities.     

Separation of EPA and DHA in fish oil by lipase-catalyzed esterification with glycerol

The objective of this study was to investigate the use of lipases as catalysts for separating EPA and DHA in fish oil by kinetic resolution based on their FA selectivity. Esterification of FFA from various types of fish oils with glycerol by immobilized Rhizomucor miehei lipase under water-deficient, solvent-free conditions resulted in a highly efficient separation of EPA and DHA. Reactions were conducted at 40°C with a 10% dosage of the lipase preparation under vacuum to remove the coproduced water, thus rapidly shifting the reaction toward the products. The bulk of the FA, together with EPA, were converted into acylglycerols, whereas DHA remained in the residual FFA. As an example, when FFA from tuna oil comprising 5% EPA and 25% DHA were esterified with glycerol, 90% conversion into acylglycerols was obtained after 48 h. The residual FFA contained 78% DHA and only 3% EPA, in 79% DHA recovery. EPA recovery in the acylglycerol fraction was 91%. The type of fish oil and extent of conversion were highly important parameters in controlling the degree of concentration.     

Enantioselective Synthesis of 4‐(Dimethylamino)pyridines through a Chemical Oxidation‐Enzymatic Reduction Sequence. Application in Asymmetric Catalysis

Enantiomerically pure 4‐(dimethylamino)‐3‐(1‐hydroxyalkyl)pyridines and 4‐(dimethylamino)‐3‐[hydroxy(phenyl)methyl]pyridine have been prepared through efficient chemoenzymatic routes. For this purpose different lipases and oxidoreductases have been tested in the preparation of optically active 4‐chloro derivatives and baker’s yeast was found to be an excellent catalyst for the bioreductions of the corresponding ketones. Their applications as enantioselective nucleophilic catalysts have been studied, important catalytic properties were observed in the stereoselective construction of quaternary centers.     

Separation of eicosapentaenoic acid and docosahexaenoic acid in fish oil by kinetic resolution using lipase

The objective of this study was to investigate the use of lipases as catalysts for separating eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fish oil by kinetic resolution. Transesterification of various fish oil triglycerides with a stoichiometric amount of ethanol by immobilized Rhizomucor miehei lipase under anhydrous solvent-free conditions resulted in a good separation. When free fatty acids from the various fish oils were directly esterified with ethanol under similar conditions, greatly improved results were obtained. By this modification, complications related to regioselectivity of the lipase and nonhomogeneous distribution of EPA and DHA into the various positions of the triglycerides were avoided. As an example, when tuna oil comprising 6% EPA and 23% DHA was transesterified with ethanol, 65% conversion into ethyl esters was obtained after 24 h. The residual glyceride mixture contained 49% DHA and 6% EPA (8:1), with 90% DHA recovery into the glyceride mixture and 60% EPA recovery into the ethyl ester product. When the corresponding tuna oil free fatty acids were directly esterified with ethanol, 68% conversion was obtained after only 8h. The residual free fatty acids comprised 74% DHA and only 3% EPA (25:1). The recovery of both DHA into the residual free fatty acid fraction and EPA into the ethyl ester product remained very high, 83 and 87%, respectively.     

Asymmetric organic catalysis with modified cinchona alkaloids

Insights into the role played by modified cinchona alkaloids in the Sharpless asymmetric dihydroxylation inspired studies of modified cinchona alkaloids as chiral organic catalysts that lead to the development of highly enantioselective alcoholyses for the desymmetrization, kinetic resolution, and dynamic kinetic resolution of cyclic anhydrides, cyanation of ketones, and 1,4-addition of thiols to cylic enones. These studies demonstrate the potential of modified cinchona alkaloids as broadly useful chiral organic catalysts for asymmetric synthesis.