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。     

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。     

酶法制备手性芳香胺化合物的研究进展

手性芳香胺是药物合成的重要中间体,同时也可用作手性助剂及手性拆分剂。本文综述了近年来国内外酶法制备手性芳香胺化合物的研究进展,包括脂肪酶催化的选择性酰胺化反应和转氨酶催化的不对称合成、拆分反应。并展望了其今后研究发展的方向:使用脂肪酶催化时可以研究动态动力学拆分来提高产率;使用转氨酶催化时可以尝试研究辅酶再生系统以降低成本,还可以通过反应体系和工艺路线进行改进以提高反应效率。     

l-薄荷醇的合成及手性拆分研究进展

阐述了l–薄荷醇的理化性质及其应用现状,介绍了最新的化学合成和拆分方法,其中着重介绍和探讨了以异戊二烯为原料合成l–薄荷醇的技术路线。同时,介绍了生物催化合成薄荷醇和手性拆分技术的研究进展和闭环机理,展望了其发展的前景。     

薄荷醇手性拆分的研究进展

薄荷醇是工业上应用广泛的一类重要的环萜醇.光学活性的左旋薄荷醇在医药卫生方面可用作清凉剂、止痒剂、杀菌剂等;在香料行业是需求量最大的环状单萜醇,可用作日化香精的调配剂,还能充作多种食品的调味剂;其需求量正大幅度增加,因此寻求一种好的拆分外消旋体薄荷醇的方法是极其重要的.主要综述了目前国内外薄荷醇拆分的一些方法,比较了这些拆分方法的优缺点,其中生物酶法拆分是一个很有发展潜力的方法.     

生物柴油制备方法的应用研究进展

生物柴油以其优良的环境友好性和可再生性引起广泛关注,但较高的生产成本是其商业化生产和应用的障碍之一。综述了生物柴油的化学转酯化法和以游离脂肪酶、固定化脂肪酶、全细胞为催化剂的生物转酯化法的工业研究进展,同时还指出了采用生物转酯化法制备生物柴油时面临的一些问题。     

脂肪酶手性拆分的研究进展

手性拆分广泛应用于手性药物的制备,具有重要的科学意义与实用价值。脂肪酶由于其独特的界面催化特性,可在有机相中进行酶促合成,已成为手性拆分研究中的热点之一。本文重点综述了脂肪酶对手性醇、手性酯和手性胺类等有机合成中间体催化拆分作用的最新研究进展,并从脂肪酶来源、底物分子结构和固定化方法等角度对脂肪酶催化手性拆分机理进行了介绍。     

脂肪酶在光学活性化合物合成中的应用

本文介绍了脂肪酶在不对称合成中的应用现状及发展趋势 ,特别是脂肪酶在有机溶剂中的拆分反应 ,以及脂肪酶催化的二次拆分法     

反应器操作方式对酶动力学拆分立体选择性的影响

描述了在批式反应器和连续流搅拌反应器（ＣＳＴＲ）中酶动力学拆分对映异构体的不同之处，从宏观反应器平衡角度，推导出了在ＣＳＴＲ反应器中不同于在批式反应器中的一定酶立体选择性（Ｅ）下，底物或产物的对映体过量值与反应的转化率之间关系的定量关系式。并通过商品脂肪酶及芽胞杆菌Ｅ－５３脂肪酶催化的萘普生甲酯的不对称水解反应得到了证实。分别在批式反应器和ＣＳＴＲ反应器中进行萘普生的酶法拆分，在一定转化率下，批式     

酶法合成光学活性化合物

综述了手性药物的发展近况及光学活性化合物的制备方法,重点介绍了酶催化过程的特点,结合实例介绍了脂肪酶催化拆分和酶催化不对称合成的方法,展望了酶催化的工业化应用前景。     

L-二苯甲酰酒石酸为拆分剂结晶拆分L,D-薄荷醇

以L-酒石酸为原料,合成并纯化了结晶拆分剂L-二苯酒石酸;考察了L-二苯酒石酸结晶拆分过程的动力学控制,L-薄荷醇的收率提高23%。同时,研究了结晶拆分过程的溶剂影响。结果表明,用氯化锌代替氯化铁作为催化剂,L-二苯酒石酸的合成温度可降低12℃,重结晶纯化只需一次,可达到拆分剂的要求;L-二苯酒石酸结晶拆分消旋体薄荷醇喜好弱极性的组合溶剂（环己烷/水=80：20,V/V）,单一的高极性和非极性溶剂对结晶拆分不利。同时,展望了未来研究方向。     

Enantioselective Hydrolysis of d,l‐Menthyl Benzoate to L‐(–)‐Menthol by Recombinant Candida rugosa Lipase LIP1

The stereoselective synthesis of L ‐menthol is an attractive process in the flavor and fragrance industry. One promising way to obtain optically pure menthol is the enantioselective hydrolysis of menthol esters under enzymatic catalysis. We developed an effective and highly enantioselective method for the synthesis of L ‐(−)‐menthol (>99% EE) by hydrolyzing the key industrial starting compound, d, l ‐menthyl benzoate. The enzyme of choice was the lipase from Candida rugosa (CRL). While commercially available preparations of this lipase showed only minor selectivity (E=15), excellent enantiomeric purity (E>100) was achieved using the heterologously expressed isoenzyme LIP1.     

Resolution of N‐hydroxymethyl vince lactam catalyzed by lipase in organic solvent

BACKGROUND: The enantiomers of N‐hydroxymethyl vince lactam are important intermediates during the synthesis of chiral drugs. The preparation of its single enantiomer can be performed through enzymatic resolution. The aim of this work is to obtain (1S, 4R)‐N‐hydroxymethyl vince lactam with high enantiomeric purity via lipase‐catalyzed enantioselective transesterification in organic solvents. To achieve this, effects of various reaction conditions (including lipase sources, acyl donor, substrate molar ratio, organic solvent, temperature, and water activity) on the enzyme activity as well as enantioselectivity were investigated. RESULTS: The results of the study showed that the enantiopreference for all the selected enzymes was (4S, 1R)‐N‐hydroxymethyl vince lactam in enantioselective transesterification of racemic N‐hydroxymethyl vince lactam. Under the selected optimum conditions, the highest enantioselectivity (E = 33.8) was obtained with a higher enzyme activity (20.3 µmol g^?1 min^?1) for Mucor miehei lipase (MML) when vinyl valerate was used as the acyl donor. Besides, the remained (1S, 4R)‐N‐hydroxymethyl vince lactam with high enantiomeric purity (ee > 99%) was obtained when the conversion was about 60%. CONCLUSION: The results obtained clearly demonstrated potential for industrial application of lipase in resolution of N‐hydroxymethyl vince lactam through enantioselective transesterification. © 2012 Society of Chemical Industry     

Enzymatic esterification of DL‐menthol with propionic acid by lipase from Candida cylindracea

This work deals with the resolution of DL ‐menthol with propionic acid by Candida cylindracea lipase (Ccl) in organic solvent reaction systems and a reverse micelles system of sodium 1,4‐bis (2‐ethylhexyl) sulfosuccinate (AOT). The activity and stability as well as enantioselectivity of the lipase in two systems were studied. The results indicate that the lipase showed higher stability in reverse micelles than in organic solvent, which proved that the reverse micelles system has potential application for maintaining the activity of the enzyme for a long time. This is because lipase molecules can be entrapped in water‐containing micro‐drops of reverse micelles, avoiding direct‐contract with unfavorable organic medium. The enantioselectivity (E > 30, ee_p = 92.5) in the two systems is relatively high, although the conversion is moderate. The influence of the characteristic parameters of the two systems, such as pH, temperature, w₀ (molar ratio of water to AOT in reverse micelles systems) and water content (organic solvent) on the conversion of DL ‐menthol was also investigated. Copyright © 2005 Society of Chemical Industry     

Kinetic resolution of 1‐phenylethanol integrated with separation of substrates and products by a supported ionic liquid membrane

BACKGROUND: In the present study, the kinetic resolution of rac‐1‐phenylethanol by transesterification with several vinyl esters catalysed by a commercial immobilized Candida antarctica lipase B (Novozym 435) was carried out in n‐hexane at different water contents. The subtrates and products involved in the kinetic resolution were separated using a membrane bioreactor containing a supported liquid membrane based on the ionic liquid 1‐butyl‐3‐methylimidazolium tetrafluoroborate [bmim⁺][BF₄^?]. RESULTS: Variables affecting the kinetic resolution performance of the enzyme were studied. First, the influence of water content of the medium on the synthetic activity, selectivity and enantioselectivity of the enzyme was analysed in order to establish the optimal amount of water. The use of vinyl esters of different alkyl chain length (vinyl propionate, vinyl butyrate and vinyl laurate) as acyl donors to kinetic resolution was studied. Finally, the integrated reaction/separation process for the resolution of rac‐1‐phenylethanol was carried out in the optimal conditions found. CONCLUSION: These investigations demonstrate that the coupling of lipase enantioselectivity with the selective separation of supported liquid membranes based on ionic liquids provides a promising basis for practical production of enantiomerically pure or enriched compounds. Copyright © 2008 Society of Chemical Industry     

吸附-聚合物修饰组合固定化Candida antarctica脂肪酶研究

通过吸附法联合PEG非共价修饰,研发了一种固定化南极假丝酵母脂肪酶(Candida antarctica lipase)的新方法,可以有效提高固定化酶在非水介质中的催化活性。最佳固定化条件为硅藻土:酶粉(W/W)=8,PEG4000:酶粉(W/W)=0.6,缓冲液pH7.5。采用三油酸甘油酯与甲醇的转酯化反应,测定了固定化酶的转酯活性。结果表明,固定化酶同时加入PEG进行非共价修饰,可显著提高固定化酶的转酯活力。PEG修饰的固定化酶转酯比活是未经PEG修饰的固定化酶的4.1倍,转酯酶活回收率为604.8%,说明PEG两性分子的特性对制备用于非水介质的固定化酶有重要作用。该固定化方法可显著提高Candida antarctica脂肪酶在非水介质中的催化效率,且固定化方法简单、成本低,具有工业应用价值。     

A structure-controlled investigation of lipase enantioselectivity by a path-planning approach

A novel approach based on efficient path-planning algorithms was applied to investigate the influence of substrate access on Burkholderia cepacia lipase enantioselectivity. The system studied was the transesterification of 2-substituted racemic acid derivatives catalysed by B. cepacia lipase. In silico data provided by this approach showed a fair qualitative agreement with experimental results, and hence the potential of this computational method for fast screening of racemates. In addition, a collision detector algorithm used during the pathway searches enabled the rapid identification of amino acid residues hindering the displacement of substrates along the deep, narrow active-site pocket of B. cepacia lipase and thus provided valuable information to guide the molecular engineering of lipase enantioselectivity.     

工业脂肪酶拆分烯丙酮醇

研究了工业脂肪酶拆分消旋体烯丙酮醇。采用龙马脂肪酶不对称水解烯丙酮醇乙酸酯 ,反应 72h后中止反应 ,经硅胶柱层析进行醇、酯分离 ,得到S 烯丙酮醇乙酸酯的过量对映值ee=87%,收率 68%;R 烯丙酮醇的过量对映值ee=73%,收率 52 %。     

Direct Asymmetric Dynamic Kinetic Resolution by Combined Lipase Catalysis and Nitroaldol (Henry) Reaction

The asymmetric synthesis of β‐nitroalkanol derivatives was simply achieved by a combined nitroaldol (Henry) reaction with lipase‐catalyzed transesterification in high yield and enantiomeric purity (up to 92% and 99% ee) through a direct one‐pot procedure.