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.     

利用乳液酶膜反应器拆分萘普生甲酯实验研究

利用乳液酶膜反应器进行外消旋萘普生甲酯的水解反应,以制备光学纯对映体(S)-萘普生,反应同时从膜透过侧收集产物,实现反应分离一体化。实验研究了固定酶前后膜传质阻力和反应过程的水相跨膜通量,考察了透过侧的产物浓度、反应器的转化率、产量和对映体选择性。结果表明:固定化酶引起的传质阻力远大于膜本身的阻力;透过侧的产物浓度与水相渗透通量密切相关,通量较低时,产物浓度较高;固定化酶的初始反应速率为3.660μmol/(h.g),为自由酶的20倍以上,固定化酶的对映体过剩值为99%—100%,远高于自由酶的选择性,表明该反应体系为脂肪酶催化拆分反应提供了良好环境。     

用壳聚糖修饰的大孔SiO_2材料固定化脂肪酶拆分萘普生甲酯

以壳聚糖(Chitosan,CS)修饰的大孔SiO_2材料为载体,通过吸附法固定柱状假丝酵母菌脂肪酶(Candida rugosa lipase,CRL)获得了CRL/CS-SiO_2固定化脂肪酶。并以催化拆分萘普生甲酯水解反应为对象,研究大孔SiO_2载体性能以及CRL固定量对反应的影响。结果表明,该CRL/CS-SiO_2固定化酶在结构上仍然保持载体Si O_2材料的微米级孔道,且CRL以纳米薄层的形式较为均匀地涂覆在孔道表面上。该固定化酶催化生成(S)-萘普生的转化率和选择性都远高于游离酶,其产物转化率随着CRL酶固定量的增加而增大,当CRL负载量为53.2 mg/g,反应120 h时,(S)-萘普生的转化率可达到44.6%,对映体过剩值eep达到100%,对映体选择性远大于200。     

分子筛催化下苯与长直链烯烃的烷基化反应研究

在全混釜批式反应器（ＣＳＴＲ）中研究了Ｙ型分子筛催化剂作用下苯与长直链烯烃的烷基化反应，探讨了投料比对烯烃转化率以及温度对产物选择性的影响。在所设计的新型液固循环反应－再生流化床反应系统中，用工业原料验证了在分子筛催化剂作用下采用该反应系统连续合成长直链基苯的工业可行性     

拟低共熔体系中脂肪酶水解拆分萘普生酯

引　言近年来已有许多用圆柱状假丝酵母脂肪酶(CCL)拆分消旋萘普生的报道[1～ 4 ] ,一般都是将底物萘普生酯完全溶解在有机溶剂中进行拆分反应 .然而有机溶剂的用量太大 ,不但对酶的催化活性有影响 ,而且还会带来安全和环保问题 .新发展的拟低共熔酶促反应体系恰能克服这一弊端     

反应条件对脂肪酶酯化活性和对映选择性的影响

分别测定了２－萘基丙酸类药物萘普生Ｒ－,Ｓ－对映体在有机溶剂中的酶促酯化反应初速度,并研究了反应温度,酰基受体和有机溶剂等反应条件对脂肪酶的反应活性和对映选择性的影响。在一定范围内,酶反应活性随温度升高而增加,温度过高易使酶失活;酶选择性则随温度升高而下降;反应温度以３５￣４０℃为佳。     

己内酰胺水解聚合过程数学模型化与优化研究进展

综述了己内酰胺水解聚合反应动力学模型，并系统论述了ＰＡ６工业聚合反应器包括高压间歇釜反应器（ＢＳＴＲ）、活塞流反应器（ＰＦＲ）、连续搅拌釜反应器（ＣＳＴＲ）和ＣＳＴＲ与ＰＦＲ组合反应器模型化与优化研究，对数值计算方法也作了简要评价，同时就ＰＡ６聚合过程有待进一步研究的问题提出了几点建议。     

膜分离式酶解反应器流体流动特性

讨论了膜分离式酶解反应器进行酶解反应操作时流体流动的特性。导出停留时间分布函数方程式，采用降阶法的阶跃方式进行了实验验证。结果表明：实验值与按分布函数方程式的计算值吻合良好，通过与连续釜式反应器（ＣＳＴＲ）停留时间分布的特征值的比较，显示出这种反应器的优越性。     

非水相酶促合成萘普生油酸甘油酯前药

在非相有机试剂异辛烷中通过固定化脂肪酶Novozym435催化萘普生甲酯与三油酸甘油酯反应,通过薄层层析色谱与高效液相色谱对反应液进行分析,并考察了底物摩尔比、反应时间、反应温度、酶添加量、溶剂添加量对转化率的影响。结果表明,当三油酸甘油酯与萘普生甲酯摩尔比3.85,反应时间144h,反应温度50℃,酶添加量150mg,溶剂添加量5m L时,转化率最高达到65.91%。     

非水相酶促合成萘普生油酸甘油酯前药

在非相有机试剂异辛烷中通过固定化脂肪酶Novozym435催化萘普生甲酯与三油酸甘油酯反应,通过薄层层析色谱与高效液相色谱对反应液进行分析,并考察了底物摩尔比、反应时间、反应温度、酶添加量、溶剂添加量对转化率的影响。结果表明,当三油酸甘油酯与萘普生甲酯摩尔比3.85,反应时间144h,反应温度50℃,酶添加量150mg,溶剂添加量5m L时,转化率最高达到65.91%。     

Dynamic enzymatic resolution of Naproxen methyl ester in a membrane bioreactor

A lipase‐catalyzed enantioselective continuous hydrolysis process under in situ racemization of substrate using sodium hydroxide as catalyst was developed for the production of (S)‐Naproxen from racemic Naproxen methyl ester in an aqueous–organic biphase system. Use of a tubular silicone rubber membrane in the stirred tank reactor to separate the chemical catalytic racemization and biocatalytic resolution processes, served to avoid the key problem associated with conventional dynamic resolution, viz the incompatibility of in situ chemical racemization with the presence of a biocatalyst. To overcome product inhibition and to facilitate product recovery from the aqueous–organic emulsion containing substrate and lipase, a hydrophilic porous semipermeable membrane was used in the stirred tank reactor. Greater than 60% conversion of the racemate with an enantiomeric excess of product (ee_p) greater than 96% was obtained. In addition, transformation of Candida rugosa lipase (CRL) isoenzymes was observed in the reaction process. © 2001 Society of Chemical Industry     

Einfluss der Reaktorkonfiguration auf die Enantioselektivität einer kinetischen Racematspaltung

The optical purity of a product at the reactor outlet depends not only on the enantioselectivity of the catalyst, but also on the reactor configuration. Different reactor configurations are compared with respect to the enantiomeric excess (ee) at a respective conversion that can be achieved in a kinetic resolution of a racemate. For batch, fed‐batch and plug flow reactors enantioselectivities (E value) of 35 are sufficient to achieve high enantiomeric excess. For a continuously operated stirred tank reactor high ee values are only obtained for E values higher than 190.     

酶解反应与膜分离耦合连续制备酪蛋白磷酸肽

采用酶解反应与膜分离耦合新工艺连续水解全酪蛋白制备酪蛋白磷酸肽(CPPs)。考察了超滤膜对胰蛋白酶及底物溶液的截留效果;研究了初始底物质量浓度、初始酶质量浓度、反应体积、膜渗透通量等参数对反应器性能和反应转化率的影响规律;利用高效凝胶排阻色谱系统(HPSEC)对酶解产物进行检测分析;建立了酶膜反应器连续水解动力学模型,并对间歇与连续酶解过程进行比较分析,证明反应-分离耦合技术可使酶解效率及蛋白酶利用率大幅提高,并使产物得到调控与富集,为CPPs的酶法制备提供了一种更为有效的方法。     

Non-isothermal lipase-catalyzed kinetic resolution in a packed bed reactor: Modeling, simulation and miniplant studies

A rigorous model is developed for the exothermic kinetic resolution of 1-methoxy-2-propanol with vinyl acetate catalyzed by immobilized Candida antarctica lipase B in a packed bed reactor. The non-isothermal two-dimensional heterogeneous model takes into account the coupled mass and energy balances, the uneven flow distribution and irreversible ping-pong bi-bi kinetics with competitive substrate inhibition by both enantiomers. This model is based on kinetic parameters, which were estimated in earlier work. The model simulation is validated with experimental results obtained in a fully automated modular miniplant and is shown to be capable of predicting the key parameters needed for process design of a kinetic resolution, the enantiomeric excess and the extent of conversion at a given superficial velocity.     

Continuous Application of Polyglycerol‐Supported Salen in a Membrane Reactor: Asymmetric Epoxidation of 6‐Cyano‐2,2‐dimethylchromene

In the current work, suitability of hyperbranched polyglycerol as a high loading catalyst support is demonstrated. A polyglycerol‐supported manganese‐salen complex (chemzyme) is applied as a homogeneous catalyst in the epoxidation of 6‐cyano‐2,2‐dimethylchromene. The recyclability of the corresponding catalyst was investigated in repetitive batch experiments as well as a continuous operation of the reaction in an ultrafiltration membrane reactor. An enhanced stability of the catalyst in repetitive batches was observed as a result of immobilization whereby the total turnover number increased from 23 in a single batch to 80 in four repetitive batches. To enable continuous operation, a continuously operated, stirred tanked reactor (CSTR) was equipped with an ultrafiltration membrane (MPF‐50) and a retention of 98% was determined. The continuous chemzyme membrane reactor was operated over the course of 20 residence times. After approximately 12 residence times, the steady state was reached yielding 70% conversion as well as an enantiomeric excess up to 92%. A space‐time yield (sty) of 458 g L ⁻¹ d⁻¹ and a turnover frequency (TOF_reaction) of up to 18 h⁻¹ was reached in the steady state. It was determined that the total turnover number (TTN) was enhanced by a factor of 10 from 24 (batch) up to 240 for 20 residence times in CSTR operation.     

Study on the enzymatic hydrolysis of racemic methyl ibuprofen ester

The hydrolysis of racemic methyl ibuprofen ester in the presence of lipase from Candida rugosa was investigated in shake flasks. Experiments were performed to study the effect of temperature, pH and shaking speed on the reaction rate. Different hydrophobic co‐solvents were screened for the highest reaction rate and the presence of enzyme inhibition by substrate and products was examined. A kinetic expression was then proposed to describe the reaction. Kinetic parameters were determined for the optimum operating conditions and the proposed model was verified with the experimental results. Next, this reaction was scaled up to a fed batch stirred tank reactor. Batch reactor and fed batch reactor configurations were compared for better conversions. The effects of aqueous phase hold‐up, substrate concentration and feed flow rate on the conversion of the reaction were also studied. Higher conversions were obtained in a fed batch reactor when compared with the batch reactor. In the fed batch reactor, increased conversions were observed with lower feed flowrates and high aqueous phase hold‐up. © 2001 Society of Chemical Industry     

有机相中固定化酶催化反应拆分手性化合物--间歇反应器内非定态动力学模拟

建立了有机相间歇反应器内球形多孔载体固定化酶催化反应拆分手性化合物的非定态动力学模型.采用正交配置法求解,讨论了对映体选择性E、内外传质阻力以及底物和水的抑制作用对酶促拆分手性化合物的拆分效果和速率的影响.结果表明:对映体选择性E是决定手性化合物能否拆分的关键参数;若一拆分过程对S-对映体优先反应,传质阻力可以忽略,E≥100,则R-和S-对映体几乎完全被拆分;如果存在传质阻力,则酶的对映体选择性降低,拆分效果不好,且拆分速率下降;底物和水的抑制作用对酶促拆分的效果影响不大,但拆分所需的时间相应增加.     

Soy protein hydrolysis in membrane reactors

An Ultrafiltration (UF) based reactor system for continuous hydrolysis of proteins was developed to overcome limitations of the traditional batch process. A continuous stirred tank reactor was coupled to a hollow fiber module in a semiclosed loop configuration. Capacity of the reactor, defined as quantity of hydrolysate produced/time/weight of enzyme, was a sensitive function of enzyme concentration between 55 and 94% substrate conversion levels for the Pronase-Promine D system. Increasing flow rate also improved capacity, but substrate concentration and reactor volume had small effects on capacity within the levels of expected use. Productivity (defined as weight of hydrolysate/weight of enzyme) was at least 10-20 times greater for the continuous UF reactor than a batch reactor operating under otherwise identical conditions.     

Mathematical modelling and simulation of a recycle dialysis membrane reactor in a reversed micellar system

A mathematical framework was developed for the evaluation of a recycle dialysis membrane reactor (RDMR). The lipase-catalyzed hydrolysis of olive oil in an AOT-iso-octane reversed micellar system was employed as a model. Three specific operational strategies have been considered, namely batch, fed-batch, and fed-batch-bleed. Simulation shows the conversion of substrate to be strongly dependent on efficient use of the substrate, since the permeability coefficients of both substrate and product are quite similar. Sensitivity analyses were performed to assess the influences of various parameters (membrane area, substrate feed rate, solvent bleed rate and permeability) on the performance of the reactor in different modes of operation. The analyses presented are useful to assist the optimization of the operational strategy used for the RDMR system.