模拟移动床色谱分离制备手性农药甲霜灵的研究

利用自行组建的模拟移动床色谱(SMBC),在正相条件下,在自制的涂敷型纤维素-三(3,5-二甲基苯基氨基甲酸酯)手性固定相上成功制备出甲霜灵对映体,所制备的对映体纯度达到99%以上,与高效液相色谱法制备相比较,模拟移动床技术制备甲霜灵对映体的效率以及流动相的利用率均明显高于高效液相色谱法.     

模拟移动床色谱在手性药物大规模拆分中的应用

模拟移动床色谱作为手性药物大规模拆分领域中的强有力工具,越来越受到人们的重视,该文介绍了模拟移动床色谱技术的发展情况及其工作原理,对描述模拟移动床色谱分离行为的理论模型和分离操作中操作参数的确定也作了介绍。     

模拟移动床色谱法分离纯化链甾醇

以羊毛脂中提取的链甾醇为原料,采用模拟移动床色谱法(SMBC)进行了分离纯化。以C18为固定相,甲醇为洗脱液,采用四区SMBC系统,每区有两根色谱柱(150 mm×10 mm×10μm),经过两次SMBC分离,得到高纯度链甾醇产品。以纯度、生产率和溶剂消耗量为指标,确定链甾醇在SMBC中的最佳分离条件为:切换时间6.4 min,四区流量分别为9.97,7.53,8.53和4.97 mL/min,进料流量1.00 mL/min(第一次SMBC分离);切换时间6.0 min,四区流量分别为9.95,7.98,8.53和6.62 mL/min,进料流量0.55 mL/min(第二次SMBC分离)。结果表明,以90.1%含量的链甾醇粗品为原料,在优化实验条件下,先除去吸附能力比链甾醇强的杂质,再除去吸附能力比链甾醇弱的杂质,得到高纯度(≥98.9%)的链甾醇产品,回收率为93.8%。     

制备分离农药甲霜灵对映体的高效液相色谱法

用高效液相色谱法对自制的纤维素－三（3，5－二甲基苯基氨基甲酸酯）手性制备柱的手性拆分能力进行了评价，并且在此制备柱上完成了对手性农药甲霜灵进行了半制备分离；同时对手性农药甲霜灵在纤维素－三（苯基氨基甲酸酯）、直链淀粉－三（苯基氨基甲酸酯）、纤维素－三（4－甲基苯甲酸酯）手性分析柱上的手性拆分进行了研究。     

模拟移动床色谱技术及其应用

详细地介绍了一种现代化分离技术模拟移动床色谱技术的发展历史及其工作原理,同时介绍了模拟移动床色谱在石油化工、糖醇分离、手性化合物及其他方面的主要应用。     

农药甲霜灵对映体的高效液相色谱分离及手性拆分热力学研究

以正己烷 异丙醇为流动相 ,在纤维素 三 (3 ,5 二甲基苯基氨基甲酸酯 ) (CDMPC)涂敷型手性固定相上 ,对农药甲霜灵外消旋体进行了拆分 ,考察了流动相组成、柱温等对甲霜灵对映体的保留和分离的影响 ;对甲霜灵R、S对映体与固定相之间的保留和分离的热力学机理进行了讨论     

模拟移动床色谱技术研究进展

根据模拟移动床色谱技术的发展历程,对其工艺研发,包括异步切换模拟移动床和间歇式模拟移动床等新型操作工艺,以及模拟移动床色谱反应器等进行了综述。总结了近几年模拟移动床色谱技术在手性化合物拆分和糖醇分离中的应用研究进展;展望了模拟移动床色谱的研究方向和发展趋势。     

反相高效液相色谱法直接拆分舒必利对映体

以反相高效液相色谱法,建立了舒必利在大环抗生素类固定相(chirobiotic T)上手性拆分的方法。考察了不同流动相组成对分离的影响。推荐流动相条件为V(甲醇)：V(磷酸)：V(三乙胺)=100：1．5：3。     

高效液相色谱法拆分硅氟唑对映体

在纤维素-三-(3,5-二甲基苯基氨基甲酸酯)(Chiralcel OD-H)手性柱上对硅氟唑对映体的分离进行了研究.考察了流动相中改性剂的种类和浓度、流速以及柱温对分离效果的影响,并对手性拆分机制进行了讨论.实验结果表明:5种醇改性剂中,异丙醇的改性效果最佳,当异丙醇含量为2%时,分离度(Rs)达最大值10.19;在...     

薄层色谱法拆分手性药物对映体

用性能稳定的薄层色谱用β-环糊精(β-CD)、硅胶手性固定相拆分手性药物对映体.在适当比例的乙腈-1%乙酸三乙胺(TEAA)、己烷-异丙醇、乙腈-甲醇-乙酸-三乙胺、甲醇-1%TEAA及乙腈-1%TEAA-三乙胺溶剂系统中展开,8种临床常用的手性药物对映体得到有效分离,对映异构体之间的相对比移值α为1.53～4.89.     

模拟移动床色谱分离二十碳五烯酸乙酯和二十二碳六烯酸乙酯

二十碳五烯酸和二十二碳六烯酸是两种非常重要的ω-3多不饱和脂肪酸,广泛用于膳食补充剂和药品,同时它们的生理作用并不完全相同,因此分离制备它们的高纯度单体十分必要。首先以聚苯乙烯/二乙烯基苯（PS/DVB）聚合物为固定相,在液相色谱上分离二十碳五烯酸乙酯（EPA-EE）和二十二碳六烯酸乙酯（DHA-EE）,考察了流动相、填料粒径、温度对分离的影响。然后采用粒径20 μ m、孔径10 nm的PS/DVB填料装填了8根150 mm×10 mm的半制备色谱柱,测定了半制备柱装填的均一性。最后尝试在模拟移动床（SMB）色谱上分离EPA-EE和DHA-EE的混合物,探究了Ⅱ区和Ⅲ区的流量、进料流量、进料浓度对分离的影响,结果表明SMB制备的EPA-EE和DHA-EE的相对纯度分别为91.6%和93.6%,回收率分别为97.0%和91.6%,固定相生产率为5.97 g/（L\5h）,溶剂消耗为1.52 L/g。SMB制备EPA-EE和DHA-EE具有较大的应用潜力。     

Enantioseparation of a chiral epoxide by simulated moving bed chromatography using Chiralcel-OD

Summary The feasibility of using simulated moving bed (SMB) chromatography for the chiral separation of a racemic epoxide with Chiralcel-OD as the stationary phase is demonstrated on a semi-preparative scale. Operating conditions for the separation are chosen with the help of a simple chart that depicts visually the interrelationships between the system flow rates and the SMB design criteria. The 12 column (each 100 mm×16 mm ID) SMB system continuously resolved the racemic mixture at a rate of 11.5 g/24 hr into streams with 95% and 94.4% e.e. (enantiomeric excess). A comparison of the SMB process with an optimized multiple-injection conventional chromatographic separation showed similar specific production rates for both methods, but a seven-fold lower solvent consumption for the SMB.     

Simulated moving bed chromatography under linear conditions

Summary The authors review their recent contributions to the theory of Simulated Moving Bed (SMB) chromatography. SMB is an implementation of preparative chromatography which is attracting much interest in the pharmaceutical industry, especially (but not only) for the purification of enantiomers. This process is more complex than those conventionally used for preparative applications. Its operation under linear conditions is illustrated using the numerical solutions derived from different simple models (ideal, equilibrium-dispersive). The influence of nonideal effects (e.g., dispersion and mass transfer resistances), of section subdivision into several columns are discussed. The importance of the differences between the flow rates in the different sections of the SMB is also illustrated. Experimental results are well explained by theoretical considerations. Presented at the 21^st ISC held in Stuttgart, Germany, 15^th–20^th September, 1996     

Improving performance of a five-zone simulated moving bed chromatography for ternary separation by simultaneous use of partial-feeding and partial-closing of the product port in charge of collecting the intermediate-affinity solute molecules

The performance of a five-zone simulated moving bed (SMB) chromatographic process for ternary separation has been improved to a certain extent in previous researches by applying either a partial-feeding (PF) or a partial-closing of the extract-2 port (PCE(2)) to its operation. To make a further improvement, the strategy of applying both PF and PCE(2) simultaneously to the five-zone SMB operation was proposed in this study. The results from both equilibrium-theory analysis and detailed simulation proved that the proposed strategy, which was called PF-PCE(2) in this article, had the benefit of a synergy between the individual merits of PF and PCE(2) in the five-zone SMB performance. As a consequence, the PF-PCE(2) mode could surpass the PF and the PCE(2) modes by a wide margin and the standard mode by a much wider margin in the aspects of ternary-separation performance and throughput. For the separation system considered, the PF-PCE(2) mode was found to achieve more than 100% improvement, compared to the standard mode. Furthermore, such advantage of the PF-PCE(2) over all the other modes was greater as the selectivity between the intermediate-affinity and the highest-affinity components was reduced.     

Less common applications of simulated moving bed chromatography in the pharmaceutical industry

Simulated moving bed (SMB) chromatography is often perceived in the pharmaceutical industry as chromatographic method for separating binary mixtures, like racemates. However, SMB can also be used for unbalanced separations, i.e. binary mixtures of varying compositions and multi-component mixtures. These less common application modes of isocratic SMB chromatography are exemplified for four different compounds (racemates and diastereomers) and discussed in view of the so-called 'triangle theory' from an industrial perspective.     

Optimization of simulated moving bed chromatography with fractionation and feedback: Part I. Fractionation of one outlet

A novel modification of simulated moving bed (SMB) technology, referred to as fractionation and feedback SMB (FF-SMB), has been introduced recently. This concept is based on fractionating one or both outlet streams and feeding the off-spec fractions back into the unit alternatingly with the original feed mixture. In this paper, the optimization problem of FF-SMB realizing one outlet fractionation is considered. A mathematical optimization framework based on a detailed process model is presented which allows to evaluate quantitatively the potential of this operating scheme. Detailed optimization studies have been carried out for a difficult separation characterized by small selectivity and low column efficiency. The results reveal that the proposed fractionation and feedback regime can be significantly superior to the classical SMB chromatography, in terms of both feed throughput and desorbent consumption. The effect of the feeding sequence on the performance of FF-SMB is also examined.     

True moving bed electrophoresis using stepped electric field gradients

True moving bed electrophoresis has been shown to be an effective technique for the bench-scale separation of enantiomers, and it is desired to increase the maximum possible throughput attainable with the process by using electric field gradients. Homatropine enantiomer separations were performed and results using a stepped electric field gradient were compared to those using a traditional non-gradient separation. In order to accomplish this, a newly designed stator was constructed for use with the Vortex-Stabilized Electrophoresis Apparatus that has three sets of electrode housings, one set at both ends and one in the middle of the chamber. There were several problems related to the membranes used at the middle electrode. The dialysis membranes were permeable to the homatropine enantiomers, and while a switch to anion exchange membranes prevented the permeation of the homatropine, this caused a pH shift that interrupted binding to the hydroxypropyl-ss-cyclodextrin chiral selector. These problems prevented any meaningful data from being collected using homatropine enantiomers, and due to this, a proof of concept study was conducted using two bovine proteins. The separations using fluorescein-labeled BSA and bovine hemoglobin showed that a 63% increase in the maximum processing rate was attainable. The maximum throughput using the non-gradient process was 30.6 mg/h and the maximum was 50.0 mg/h using an electric field gradient that was 10% lower than the non-gradient field in section II and 10% higher in section III.     

Enantioseparation of 1-phenyl-1-propanol by supercritical fluid-simulated moving bed chromatography

The enantioseparation of 1-phenyl-1-propanol through the supercritical fluid-simulated moving bed (SF-SMB) process is studied. Non-linear isotherms were measured on an analytical column, and used together with the triangle theory for SMB design to select operating conditions for the SF-SMB. Experiments were carried out on a pilot-scale SF-SMB plant at conditions that corresponded to the non-linear range of the isotherm. Under conditions of low feed concentration, complete separation (extract purity = 99.5%; raffinate purity = 98.4%) was achieved. Under conditions of larger feed concentration, the best separation corresponded to an extract purity of 98.0% and a raffinate purity of 94.0%, and yielded a productivity of 110 g of racemate per kg stationary phase per day.     

Optimization of simulated moving bed chromatography with fractionation and feedback: Part II. Fractionation of both outlets

A new improvement based on outlet fractionation and feedback has been developed for simulated moving bed (SMB) chromatography. In this contribution, this fractionation and feedback SMB (FF-SMB) concept is extended to the general scenario which integrates a simultaneous fractionation of both outlet streams. A model-based optimization approach, previously adopted to investigate single fractionation, is extended to consider this flexible fractionation policy. Quantitative optimization studies based on a specific separation problem reveal that the double fractionation is the most efficient operating scheme in terms of maximum feed throughput, while the two existing single fractionation modes discussed in our previous study are also significantly superior to the conventional SMB operation. The advantages of the double fractionation extension are further demonstrated in terms of several more detailed performance criteria. In order to evaluate the applicability of the fractionation and feedback modification, the effect of product purity, adsorption selectivity, column efficiency and column number on the relative potential of FF-SMB over SMB is examined.