基于泡沫分馏技术立体选择拆分蛋氨酸外消旋体

以青霉素G钾盐(PEN-K)为手性捕集剂,十二烷基硫酸钠(SDS)为起泡剂,采用泡沫分馏技术对蛋氨酸外消旋体进行拆分,采用正交实验法考察了回流时间(A)、溶液pH值(B)、柱填料高度(C)、回流气速(D)和待分馏溶液中各物质浓度比(E)等对拆分性能的影响。通过直观分析和方差分析研究可知,五因素中对对映体过量值影响次序为:DEBAC,从而得到拆分蛋氨酸外消旋体的优化工艺条件为D2E2B1A4C4。在回流时间60min、溶液pH值2.0、柱填料高度28cm、回流气速40L/h、溶液中各物质浓度比60∶1∶0.6的条件下得到的对映体过量值为50.0。     

High Resolution of Racemic Mandelic Acid through a Method of Bubble Fractionation

A method of bubble fractionation was developed for the resolution of racemic mandelic acid (MA), using 2‐hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) as chiral collector. The influences of concentration of HP‐β‐CD, reflux equilibriation time, gas flow rate, packing height of column and pH of buffer on resolution performance were investigated, respectively. According to the similar physical behavior of bubble fractionation and chemical reaction processes, the equivalent chemical reaction constant was introduced. The resolution process was preliminarily analyzed by means of kinetics. The results show that the enantiomeric excess of 60.7% can be obtained under the optimal conditions. The process could be regarded as a first order chemical reaction, where the equivalent speed constant was k_l=0.00376. This method is helpful for realizing high resolution and linear amplification of device.     

β-甲基苯丙氨酸的合成与拆分

β-甲基苯丙氨酸是一种含有两个手性中心的非基本氨基酸,本文先合成外消旋的β-甲基苯丙氨酸的衍生物,再通过酶促拆分,得到四种光学纯的异构体。     

组合手性萃取拆分克伦特罗外消旋体

以D-二苯甲酰酒石酸(D-DBTA)和D-二对甲苯甲酰酒石酸(D-DTTA)的组合作为手性选择剂,研究克伦特罗对映体在水相和有机相中的萃取分配行为,优化了手性萃取条件,考察了组合手性选择剂的不同摩尔浓度比、有机溶剂、水相pH值和亲脂性阴离子BPh4-对手性萃取性能的影响,并测定了手性萃取拆分过程中的热力学函数.在优化的手性萃取条件下,有机相中的对映体过量值(e.e.%)可大于10%,而所使用的选择剂量相对大为降低.热力学数据分析表明,该手性萃取过程为焓控过程.     

西他列汀外消旋体的合成及拆分

以2-氯吡嗪与2,4,5-三氟苯乙酸为原料,经亲核取代、环化、氢化等6步反应合成了制备西他列汀的重要中间体——4-氧代-4-{3-(三氟甲基)-5,6-二氢-[1,2,4]三唑并[4,3-a]哌嗪-7(8H)-基}-1-(2,4,5-三氟苯基)丁烷-2-烯胺(6);以NaBH4为还原剂,甲基磺酸为辅助添加剂,还原6制得西他列汀外消旋体(7);7经(-)-二对甲苯酰-L-酒石酸拆分制得光学纯度高于93%的西他列汀,其结构经1H NMR,IR和MS表征。     

外消旋盐酸西布曲明的手性拆分

以(D)-(+)-二苯甲酰酒石酸为手性拆分剂,外消旋盐酸西布曲明在乙酸乙酯中被拆分为(R)-(+)-盐酸西布曲明(收率35.4%,99%ee)和(S)-(-)-盐酸西布曲明(收率33.7%,99%ee).     

几种外消旋环氧化合物的水解动力学拆分

2 羟基 3 叔丁基 5 甲基苯甲醛 (5 )与 (S ,S) 1 ,2 二苯基乙二胺 ((S,S) 1 1 )缩合 ,得手性Salen 1 2 ,再与Co(OAc) 2 ·4H2 O反应得钴络合物 1 3 ,后者经氧化制得Salen型手性催化剂 (S ,S) 2。几种外消旋环氧化合物用 (S ,S) 2催化水解进行动力学拆分 ,同时得到光学活性环氧化合物和二醇 ,对映体过量最高达 61 6%。根据分子力学对催化剂构象优化的结果讨论了催化剂结构对其催化效率和选择性的影响     

Resolution of Racemic 1,2-Dibromohexafluoropropane through Halogen-Bonded Supramolecular Helices

Halogen bonds , attractive intermolecular interactions between perfluoroalkyl bromides and bromide ions, are present in cocrystals of (−)-sparteinium hydrobromide ( 1 ) and (S)-1,2-dibromohexafluoropropane ( 2 ; shown schematically), and result in enantiopure and infinite supramolecular helices. The perfluorocarbon–hydrocarbon self-assembly allows the resolution of racemic 2 .     

厚体液膜动力学拆分普萘洛尔外消旋体

以S,S-酒石酸正十二酯和H3BO生成的配合物为手性载体, 通过量热分析结果初步证明该配合物的存在, 采用厚体液膜拆分了普萘洛尔外消旋体. 考察了S,S-酒石酸十二酯浓度和水相pH值对拆分性能的影响, 优化了其拆分操作条件, 同时进行了动力学分析. 得出厚体液膜拆分的一般规律, 即其拆分属于动力学拆分过程, 适当提高手性载体的浓度有利于提高对映单体流量和拆分的立体选择性, 水相pH值对于拆分性能有着重要的影响. 其拆分过程中萃取反应过程为控速步骤, 对映单体的跨膜传递可以用两个串联的准一级不可逆过程进行描述.     

厚体液膜拆分克伦特罗外消旋体及其动力学研究

以D-( )-二苯甲酰酒石酸(D-( )-DBTA)为流动载体,研究了克伦特罗(clenbuterol,Cle)对映体的厚体液膜法拆分,建立了手性拆分条件和动力学拆分模型。考察了D-( )-DBTA浓度、缓冲液pH值对手性拆分性能的影响,进行了动力学分析,并测定了膜-料液界面的萃取反应表观速率常数k1和膜-反萃相界面的反萃取表观速率常数k2。结果表明:在优化的实验条件下(pH为7,手性载体与Cle浓度比为1∶4),Cle外消旋体能被含有手性载体D-( )-DBTA的厚体液膜有效拆分,分离因子大于1.08;Cle单体的跨膜迁移过程可以用两个串联的准一级不可逆过程进行描述。     

Iron‐Catalyzed Imidative Kinetic Resolution of Racemic Sulfoxides

Kinetic resolution of racemic sulfoxides requires either custom substrates or shows moderate enantioselectivity, leading to achiral coproducts (such as sulfones) as an intrinsic part of the process. A new strategy is demonstrated that allows the resolution of racemic sulfoxides through catalytic asymmetric nitrene‐transfer reactions. This approach gives rise to both optically active sulfoxides and highly enantioenriched sulfoximines. By using a chiral iron catalyst and a readily available iodinane reagent, high selectivity factors have been achieved under very practical reaction conditions. With respect to the substrate scope, it is noteworthy that this unprecedented imidative kinetic resolution of racemic sulfoxides provides access to both aryl–alkyl and dialkyl sulfoximines in highly enantioenriched forms.     

粉煤灰基氧氟沙星分子印迹聚合物的制备及其应用

以工业废料粉煤灰微球为基质,氧氟沙星 (OFL) 为模板分子,采用表面印迹法制备印迹材料MIP。通过紫外光谱法结合理论分析选择实验条件,并对该印迹材料结构、吸附行为进行研究。结果表明,该印迹材料对氧氟沙星具有良好的特异识别性和优良的亲和性。与以硅胶为载体制备的印迹聚合物相比,该材料吸附容量更高和印迹效果更好。将其作为固相萃取填料对鸡产品进行分离富集,与C18柱相比,分离富集效果更好。结合UPLC,对实际样品中氧氟沙星进行分析,回收率为82.0%-96.7%,相对标准偏差低于5.5%,可用于鸡产品中氧氟沙星分离分析。     

Ligand-Exchange TLC Resolution of Some Racemic β-Adrenergic Blocking Agents

JPC – Journal of Planar Chromatography – Modern TLC -     

胺类拆分剂从水溶液中拆分外消旋有机酸的研究

具有光学活性的化学物质目前已在药物、食品、饮料、农药等领域得到了广泛的应用,需求日益增长,但化学合成的产物多为无活性的外消旋体(混合物、化合物或固体溶液),要从中得到单一对映体必须进行拆分,非对映体盐结晶法是目前工业应用最广泛的一种拆分技术,其原理是采用一种光学活性物质与外消旋体反应生成一对非对映立体异构体,依据两者在特定溶剂中的溶解度差异实现拆分.该技术尤其适合于外消旋的有机酸、有机碱的拆分,有关这方面拆分实例的报道较多[1～3].但迄今为止,还没有该技术系统的规律性研究报道.本文以若干外消旋有机酸为对象,试图通过以水为溶剂的拆分实验研究,探讨有机酸拆分过程的特性,从而为非对映体盐结晶拆分技术规律性的研究及外消旋有机酸拆分过程工业化的实施创造条件.     

氧氟沙星的荷移分光光度法测定

研究了氧氟沙星与７，７，８，８－四氰基对二次甲基苯醌（ＴＣＮＱ）的荷移反应，确定了反应的最佳条件，在甲醇－丙醇（３：２）介质中，二者于３０℃水浴中恒温３０ｍｉｎ即可形成１：１络合物，在测定波长７４３ｎｍ处络合物的表观摩尔吸光系数为３．５８×１０＾４Ｌ．ｍｏｌ＾－１．ｃｍ＾－１，氧氟沙星浓度在０～１５ｍｇ／Ｌ范围内符合比尔定律，方法的相对标准差小于３％。     

Rhodium‐Catalyzed Asymmetric Cycloisomerization and Parallel Kinetic Resolution of Racemic Oxabicycles

While desymmetrizations by intermolecular asymmetric ring‐opening reactions of oxabicyclic alkenes with various nucleophiles have been reported over the past two decades, the demonstration of an intramolecular variant is unknown. Reported herein is the first rhodium‐catalyzed asymmetric cycloisomerization of meso‐oxabicyclic alkenes tethered to bridgehead nucleophiles, thus providing access to tricyclic scaffolds through a myriad of enantioselective C?O, C?N, and C?C bond formations. Moreover, we also demonstrate a unique parallel kinetic resolution, whereby racemic oxabicycles bearing two different bridgehead nucleophiles can be resolved enantioselectively.     

Kinetic and Dynamic Kinetic Resolution of Racemic Tertiary Bromides by Pentanidium-Catalyzed Phase-Transfer Azidation

We have developed a method to afford enantiomerically enriched tertiary azides and bromides through pentanidium-catalyzed kinetic resolution (KR) of racemic tertiary bromides under base-free conditions. We found that the absence of water is crucial to attain a high selectivity factor (s). On the other hand, new experimental observations and DFT modeling led us to propose that enantioconvergent azidation of tertiary bromides proceeded through dynamic kinetic resolution (DKR). The investigations particularly identified the crucial roles of base and water in the enantioconvergent process, thus supporting the proposal that the tertiary bromide isomerizes in the presence of base and water through a S_N2X pathway.