3种芳香连二醇对映体的毛细管区带电泳手性拆分及其光学纯度分析

以磺化环糊精为毛细管区带电泳(CZE)手性选择剂,成功地分离了3种烯烃的不对称二羟化产物苯基乙二醇、β-甲基苯基-乙二醇和1,2-二苯基乙二醇对映体;考察了不同手性选择剂及其浓度、背景电解质pH值、操作电压等因素对分离的影响,优化了分离条件;对该3种芳香连二醇对映体样品进行了光学纯度检查,并与HPLC测定结果作比较,评价该方法的准确性。结果表明:两批样品中对映体过量(ee)测定值与HPLC法结果相一致,CZE方法简单、准确、分离度好,可用于该芳香连二醇中性化合物的手性拆分和ee值的测定。     

双相识别手性萃取佐匹克隆对映体动力学研究

以羟丙基-β-环糊精(HP-β-CD)和L-酒石酸异丁酯(L-IBTA)分别为水相和有机相中手性选择体构成双相识别手性萃取体系, 研究其对佐匹克隆(ZPC)对映体的萃取动力学. 分别考察了搅拌速度、两相接触面积、水相中ZPC对映体浓度、水相及有机相中手性选择体浓度以及水相pH值对ZPC对映体萃取动力学的影响. 结果表明, L-IBTA萃取ZPC对映体的反应为“快反应”|对ZPC对映体反应是一级反应, 对L-IBTA反应是二级反应|对R-ZPC和S-ZPC反应速率常数分别为31.25×10^－5和48.74×10^－5 mol^－2•m⁶•s^－1. 萃取速率随HP-β-CD浓度的增加而降低. 以上研究结果将为手性萃取的工程设计提供参考.     

手性流动相添加剂高效液相色谱法分离苯基琥珀酸对映体

以七(2,3,6三-O-甲基)-β-环糊精(TM-β-CD)作为手性流动相添加剂,反相高效液相色谱研究苯基琥珀酸(PSA)对映体拆分;在Nova—pak C18色谱柱上,采用0．30mmol/L TM-β-CD、含0．05％三氟乙酸的乙腈一水(体积比16：84)为流动相,(R)-(-)-PSA和(s)-( )-PSA的容量因子分别为5．43和6．42,对映体分离因子为1．18,分离度为2．50;对比：PSA在β-CD手性流动相法和2,6-丁基化-β-CD涂渍C18柱的色谱行为,探讨环糊精分子对PSA的手性拆分机理：本法已用于测定L-脯氨酸化学拆分苯基琥珀酸对映体产品的光学纯度。     

手性离子对色谱法

阐述了手性离子对色谱分离药物对映体的基本原理。在ＨＰＬＣ流动相中加入光学纯反离子可与流动相中的对映体生成非对映体复合物（离子对）,离子对复合物之间具有不同的稳定性和分配性质,并可与固定相发生不同的静电、疏水和氢键作用,进而差速迁移得以分离。影响方法立体选择性的主要因素有：反离子的性质（酸碱性、亲脂性、光学纯度）、反离子的浓度、流动相的组分、流动相的流速、固定相的性质和色谱柱的温度等。     

单环手性胍催化的对映选择性Henry反应

从取代乙二胺方便地合成了4个手性单环胍．它们催化苯甲醛或异丁基醛同硝 基甲烷的Henry反应．能以较好的产率得到产物，但产物的对映体纯度不高．苯甲 醛Henry反应产物ee值最高为31％，异丁基醛获得的ee值最高为34％．这一反应速 度快，条件温和，是合成手性硝基醇的有效方法．     

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.     

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.     

HP-β-CD对苯基琥珀酸对映体色谱保留机制及拆分机理的研究

利用反相液相色谱(RP-HPLC)法,以羟丙基-β-环糊精(HP-β-CD)为手性流动相添加剂,研究了苯基琥珀酸(PSA)对映体的色谱保留机制.苯基琥珀酸对映体达到基线分离的最佳色谱分离条件为:10 mmol/L HP-β-CD,20% (体积分数)乙腈,0.05%(体积分数)三氟乙酸,pH 2.5,柱温25 ℃,流速1.0 mL/min,进样量为20 μL,检测波长为254 nm.该文建立了保留因子(k)与ce(HP-β-CD)、ce(H+)、包结平衡常数以及苯基琥珀酸的解离常数的关系式,并结合实验对该关系式进行了验证.保留因子的倒数1/k对ce(HP-β-CD)呈良好的线性关系,证明HP-β-CD与苯基琥珀酸对映体形成了包合比1 ∶ 1的包合物.在低酸度值下,包结平衡常数的计算结果显示,R-(-)-苯基琥珀酸与HP-β-CD所形成的包合物的包结平衡常数(162.5)比S-(+)-苯基琥珀酸(97.4)的大很多.手性拆分过程中热力学参数的计算结果表明,HP-β-CD对苯基琥珀酸对映体的分离过程主要是一个焓驱动的过程,包合过程是一个放热过程.通过比较手性选择体结构,探讨了HP-β-CD拆分苯基琥珀酸对映体的机理. 研究表明,分子尺寸大小相匹配以及构象诱导作用大小不同可能是HP-β-CD拆分苯基琥珀酸对映体的主要因素.     

手性高效液相色谱法测定SR-生物丙烯菊酯对映体的光学纯度

 在自制的球形氨丙基硅胶上涂敷纤维素 三 (3,5 二甲基苯基氨基甲酸酯 ) (CDMPC) ,制备了手性固定相(CSP)。用该固定相优化了生物丙烯菊酯对映体的分离条件 ,利用色谱峰面积测定了 3种SR 生物丙烯菊酯对映体的光学纯度。结果表明 ,在CDMPC CSP上用高效液相色谱法 (HPLC)测定SR 生物丙烯菊酯对映体的光学纯度、评价样品的质量优劣是一种非常理想的方法。     

双相(O/W)识别手性萃取分离α-环己基扁桃酸对映体

提出一种新的手性分离技术双相(O/W)识别手性萃取. 研究了α-环己基扁桃酸对映体在D(L)-酒石酸异丁酯1,2-二氯乙烷有机相和β-环糊精衍生物水相萃取体系中的分配行为; 考察了β-环糊精衍生物种类和浓度、酒石酸酯构型和浓度、水相pH 值等因素对萃取性能的影响. 实验结果表明, 双相(O/W)识别手性萃取具有很强的手性分离能力, 羟丙基β-环糊精、羟乙基β-环糊精、甲基β-环糊精均对S-α-环己基扁桃酸对映体的识别能力大于对R-α-环己基扁桃酸对映体的识别能力, 其中以羟丙基β-环糊精的识别能力最强; 而D-酒石酸异丁酯的识别能力刚好相反; 在羟丙基β-环糊精和D-酒石酸异丁酯萃取体系中, α-环己基扁桃酸外消旋体一次萃取分离后, 水相中S-对映体e.e.%达到27.6%, R-和S-对映体的分配系数(k_R和k_S)分别为2.44和0.98, 分离因子(α)达2.49; 同时pH值和萃取剂浓度对手性分离能力有显著影响. 双相(O/W)识别手性萃取对外消旋体化合物的制备性分离有着十分重要的意义.     

反应萃取手性分离苯基琥珀酸对映体动力学研究

通过恒界面池研究了羟丙基-β-环糊精(HP-β-CD)萃取苯基琥珀酸对映体(PSA)动力学.采用伴随化学反应的萃取理论获得萃取动力学.实验分别考察了搅拌速率、界面面积、对映体浓度和萃取剂浓度等条件对PSA对映体萃取动力学的影响.实验结果表明:HP-β-CD萃取PSA对映体的反应为快反应;对对映体反应是一级反应,对萃取剂反应是二级反应;R-PSA,S-PSA反应速率常数分别为3.4×10-2m6mol-2s-1,9.96×103m6mol-2s-1.这些数据对萃取过程的设计是很重要的.     

Continuous chromatographic separation of a baclofen precursor (N-Boc-4-[p-chloro-phenyl]-2-pyrrolidone) in a simulated moving bed using a polysaccharide carbamate as chiral stationary phase

Liquid chromatography is known as one of the most flexible, efficient and cost-effective methods to resolve racemic mixture in order to attend the growing demand of the pharmaceutical industry for pure enantiomeric compounds. Cellulose tris(3,5-dimethylphenylcarbamate) is frequently used as a stationary phase for enantiomeric separations because of its attractive properties, including high enantioselectivity, high loading capacity and good mechanical stability. In this study, we investigated the usefulness of cellulose tris(3,5-dimethylphenylcarbamate) as the stationary phase and of ethanol and hexane mixtures as the mobile phases for the chromatographic separation of potential pharmaceutical intermediates. Using adsorption equilibrium data, we determined the optimal operational conditions for the separation of the N-Boc-4-[p-chloro-phenyl]-2-pyrrolidone enantiomers - a baclofen precursor - in a semi-preparative scale simulated moving bed unit. This unit was used to obtain high purity enantiomers on a scale of 1g/day. The outlet streams were analyzed by an on-line system that consisted of a UV-vis spectrophotometric unit, a polarimeter, and HPLC. Enantiomeric purities of up to 97% were obtained for the raffinate stream and up to 90% for the extract stream.     

螺[4,4]-1,6-壬二烯骨架手性双膦配体的合成

从方便易得的原料出发,以钯催化的烯基三氟甲磺酸酯与二苯基膦氧化物的偶联反应为关键步骤,合成了螺[4,4]-1,6-壬二烯骨架的手性双膦配体1.其中,关键中间体5的拆分是通过半制备手性液相色谱实现的,并通过该化合物的X射线单晶衍射分析确定了其中螺碳原子的绝对构型.配体(S)-1的Rh(I)络合物在α-乙酰氨基肉桂酸的氢化中表现出中等的对映选择性(53%ee).配体(S)-1的Cu(I)络合物能以较好的反应活性实现苯乙酮的不对称氢化,产物的对映体过量可以达到67%.     

On-line monitoring of enantiomer concentration in chiral simulated moving bed chromatography

Simulated moving bed chromatography is a key technology for the pilot and production scale separation of enantiomers of chiral chemical species. Product quality control is probably the most important issue in this kind of separation at both scales, and for this it is clear that on-line monitoring of absolute enantiomer concentrations plays a major role. In this work, an on-line system consisting of a UV detector and a polarimeter in series is used to monitor the composition of the extract and raffinate streams of a laboratory SMB unit. The model system adopted is the separation of the enantiomers of the Tr?ger's base on microcrystalline cellulose triacetate (CTA) using ethanol as mobile phase. The technique is effective and accurate, thus providing promising perspectives for SMB process control and dynamic optimization.     

Resolution of N-methylamphetamine enantiomers with tartaric acid derivatives by supercritical fluid extraction

The resolution of N-methylamphetamine (MA) was carried out with the resolution agents O,O′-dibenzoyl-(2R,3R)-tartaric acid monohydrate (DBTA) and O,O′-di-p-toluoyl-(2R,3R)-tartaric acid (DPTTA). After partial diastereomeric salt formation, the unreacted enantiomers were extracted by supercritical fluid extraction (SFE). The effects of resolution agent molar ratio to the racemic mixture (mr), extraction pressure (P) and temperature (T) on the resolution efficiency were studied. The best chiral separation was obtained at a quarter of an equivalent resolution agent molar ratio for both resolution agents. Extraction conditions [pressure (100–200 bar), temperature (33–63 °C)] did not influence the resolution efficiency, which makes the enantiomer separation robust. In one extraction step, both enantiomers can be produced with high enantiomeric excess (ee) and remarkable yield (Y). Using DBTA as a resolution agent ee_E=83%, Y_E=45% for the extract and ee_R=82%, Y_R=42% for the raffinate were obtained.     

用手性高效液相色谱法拆分并测定氯苄哌醚联苯酰苯甲酸盐(英文)

氯苄哌醚联苯酰苯酸盐主要用于止咳,L-氯苄哌醚联苯酰苯酸盐具有更高活性.采用手性色谱柱,建立了氯苄哌醚联苯酰苯酸盐光学异构体的拆分方法,并将其用于氯苄哌醚联苯酰苯酸盐的检测.结果表明,采用Chiralcel OD-H柱,在流动相V(正己烷)∶V(异丙醇)∶V(二乙胺)=98∶2∶0.1的条件下,2个异构体能同时达到基线分离,检测波长为254nm,氯苄哌醚联苯酰苯酸盐检测极限为10ng.这表明所建立的分离分析方法可方便可靠地用于该化合物的光学纯度检测.     

万古霉素手性固定相分离克伦特罗对映体

应用万古霉素手性固定相对克伦特罗对映体进行了分离,考察了洗脱模式、流动相组成、柱温等因素对分离的影响,并对其分离机制进行了探讨.最佳色谱条件为:甲醇-冰醋酸-三乙胺(体积比100:0.01:0.01),流速1.0mL/min,柱温20℃.在此条件下,克伦特罗对映体可实现基线分离,最大分离度可达2.67.克伦特罗对映体与固定相之间的离子相互作用是实现对映体分离的最主要分离机制.     

π-Extended Diaza[7]helicenes by Hybridization of Naphthalene Diimides and Hexa-peri-hexabenzocoronenes

The synthesis of an unprecedented, π-extended hexabenzocorene (HBC)-based diaza[7]helicene is presented. The target compound was synthesized by an ortho-fusion of two naphthalene diimide (NDI) units to a HBC-skeleton. A combination of Diels–Alder and Scholl-type oxidation reactions involving a symmetric di-NDI-tolane precursor were crucial for the very selective formation of the helical superstructure via a hexaphenyl-benzene (HPB) derivative. The formation of the diaza[7]helicene moiety in the final Scholl oxidation is favoured, affording the symmetric π-extended helicene as the major product as a pair of enantiomers. The separation of the enantiomers was successfully accomplished by HPLC involving a chiral stationary phase. The absolute configuration of the enantiomers was assigned by comparison of circular dichroism spectra with quantum mechanical calculations.     

Separation of phenylsuccinic acid enantiomers using biphasic chiral recognition high‐speed countercurrent chromatography

High‐speed countercurrent chromatography (HSCCC) combined with biphasic chiral recognition was successfully applied to the resolution of phenylsuccinic acid enantiomers. d ‐Isobutyl tartrate and hydroxypropyl‐β‐cyclodextrin were employed as lipophilic and hydrophilic selectors dissolved in the organic stationary phase and aqueous mobile phase, respectively. The two‐phase solvent system was made up of n‐hexane/methyl tert‐butyl ether/water (0.5:1.5:2, v/v/v). Impacts of the type and concentration of chiral selectors, the pH value of the aqueous phase solution as well as the temperature on the separation efficiency were investigated. By means of preparative HSCCC, pure enantiomer was obtained by separating 810 mg of racemate with a purity >99.5% and a recovery rate between 82 and 85%. The experimental results indicate that biphasic recognition HSCCC provide a promising means for efficient separation of racemates.     

Kinetic study on reactive extraction for chiral separation of phenylsuccinic acid enantiomers

The kinetics of the extraction of phenylsuccinic acid (PSA) enantiomers by hydroxypropyl-β-cyclodextrin (HP-β-CD) in a modified Lewis cell was studied, in which HP-β-CD dissolved in 0.1 mol L^?1 NaH₂PO₄/H₃PO₄ buffer solution (pH = 2.5) was selected as the chiral extractant. PSA enantiomers were extracted from organic phase to aqueous phase in the extraction module. The theory of extraction accompanied by a chemical reaction has been used to obtain the intrinsic kinetics of this extraction module. The different parameters affecting the extraction rate such as agitation speed, interfacial area, initial concentration of PSA enantiomers in organic phase as well as HP-β-CD concentration in aqueous phase were separately studied. The experimental results demonstrate that the extraction reactions are fast. The reactions were found to be first order with respect to PSA and second order with respect to HP-β-CD with forward rate constants of 3.4 × 10^?2 m⁶ mol^?2 s^?1 for R-PSA and 9.96 × 10^?3 m⁶ mol^?2 s^?1 for S-PSA. These data will be useful in the design of extraction processes.