Synthesis and reversible photocleavage of novel polyurethanes containing coumarin dimer components

Six polyurethanes containing coumarin dimer components in the main chain have been prepared by polyaddition of diisocyanates with anti head-to-head 7-hydroxycoumarin dimer or anti head-to-tail 7-hydroxy-4-methylcoumarin dimer. 7-Acetoxycoumarin and 7-acetoxy-4-methylcoumarin were first prepared and then photodimerized under 350 nm UV light to give anti head-to-head 7-acetoxycoumarin dimer and anti head-to-tail 7-acetoxy-4-methylcoumarin dimer, respectively. After hydrolyzing under acidic conditions to 7-hydroxycoumarin dimer and anti head-to-head 7-hydroxycoumarin dimer, they were polymerized with aliphatic and aromatic diisocyanates in N,N-dimethylacetamide to give the polyurethanes. Addition of dibutyltin dilaurate (T-12) as catalyst increases the polymer yield with the viscosity remaining almost unchanged. It was also found that lithium chloride enhances both the yield and viscosity of the polyurethanes by increasing their solubility possibly through complexation. The polyurethanes are symmetrically photocleaved at cyclobutane rings under 254 nm UV light to dicoumarins. Reversible photodimerization of the photocleaved compounds have also been investigated under 300 and 350 nm UV light. The polyurethanes from aromatic diisocyanates or with 4-methyl substituent exhibit greater reactivity in the photocleavage reaction. © 1997 John Wiley & Sons, Inc.     

高效液相色谱法拆分雷喏嗪

用高效液相色谱法(HPLC)在正相条件下,用自制的涂敷直链淀粉-三(3,5-基苯基氨基甲酸酯)(ADMPC)手性固定相直接拆分了高效低毒的抗心绞痛药物雷喏嗪外消旋体(Ranolazine),并考察了二元及三元流动相体系对样品分离的影响,结果表明,三元流动相中的拆分结果远远好于二元流动相,流动相中不同种类醇改性剂及含量对样品保留时间和立体选择性有不同程度的影响．     

Preparation and chiral recognition ability of cellulose 3,5-dimethylphenylcarbamate immobilized on silica gel through radical polymerization

Polysaccharide-immobilized chiral stationary phases (CSPs) were prepared by the polymerization of cellulose 3,5-dimethylphenylcarbamate, having a polymerizable vinyl group, such as 4-vinylphenylcarbamate or 2-methacryloyloxyethylcarbamate, at the 6-position, with a vinyl monomer, such as styrene, isoprene, t-butyl acrylate, or t-butyl methacrylate, on silica gel under various conditions. Their chiral recognition abilities were then evaluated with high-performance liquid chromatography. The immobilized cellulose 3,5-dimethylphenylcarbamate remained on the silica gel even if washed with tetrahydrofuran, which could dissolve the cellulose derivative. The chiral recognition abilities of the immobilized CSPs were similar to those of the coated CSPs when the vinyl monomer content was low. The chiral recognition abilities of the obtained immobilized CSPs slightly depended on the vinyl monomers. The immobilization of the cellulose derivatives was more efficiently attained on the silica gel modified with a vinyl compound. The cellulose derivatives, randomly having a vinyl group at the 2-, 3-, or 6-position of the glucose unit, were prepared by a one-pot reaction. The immobilization efficiency of these derivatives was slightly lower than that of the derivative with the vinyl group at the 6-position. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3703–3712, 2003     

Chiralpak AD-H和Chiralcel OJ-H手性固定相拆分扁桃酸系列化合物

对比了商品化的淀粉型手性固定相Chiralcel OJ-H和纤维素型手性固定相Chiralpak AD-H柱在正相条件下对扁桃酸系列8个化合物的拆分,结果表明Chiralcel OJ-H柱对扁桃酸系列化合物具有更强的手性识别能力,8个外消旋扁桃酸化合物在36 min内都得到了基线分离。研究发现,扁桃酸苯环上的取代基对其拆分的难易程度影响很大,其电子诱导效应影响扁桃酸类化合物在固定相上的保留时间,其空间位阻效应是扁桃酸在固定相上被拆分成败的决定因素。通过对比分析扁桃酸和手性柱的结构,探讨了可能的手性拆分机理是基于Chiralpak AD-H(Chiralcel OJ-H)手性固定相和扁桃酸系列化合物之间的氢键-氢键、偶极-偶极、π-π电子相互作用以及空间适应性等诸多因素的综合影响,其中空间适应性起到至关重要的作用。本研究可为一些实际光学活性扁桃酸及其类似物的对映体纯度测定与拆分研究提供参考。     

键合型聚丙烯酰胺衍生物手性固定相的制备与手性识别性能

高效液相色谱(HPLC)被广泛认为是分离制备光学纯单一对映体的最有效方法。在高效液相色谱手性拆分中,手性固定相(CSP)的性能直接影响到色谱柱的手性分离能力。在众多手性固定相中,键合型手性固定相具有溶剂耐受性好,分离模式灵活等优点,已经发展成为一类重要的手性固定相。本文通过两步化学反应合成了新型的光学活性丙烯酰胺衍生物--(S)-1-丙烯酰-2-(N-苯基甲酰胺基)吡咯烷((S)-APACP),采用核磁共振氢谱表征了(S)-APACP的化学结构;通过3步化学反应制备了键合型聚丙烯酰胺衍生物手性固定相,采用热重分析法表征了聚合物的键合量,采用HPLC评价了键合型手性固定相的识别能力,分析了影响其手性识别能力的因素。研究结果表明,APACP聚合物成功地键合到硅胶表面制备了具有良好溶剂耐受性的键合型手性固定相,其聚合物键合量为10.2%~11.8%,该键合型手性固定相对若干种对映体显示了较好的手性识别能力。     

用高效液相色谱手性固定相法拆分芳香仲醇及芳香乙二 醇类手性化合物

在ChiralcelOD和ChiralcelOJ两支多糖类手性固定相上，以各种不同配比的正己烷-异丙醇为洗脱剂对38种带有不同取代基的芳香仲醇及芳香乙二醇类手性化合物的对映体进行拆分，考察了这些外消旋体在这两支手性柱上的色谱行为。结果表明，扬长避短一柱对这些化合物的拆分能力与化合物取代基的性质和位置有关，这些化合物与手性固定相之间的氢键作用和π-π作用是影响手性拆分的重要原因。拆分方法已应用于潜手性酮不对称还原产物的光学纯度的鉴定，并取得了很好的效果。     

Immobilized polysaccharide derivatives: chiral packing materials for efficient HPLC resolution

Polysaccharide-based chiral packing materials (CPMs) for high-performance liquid chromatography have frequently been used not only to determine the enantiomeric excess of chiral compounds but also to preparatively resolve a wide range of racemates. However, these CPMs can be used with only a limited number of solvents as mobile phases because some organic solvents, such as tetrahydrofuran, chloroform, and so on, dissolve or swell the polysaccharide derivatives coated on a support, e.g., silica gel, and destroy their packed columns. The limitation of mobile phase selection is sometimes a serious problem for the efficient analytical and preparative resolution of enantiomers. This defect can be resolved by the immobilization of the polysaccharide derivatives onto silica gel. Efficient immobilizations have been attained through the radical copolymerization of the polysaccharide derivatives bearing small amounts of polymerizable residues and also through the polycondensation of the polysaccharide derivatives containing a few percent of 3-(triethoxysilyl)propyl residue.     

非均匀取代淀粉衍生物手性固定相的制备及其手性识别能力

通过区域选择性方法制备了两种新型淀粉衍生物,分别为淀粉2-苯甲酸酯-3-(4-甲基苯基氨基甲酸酯)-6-(3,5-二氯苯基氨基甲酸酯)和淀粉2-苯甲酸酯-3-(3,5-二氯苯基氨基甲酸酯)-6-(4-甲基苯基氨基甲酸酯),将二者分别涂覆于氨丙基硅胶后用作液相色谱手性固定相。研究表明:所制备的手性固定相显示出特异的手性识别能力,其手性识别能力明显高于均匀取代淀粉衍生物——淀粉三(3,5-二氯苯基氨基甲酸酯),取代基的性质及在葡萄糖单元上的位置对手性固定相的手性识别能力有较大的影响。一些未在商品化的手性柱Chiralpak AD上得到有效分离的手性化合物在所制备的固定相上得到了更好的分离。所测试的8对对映体在淀粉2-苯甲酸酯-3-(4-甲基苯基氨基甲酸酯)-6-(3,5-二氯苯基氨基甲酸酯)固定相上均得到了分离,因而此固定相的手性识别能力较强,具有潜在的应用价值。     

Comparative studies of immobilized polysaccharide derivatives chiral stationary phases for enantioseparation of furanocoumarins and dihydroflavones and discussion on chiral recognition mechanism

Enantiomeric separation of furanocoumarins and dihydroflavones compounds were systematically studied in the normal-phase mode using four different polysaccharide-type chiral stationary phases, namely, Chiralpak IA, Chiralpak IC, Chiralpak IG, and Chiralpak IK-3 by high-performance liquid chromatography. The effect of alcohol modifiers and alcohol content on enantiomeric separation was evaluated for the separation of furanocoumarins and dihydroflavones. All the eight compounds have achieved baseline separation with the resolutions ranging between 1.52 and 23.11. For a better insight into the enantiorecognition mechanisms, thermodynamic analysis was carried out. The mechanisms of chiral recognition have been discussed. Among four chiral columns, Chiralpak IG exhibited the most universal and the best enantioseparation ability toward furanocoumarins and dihydroflavones when used n-hexane-isopropanol and n-hexane-ethanol as mobile phase, respectively. The steric hindrance, hydrogen bonding, and π-π interaction played major roles in chiral recognition on Chiralpak IG. By comparing four chiral columns, this work systematically analyzed the separation methods of furanocoumarins and dihydroflavones for the first time and reported some active chiral ingredients of traditional Chinese medicine that have never been separated, which provided a further insight into the enantioseparation of furanocoumarins and dihydroflavones on chiral stationary phases.     

环氧酰胺类化合物在OD和AD柱上手性拆分的比较

在ChiralcelOD和ChiralpakAD等二支多糖类手性固定相上,以各种不同配比的正己烷-异丙醇为洗脱剂对十三种带有不同取代基的环氧酰胺类化合物的对映体进行了手性拆分。考察了这些外消旋体在这二支手性柱上的色谱行为。实验表明,环氧酰胺与手性固定相之间的手性作用(例如:偶极-偶极作用、氢键作用、π-π作用)和非手性作用(例如:空间效应)等的综合因素是支配手性拆分过程的主要原因。方法已用于环氧酰胺不对称反应产物的光学纯度鉴定。     

Preparation and evaluation of novel chiral stationary phases covalently bound with chiral pseudo-18-crown-6 ethers

Novel chiral stationary phases consisting of silica gel covalently bound with chiral pseudo-18-crown-6 type hosts, which possess either an OH or OMe group as a binding functionality, were prepared for enantiomer-separation of lipophilic amines.     

量子化学计算解析手性共价有机框架材料6色谱固定相的手性拆分机理

为探究手性共价有机框架材料6(Chiral Covalent Organic Frameworks 6, CCOF6)色谱固定相的手性拆分机理,首先运用ORCA程序对CCOF6及4对手性对映体进行结构优化,然后使用AutoDock程序对CCOF6及各对映体分子进行分子对接,获得CCOF6与对映体相互作用的初始构型;采用ORCA程序(B3LYP泛函,带DFT-D3校正,轨道基组为def2-TZVP, def2/J作为RI-J的辅助基组,RIJCOSX用来加速计算)对初始构型进行能量计算,以最终确定CCOF6与对映体的相互作用构型,并获得相应的结合自由能和结合自由能差;使用Multiwfn程序对ORCA结果进行独立梯度模型分析,并应用视觉分子动力学程序可视化展示CCOF6与对映体的弱相互作用。结果表明:(1)在计算结合自由能方面,考虑了溶剂效应的ORCA计算方法比不考虑溶剂效应的ORCA以及AutoDock计算方法更为精确;(2)CCOF6色谱固定相与对映体之间的结合自由能差绝对值越大,对映体的选择性因子也越大,然而对映体的分离度不一定会越大;(3)除S-1-苯基-1-丙醇是以羟基和CCO...     

Synthesis and chiral recognition of novel amylose derivatives containing regioselectively benzoate and phenylcarbamate groups

A new class of regioselectively substituted amylose derivatives bearing three different substituents at 2-, 3- and 6-positions, and two different substituents at 2-position and 3-, 6-positions were synthesized by a sequential process based on the esterification of 2-position of a glucose unit. Their chiral recognition abilities were evaluated as chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC). Each derivative had its own characteristic recognition ability depending on the arrangement of side chains at the three positions. Among the derivatives, amylose 2-(4-t-butylbenzoate) and amylose 2-(4-chlorobenzoate) series exhibited high chiral recognition. Some racemates can be efficiently separated on these derivatives as well as on the amylose tris-3,5-dimethylphenylcarbamate, which is commercially available as Chiralpak AD and one of the most powerful CSPs. The structures of the amylose derivatives were also investigated by circular dichroism spectroscopy.     

异噁唑啉及异噁唑烷类化合物在多糖衍生物类柱上的手性拆分

在ＣｈｉｒａｌｃｅｌＯＤ，ＣｈｉｒａｌｃｅｌＯＪ及ＣｈｉｒａｌｐａｋＡＤ等３种多糖类手性固定相上，以各种配比的正己烷－异丙醇为洗脱剂，对７种异口恶唑啉及异口恶唑烷类化合物的对映体进行了手性拆分。考察了这些外消旋物在这些手性柱上的色谱行为。实验结果表明，手性固定相上葡萄糖片段构型的差异和它们高级结构的不同以及手性固定相上的二甲基苯基氨基甲酸酯或对甲基苯甲酸酯等功能团与样品的极性基团之间的相互作用，可能是支配手性拆分的主要原因。方法已用于不对称１，３－偶极环加成反应产物的光学纯度鉴定。     

纤维素-三（3,5-二甲苯基氨基甲酸酯）手性固定相拆分氨鲁米特对映体

以纤维素-三（3,5-二甲苯基氨基甲酸酯）为手性固定相（Chiralcel OD-H）在高效液相色谱上拆分了氨鲁米特对映体。通过测定氨鲁米特在正己烷/乙醇和正己烷/异丙醇中的溶解度,优选了对样品溶解度大的流动相体系,并考察了流动相添加剂乙醇胺对拆分效果的影响。在此基础上进一步研究了流动相中乙醇含量、柱温和进样量对分离因子、分离度、不对称因子和理论板数的影响,从而确定了最佳的拆分条件：固定相为Chiralcel OD-H,流动相为正己烷/乙醇/乙醇胺（体积比为30：70：0.1）,柱温25℃。本文所得结果可为工业放大提供基础数据。     

Preparation and chiral recognition ability of crosslinked beads of polysaccharide derivatives

The spherical beads consisting of cellulose 3,5-dimethylphenylcarbamate with partial hydroxyl groups were prepared to be used as chiral packing materials (CPMs) for HPLC. The beads were obtained without using macroporous silica gel, which is usually used as the support of the CPMs based on the polysaccharide derivatives. After the crosslinking in the bead with diisocyanates, such as 4,4'-diphenylmethane diisocyanate (MDI), 4,4'-dibenzyl diisocyanate (DBDI), tolylene-2,4-diisocyanate (TDI), and m-xylylene diisocyanate (XDI), the obtained beads were packed into an HPLC column. As the content of the hydroxyl groups of the cellulose derivatives decreased, the obtained CPM exhibited a higher chiral recognition ability. The beads possessed a higher loading capacity than the CPM prepared by coating the cellulose derivative on silica gel. The crosslinked beads could be used with the eluent containing chloroform. The amylose derivative beads were also prepared as a CPM for chiral HPLC.     

药物曲美布汀对映体在涂敷三(4-甲基苯甲酸)纤维素酯手性固定 相上的HPLC分 离

涂敷15%(wt)三(4-甲基苯甲酸)纤维素酯于大孔硅胶担体上,制备手性固定相,以此手性固定相作填料,湿法装填液相色谱柱,直接分离(±)-曲美布汀对映体。确定对映体在固定相与洗脱液之间分配的自由能变之差值、焓变之差值和熵变之差值,考察洗脱液正己烷-异丙醇(v/v)中异丙醇含量在色谱分离对映体性能方面的影响。当洗脱液中异丙醇含量增加时,对映体的容量因子逐渐降低,分离因子变化不大,分离度逐渐降低。     

Novel chiral PEDOTs for selective recognition of 3,4‐dihydroxyphenylalanine enantiomers: Synthesis and characterization

Two new 3,4‐ethylenedioxythiophene (EDOT) derivatives, (2R)‐(2,3‐dihydrothieno[3,4‐b][1,4]dioxin‐2‐yl)methyl 2‐phenylpropanoate ((R)‐EDTM‐PP) and (2S)‐(2,3‐dihydrothieno[3,4‐b][1,4]dioxin‐2‐yl)methyl 2‐phenylpropanoate ((S)‐EDTM‐PP), were synthesized and electropolymerized in dichloromethane (CH₂Cl₂) and terabutylammonium hexafluorophosphate (Bu₄NPF₆) system. As chiral electrodes, poly((2R)‐(2,3‐dihydrothieno[3,4‐b][1,4]dioxin‐2‐yl)methyl 2‐phenylpropanoate) ((R)‐PEDTM‐PP) and poly((2S)‐(2,3‐dihydrothieno[3,4‐b][1,4]dioxin‐2‐yl)methyl 2‐phenylpropanoate) ((S)‐PEDTM‐PP)‐modified glassy carbon electrodes (GCEs) were employed to successfully recognize 3,4‐dihydroxyphenylalanine (DOPA) enantiomers. Cyclic voltammetry presents that (R)‐PEDTM‐PP and (S)‐PEDTM‐PP had good redox activity and stability. Spectroelectrochemistry studies revealed (R)‐PEDTM‐PP and (S)‐PEDTM‐PP polymers have electronic bandgap of 1.68 and 1.66 eV, and could be reversibly oxidized and reduced accompanying with obvious color changes from dark blue to light purple. In addition, the electrochemical behavior, structural characterization, thermal stability, morphology and circular dichroism of (R)‐PEDTM‐PP and (S)‐PEDTM‐PP films were investigated in detail. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2238–2251     

QSERRs方法及其在色谱手性识别机理研究中的应用

介绍了定量结构-对映保留关系(QSERRs)方法及其在色谱手性识别机理研究中的应用。引用文献31篇。     

Synthesis and Resolution of 10, 11-Dihydro- 10-hydroxycyproheptadine

10, 11-Dihydro-10-hydroxycyproheptadine was synthesized in a new and facile synthetic route and resolved by L-(-)-2-(1, 3)-dioxo-1, 3-dihydroisoindol-2-yl)-propionic acid and D-( )-tartaric acid, respectively. The free base of the two enantiomers has the same absolute specific rotation value.