乙内酰脲法合成外消旋萘普生

研究了以２－甲氧基萘为原料，经乙酰基化、Ｂｕｃｈｅｒｅｒ－Ｂｅｒｇ＇ｓ反应、Ｎ－甲基化和催化氢解等反应制得外消旋体萘普生１。通过＾１Ｈ ＮＭＲ、＾１３Ｃ ＮＭＲ、ＩＲ和元素分析确证了中间体和产物的结构。     

高效液相色谱法对外消旋药物的拆分

综述了近年来高效液相色谱法在药物对映体拆分与测定中的应用，介绍了许多有代表性的具有不同药理性能对映异构体药物，并指出出拆份的重要意义，共引用文献３２篇。     

吉非替尼的合成工艺改进

以3-羟基-4-甲氧基苯甲醛为原料,先与N-(3-氯丙基)吗啉缩合,后依次经过醛基转化为氰基、硝化、还原、与3-氯-4-氟苯胺环合等反应合成了抗肿瘤药物吉非替尼,总收率约50%。其结构经1H NMR,MS和元素分析表征。     

斯替宁碱的合成方法研究进展

具有1H-吡咯并[1,2-a]氮杂和多取代全氢吲哚结构的斯替宁碱是百部生物碱的代表性结构,其多环结构和连续的七个手性中心对不对称合成化学极具挑战性.按斯替宁碱合成中使用的关键方法分类,对斯替宁碱的合成研究进展进行了综述.     

乳胶制品中N-亚硝胺析出物的GC-MS/SIM检测

使用气相色谱-质谱(GC-MS/SIM)检测了乳胶制品中5种N-亚硝胺析出物,样品经过二氯甲烷萃取,用Rtx-5MS石英毛细管柱分离,采用内标法进行检测计算.实验得出5种N-亚硝基化合物的内标标准曲线日内RSD(小于5%),日间RSD(小于14%).N-亚硝基二乙胺(NDEA)、N-亚硝基二丙胺(NDPA)、N-亚硝基哌啶(NPIP)、N-亚硝基二丁胺(NDBA)、N-亚硝基二苯胺(NDPhA)的方法的检出限分别为2.0,5.0,10.0,1.0,112.0μg/L.运用该法对北京市场的乳胶制品进行了检测.     

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.     

氨基酰化酶的固定化和苯丙氨酸消旋体的拆分

本文合成了一种功能高分子材料,利用其适宜的物理性质和匹配的功能基来固定氨基酰化酶,并进行苯丙氨酸消旋体的拆分,研究结果表明:这种载体对氮基酰化酶蛋白固定容量大,固定化酶比活力高,活力损失小,本文系统地研究了氮基酰化酶拆分苯丙氨酸消旋体的理化性质,包括温度、pH、离子浓度、热稳定性、激活离子、底物浓度以及蛋白变性剂等,并进行苯丙氨酸消旋体的连续拆分,对拆分产物采用离子交换法进行分离精制,真空浓缩得到L-苯丙氨酸的盐酸盐,产率高,对产品进行旋光检验,纯度高。     

不对称1,3,2—苯并二氧碳杂环己烷非对映消旋体的合成及生 …

通过相转移催化关环反应合成了新的６－取代－２－硫－２－烷（芳）氧－４（２，４－二氯苯基）－４－氢－１，３，２－苯并二氧磷杂环己烷（３ａ－３ｇ），用结晶法分离得到了７对非对映消旋体，其结构经ＨＮＭＲ、＾３１ＰＮＭＲ和元素分析确证，化合物３ａ－Ａ单晶Ｘ射线分析表明其构型为（２Ｒ，４Ｓ；２Ｓ，４Ｒ），生物活性测定结果表明，化合物３ｃ有良好的杀虫活性，非对映消旋体Ａ和Ｂ具有协同杀虫作用。     

甲磺酸迈瑞替尼的合成工艺改进

以3-(2-氯嘧啶-4-基)-1-甲基吲哚和4-氟-2-甲氧基-5-硝基苯胺为起始原料,经缩合、取代、还原、酰化及成盐反应合成了抗肿瘤药物--甲磺酸迈瑞替尼,总收率66.2%,其结构经¹ H NMR, IR 和MS确证。     

阿法替尼的合成工艺改进

以2-氨基-4-氯苯甲酸为原料,经环合、硝化、氯代和胺化后,采用一锅两步法制得关键中间体4-［(3-氯-4-氟苯基)氨基］-6-硝基-7-［(S)-四氢呋喃-3-基氧基]-喹唑啉(4); 4依次经还原、酰胺化、HWE反应合成阿法替尼,总收率55.7%,含量98%,其结构经¹H NMR和LC-MS确证。     

苯丙氨酸光学异构体的酶法拆分

氨基酰化酶;苯丙氨酸光学异构体的酶法拆分     

Zur Frage der Existenz anomaler Racemate

Zusammenfassung Eines der wenigen Beispiele, bei denen in neuerer Zeit anomale Racemate beschrieben wurden, 1st die Äpfelsäure; sie diente als Studienobjekt.Eine Neubearbeitung des Phasendiagramms ergab, daß DL-Äpfelsäure dimorph ist und Mod. II als stabilisierte Zwischenphase auftritt, so daß in dem System D-Äpfelsäure-L-Äpfelsäure statt der bei Racematdiagrammen üblichen zwei Kristallphasen drei verschiedene Phasen vorliegen. Dadurch wird ein System mit einer homogen schmelzenden (normales Racemat) und zwei inhomogen schmelzenden Verbindungen (anomale Racemate) vorgetäuscht.Es wird die Meinung vertreten, daß keine anomalen Racemate existieren, sondern daß die vermeintlichen Anomalien bei enantiomeren Verbindungen ebenso wie bei anderen Zweistoffsystemen auf Polymorphie und Mischkristallbildung beruhen.

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On the existence of anomalous racemates

Summary Malic acid is one of the few substances in which anomalous racemates have been recently described, and it was the object of this study. A new processing of the phase diagram revealed that DL malic acid is dimorphic and that Mod. II occurs as a stabilized intermediate phase. Instead of the two crystal phases usual in the racemate diagram, three different phases are present in the system D malic acid-L malic acid. A system is thereby simulated with a homogenously melting (normal racemate) and two inhomogenously melting compounds (anomalous racemates).The opinion is expressed that no anomalous racemates exist, but that the supposed anomalies in enantiomeric substances as in other twosubstance systems are based on polymorphism and formation of mixed crystals.

     

Metastable Chiral Azobenzenes Stabilized in a Double Racemate

The self‐assembly of chiral organic chromophores is gaining huge significance due to the abundance of supramolecular chirality found in natural systems. We report an interdigitated molecular assembly involving axially chiral octabrominated perylenediimide (OBPDI) which transfers chiral information to achiral aromatic moieties. The crystalline two‐component assemblies of OBPDI and electron‐rich aromatic units were facilitated through π‐hole???π donor–acceptor interactions, and the charge‐transfer characteristics in the ground and excited states of the OBPDI cocrystals were established through spectroscopic and theoretical techniques. The OBPDI cocrystals entail a remarkable homochiral segregation of P and M enantiomers of both molecular entities in the same crystal system, leading to twisted double‐racemic arrangements. Synergistically engendered cavities with the stored chiral information of the twisted OBPDI stabilize higher‐energy P/M enantiomers of trans‐azobenzene through non‐covalent interactions.     

Disappearing Enantiomorphs: Single Handedness in Racemate Crystals

Although crystallization is the most important method for the separation of enantiomers of chiral molecules in the chemical industry, the chiral recognition involved in this process is poorly understood at the molecular level. We report on the initial steps in the formation of layered racemate crystals from a racemic mixture, as observed by STM at submolecular resolution. Grown on a copper single‐crystal surface, the chiral hydrocarbon heptahelicene formed chiral racemic lattice structures within the first layer. In the second layer, enantiomerically pure domains were observed, underneath which the first layer contained exclusively the other enantiomer. Hence, the system changed from a 2D racemate into a 3D racemate with enantiomerically pure layers after exceeding monolayer‐saturation coverage. A chiral bias in form of a small enantiomeric excess suppressed the crystallization of one double‐layer enantiomorph so that the pure minor enantiomer crystallized only in the second layer.     

Rational Fabrication of Multiple Dimensional Assemblies from Tryptophan-Based Racemate

Fabricating structural complex assemblies from simple amino acid-based derivatives is attracting great research interests due to their easy accessibility and preparation. However, the morphological regulation of racemates (an equimolar mixture of enantiomers) were largely overlooked. In this work, through rational modulation of kinetic and thermodynamic parameters, we achieved multiple dimensional architectures employing tryptophan-based racemate (RPWM). Upon assembling, 1D bundled nanofibers, 2D lamellar nanostructure and 3D urchin-like microflowers could be obtained depending on the solvents used. The corresponding morphology evolutions were successfully illustrated by changing the enantiomeric excess (ee) value. Moreover, for RPWM, uniform 0D nanospheres were formed in H₂O under 4 °C, which could spontaneously convert into lamella under ambient temperature. Taking advantages of its temperature-responsive phase change behavior, RPWM assemblies exhibited excellent removal efficiency for organic dye RhB, and could be reused for several consecutive cycles without significant changes in its removal performance. Taken together, it's rational to envision that the engineering of racemates assembly pathways can greatly increase the robustness in a wide variety of supramolecular materials and further lead to their blooming versatile applications.     

The Potential Energies of Cohesion of a Crystalline Organic Enantiomer and the Racemate; on the Energy for the Liquid Racemate [1]

Summary. The cohesion potential energy of the crystal of one enantiomer of ethyl 3-cyano-3-(3,4-dimethyloxyphenyl)-2,2,4-trimethylpentanoate, −47.7 ± 0.1 kJ mol⁻¹ (0–90°C), was found out from the heat of sublimation (123.2 ± 5.1 kJ mol⁻¹, 78.6°C) and the kinetic energies for the gas phase and the crystal. It was found that the entropy function of Debye’s theory of solids mathematically agreed with the vibrational entropy of the gas (variationally obtained), allowing to disclose the vibrational energy using the Debye energy function (E _vib 835.0 kJ mol⁻¹ (78.6°C), E ⁰ included). E _kin for the crystal (771.1 kJ mol⁻¹ (78.6°C)) was obtained by Debye’s theory with the experimental heat capacity. The cohesion energy represented a moderate part of the sublimation energy. The cohesion energy of the racemic crystal, −44.2 kJ mol⁻¹, was obtained by the heat of formation of the crystal in the solid state (3.0 kJ mol⁻¹, 83.3°C) and E _kin for the crystal (by Debye’s theory). The decrease in cohesion on formation of the crystal accounted for the energy of formation. The change in potential energy on liquefaction of the racemate from the gas state was disclosed obtaining added-up E _{vib + rot} for the liquid in the way as to E _vib for the gas, the Debye entropy function being increasedly suited for the liquid (E _{vib + rot} 763.4 kJ mol⁻¹ (115.4°C)). Positive ΔE _pot, 13.0 kJ mol⁻¹, arised from the increase in electronic energy (Δ _l ν_mean − 154.3 cm⁻¹, by the dielectric nature of the liquid), added to the cohesion energy.     

Synthese der Racemate der beiden stereoisomeren Evoninsäuren

The synthesis of the title compounds in accordance with Table 1 is reported.     

The Potential Energies of Cohesion of a Crystalline Organic Enantiomer and the Racemate; on the Energy for the Liquid Racemate [1]

The cohesion potential energy of the crystal of one enantiomer of ethyl 3-cyano-3-(3,4-dimethyloxyphenyl)-2,2,4-trimethylpentanoate, −47.7 ± 0.1 kJ mol⁻¹ (0–90°C), was found out from the heat of sublimation (123.2 ± 5.1 kJ mol⁻¹, 78.6°C) and the kinetic energies for the gas phase and the crystal. It was found that the entropy function of Debye’s theory of solids mathematically agreed with the vibrational entropy of the gas (variationally obtained), allowing to disclose the vibrational energy using the Debye energy function (E _vib 835.0 kJ mol⁻¹ (78.6°C), E ⁰ included). E _kin for the crystal (771.1 kJ mol⁻¹ (78.6°C)) was obtained by Debye’s theory with the experimental heat capacity. The cohesion energy represented a moderate part of the sublimation energy. The cohesion energy of the racemic crystal, −44.2 kJ mol⁻¹, was obtained by the heat of formation of the crystal in the solid state (3.0 kJ mol⁻¹, 83.3°C) and E _kin for the crystal (by Debye’s theory). The decrease in cohesion on formation of the crystal accounted for the energy of formation. The change in potential energy on liquefaction of the racemate from the gas state was disclosed obtaining added-up E _{vib + rot} for the liquid in the way as to E _vib for the gas, the Debye entropy function being increasedly suited for the liquid (E _{vib + rot} 763.4 kJ mol⁻¹ (115.4°C)). Positive ΔE _pot, 13.0 kJ mol⁻¹, arised from the increase in electronic energy (Δ _l ν_mean − 154.3 cm⁻¹, by the dielectric nature of the liquid), added to the cohesion energy.     

Spontaneous Enantiomeric Resolution in a Fluid Smectic Phase of a Racemate

Right- and left-handed homochiral domains segregate in a fluid smectic phase of the racemic (R*,S*)-β-Me-TFMHPOBC analogue shown. This CF₃-containing liquid crystalline compound exhibits an electrooptic response in a homogeneous cell, although no macroscopic dipole is expected to exist. Moreover, the homeotropic cells of this material exhibit striped domains, which are associated with fine stripes having two opposite tilt senses with respect to the predominant stripes.     

万古霉素手性固定相的制备与对映体分离研究

采用双官能团试剂4,4′-二苯基甲烷二异氰酸酯在无水二甲基甲酰胺(DMF)中直接与大环糖肽类抗生素万古霉素及γ-氨丙基硅胶键合,得到环状抗生素手性固定相(CSP)并用于高效液相色谱手性分析。实验结果证实,合成的万古霉素CSP在正相和反相条件下均有一定的拆分能力,其中在反相条件下拆分了17种对映体,显示出其较为广泛的拆分范围,且磷酸缓冲体系略优于三乙胺-乙酸缓冲体系;对一些物质,如D,L-丹酰化氨基酸的拆分有一定的规律,能给出绝对构型信息。所制备的CSP在相体系转化时不发生老化和变性,显示了一定的稳定性。对该CSP的拆分机理进行分析所得到的结果与Armstrong等的分析结果基本一致。