测定手性有机酸对映体纯度的新试剂

用NMR技术测定微量手性化合物的对映体纯度,已有多种方法。其中,加手性镧化物位移试剂法适用面最广,但对有机酸,结果常不理想。另一种使用较广的方法是加手性试剂,将样品中两对映体转变成非对映异构体,然后比较非对映基因NMR信号的强度,确定原样品中对映体的组成比例。国外已出售的手性试     

衍生化-手性毛细管色谱分离和测定水中的2,4-滴丙酸

建立了一种采用手性气相色谱分离、测定水中2,4-滴丙酸(DCPP)的分析方法。通过对样品的酯化处理降低了被测物的沸点,提高了其挥发性;利用手性气相色谱-ECD检测灵敏度高、量程宽的优点,实现了水中DCPP的手性分离、定量分析,平均回收率达90％。该方法安全、快速、准确,可用于水中2,4-滴丙酸和2,4-滴丙酸甲酯对映体定量分析。     

手性试剂TMPEA用于手性酮对映体纯度测定的研究

β-三氟甲基-β甲氧基β-苯基乙胺（TMPEA）是含氨基功能团的手性试剂[1]．由于胺可将按酸转变成酸胺，该试剂已成功地用于手性有机酸对映体的纯度测定[2]．考虑到胺同样可将醛酮转变成亚胺，本文进一步探讨了TMPEA用于手性醒酮对映体纯度测定的可行性．用R－（－）－TMPEA及dl－TMPAE分别与下列4种手性酮反应，制备相应的非对映异构亚胶：比较光活亚胺及相应的非对映异构体混合物亚腔的NMR谱，可确定各组非对映异构亚胺‘HNMR位移差（以OCH为探针基团）和’‘FNMR的位移差（以CF为探针基团）（表1）．TablelCheffiicalshif…     

核磁共振在对映体纯度测定中的应用

综述了核磁共振技术对映体纯度测定中的应用，它包括三个方面：（１）手性衍生剂法；（２）手性镧系位移试剂法；（３）手性溶剂法，对三种方法的测定机理和特点也做了讨论，全文共６５篇参考文献。     

手性镧系位移试剂核磁共振法测定芳氧丙酸酯类除草剂对映体纯度

以Eu(hfc)3和Pr(hfc)3为手性镧系位移试剂(CLSR),比较了两种CLSR对2,4-滴丙酸甲酯的1HNMR和13C NMR谱手性分离效果,结果表明:Pr(hfc)3比Eu(hfc)3对手性中心相连的甲基具有更好的手性分离效果。首次应用Pr(hfc)3测定了盖草能、稳杀得和喹禾灵3种手性芳氧丙酸酯类除草剂的1HNMR和13CNMR谱,其1HNMR谱分离度R约为1,盖草能和喹禾灵的13C NMR谱分离度R大于1.5,说明1H NMR和13CNMR谱手性分离效果适用于对映体纯度测定。与手性色谱法相比,CLSR-NMR法测定对映体纯度具有操作简便、分析速度快的显著优势。     

2,4,5-涕丙酸的NMR手性分离条件

以1，2－二苯基二氨基乙烷（简称DPEDA，化合物1）的（1R，2R）体（简称（R）－1）为手性溶剂（CSA），解决了外消旋2，4，5－涕丙酸（化合物2）在氯仿溶剂中溶解性不良的问题，并且化合物2的^1H谱获得了出色的手性分离效果；通过研究包括温度、浓度、底物与CSA的摩尔比、CSA结构等影响化学位移不等价的因素得出结论，对于手性中心CH，在化合物2与（R）－1的摩尔比为2：1时，提高底物浓度和降低测试温度有利于增加手性分离度；而对于与手性中心相连的CH3，增大（R）－1的比例，减小底物浓度，提高测试温度，有利于增大△δH；化合物1的（1S，2S）体（简称（S）－1）与（R）－1具有相同的手性分离作用；另外还对各影响因素的作用机理进行了探讨。     

反相液相色谱法分离2-(4-羟基苯氧基)丙酸酯对映体

合成了三-(4-甲基苯甲酸)纤维素酯(MCTB)手性固定相，用反相高效液相色谱法在该手性固定相上对2-(4-羟基苯氧基)丙酸酯对映体进行拆分．实验结果表明，在三-(4-甲基苯甲酸)纤维素酯手性固定相上，以甲醇与水的体积分数为75：25做流动相能较好的拆分2-(4-羟基苯氧基)丙酸甲酯、乙酯和丁酯对映体，其分离因子分别为1．38、1．49、0．98；同时还发现2-(4-羟基苯氧基)丙酸酯中酯基团的大小对其对映体的分离也有明显的影响，其中以乙酯的拆分效果最佳。     

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。     

手性药物的对映体选择性释放

手性和手性物质的重要性已不言而喻,手性药物的开发也已成为主要发展趋势,但目前仍有部分手性药物以消旋体的形式出售和使用。如何合理、有效地使用这些消旋体药物,一直是值得深入研究的课题。对映体选择性释放将手性拆分和控释两个概念结合于一体,有望为消旋体药物的使用提供新的途径。基于本课题组的研究,本文综述了近年来对映体选择性释放研究领域所取得的主要进展。为便于讨论,本文根据构成药物控释载体的手性分子或结构(手性因素),将手性药物释放体系分为有机材料(水凝胶和粒子等)、无机材料和分子印迹材料等控释体系。关于对映体选择性释放以及释放过程中的对映选择性作用的研究,可进一步提升我们对于手性、手性物质和手性作用的认识。     

核磁共振技术测定联萘酚的对映体纯度

手性联萘酚((±)-BINOL)制备是国内高校常开设的一个实验,其产品的对映体纯度测试是实验的重要一环。以2-甲酰基苯硼酸和(S)-(?)-1-苯乙胺的混合物作为手性试剂与联萘酚发生Bull-James Assembly反应,以此设计了核磁共振氢谱(¹H NMR)测定联萘酚对映体纯度的实验。实验结果表明,通过反应生成的对映体混合物的核磁信号,能准确地计算出(±)-BINOL的对映体纯度。以选定的苯环氢核信号计算出的(R)-BINOL含量与理论ee值有着良好的线性关系(R²=0.9999)。此实验方法能够快速完成大量学生样品的测量,同时大大减少实验废液的产生量。学生通过此实验可对核磁共振技术有更进一步的了解。     

Phenylselenenylmenthane derivatives and their enantiomeric discrimination by 1H and 13C NMR spectroscopy in the presence of a chiral dirhodium complex

The phenylselenenylmenthane and ‐menthene derivatives 1–4 were studied in terms of ¹H and ¹³C signal assignments, conformational analysis and also complexation shifts (Δδ) and dispersion effects (Δν) observed when non‐racemic (ca 2 : 1) mixtures of the chiral selenides were exposed to an equimolar amount of the chiral dirhodium complex Rh^*. The complexation site is the selenium atom exclusively. Whereas Δδ values are moderate or small, dispersed signals (split into two owing to the existence of diastereomeric adducts) can be observed, many of which are large enough for a facile determination of enantiomeric ratios of the selenides irregardless of the conformational behaviour of the selenides and the adduct composition. Thus, the ‘dirhodium method’ is simple and reliable for chiral recognition in the class of organoselenium compounds which is gaining increasing importance in developing new techniques of asymmetric synthesis. Copyright © 2002 John Wiley & Sons, Ltd.     

Quantitative determination of aliphatic hydrocarbon compounds by 2D NMR

Quantitative analysis of complex mixtures by NMR is often hampered by heavily overlapping signals in 1D ¹H or ¹³C spectra. To resolve the overlap problem, we have been looking at the possibilities of using heteronuclear correlated 2D NMR methods for quantification. In this work, we applied 2D INEPT to analyze mixtures of tetradecane and squalane, which represent typical substructures of lube oil fractions. The factors affecting correlation peak volumes, namely the polarization transfer delays within pulse sequence, multiplicity of CH_n group and the magnitude of ¹J_{(C, H)} couplings were taken into account by product operator formalism calculations. The results indicate that if absolute precision in quantification is not essential, the current approach can be used for the quantitative analysis of the molecular composition of complex mixtures when conventional 1D NMR methods fail. Copyright © 2002 John Wiley & Sons, Ltd.     

Quantitative 1H NMR method for the routine spectroscopic determination of enantiomeric purity of active pharmaceutical ingredients fenfluramine, sertraline, and paroxetine

Determining the enantiomeric purity of chiral therapeutic agents is important in the development of active pharmaceutical ingredients (API). A strategy for determining the enantiomeric purity of three APIs was developed using nuclear magnetic resonance (NMR) and the chiral solvating agent (CSA) 1,1-bi-2-naphthyl (1). While chiral chromatography is widely used to evaluate enantiomeric purity, it can sometimes suffer from tedious sample preparation obviating rapid measurements that are sometimes needed during the manufacture of such agents. The techniques described herein provide comparable enantiomeric purity results with those obtained with traditional chiral HPLC and other published methods for these compounds. Chiral analysis of standard samples of methylbenzylamine enantiomeric mixtures using 1 were found to be quantitative to approximately 1% minor enantiomer. Enantiomeric purity determination by NMR utilizing chiral solvating agents do not require special instrumental techniques, chemical derivatization or standards and is therefore ideally suited for rapid routine analysis. As a result, the technique demonstrated is commonly used in our laboratory as a complementary or alternative method to chiral HPLC or optical rotation measurements for routine determination of enantiomeric purity.     

Structure determination of selaginellins G and H from Selaginella pulvinata by NMR spectroscopy

Selaginellins G ( 1 ) and H ( 2 ), two new selaginellin derivatives, were isolated from the whole plant of Selaginella pulvinata. Their structures were elucidated, and complete assignments of the ¹H and ¹³C NMR spectroscopic data were achieved by 1D and 2D NMR experiments (HSQC, HMBC, COSY and ROESY). Compound 1 displayed good antifungal activity against Candida albicans with an IC₅₀ value of 5.3 µg/ml. Copyright © 2010 John Wiley & Sons, Ltd.     

A chiral tellurium ferrocene as a chiral agent in NMR enantiomeric purity determination

The tellurium nuclear magnetic resonance spectrum of chiral tellurium ferrocene 2 produces a single signal at different chemical shifts when solubilized together with different enantiomeric proportions of chiral compounds.     

NMR spectroscopy as a tool to investigate the degradation of aromatic compounds by a Pseudomonas putida strain

Pseudomonas putida strain KT2442, harbouring the pWW0 TOL plasmid, was grown with a number of different homologous aromatic acids as carbon sources. Small samples of liquid culture supernatant were collected and directly analysed by 2D NMR spectroscopy. In all cases similar compounds with olefinic signals were observed to accumulate. To elucidate the structures of these compounds, 2D NMR experiments with 500 and 600 MHz spectrometers equipped with a CryoProbe (Bruker BioSpin) were performed on samples obtained from a culture growing on 4‐methylbenzoate and, for ¹³C spectroscopy, on ¹³C‐labelled 4‐methylbenzoate. In all cases a 1,2‐dihydroxycyclohexa‐3,5‐diene‐carboxylate derivative was identified. The use of this technique helped us to identify easily some metabolites that were released into the solution by bacteria and to follow their secretion as a function of time. The high sensitivity of the present approach allowed a clear and rapid acquisition of spectra, notwithstanding the low concentration of the compounds. The benefits of introducing the use of NMR cryoprobes to perform metabolic pathway studies is demonstrated. Copyright © 2003 John Wiley & Sons, Ltd.     

一种金属洗涤剂的NMR分析

由于精细化工行业的迅速发展,作为“工业味精”的表面活性剂,已广泛进入日化、轻工、纺织、建筑、石化、金属加工等生产领域,对其的分析也显得日益重要。表面活性剂的分析历来是比较困难的课题之一,而通过核磁共振(NMR)进行定性和定量的文献则更少[1]。本文利用NMR为多种表面活     

Structure determination of two new trichothecenes from a halotolerant fungus Myrothecium sp. GS‐17 by NMR spectroscopy

Two new trichothecenes, named 8α‐hydroxyroridin H and myrothecin A, along with six known compounds, 8α‐acetoxy roridin H, isororidin K, verrucarin A, verrucarin J, verrucarin L and 8α‐acetoxy verrucarin L, were isolated from the fermentation broth of a halotolerant fungus Myrothecium sp. GS‐17, which was separated from the soil sample of a salina. Structure elucidation and NMR signal assignments were achieved on the basis of spectroscopy. In addition, compounds 1 and 2 were active against plant pathogenic fungi Rhizoctonia solani and Fusarium oxysporum. Copyright © 2012 John Wiley & Sons, Ltd.     

Structure determination of two new indole‐diterpenoids from Penicillium sp. CM‐7 by NMR spectroscopy

Two new indole‐diterpenoids 4b‐deoxy‐1′‐O‐acetylpaxilline (1) and 4b‐deoxypenijanthine A (2) were isolated from the fermentation broth and the mycelia of the soil fungus Penicillium sp. CM‐7, along with three known structurally related compounds, 1′‐O‐acetylpaxilline (3), paspaline (4) and 3‐deoxo‐4b‐deoxypaxilline (5). The structures of compounds 1 and 2 were elucidated by extensive spectroscopic methods, especially 2D NMR, and their absolute configurations were suggested on the basis of the circular dichroism spectral analysis and the NOESY data. Copyright © 2014 John Wiley & Sons, Ltd.     

Isotopic labeling for determination of enantiomeric purity by 2H NMR spectroscopy

The use of 2H NMR spectroscopy as a tool for the analysis of enantiomeric purity is reported. Enantiopure isotopically chiral substrates bearing a monodeuterated methylene unit were prepared; introduction of an additional asymmetric center leads to diastereomers which can be distinguished by 2H NMR on a standard spectrometer. The assays allow for simple semiquantitative analysis of asymmetric transformations.