Separation of Cinchona alkaloids on a novel strong cation-exchange-type chiral stationary phase—comparison with commercially available strong cation exchanger and reversed-phase packing materials

A recently reported chiral strong cation exchanger (cSCX) type stationary phase was investigated for the LC separation of a series of Cinchona alkaloids and synthetic derivatives thereof to test its usefulness as alternative methodology for the separation of those important pharmaceuticals. The cSCX column-packing material was qualitatively compared on the one hand against a commercially available non-enantioselective SCX-material, PolySulfoethyl-A, and, on the other hand, against a modern C18 reversed-phase stationary phase which is commonly employed for Cinchona alkaloid analysis. Both SCX columns showed no pronounced peak-tailing phenomena which typically hamper Cinchona alkaloid RP analysis and require specific optimization. Thus, the cSCX-based assay provided new feasibilities for the separation of the Cinchona alkaloids in polar organic mode as opposed to conventional reversed-phase methodologies. In particular, a method for the simultaneous determination of eight Cinchona alkaloids (quinine, quinidine, cinchonine, cinchonidine, and their corresponding dihydro analogs) using the cSCX column in HPLC has been developed and exemplarily applied to impurity profiling of a commercial alkaloid sample. Furthermore, both SCX materials allowed successful separation of C9-epi and 10,11-didehydro derivatives from their respective educts in an application in synthetic Cinchona alkaloid chemistry. Figure An alternative separation principle - HPLC separation of strongly basic natural Cinchona alkaloids and synthetic derivatives thereof by means of a strong cation-exchanger type chiral stationary phase     

奎尼丁分子印迹聚合物的制备及其吸附性能

以奎尼丁(Quinidine)为模板分子,合成奎尼丁分子印迹聚合物(MIP)。通过封管聚合法研究不同功能单体对奎尼丁分子印迹聚合物的影响,并运用Scatchard方程研究奎尼丁分子印迹聚合物选择吸附特性。以甲基丙烯酸(MAA)为功能单体合成的分子聚合物具有较高的选择吸附性,并且印迹聚合物大于非印迹聚合物的吸附量。奎尼丁印迹聚合物用于临床对奎尼丁的富集与检测有应用前景。     

Direct catalytic asymmetric method for the synthesis of tetrahydropyranopyrazoles through allene zwitterion chemistry

The enantioselective synthesis of the tetrahydropyranopyrazole scaffold has been achieved. The quinidine catalyzed reaction of allenoates with arylidenepyrazolones proceeded with high enantio- and diastereoselectivity while the reactions of alkylidenepyrazolones were less efficient. Allene ketones also afforded tetrahydropyranopyrazole derivatives in high yields, however, with only moderate enantioselectivity. The primary adduct undergoes further functional group transformations without effecting the initially formed chiral centre.     

金鸡纳生物碱电喷雾质谱裂解规律研究

利用电喷雾离子阱质谱（ES-ITMS）技术进行了金鸡纳中4种喹啉类生物碱（奎宁、奎尼定、辛可宁和辛可尼定）的电喷雾质谱研究。在优化的质谱条件下,正离子全扫描时,4种生物碱都易形成带一个质子的分子离子;进一步碰撞诱导解离四种母离子,二级质谱表明羟基丢失、奎宁环断裂及重排为其主要裂解方式。     

Asymmetric sulfenylation of 3-CF3-Oxindoles through organocatalysis with a quinidine derivative

An asymmetric sulfenylation of 3-CF₃-oxindoles catalyzed by a quinidine derivative was described. 3-CF₃-oxindoles with electro-donating groups led to corresponding products in good yield and with good enantioselectivity while 3-CF₃-oxindoles bearing electro-withdrawing groups were not competent substrates due to its significant decomposition at the optimal reaction conditions. As for the sulfenylation reagents based on thiophenol, both electro-donating groups and electro-withdrawing groups were well tolerated.     

共振散射比率法研究表面活性剂十二烷基磺酸钠与奎尼丁的相互作用

在pH 1.81的B-R缓冲介质中,由十二烷基磺酸钠(SDBS)与奎尼丁的相互反应导致其分别在278.0,377.0 nm两波长处所测得的共振散射信号(I)大大增强。当SDBS的浓度为3.0×10~(-4)mol·L~(-1)时,分别在上述两波长处测得的共振散射强度值(I_(278.0)及I_(377.0))与相应的奎尼丁浓度依次在0.067～40,0.062～40μmol·L~(-1)范围内呈线性关系,其检出限(3σ)分别为6.71,6.15nmol·L~(-1)。据此可作奎尼丁的单波长法共振散射光谱测定。进一步研究发现:如采用分别在240.0nm(波谷)及275.0nm(波峰)测得的共振散射强度的比率(即I_(240.0)/I_(375.0))作为参数,则其与奎尼丁浓度在0.007～75μmol·L~(-1)范围内呈线性关系,且奎尼丁检出限(3σ)为0.691nmol·L~(-1)。由此可见,采用双波长测量技术的共振散射比率法测定奎尼丁的效果优于前者。     

Photoluminescence Properties of Quinidine and Quinidine Sulfate in the Sol‐gel System

The emission spectra of quinidine and quinidine sulfate doped in sol‐gels (tetraethoxysiliane system) have been measured during the sol‐gel transformation. Shifts in the emission spectra from 370 nm to 435 nm were observed in both molecules as the system changed from sol stage to dried glass over a period of two weeks. These shifts are attributed to the conformational changes of the doped molecules. In addition, the process of the signal changes was observed by an emerging new band at ?435 nm with a concomitant decline of the original band at 370 nm during the sol‐gel transformation. These results indicate that the conformational changes induced by the sol‐gel transformation are accomplished in one step instead of several intermediate states.     

Determination of quinine and quinidine by continuous-flow chemiluminescence

A rapid and precise continuous-flow method is described for the determination of quinine and quinidine (5.00–500 μg ml^?1) which is based on the sensitizing effect of the compounds on the chemiluminescent oxidation of sulphite by cerium(IV). When applied to tablets, the procedure is relatively free from interferences from common excipients. The results obtained for the assay of commercial formulations compared well with those obtained by an official method and demonstrated good accuracy and precision.     

新型可回收高聚物负载手性配体在苯乙烯类化合物均相不对称双羟化反应中的催化性能研究

在多聚磷酸和AlCl3存在下，邻苯二甲酸酐与对二氟苯中通过Friedel-Crafts反应环化，以60％的产率生成1，4-二氟蒽醌．在碱性条件下，聚乙二醇单甲醚(HO-OPEG-OMe)与1，4-二氟蒽醌进行亲核单取代反应生成中间体F-AQN-OPEG-OMe，产率88％．然后F-AQN-OPEG-OMe与奎尼丁的锂盐再进行亲核取代反应，以91．7％的产率得到新型手性配体QD-AQN-OPEG-OMe．QD-AQN-OPEG-OMe与OsO4原位配位生成的均相催化剂在4种苯乙烯类化合物的不对称双羟化反应中表现出高的立体选择性(80％～94％ee)和催化活性(产率88％～96％)．催化活性和立体选择性与Sharpless手性配体(DHQD)2AQN相当．反应结束后，加入乙醚可使配体沉淀和回收，配体的回收率均在95％～97％之间．循环使用5次，催化剂的催化活性和立体选择性无明显改变．     

Adsorption behaviour of a quinidine carbamate-based chiral stationary phase: Role of the additive

In this study, we incorporate the additive properties into the theoretical model of a general preparative chromatographic system; this is normally not done and this limits a proper process optimization. As a model phase system, we used the adsorption of 9H-fluoren-9-ylmethoxycarbonyl-allylglycine (Fmoc-allylglycine) enantiomers on a quinidine carbamate-based chiral stationary phase (anion exchanger) together with a methanol–glacial acetic acid–ammonium acetate eluent. The inverse method was used to measure the competitive adsorption isotherms of both the Fmoc-allylglycine enantiomers as well as the non-detectable additive acetic acid. It was concluded that this enantioselective preparative system is well described by a non-heterogeneous adsorption model and that the loading capacity is very high. The proposed model is valid over a wide range of additive concentrations, which is important for process optimization.