Challenges of HPLC determination of quinoline derivatives used in the treatment of malaria

Fully effective antimalarial drugs are yet to be isolated or synthesized, hence the search them continues. The study was aimed at establishing the most suitable conditions for the separation and determination of six biologically active alkaloids, quinoline derivatives, using high performance liquid chromatography with UV/Vis detection. The experiments involved the following derivatives: quinine, quinidine, cinchonine, cinchonidine, acetylcinchonine and acetylquinidine. Of the six stationary phases used, only the naphthylpropyl column enabled the separation of all alkaloids. The octadecyl column, considered by many analysts as a reference, did not provide successful separation. The naphthylpropyl column had also very good validation parameters, including a wide range of linearity, high values of correlation coefficients (0.9990?0.9998) and low standard measurement uncertainty (1.8?2.3?µg?L^?1). The newly developed method was employed to evaluate the content of quinine in tonic-like beverages. The naphthylpropyl stationary phase provided ≤5% repeatability of quinine determination.     

C−H Activation Enables a Concise Total Synthesis of Quinine and Analogues with Enhanced Antimalarial Activity

We report a novel approach to the classical natural product quinine that is based on two stereoselective key steps, namely a C?H activation and an aldol reaction, to unite the two heterocyclic moieties of the target molecule. This straightforward and flexible strategy enables a concise synthesis of natural (?)‐quinine, the first synthesis of unnatural (+)‐quinine, and also provides access to unprecedented C3‐aryl analogues, which were prepared in only six steps. We additionally demonstrate that these structural analogues exhibit improved antimalarial activity compared with (?)‐quinine both in vitro and in mice infected with Plasmodium berghei.     

2BOB – extracting an H2BC and an HSQC‐type spectrum from the same data set,and H2OBC – a fast experiment delineating the protonated 13C backbone

Two new related methods, 2BOB and H2OBC, for tracking out the backbone of protonated ¹³C nuclei are presented. 2BOB extracts an H2BC and an HSQC‐type spectrum from one and the same data set, and the combined information of these two spectra tracks out the molecular backbone. The faster method, H2OBC, typically requiring only a few minutes of instrument time, yields a single spectrum with distinct and different phases imposed on the H2BC and one‐bond peaks thus obviating the need to separate them in the absence of complicating spectral overlap. Copyright © 2017 John Wiley & Sons, Ltd.     

Application of cinchona-sulfonate-based chiral zwitterionic ion exchangers for the separation of proline-containing dipeptide rotamers and determination of on-column isomerization parameters from dynamic elution profiles

The interconversion of cis and trans isomers of dipeptides containing C-terminal proline was studied by dynamic chromatography on zwitterionic chiral stationary phases at temperatures ranging from −15 °C to +45 °C The cis–trans isomers could be separated below 0 °C and above 0–10 °C plateau formation and peak coalescence phenomena occurred, which is characteristic for a dynamic process at the time-scale of partitioning. At and above room temperature, full coalescence was observed, which allowed separations of enantiomers without interference from interconversion effects. Analysis of the dynamic elution profiles of the interconverting peptides allowed the determination of isomerization rate constants and thermodynamic activation parameters (isomerization enthalpy, entropy and activation energy). In accordance with established results, isomerization rates and thermodynamic parameters were found to depend on the nature of the N-terminal amino acid. Isomerization barriers were only slightly lower than values determined with other methods but significant differences in the relative contributions of the activation enthalpy and entropy as well as isomerization rates pointed toward selector-moderated isomerization dynamics.     

Highly Diastereoselective Vinylogous Mukaiyama Aldol Reaction of Isatins with 2-(Trimethylsilyloxy)furans Catalyzed by Quinine

The diastereoselective formation of δ-hydroxyalkyl butenolide oxindoles has been achieved via a vinylogous Mukaiyama aldol reaction. The reaction was performed using various (N-alkyl)isatins 1 with 2-(trimethylsilyloxy)furan 2 catalyzed by quinine in tetrahydrofuran (THF). The reaction proceeds rapidly and affords the corresponding 3-hydroxy-(5-oxo-2,5-dihydrofuran-2-yl)indolin-2-ones in good yields with high diastereoselectivities (anti/syn ratio up to 96:4).

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Asymmetric catalysis as a method for the synthesis of chiral organophosphorus compounds

This review discusses methods for the metallo-, organo- and biocatalytic asymmetric synthesis of chiral organophosphorus compounds with many applications in stereoselective synthesis with references to updated literature reports as well as the author’s original research. Asymmetric catalytic hydrogenation and reduction with chiral organometallic complexes, together with actively used asymmetric organocatalytic versions of various reactions enable us to synthesize chiral organophosphonates and phosphinates with high enantioselectivity and purity. Asymmetric catalysis is also an effective tool to realize some classic reactions of phosphorus chemistry in a stereospecific manner.     

奎宁功能化聚乙烯咪唑修饰硅胶亲水相互作用色谱固定相的制备及应用

通过表面自由基链转移聚合和亲核取代反应制备了一种新型奎宁功能化聚乙烯咪唑修饰硅胶亲水色谱固定相(Sil-PIm-Qn)。通过元素分析和红外光谱对该固定相进行表征,并在亲水相互作用色谱(HILIC)模式下对其进行了色谱性能评价。结果表明,该固定相对5种氨基酸、9种磺胺以及10种碱基核苷有较好的分离选择性。实验考察了流动相中有机相乙腈体积分数和水相中乙酸铵浓度对待分离物质保留行为的影响,并进一步对固定相分离的重复性进行了考察,其保留时间的相对标准偏差(RSD)为0.08%~2.30%(n=10)。该亲水色谱固定相制备方法简单,并且表现出了优异的亲水色谱分离性能,有望在磺胺类药物及生物样品中碱基核苷等亲水性物质的分离分析中有一定应用。     

Vibrational analysis of cinchona alkaloids in the solid state and aqueous solutions

Cinchona alkaloids are well‐known antimalarial compounds also used in asymmetric synthesis in organic chemistry. In this work, vibrational spectra of quinine, quinidine, cinchonine, and cinchonidine were acquired and interpreted on the basis of theoretical calculations. Normal Raman spectra of the alkaloids in solution exhibit similar patterns and cannot be used for differentiation between the derivatives (e.g. quinine and cinchonidine) and corresponding pseudoenantiomers (e.g. quinine and quinidine). Thus, Raman Optical Activity (ROA) method was applied to show distinct differences related to the configuration of chiral atoms. ROA allowed unequivocal identification of the pseudoenantiomers based on the sign of the characteristic bands from a single measurement. The experiments were supported by the theoretical approach including conformational study followed by wavenumber calculations and Potential Energy Distribution (PED) analysis. For quinine, vibrational spectroscopy was additionally used to show its structural changes in aqueous solutions at various pH and its distribution in a pharmaceutical product. Spatial distribution of quinine in a drug was observed by the FT‐Raman mapping technique. Copyright © 2015 John Wiley & Sons, Ltd.     

偏振同步光散射和同步光散射光谱区分与同时测定奎宁和奎尼丁对映异构体

在酸性缓冲溶液中,阴离子表面活性剂十二烷基苯磺酸钠SDBS能与金鸡纳类生物碱药物体系中一对对映异构体QN和QD作用产生增强的同步光散射(synchronous light scattering,SLS)信号,本文首先利用偏振同步光散射(polarized synchronous light scattering)信号,建立了同步光散射偏振度(P)区分QN和QD这对对映异构体,同时利用同步散射光谱和双标准曲线计量分析法对2种金鸡纳类生物碱药物进行同时测定,并将该方法应用于尿样中QN和QD的同时测定,结果令人满意。