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Selenium-containing amino acids are valuable targets but methods for the stereoselective α-selenation of simple amino acid precursors are rare. We herein report the enantioselective electrophilic α-selenation of azlactones (masked α-amino acid derivatives) and isoxazolidin-5-ones (masked β-amino acids) using Cinchona alkaloids as easily accessible organocatalysts. A variety of differently substituted derivatives was accessed with reasonable levels of enantioselectivities and further studies concerning the stability and suitability of these compounds for further manipulations have been carried out as well.

Alkaloids represent a major group of natural products (NPs), derived from highly diverse organisms. These structurally varied specialized metabolites are widely used for medicinal purposes and also known as toxic contaminants in agriculture and dietary supplements. While the detection of alkaloids is generally facilitated by GC- or LC-MS, these techniques do require considerable efforts in sample preparation and method optimization. Bypassing these limitations and also reducing experimental time, matrix-free laser desorption ionization (LDI) and related methods may provide an interesting alternative. As many alkaloids show close structural similarities to matrices used in matrix-assisted laser desorption ionization (MALDI), they should ionize upon simple laser irradiation without matrix support. With this in mind, the current work presents a systematic evaluation of LDI properties of a wide range of structurally diverse alkaloids. Facilitating a direct comparison between LDI and ESI-MS fragmentation, all tested compounds were further studied by electrospray ionization (ESI). Moreover, crude plant extracts of Atropa belladonna, Cinchona succirubra, and Colchicum autumnale were analyzed by LDI in order to evaluate direct alkaloid detection and dereplication from complex mixtures. Finally, dose-dependent evaluation of MALDI and LDI detection using an extract of Rosmarinus officinalis spiked with atropine, colchicine, or quinine was conducted. Overall, present results suggest that LDI provides a versatile analytical tool for analyzing structurally diverse alkaloids as single compounds and from complex mixtures. It may further serve various potential applications ranging from quality control to the screening for toxic compounds as well as the build up of MS databases. Graphical abstract.

Aim: Quinine, a frequently used anti-malaria alkaloid isolated from the Cinchona bark, possesses numerous toxic properties, the majority of which arrive from a dysfunction of the gastrointestinal tract. Similarly, cinchonine, another alkaloid from the Cinchona bark, displays a great potential for treating malaria (especially the resistant forms)., Methods: In this work, we aimed to evaluate the effects of cinchonine on spontaneous and induced Wistar rat ileum contractions in order to uncover potential side effects that might arise after its application., Results: Cinchonine produced a concentration-dependent spasmolytic activity, which was found to be reversible (i.e. disappeared after tissue wash-up), with an IC50 value of 273 µM. Furthermore, the mechanism of action of cinchonine at IC50 elucidated through experiments with acetylcholine and Ca2+-induced ileum contractions. The applied IC50 concentration of cinchonine statistically significantly prevented the occurrence of contractions after the application of specific agonist. The obtained results are in a range with the effects seen with standard receptor antagonists, i.e. atropine and verapamil., Conclusions: The obtained results showed that cinchonine inhibited both types of induced contractions, suggesting a Ca2+-channels mediated modus operandi (Fig. 4, Ref. 19).

Chinoline alkaloids found in Cinchona bark still play an important role in medicine, for example as antimalarial and antiarrhythmic drugs. For the first time Supercritical Fluid Chromatography has been utilized for their separation. Six respective derivatives (dihydroquinidine, dihydroquinine, quinidine, quinine, cinchonine and cinchonidine) could be resolved in less than 7 min, and three of them quantified in crude plant extracts. The optimum stationary phase showed to be an Acquity UPC 2 Torus DEA 1.7 μm column, the mobile phase comprised of CO 2 , acetonitrile, methanol and diethylamine. Method validation confirmed that the procedure is selective, accurate (recovery rates from 97.2% to 103.7%), precise (intra-day ≤2.2%, inter-day ≤3.0%) and linear (R 2  ≥ 0.999); at 275 nm the observed detection limits were always below 2.5 μg/ml. In all of the samples analyzed cinchonine dominated (1.87%-2.30%), followed by quinine and cinchonidine. Their total content ranged from 4.75% to 5.20%. These values are in good agreement with published data, so that due to unmatched speed and environmental friendly character SFC is definitely an excellent alternative for the analysis of these important natural products., (Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.)

An operationally simple protocol for the enantioselective electrophilic α-cyanation of β-keto amides catalyzed by cinchona-derived catalysts has been demonstrated. The resulting products could be obtained with good to high enantioselectivities (up to 88% ee) and with excellent yields (up to 94%) by employing the mild active 4-acetylphenyl cyanate as the cationic cyano source in the catalytic asymmetric α-cyanation reaction.

Introduction: Authentication of herbal products to ensure efficacy and safety require efficient separation and quantification of constituents. Standard assays for Cinchona bark used for the treatment of malaria and production of quinine, either use only spectrophotometry to detect two pairs of diastereoisomers of quinine and cinchonine type alkaloids (European Pharmacopoeia, Ph.Eur.) or liquid chromatography primarily optimised for detection of the four major alkaloids. However, numerous minor alkaloids occur in Cinchona and related species and efficient separation including gradient elution is necessary in order to obtain the full pattern of constituents in bark samples., Objective: To develop an optimised HPLC method for separation and quantitative analysis of the four major alkaloids in Cinchona bark using UV detection., Methodology: Dimethyl sulphoxide (DMSO) extracts of 50 mg of pulverised barks were prepared using ultrasonication. The chromatographic separation was performed on an XB-C18 column packed with 2.6 μm particles. Gradient elution using an ammonium formate buffer and methanol as organic modifier over 26 min was based on non-chiral separation of the diastereoisomers and the high solvent selectivity of methanol. Post column UV detection was performed at 250 nm and 330 nm. Fluorescence detection was performed using 330 nm for excitation and 420 nm for emission., Results: The optimised HPLC method facilitates efficient separation and quantification of the four major alkaloids in 26 min with a limit of quantification of 5 μg/g from 50 mg bark sample., Conclusion: The optimised HPLC method offers a simple and efficient quantification of the four major alkaloids. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Two chiral stationary phases containing a quinine- or a quinidine-based zwitterionic ion-exchanger as chiral selector were applied for the enantioseparation of 27 unusual cyclic secondary α-amino acids. The effects of the nature and concentration of the bulk solvent, the acid and base additives, the structures of the analytes and temperature on the enantioresolution were investigated. To study the effects of temperature and to obtain thermodynamic parameters, experiments were carried out at constant mobile phase compositions in the temperature range -5 to 55 °C. The thermodynamic parameters indicated that in most cases the separations were enthalpy-driven, but some entropy-driven separations were also observed. The sequence of elution of the enantiomers was determined in most cases., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Cinchona-alkaloid-urea-based bifunctional organocatalysts facilitate the catalytic asymmetric synthesis of chroman derivatives via an intramolecular oxy-Michael addition reaction. Phenol derivatives bearing an easily available (E)-α,β-unsaturated ketone or a thioester moiety are useful substrates for the title transformation. This method represents a facile synthesis of various optically active 2-substituted chromans in high yield.

A catalytic enantioselective monofluoromethylation of aldehydes using 2-fluoro-1,3-benzodithiole-1,1,3,3-tetraoxide (FBDT) was realized. With a bifunctional thiourea-titanium catalytic system, the monofluoromethylated-adducts were obtained in good yields and high enantioselectivities, up to 96% ee.

Thiourea derived cinchona alkaloids promote the asymmetric decarboxylative protonation of cyclic, acyclic, or bicyclic alpha-aminomalonate hemiesters under mild and metal-free conditions to afford enantioenriched aminoesters in high yields and enantioselectivities up to 93%. Both enantiomers of the aminoesters have been synthesized with the same selectivity when using organic base 3 and its pseudoenantiomer 6 derived from quinine.

Alkaloids such as cinchonidine, quinine and N-methylephedrine have been N-alkylated using polymeric benzyl halides or co-polymerized and then N-alkylated, thus affording a series of polymer-supported chiral ammonium salts which have been employed as phase-transfer catalysts in the asymmetric benzylation of an N-(diphenylmethylene)glycine ester. These new polymeric catalysts can be easily recovered by simple filtration after the reaction and reused. The best ee's were achieved when Merrifield resin-anchored cinchonidinium ammonium salts were employed.