Chiral zwitterionic stationary phases based on Cinchona alkaloids and dipeptides - design, synthesis and application in chiral separation.

Chiral resolution of polar organic compounds such as amino acids and peptides represents an important chromatographic task due to increasing significance of natural species, which play important signaling and regulatory roles in the living organisms. Despite the number of available chiral stationary phases, this task remains challenging, since not many of the commercially available systems are capable to resolve non-derivatized zwitterionic species. In this study, we present a target-oriented design of a new class of chiral selectors. Pursuing the goal to separate amino acids, and especially short peptides, we have combined Cinchona alkaloids - quinine and quinidine - with three different biogenic dipeptides. We have synthesized six different chiral stationary phases, with selector loading of ∼200 µmol g-1, and tested their chiral recognition capabilities for acidic, basic and zwitterionic analytes using various mobile phases. We have observed that all chiral stationary phases retain the chiral anion exchange capability known for commercially available Cinchona-based columns leading to baseline or partial resolution of six out of ten analytes. The performance in chiral resolution of basic analytes is not optimum due to the weak cation exchange character of the peptidic residue. However, we report on encouraging results in the chiral resolution of short peptides, for which, depending on their structure, we see the chiral resolution of up to three stereoisomers (from four possible) in a preliminary screening.

Antiviral Activity of Cinchona officinalis, a Homeopathic Medicine, against COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a potentially fatal disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several studies have shown that hydroxychloroquine (HCQ) significantly inhibits SARS-CoV-2 infections in vitro. OBJECTIVE: Since the phytoconstituents of Cinchona officinalis (CO) are similar to those of HCQ, the objective of this study was to test the antiviral potential of different homeopathic formulations of CO. METHODS: An analysis of the molecular composition of CO was carried out using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by a detailed docking study. The constituents of CO were docked against various targets of SARS-CoV-2, and the binding potential of the phytoconstituents was compared and quantified. The ligand with the lowest Glide docking score is considered to have the best binding affinity. The cytotoxicity of several homeopathic formulations, including CO mother tincture (CO-MT), was also checked on VeroE6 cells. A known antiviral, remdesivir, was used as a positive control for the in vitro assays to evaluate the effects of CO-MT against SARS-CoV-2-infected VeroE6 cells. RESULTS: Molecular docking studies showed that constituents of CO exhibited binding potential to various targets of SARS-CoV-2, including Mpro, PLpro, RdRp, nucleocapsid protein, ACE2 (in host) and spike protein. Quinoline, one of the constituents of CO, can potentially bind the spike protein of SARS-CoV-2. Quinic acid showed better binding capabilities with Mpro, PLpro RdRp, nucleocapsid protein and ACE2 (allosteric site) than other constituents. Quinidine exhibited better binding to ACE2. Compared to HCQ, other phytoconstituents of CO had the equivalent potential to bind the RNA-dependent RNA polymerase, nucleocapsid protein, Mpro, PLpro and spike protein of SARS-CoV-2. In vitro assays showed that homeopathic CO-MT was not cytotoxic and that CO-MT and remdesivir respectively caused 89% and 99% inhibition of SARS-CoV-2 infection in VeroE6 cells. CONCLUSION: Based on this in silico and in vitro evidence, we propose CO-MT as a promising antiviral medicine candidate for treating COVID-19. In vivo investigation is required to clarify the therapeutic potential of CO-MT in COVID-19.

The Effects of a Cinchona Supplementation on Satiety, Weight Loss and Body Composition in a Population of Overweight/Obese Adults: A Controlled Randomized Study.

Obesity is a risk factor for several diseases present worldwide. Currently, dietary changes and physical activity are considered the most effective treatment to reduce obesity and its associated comorbidities. To promote weight loss, hypocaloric diets can be supported by nutraceuticals. The aim of this study was to evaluate the effects of a hypocaloric diet associated with Cinchona succirubra supplementation on satiety, body weight and body composition in obese subjects. Fifty-nine overweight/obese adults, were recruited, randomized into two groups and treated for 2 months. The first group (32 adults) was treated with a hypocaloric diet plus cinchona supplementation (the T-group); the second one (27 adults) was treated with a hypocaloric diet plus a placebo supplementation (the P-group). Anthropometric-measurements as well as bioimpedance analysis, a Zung test and biochemical parameters were evaluated at baseline and after 60 days. T-group adults showed significant improvement in nutritional status and body composition compared to those at the baseline and in the P-group. Moreover, T-group adults did not show a reduction in Cholecystokinin serum levels compared to those of P-group adults. In conclusion, our data demonstrate that a hypocaloric diet associated with cinchona supplementation is effective in inducing more significant weight loss and the re-establishment of metabolic parameters than those obtained with a hypocaloric diet.

Green nanoarchitectonics of carbon quantum dots from Cinchona Pubescens Vahl as targeted and controlled drug cancer nanocarrier.

Carbon quantum dots (CQDs) are a new carbon-based nanomaterial that has attracted tremendous attention due to their excellent fluorescent properties, chemical stability, water solubility, and biocompatibility features. Here, fluorescent CQDs synthesized by a green nanoarchitectonic method using Cinchona Pubescens Vahl extract were evaluated as drug nanocarriers for carboplatin (CBP) delivery. The characterization methods showed CQDs with semispherical shapes and sizes around 5 nm, temperature- and pH-dependent functional groups that interact with the CBP molecule adding specificity to the drug-delivery system. Based on the load efficiency results, it seems that the CQDs can carry almost 100 µg of carboplatin for every 1 mg of CQDs. This is possible due to the self-assembly process that takes place through the interaction between the protonation/deprotonation functional groups of CQDs and the hydrolyzed CBP molecule. Through this process, it is created spherical nanoparticles with an average size of 77.44 nm. The CQDs-CBP nanoparticles release the drug through a diffusion-controlled release mechanism where the acidic media is preferred, and the EPR effect also plays a helpful role. Besides, the viability test shows that the CQDs have almost null cytotoxicity suggesting that they could be used as a promising cancer treatment, improving the efficiency of cell internalization and significantly increasing their drug delivery.

Cinchona-Alkaloid-Derived NN Ligands and Achiral Phosphines for Iridium-Catalyzed Asymmetric Hydrogenation of Heteroaromatic and α-Chloroheteroaryl Ketones.

A concise synthesis of cinchona-alkaloid-derived NN ligands bearing alkyl substituents on chiral nitrogen atoms was described. Iridium catalysts containing new chiral NN ligands and achiral phosphines were effective for the asymmetric hydrogenation of heteroaromatic ketones, which afforded corresponding alcohols in up to 99.9% ee. The same protocol was applicable to the asymmetric hydrogenation of α-chloroheteroaryl ketones. Most importantly, the gram-scale asymmetric hydrogenation of 2-acetylthiophene and 2-acetylfuran proceeded smoothly even under 1 MPa of H2.

Comprehensive evaluation of corrosion inhibition performance and ecotoxicological effect of cinchona IIa as a green corrosion inhibitor for pickling of Q235 steel.

Here, to prevent the corrosion of Q235 steel in the pickling and discover novel green corrosion inhibitors, the corrosion inhibition performance and eco-toxicity of cinchonain IIa were evaluated. Electrochemical experiments confirms that 200 mg/L cinchonain IIa reveals good corrosion inhibition performance with 94.08% on Q235 steel in HCl for 48 h. Scanning electron microscope (SEM) and atomic force microscope (AFM) observations suggest that cinchonain IIa can be firmly attached to the metal surface by forming a barrier film. The X-ray photoelectron spectroscopy (XPS) results further verify the bonding interaction between the functional groups and the steel matrix, and indicate the existence of protective film on the steel. Meanwhile, the inhibition mechanism at the molecular/atomic level is revealed through molecular dynamics simulation. Additionally, acute toxicity test shows that cinchonain IIa is a low toxic corrosion inhibitor. Moreover, the antioxidant enzyme activity experiments confirm that cinchonain IIa discloses no obvious damage to the antioxidant system of zebrafish. Overall, cinchonain IIa exhibits low potential risks to the healthy development of aquatic organisms and ecosystems. As a proven green and low toxic corrosion inhibitor, cinchonain IIa has a sustainable application in the anti-corrosion industry.

What Historical Records Teach Us about the Discovery of Quinine.

The origin of quinine from Peru remains a mystery because of the lack of primary data-in particular, those produced by the Jesuits working in Peru. The discovery of cinchona bark and its use in malaria treatment must have come from the Jesuits, who worked with the native Andeans, the Quichuan people, and learned how the bark of the cinchona tree could be used for chills. Unknown is whether the Andean people used it for fever that may have been the result of malaria. We explored the literature of the 1600s, 1700s, and later to trace the history of quinine that is available. All these secondary sources lack the primary data of the Jesuits in their work with native Andeans, nor is there information on how the discovery of its use for malaria-like fevers came about. One clue comes from the Jesuits who talked with the Andean people and learned about quinine. But was it used for fever? Why did the Jesuits test it against (tertian or quartan) fevers that could have been the result of malaria? The gap in our knowledge can only be resolved with the discovery of written documents by the Jesuits about quinine for malaria.

Investigação científica e uso clínico da quina em Portugal na transição do século XVIII para o século XIX / Scientific research and clinical use of quinine in Portugal in the transition from the 18th to the 19th century

A quina, uma casca de árvores nativas da América do Sul do género Cinchona com propriedades antimaláricas, tem um importante lugar na história da medicina e da farmácia. Possivelmente já conhecida pelos espanhóis no século XVI, foi usada na terapêutica pela sua atividade febrífuga, estabelecendo-se como tratamento para as febres intermitentes nos séculos XVIII e XIX. Este artigo pretende avaliar a receção da quina em Portugal no último quartel do século XVIII e no primeiro quartel do século XIX através do estudo de obras portuguesas que descrevem pormenorizadamente as aplicações terapêuticas da quina, do estudo de uma publicação periódica médica, o Jornal de Coimbra e do estudo de receituário médico. Em Portugal, a quina foi também utilizada pela sua ação febrífuga, tendo sido publicadas várias obras descritivas da sua atividade terapêutica quer nas febres intermitentes, quer em doenças como a gota ou na gangrena. No periódico científico português Jornal de Coimbra (1812-1820) foram publicados, por indicação governamental, relatos de médicos de todo o país sobre as doenças existentes nas localidades em que exerciam e respetivo tratamento utilizado. Através da leitura desta publicação, verifica-se que a quina era um tratamento generalizado e normalmente eficaz para as febres intermitentes. No tratamento das febres intermitentes, a quina era geralmente associada a outros medicamentos como os eméticos. A quina foi também a droga mais prescrita num estudo de caso compreendendo 1954 receitas médicas. Foi prescrita por 434 vezes, entre 1779 e 1825, em receitas preparadas pelo Dispensatório Farmacêutico do Hospital da Universidade de Coimbra. Os relatos publicados no Jornal de Coimbra sobre a aplicação clínica da quina, e a percentagem elevada de receitas em que esta foi prescrita comprovam a sua importância na terapêutica em Portugal. (AU)

Quinine, a tree bark native to South America of the genus Cinchona, has antimalarial properties and occupies an important place in the history of medicine and pharmacy. Possibly already known to the Spanish in the 16th century, it was used in therapeutics for its febrifugal activity, becoming established as a treatment for intermittent fevers in the 18th and 19th centuries. This article aims to evaluate the reception of quinine in Portugal in the last quarter of the 18th century and the first quarter of the 19th century by studying Portuguese works that describe the therapeutic applications of quinine in detail, by studying a medical publication, the Jornal de Coimbra, and by examining medical prescriptions. In Portugal, quinine was also used for its febrifugal action, and several works were published describing its therapeutic activity in both intermittent fevers and diseases such as gout and gangrene. Acting on governmental instructions, the Portuguese scientific periodical Jornal de Coimbra (1812-1820) published reports by doctors throughout the country on diseases observed in the places where they practiced and on the treatments they applied. Reading this publication shows that quinine was a widespread and usually effective treatment for intermittent fevers, commonly combined with other drugs such as emetics. Quinine was also the most prescribed drug in a case study comprising 1,954 prescriptions. It was prescribed 434 times between 1779 and 1825 in prescriptions prepared by the Pharmaceutical Dispensatory of the Coimbra University Hospital. The reports in the Jornal de Coimbra on the clinical application of quinine and the high frequency of its prescription demonstrates its important therapeutic role in Portugal. (AU)

The Ir-Catalyzed Asymmetric Hydrogenation of α-Halogenated Ketones Utilizing Cinchona-Alkaloid-Derived NNP Ligand to Produce (R)- and (S)-Halohydrins.

The asymmetric hydrogenation of α-halogenated ketones with iridium catalyst was developed, utilizing easily accessed cinchona-alkaloid-based NNP ligands. Various α-chloroacetophenones, heterocyclic thienyl and furanyl substrates, and even bromoketones were completely converted to the desired chiral halohydrins by this protocol. Both (R)- and (S)-chiral halohydrins can be prepared by changing the configurations of the chiral ligand NNP with up to 99.6% ee (enantiomeric excess) and 98.8% ee, respectively. Also, a gram-scale experiment was carried out efficiently.

Cinchona bark and quinine in the Portuguese official pharmacopoeias (1794-2001).

Cinchona bark (bark from plants of the genus Cinchona with antimalarial activity) and its alkaloid quinine were widely used to treat intermittent fevers. This paper aims to quantitatively analyze the presence of Cinchona bark, quinine and other Cinchona bark-derived substances in the Portuguese official pharmacopoeias published between 1794 and 2001. The analysis showed that the Pharmacopêa Portugueza (1876) is the Portuguese official pharmacopeia with the highest percentage of medicines containing Cinchona bark (2.61%). The Farmacopeia Portuguesa IV (1935) is the official pharmacopeia with the highest percentage of quinine-containing medicines (2.34%). Medicines made from Cinchona bark are present in the Portuguese official pharmacopoeias until the Farmacopeia Portuguesa IV (1946). Medicines made from quinine have been present in Portuguese official pharmacopoeias since the Codigo Pharmaceutico Lusitano (1835).

The role of 12-lead electrocardiogram in the risk stratification of non-ST elevation acute coronary syndrome and the correlation with coronary angiography - The CINCHONa study - A prospective cohort study in Northern India.

Background: Clinical guidelines recommend risk stratification of non-ST elevation acute coronary syndrome (NST-ACS) using the GRACE risk score. However, the GRACE risk score is not followed widely in clinical practice due to various reasons. Our primary objectives of this study were to correlate the presenting electrocardiogram (ECG) of NST-ACS with coronary angiography (CAG) findings and to identify specific ECG changes that are suggestive of severe coronary artery disease (CAD) thus helping to triage all patients with NST-ACS. Materials and Methods: This prospective observational study was undertaken on patients diagnosed with NST-ACS in a medical college hospital, in Northern India over one and a ½ years. The admission ECG of the patients was compared with CAG findings to find out the correlation between the two with respect to severity of CAD. Categorical and quantitative variables were compared using the Chi-square test and independent t-test, respectively. Odds ratio (OR) were calculated using the univariate logistic regression analysis. Results: On comparing the two groups with normal and abnormal ECG, we found that smokers had significantly higher odds of having an abnormal ECG (OR 3.31; 95% confidence interval [CI] [1.29-8.50]). Patients with an abnormal ECG had significantly lower left ventricular ejection fraction compared to those with normal ECG (52.01 ± 10.56 vs. 55.96 ± 6.13%, P = 0.045). The patients with severe CAD on CAG had significantly higher odds of abnormal ECG (OR 3.68, 95% CI [1.2311.04]). Of the specific ECG abnormalities, ST depression and T-wave inversion in same or different leads were significantly associated with severity of CAD (OR 0.13, 95% CI [0.04-0.43], P = 0.001 and OR 0.13, 95% CI [0.03-0.46], P = 0.002, respectively). Conclusion: The identification of ECG changes suggestive of high-risk CAD can dictate to transfer such patients without delay to a percutaneous coronary intervention capable hospital for urgent CAG with intent to revascularization, thus helping in risk stratification of NST-ACS at the community level.

Résumé Contexte: Les directives cliniques recommandent la stratification du risque de syndrome coronarien aigu sans élévation du segment ST (SCA-NST) à l'aide du GRACE cote de risque. Cependant, le score de risque GRACE n'est pas largement suivi dans la pratique clinique pour diverses raisons. Nos objectifs premiers de cette étude étaient de corréler l'électrocardiogramme (ECG) de présentation du NST-ACS avec les résultats de l'angiographie coronarienne (CAG) et de identifier les modifications spécifiques de l'ECG qui suggèrent une maladie coronarienne (CAD) sévère, aidant ainsi au triage de tous les patients atteints de NST-ACS. Matériels et Méthodes: Cette étude observationnelle prospective a été entreprise sur des patients diagnostiqués avec un NST-ACS dans une faculté de médecine. hôpital, dans le nord de l'Inde pendant un an et demi. L'ECG d'admission des patients a été comparé aux résultats du CAG pour déterminer la corrélation entre les deux par rapport à la sévérité de la coronaropathie. Les variables catégorielles et quantitatives ont été comparées à l'aide du test du Chi-carré et test t indépendant, respectivement. Les rapports de cotes (OR) ont été calculés à l'aide de l'analyse de régression logistique univariée. Résultats: En comparant les deux groupes avec un ECG normal et anormal, nous avons constaté que les fumeurs avaient une probabilité significativement plus élevée d'avoir un ECG anormal (OR 3,31 ; Intervalle de confiance à 95 % [IC] [1,29­8,50]). Les patients avec un ECG anormal avaient une fraction d'éjection ventriculaire gauche significativement inférieure à à ceux ayant un ECG normal (52,01 ± 10,56 vs 55,96 ± 6,13 %, P = 0,045). Les patients atteints de coronaropathie sévère sur CAG avaient des taux significativement plus élevés risque d'ECG anormal (OR 3,68, IC à 95 % [1,2311,04]). Parmi les anomalies spécifiques de l'ECG, le sous-décalage du segment ST et l'inversion de l'onde T dans le même ou différentes dérivations étaient significativement associées à la sévérité de la coronaropathie (OR 0,13, IC 95 % [0,04­0,43], P = 0,001 et OR 0,13, IC 95 % [0,03­0,46], P = 0,002, respectivement). Conclusion: L'identification des modifications de l'ECG suggérant une coronaropathie à haut risque peut dicter le transfert de ces patients sans délai vers un hôpital capable d'intervention coronarienne percutanée pour CAG urgent avec intention de revascularisation, contribuant ainsi au risque stratification du NST-ACS au niveau communautaire. Mots-clés: Syndrome coronarien aigu, coronarographie, électrocardiogramme, score de risque GRACE, coronarien aigu sans sus-décalage du segment ST syndrome.

Experimental and computational studies on the Cinchona anchored calixarene catalysed asymmetric Michael addition reaction.

Lower-rim Cinchona anchored calix[4]arene cationic catalysts were developed for asymmetric Michael addition of acetylacetone to ß-nitrostyrenes. The desired Michael adducts were formed with high yields and enantioselectivities. Density functional theory investigations throw light on the catalyst-substrate interaction and the reaction mechanism.

Chiral separation of dipeptides on Cinchona-based zwitterionic chiral stationary phases under buffer-free reversed-phase conditions.

Chiral zwitterion ion exchangers represent efficient chiral stationary phases for stereoselective resolution of various analytes including chiral acids, bases, and zwitterions. In this contribution, we have focused on utilization of chiral zwitterionic sorbents, denoted as ZWIX (+A) and ZWIX (-A). These are analogical chiral systems to commercially available columns, Chiralpak ZWIX (+) and Chiralpak ZWIX (-), which are usually operated with buffered mobile phases. In this contribution, we have studied the enantiorecognition power of the ZWIX (+A) and ZWIX (-A) columns on a series of dipeptides operated under buffer-free reversed-phase conditions. Retention characteristics of zwitterionic dipeptides are discussed using an electrostatically driven adsorption model, which provides a good fit with both monotonous and U-shaped curves.

Legacies of boldness: Caldas, Humboldt and knowledge about cinchonas, 1801-1821. / Legados de la audacia: Caldas, Humboldt y el conocimiento sobre las quinas, 1801-1821.

This article examines the circulation of knowledge about Cinchona plants. Francisco José de Caldas and Alexander von Humboldt were interested in their taxonomy, distribution, trade, exploitation, production and conservation. The former's observations were better, but his contributions were silenced by Humboldt and other actors such as José Celestino Mutis. Caldas changed from a passive position of accepted subordination to one of self-advocacy, but his arguments were not widely publicized, in part because his results did not favor commercial interests and he lacked connections. Caldas used similar techniques to Humboldt to appropriate and systematize knowledge about cinchonas, silencing various sources.

El artículo reflexiona sobre la circulación de conocimiento en torno a las plantas de quina. Francisco José de Caldas y Alexander von Humboldt se interesaron por su taxonomía, distribución, comercio, explotación, producción y conservación. Las observaciones del primero fueron mejores, pero sus aportes fueron silenciados por el segundo y por otros actores como José Celestino Mutis. Caldas cambió desde una posición pasiva y de aceptada subalternidad, hasta una de reclamo, pero sus argumentos no tuvieron mayor difusión, en parte porque sus resultados no favorecían intereses comerciales y carecía de redes. Caldas usó dispositivos similares a los de Humboldt para apropiar y sistematizar conocimientos sobre las quinas, silenciando a varias fuentes.

Enantioselective high-performance liquid chromatographic separation of fluorinated ß- phenylalanine derivatives utilizing Cinchona alkaloid-based ion-exchanger chiral stationary phases: Enantioselective separation of fluorinated ß-phenylalanine derivatives.

The enantioselective separation of newly synthesized fluorine-substituted ß-phenylalanines has been performed utilizing Cinchona alkaloid-based ion-exchanger chiral stationary phases. Experiments were designed to study the effect of eluent composition, counterion content, and temperature on the chromatographic properties in a systematic manner. Mobile phase systems containing methanol or mixtures of methanol and acetonitrile together with acid and base additives ensured highly efficient enantioseparations. Zwitterionic phases [Chiralpak ZWIX (+) and ZWIX(-)] were found to provide superior performance compared to that by the anion-exchangers (Chiralpak QN-AX and QD-AX). A detailed thermodynamic characterization was also performed by employing van't Hoff analysis. Using typical liquid chromatographic experimental conditions, no marked effect of the flow rate could be observed on the calculated thermodynamic parameters. In contrast, a clear tendency has been revealed about the effect of the eluent composition on the thermodynamics for the zwitterionic phases.

Legados de la audacia: Caldas, Humboldt y el conocimiento sobre las quinas, 1801-1821 / Legacies of boldness: Caldas, Humboldt and knowledge about cinchonas, 1801-1821

Resumen El artículo reflexiona sobre la circulación de conocimiento en torno a las plantas de quina. Francisco José de Caldas y Alexander von Humboldt se interesaron por su taxonomía, distribución, comercio, explotación, producción y conservación. Las observaciones del primero fueron mejores, pero sus aportes fueron silenciados por el segundo y por otros actores como José Celestino Mutis. Caldas cambió desde una posición pasiva y de aceptada subalternidad, hasta una de reclamo, pero sus argumentos no tuvieron mayor difusión, en parte porque sus resultados no favorecían intereses comerciales y carecía de redes. Caldas usó dispositivos similares a los de Humboldt para apropiar y sistematizar conocimientos sobre las quinas, silenciando a varias fuentes.

Abstract This article examines the circulation of knowledge about Cinchona plants. Francisco José de Caldas and Alexander von Humboldt were interested in their taxonomy, distribution, trade, exploitation, production and conservation. The former's observations were better, but his contributions were silenced by Humboldt and other actors such as José Celestino Mutis. Caldas changed from a passive position of accepted subordination to one of self-advocacy, but his arguments were not widely publicized, in part because his results did not favor commercial interests and he lacked connections. Caldas used similar techniques to Humboldt to appropriate and systematize knowledge about cinchonas, silencing various sources.

Enantioselective organocatalytic syntheses of α-selenated α- and ß-amino acid derivatives.

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 ß-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.

Reflections on quinine and its importance in dermatology today.

Quinine and its D-isomer quinidine have been used medically in Europe since the 1600s. They were originally found within the bark of the cinchona tree in the jungle of the Andes. They were recognized to have multiple beneficial medical properties, ranging from a combined antipyretic and analgesic effect to the first effective treatment for malaria and later atrial fibrillation. With the development of other medications and the recognition of the potential life-threatening toxic reactions to these drugs, their medical use declined. Quinine is available without a prescription in many countries and is present in tonic water. Quinine has an extensive following of users who believe it is salutary and harmless, considering it a food supplement. In the past, dermatologists were frequently the first to recognize disease caused by these drugs owing to early findings of dermatitis or petechiae. Even though the medical use of these drugs has markedly decreased, drug eruptions may still be due to quinine, and patients may even be unaware they are taking this medication.

Recyclable fluorous cinchona organocatalysts for asymmetric synthesis of biologically interesting compounds.

Organocatalysis has unique modes of activation, mild reaction conditions, and good catalyst structural amenability. The integration of green techniques such as catalyst recovery and one-pot reactions makes organocatalysis more efficient and attractive. Presented in this article are the recyclable cinchona alkaloid-catalyzed reactions including fluorination and Michael addition-initiated cascade reactions in asymmetric synthesis of functionalized compounds of biological interest.

The influence of German science on Cinchona and quinine research in Portugal in the second half of the 19th century.

This paper examines the contribution of three Portuguese scientists to Cinchona cultivation in the former Portuguese colonies in the second half of the 19th century, while discussing the importance of their studies in Germany to their professional lives. Portuguese pharmaceutical, medical, and botanical literature from the 19 th and 20 th century was reviewed, as well as books and articles regarding the history of pharmacy and medicine in Portugal. Cinchona bark, source of the antimalarial alkaloid quinine, is obtained from a South American plant, and was an important commodity in the 19th century. Many European nations (including Portugal) tried to acclimatize and cultivate Cinchona plants in their colonies. Pharmacist Joaquim dos Santos e Silva (1842-1906) performed chemical analysis of Cinchona bark samples from the Portuguese colonies in Africa. Forester Bernardino Barros Gomes (1839-1910) wrote a book with practical instructions for Cinchona cultivation and chronicled the history of Cinchona plantations in the British and Dutch colonies. In that work he also encouraged private planters to cultivate Cinchona. Forester Adolpho Frederico Möller (1842-1920), as inspector of the Botanical Garden of Coimbra, managed Cinchona plants' cultivation in the garden's nurseries, which were later sent to the colonies, and answered queries from Cinchona planters. Silva's chemistry studies in Germany were crucial to his career and the work of the three scientists was influenced and guided by their knowledge of German science and scientific culture.