Sample records for cinchona

  1. Bioactivities examination of Cinchona leaves ethanol extracts (United States)

    Artanti, Nina; Udin, Linar Z.; Hanafi, M.; Jamilah, Kurniasih, Ida Rahmi; Primahana, Gian; Anita, Yulia; Sundowo, Andini; Kandace, Yoice Sri


    Cinchona species especially the barks are commonly known for commercial production of quinine as antimalarial. Although it is also reported for treatment of depurative, whooping cough, influenza and dysentery. In this paper we reported in vitro examination of other bioactivities (antidiabetes, antioxidant and in vitro cytotoxicity) of 70% ethanol extract of Cinchona ledgeriana and C. succirubra leaves as well as qunine, quinidine, and cinchonine the major alkaloids found in Cinchona species. Antidiabetes was conducted using α-glucosidase inhibitory activity assay. Antioxidant was conducted using DPPH free radical scavenging activity assay. In vitro cytotoxic activity was concucted by microscopic observation on growth of breast cancer cell line MCF-7. The results showed that at concentration of 100 µg/ml, C. ledgeriana leaves ethanol extracts showed the best activity as antidiabetes (98% inhibitory of α-glucosidase activity) and antioxidant (92% DPPH free radical scavenging activity), whereas at the same concentration C. succirubra, quinine, quinidine and cinchonine showed very low activities of antidiabetes and antioxidant. Microscopic observation of in vitro cytotoxicity showed that C. ledgeriana also has excellent cytotoxicity to breast cancer cell line MCF-7 which better than quinine, quinidine and cinchonine, whereas C. succirubra showed low cytotoxicity. These results suggest that cinchona species have many potential as the source of drugs discovery and development other than just for malaria treatment. Therefore it is important to conduct further studies and to maintain the available Cinchona plantation in Indonesia.

  2. Phylogeny predicts the quantity of antimalarial alkaloids within the iconic yellow Cinchona bark (Rubiaceae: Cinchona calisaya)

    DEFF Research Database (Denmark)

    Maldonado Goyzueta, Carla Brenda; Barnes, Christopher James; Cornett, Claus


    against herbivores and diseases and accelerate drug discovery. For centuries, Cinchona alkaloids were the primary treatment of malaria. Using Cinchona calisaya as a model, we generated genetic profiles of leaf samples from four plastid (trnL-F, matK, rps16, and ndhF) and one nuclear (ITS) DNA regions from...... twenty-two C. calisaya stands sampled in the Yungas region of Bolivia. Climatic and soil parameters were characterized and bark samples were analyzed for content of the four major alkaloids using HPLC-UV to explore the utility of evolutionary history (phylogeny) in determining variation within species...... of these compounds under natural conditions. A significant phylogenetic signal was found for the content of two out of four major Cinchona alkaloids (quinine and cinchonidine) and their total content. Climatic parameters, primarily driven by changing altitude, predicted 20.2% of the overall alkaloid variation...

  3. Computational Studies on Cinchona Alkaloid-Catalyzed Asymmetric Organic Reactions. (United States)

    Tanriver, Gamze; Dedeoglu, Burcu; Catak, Saron; Aviyente, Viktorya


    Remarkable progress in the area of asymmetric organocatalysis has been achieved in the last decades. Cinchona alkaloids and their derivatives have emerged as powerful organocatalysts owing to their reactivities leading to high enantioselectivities. The widespread usage of cinchona alkaloids has been attributed to their nontoxicity, ease of use, stability, cost effectiveness, recyclability, and practical utilization in industry. The presence of tunable functional groups enables cinchona alkaloids to catalyze a broad range of reactions. Excellent experimental studies have extensively contributed to this field, and highly selective reactions were catalyzed by cinchona alkaloids and their derivatives. Computational modeling has helped elucidate the mechanistic aspects of cinchona alkaloid catalyzed reactions as well as the origins of the selectivity they induce. These studies have complemented experimental work for the design of more efficient catalysts. This Account presents recent computational studies on cinchona alkaloid catalyzed organic reactions and the theoretical rationalizations behind their effectiveness and ability to induce selectivity. Valuable efforts to investigate the mechanisms of reactions catalyzed by cinchona alkaloids and the key aspects of the catalytic activity of cinchona alkaloids in reactions ranging from pharmaceutical to industrial applications are summarized. Quantum mechanics, particularly density functional theory (DFT), and molecular mechanics, including ONIOM, were used to rationalize experimental findings by providing mechanistic insights into reaction mechanisms. B3LYP with modest basis sets has been used in most of the studies; nonetheless, the energetics have been corrected with higher basis sets as well as functionals parametrized to include dispersion M05-2X, M06-2X, and M06-L and functionals with dispersion corrections. Since cinchona alkaloids catalyze reactions by forming complexes with substrates via hydrogen bonds and long

  4. The Quest for Cinchona

    DEFF Research Database (Denmark)

    Maldonado Goyzueta, Carla Brenda

    of today, in a time where traditional knowledge is disappearing faster than biodiversity. Chapter 7 describes the development of an effective grinding device for the grinding of herbal samples such as Cinchona barks. Chapter 8 describes the development of an analytical chemical method for quantification...... of the four major Cinchona alkaloids. Finally, Chapter 9 discusses the importance of collections in medicinal plant research leading into the future. D...

  5. Quinine, Malaria, and the Cinchona Bureau: Marketing Practices and Knowledge Circulation in a Dutch Transoceanic Cinchona-Quinine Enterprise (1920s-30s). (United States)

    Van Der Hoogte, Arjo Roersch; Pieters, Toine


    In this study, we will show how a Dutch pharmaceutical consortium of cinchona producers and quinine manufacturers was able to capitalize on one of the first international public health campaigns to fight malaria, thereby promoting the sale of quinine, an antimalarial medicine. During the 1920s and 1930s, the international markets for quinine were controlled by this Dutch consortium, which was a transoceanic cinchona-quinine enterprise centered in the Cinchona Bureau in the Netherlands. We will argue that during the interwar period, the Cinchona Bureau became the decision-making center of this Dutch cinchona-quinine pharmaceutical enterprise and monopolized the production and trade of an essential medicine. In addition, we will argue that capitalizing on the international public health campaign in the fight against malaria by the Dutch cinchona-quinine enterprise via the Cinchona Bureau can be regarded as an early example of corporate colonization of public health by a private pharmaceutical consortium. Furthermore, we will show how commercial interests prevailed over scientific interests within the Dutch cinchona-quinine consortium, thus interfering with and ultimately curtailing the transoceanic circulation of knowledge in the Dutch empire.

  6. A convenient microwave-assisted synthesis of cinchona alkaloid-derived ligands

    Institute of Scientific and Technical Information of China (English)


    An efficient synthesis of cinchona alkaloid-derived ligands based on solvent-free microwave-assisted reaction was described. The coupling of 1,4-dichlorophthalazine or 3,6-dichloropyridazine with quinine, cinchonine or cinchonidine provide bis- or mono-cinchona alkaloid-derived ligands in moderate to good yields (52-89%) within 15 rain under optimum microwave conditions.

  7. [Historical research of cinchona cultivation in Japan (Part 3)--A proposal to introduce cinchona by Takeaki Enomoto]. (United States)

    Nagumo, Seiji; Izawa, Kazuo


    We attempted to determine how one of the most valuable medicinal plants, cinchona, was brought to and cultivated in Japan. In the course of the study, we report that cinchona seedlings were brought to Japan for the first time in 1876, as per Takeaki Enomoto's proposal to the Meiji government. We also examine the details of his proposal in effort to clarify that the written proposal was submitted between February and March, 1874, and considered his motives leading to the submission. Cinchona is a very important medicinal plant that has saved human lives. However, there was no proof that Takeaki Enomoto's proposal made it introduction to Japan possible, nor was there any evidence that its cultivation was attempted. In addition, it was not clear that the details of the above has been found in document including the Nomutenmatsu (agricultural report published by the Meiji Government). It is significant that the details has been clarified by our series of studies not only from the standpoint of the history of pharmacy, but also from the accounts of the great predecessors involved, such as Takeaki Emonoto and Yasusade Tashiro.

  8. Using Natural Cinchona Alkaloids to Promote the Enantioselective Addition of Dialkylzinc to N-Diphenylphosphinylimines

    Institute of Scientific and Technical Information of China (English)

    张海乐; 方春梅; 李昕; 龚流柱; 宓爱巧; 崔欣; 蒋耀忠


    Cinchona alkaloids are utilized as chiral ligands to promote the enantioselective addition of dialkylzinc to N-diphenyiphosphinylirnlnes affording enantiomerically enriched N-diphenyiphosphinylamines in up to 91% ee.

  9. Experiencias comunales post-terremoto de Cinchona en el Distrito de Sarapiquí de Alajuela

    Directory of Open Access Journals (Sweden)

    Jiménez Aguilar, Elisa


    Full Text Available Se resaltan las experiencias vividas producto del impacto del Terremoto de Cinchona en el 2009, por los pobladores de las comunidades del distrito de Sarapiquí de Alajuela: San Miguel, Ujarráz, Cariblanco y Cinchona. Las diferentes situaciones vividas posteriores al terremoto y a la reubicación de la comunidad de Cinchona. Cuáles fueron las principales ayudas por parte de instituciones, nuevos proyectos, infraestructura comunal y perspectivas a futuro en el distrito?. Esta información ha sido recabada mediante conversatorios y se pretende relatar desde un punto de vista comunal The experiences of the impact of product Cinchona earthquake in 2009 are highlighted by the residents of the communities in the district Sarapiquí of Alajuela: San Miguel, Ujarráz, Cariblanco and Cinchona. The different situations experienced after the earthquake and the relocation of the community of Cinchona. Which are the main aid from institutions, new projects, communal infrastructure and future perspectives in the district were?. This information was collected through conversations and seeks to relate from a communal point of view

  10. Quinine, Malaria, and the Cinchona Bureau : Marketing Practices and Knowledge Circulation in a Dutch Transoceanic Cinchona-Quinine Enterprise (1920s-30s)

    NARCIS (Netherlands)

    Roersch van der Hoogte, Arjo; Pieters, Toine


    In this study, we show how a Dutch pharmaceutical consortium of cinchona producers and quinine manufacturers was able to capitalize on one of the first international public health campaigns to fight malaria, thereby promoting the sale of quinine, an antimalarial medicine. During the 1920s and 1930s,

  11. Nature's Chiral Catalyst and Anti-Malarial Agent: Isolation and Structure Elucidation of Cinchonine and Quinine from "Cinchona calisaya" (United States)

    Carroll, Anne-Marie; Kavanagh, David J.; McGovern, Fiona P.; Reilly, Joe W.; Walsh, John J.


    Nature is a well-recognized source of compounds of interest, but access is often an issue. One pertinent example is the cinchona alkaloids from the bark of "Cinchona calisaya." In this experiment, students at the third-year undergraduate level undertake the selective isolation and characterization of two of the four main alkaloids present in the…

  12. Antiproliferative Activity of Polyether Antibiotic--Cinchona Alkaloid Conjugates Obtained via Click Chemistry. (United States)

    Skiera, Iwona; Antoszczak, Michał; Trynda, Justyna; Wietrzyk, Joanna; Boratyński, Przemysław; Kacprzak, Karol; Huczyński, Adam


    A series of eight new conjugates of salinomycin or monensin and Cinchona alkaloids were obtained by the Cu(I)-catalysed 1,3-dipolar Huisgen cycloaddition (click chemistry) of respective N-propargyl amides of salinomycin or monensin with four different Cinchona alkaloid derived azides. In vitro antiproliferative activity of these conjugates evaluated against three cancer cell lines (LoVo, LoVo/DX, HepG2) showed that four of the compounds exhibited high antiproliferative activity (IC50 below 3.00 μm) and appeared to be less toxic and more selective against normal cells than two standard anticancer drugs.

  13. Excited-state proton transfer and ion pair formation in a Cinchona organocatalyst

    NARCIS (Netherlands)

    Kumpulainen, T.; Brouwer, A.M.


    The excited-state proton transfer and subsequent intramolecular ion pair formation of a cupreidine-derived Cinchona organocatalyst (BnCPD) were studied in THF-water mixtures using picosecond time-resolved fluorescence together with global analysis. Full spectral and kinetic characterization of all t

  14. A comparison of the antimalarial activity of the cinchona alkaloids against Plasmodium falciparum in vitro. (United States)

    Wesche, D L; Black, J


    The effects of four major cinchona alkaloids: (-) quinine, (+) quinidine, (-)cinchonidine, and (+)cinchonine against Plasmodium falciparum FCQ-27/PNG were studied. The alkaloids were tested in vitro as either single alkaloids, racemic mixtures of stereoisomers, or as an equimolar combination of all four alkaloids. Results indicate (+)quinidine to be most effective and both (+)stereoisomers were more potent than the (-)stereoisomers. Inhibitory concentrations 50% (Ki) of racemic mixtures of stereoisomers were similar to those of the (+)stereoisomers alone. The Ki of four alkaloids in equimolar combination were similar to that of the (-) cinchonidine/(+)cinchonine racemic mixture. A total alkaloidal extract of Cinchona sp. was tested and compared with the pure alkaloids. HPLC analysis indicated that (+)cinchonine, (-)cinchonidine and (-)quinine were present in a ratio of approximately 1:1:2, respectively. The total alkaloid extract, with (-)stereoisomers predominating, was less effective than the four alkaloids in combination. The nature of the interaction between stereoisomers was investigated and appears to be one of addition.

  15. Distribución de Alcaloides en la Corteza de Algunas Cinchonas Peruanas

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    Hodge W. H.


    Full Text Available Los análisis de las muestras seleccionadas de corteza de quinas silvestres que crecían,en el Perú indican que el contenido en alcaloides varía apreciablemente según la posición de la base a los puntos más altos del árbol. En algunos tipos de cinchonas los alcaloides se encuentran en mayor cantidad en la base del tronco que en las partes más altas del árbol pero, en otros tipos de cinchona ocurre lo inverso. Por lo tanto para determinar el rendimiento comercial deben tomarse muestras de estas dos partes del árbol. También aparece cierta relación entre la cantidad de alcaloides presentes en un árbol y su circunferencia (o edad. La cantidad de alcaloides aumenta o disminuye según aumente o disminuya el diámetro y dicha relación depende del alcaloide y del tipo de cinchona.

  16. Extraction of alkaloids for NMR-based profiling: exploratory analysis of an archaic Cinchona bark collection. (United States)

    Yilmaz, Ali; Nyberg, Nils T; Jaroszewski, Jerzy W


    A museum collection of Cinchonae cortex samples (n = 117), from the period 1850-1950, was extracted with a mixture of chloroform-d1, methanol-d4, water-d2, and perchloric acid in the ratios 5 : 5 : 1 : 1. The extracts were directly analyzed using 1H NMR spectroscopy (600 MHz) and the spectra evaluated using principal component analysis (PCA) and total statistical correlation spectroscopy (STOCSY). A new method called STOCSY-CA, where CA stands for component analysis, is described, and an analysis using this method is presented. It was found that the samples had a rather homogenous content of the well-known cinchona alkaloids quinine, cinchonine, and cinchonidine without any apparent clustering. Signals from analogues were detected but not in substantial amounts. The main variation was related to the absolute amounts of extracted alkaloids, which was attributed to the evolution of the Cinchona tree cultivation during the period in which the samples were collected.

  17. Crystal structure of quinine: the effects of vinyl and methoxy groups on molecular assemblies of Cinchona alkaloids cannot be ignored. (United States)

    Hisaki, Ichiro; Hiraishi, Eri; Sasaki, Toshiyuki; Orita, Hideo; Tsuzuki, Seiji; Tohnai, Norimitsu; Miyata, Mikiji


    Quinine, one of Cinchona alkaloids, has been of great interest from medical, synthetic, and supramolecular viewpoints. However, unaccountably, the guest-free (GF) crystal of quinine containing no solvent or other molecules has not been reported for nearly three decades, although GF crystals of other Cinchona alkaloids, such as quinidine, cinchonidine, and cinchonine, are already known. In this study, we successfully revealed the crystal structure of quinine, which belongs to the P2(1) space group with the cell parameters of a=6.0587(1), b=19.2492(5), c=22.2824(7) Å, β=92.1646(11)°, and V=2596.83(12) Å(3). Interestingly, the crystal has three crystallographically independent molecules in the cell (Z'=3) that are connected through a N(quinoline)⋅⋅⋅H-O hydrogen bond to form a pseudo three-two-fold (3(2)) double-helical motif. The helical motif is completely different from those observed in GF crystals of other Cinchona alkaloids. Hierarchical comparison on the crystal structures of a series of Cinchona alkaloids including quinine clearly demonstrated that only small structural differences of a molecule, particularly the position of the vinyl group, cause a significant variety of assembly manner in the crystalline state. There have been no reports systematically demonstrating such steric effect in crystals of Cinchona alkaloids, and, therefore, the present system contributes to the design of desired functional crystal structures.

  18. Non-aqueous CE-MS of cinchona alkaloids - characterization of a novel CE-ESI-MS interface

    DEFF Research Database (Denmark)

    Hansen, Frederik André; Hansen, Steen Honoré; Petersen, Nickolaj J.

    the composition of alkaloids in Cinchona bark. One common problem for sheatless interfaces for CE-MS has been establishing a stable electric contact at the end of the separation capillary that does not induce band broadening or affect the spray stability. In our device the electric contact is generated through....... Furthermore, the increased conductivity of the buffer in the fracture generates field free pumping of the analytes towards the ESI spray tip. In this study the device was used to analyze the four major alkaloids (diastereomeric pairs of quinine/quinidine and cinchonine/cinchonidine) in Cinchona bark samples...

  19. The cost of quinine Cinchona pubescens control on Santa Cruz Island, Galapagos


    Buddenhagen, Chris; Yanez, Patricio


    We analyse the cost of controlling the invasive quinine tree Cinchona pubescens Vahl in the highlands of Santa Cruz Island, Galapagos. Control costs in ten 400 m2 plots formed the basis for estimating the cost of control over the whole island. In the plots, densities were 2100–24,000 stems/ha (stems >150 cm tall) and 55,000–138,000 stems/ha (all size classes combined). Control involved uprooting small plants, and applying of a mix of metsulfuron methyl and picloram to cut stumps or to mach...

  20. A highly efficient and recoverable bi-cinchona alkaloid ligand for the catalytic asymmetric aminohydroxylation of olefins

    Directory of Open Access Journals (Sweden)



    Full Text Available A new freely recyclable bi-cinchona alkaloid ligand has been developed for the homogeneous catalytic asymmetric aminohydroxylation (AA of olefins. It can be easily recovered by precipitation and reused for 5 times without any significant loss in its catalytic efficiency in AA reactions.

  1. Endophytic Colletrotrichum spp. from Cinchona calisaya wedd. and it's potential quinine production as antibacterial and antimalaria (United States)

    Radiastuti, Nani; Mutea, Dalli; Sumarlin, La Ode


    An endophytic fungus is microorganisms that live inside plant tissues without harming its host and is capable of producing the same secondary metabolites as its host plant. The endophytic fungus is very diverse and important group of microorganisms. The objectives of the study are to identify endophyte Colletotrichum spp. using ITS rDNA analyze, alkaloid cinchona and antibacterial characteristics. Phylogenetic analysis of ITS rDNA regions and morphology are used to identify the species. The Chloroform extracts of filtrate were analyzed using the High Pressure Liquid Chromatography (HPLC) to determine the production of quinine. There were 13 isolates of Colletotrichum spp as endophytes with associated with Cinchona calisaya Wedd. from fruit (6 isolates), leaf (5 isolates), twig (1 isolate) and root (1 isolate). This is the first report as endophytes are associated with C. calisaya. Based on ITS phylogenetic analysis are introduced of 7 strains Colletotrichum sp, 1 strain closely with C. aegnigma, 2 strains closely C. cordylinicola, 1 strains C arxii, 2 strains nested C. karstii. The Colletotrichum sp. M1 (leaf), M3 (bark), M8 (fruit) and C. karstii M5 (fruit) are potential alkaloid quinine. Five strains of Colletotrichum spp. have antibacterial activity are selected against Staphylococcus aureus and nine Colletotrichum spp. against Escherichia coli. The endophyte identification of Colletotrichum species needs another gene other than ITS rDNA.

  2. Novel cinchona carbamate selectors with complementary enantioseparation characteristics for N-acylated amino acids. (United States)

    Krawinkler, Karl Heinz; Maier, Norbert M; Ungaro, Rocco; Sansone, Francesco; Casnati, Alessandro; Lindner, Wolfgang


    The synthesis and chromatographic evaluation of the enantiomer separation capabilities of covalently immobilized calix[4]arene-cinchona carbamate hybrid type receptors derived from quinine (QN) and its corresponding C9-epimer (eQN) in different solvents are reported. The receptors display complementary enantiomer separation profiles in terms of elution order, chiral substrate specificity, and mobile phase characteristics, indicating the existence of two distinct chiral recognition mechanisms. The QN-derived receptor binds the (S)-enantiomers of N-acylated amino acids more strongly, shows preferential recognition of open-chained amino acids, and superior enantioselectivity in polar media such as methanol/acetic acid. In contrast, the eQN congener preferentially recognizes the corresponding (R)-enantiomers, displays good enantioselectivity (alpha up to 1.74) for cyclic amino acids, and enhanced stereodiscriminating properties in apolar mobile phases, e.g., chloroform/acetic acid. A comparison of the enantiomer separation profiles with those of the corresponding QN and eQN tert-butyl carbamate congeners indicates no significant level of cooperativity between the calix[4]arene module and the cinchona units in terms of overall chiral recognition, most probably as a consequence of residual conformational flexibility of the calixarene module and the carbamate linkage.

  3. Chiral modification of platinum: ab initio study of the effect of hydrogen coadsorption on stability and geometry of adsorbed cinchona alkaloids. (United States)

    Hahn, Konstanze R; Seitsonen, Ari P; Baiker, Alfons


    The cinchona alkaloids cinchonidine and cinchonine belong to the most efficient chiral modifiers for the noble metal-catalyzed enantioselective hydrogenation of C=O and C=C bonds. Under reaction conditions these modifiers are coadsorbed on the noble metal surface with hydrogen. Using density functional theory, we studied the effect of coadsorbed hydrogen on the adsorption mode of cinchonidine and cinchonine on a Pt(111) surface at different hydrogen coverages. The theoretical study indicates that the presence of coadsorbed hydrogen affects both the adsorption geometry as well as the stability of the adsorbed cinchona alkaloids. At all hydrogen coverages the cinchona alkaloids are found to be adsorbed via anchoring of the quinoline moiety. In the absence of hydrogen as well as at low hydrogen coverage the quinoline moiety adsorbs nearly parallel to the surface, whereas at higher hydrogen coverage it becomes tilted. Higher hydrogen coverage as well as partial hydrogenation of the quinoline part of the cinchona alkaloid and hydrogen transfer to the C[double bond, length as m-dash]C double bond at 10, 11 position of the quinuclidine moiety destabilize the adsorbed cinchona alkaloid, whereas hydrogen transfer to the nitrogen atom of the quinoline and the quinuclidine moiety stabilizes the adsorbed molecule. The stability as well as the adsorption geometry of the cinchona alkaloids are affected by the coadsorbed hydrogen and are proposed to influence the efficiency of the enantiodifferentiating ability of the chirally modified platinum surface.

  4. Salts of phenylacetic acid and 4-hydroxyphenylacetic acid with Cinchona alkaloids: Crystal structures, thermal analysis and FTIR spectroscopy (United States)

    Amombo Noa, Francoise M.; Jacobs, Ayesha


    Seven salts were formed with phenylacetic acid (PAA), 4-hydroxyphenylacetic acid (HPAA) and the Cinchona alkaloids; cinchonidine (CIND), quinidine (QUID) and quinine (QUIN). For all the structures the proton was transferred from the carboxylic acid of the PAA/HPAA to the quinuclidine nitrogen of the respective Cinchona alkaloid. For six of the salts, water was included in the crystal structures with one of these also incorporating an isopropanol solvent molecule. However HPAA co-crystallised with quinine to form an anhydrous salt, (HPAA-)(QUIN+). The thermal stability of the salts were determined and differential scanning calorimetry revealed that the (HPAA-)(QUIN+) salt had the highest thermal stability compared to the other salt hydrates. The salts were also characterized using Fourier transform infrared spectroscopy. (PAA-)(QUID+)·H2O and (PAA-)(QUIN+)·H2O are isostructural and Hirshfeld surface analysis was completed to compare the intermolecular interactions in these two structures.

  5. Iron(III) protoporphyrin IX complexes of the antimalarial Cinchona alkaloids quinine and quinidine. (United States)

    de Villiers, Katherine A; Gildenhuys, Johandie; le Roex, Tanya


    The antimalarial properties of the Cinchona alkaloids quinine and quinidine have been known for decades. Surprisingly, 9-epiquinine and 9-epiquinidine are almost inactive. A lack of definitive structural information has precluded a clear understanding of the relationship between molecular structure and biological activity. In the current study, we have determined by single crystal X-ray diffraction the structures of the complexes formed between quinine and quinidine and iron(III) protoporphyrin IX (Fe(III)PPIX). Coordination of the alkaloid to the Fe(III) center is a key feature of both complexes, and further stability is provided by an intramolecular hydrogen bond formed between a propionate side chain of Fe(III)PPIX and the protonated quinuclidine nitrogen atom of either alkaloid. These interactions are believed to be responsible for inhibiting the incorporation of Fe(III)PPIX into crystalline hemozoin during its in vivo detoxification. It is also possible to rationalize the greater activity of quinidine compared to that of quinine.

  6. Science in the service of colonial agro-industrialism: the case of cinchona cultivation in the Dutch and British East Indies, 1852-1900. (United States)

    Roersch van der Hoogte, Arjo; Pieters, Toine


    The isolation of quinine from cinchona bark in 1820 opened new possibilities for the mass-production and consumption of a popular medicine that was suitable for the treatment of intermittent (malarial) fevers and other diseases. As the 19th century European empires expanded in Africa and Asia, control of tropical diseases such as malaria was seen as crucial. Consequently, quinine and cinchona became a pivotal tool of British, French, German and Dutch empire-builders. This comparative study shows how the interplay between science, industry and government resulted in different historical trajectories for cinchona and quinine in the Dutch and British Empires during the second half of the 19th century. We argue that in the Dutch case the vectors of assemblage that provided the institutional and physical framework for communication, exchange and control represent an early example of commodification of colonial science. Furthermore, both historical trajectories show how the employment of the laboratory as a new device materialised within the colonial context of agricultural and industrial production of raw materials (cinchona bark), semi-finished product (quinine sulphate) and plant-based medicines like quinine. Hence, illustrating the 19th century transition from 'colonial botany' and 'green imperialism' to what we conceptualise as 'colonial agro-industrialism'.

  7. From Colonial Agro-Industrialism to agro-industrialism : Game-changing evolution of the Dutch transoceanic cinchona-quinine Enterprise (1940's-1960s)

    NARCIS (Netherlands)

    Pieters, A.H.L.M.


    By the turn of the twentieth century, the Dutch colony of the Netherlands Indies dominated the worldwide supply of antifebrifuge (to reduce fever) cinchona bark, the raw material for quinine, an antimalarial medicine. Over the next four decades, the high-quality and laboratory-conditioned cultivatio

  8. Science, industry and the colonial state : a shift from a German- to a Dutch-controlled cinchona and quinine cartel (1880–1920)

    NARCIS (Netherlands)

    Roersch van der Hoogte, Arjo; Pieters, Toine


    This study shows how control over delicately balanced supply chains from raw material to the final product shifted from one national industry to another. By 1920, Dutch cinchona producers and quinine manufacturers dominated the international cartel that controlled the worldwide production and distri

  9. Non-aqueous CE-MS of cinchona alkaloids - characterization of a novel CE-ESI-MS interface

    DEFF Research Database (Denmark)

    Hansen, Frederik André; Hansen, Steen Honoré; Petersen, Nickolaj J.

    . Furthermore, the increased conductivity of the buffer in the fracture generates field free pumping of the analytes towards the ESI spray tip. In this study the device was used to analyze the four major alkaloids (diastereomeric pairs of quinine/quinidine and cinchonine/cinchonidine) in Cinchona bark samples...

  10. Science in the service of colonial agro-industrialism : the case of cinchona cultivation in the Dutch and British East Indies, 1852-1900

    NARCIS (Netherlands)

    Roersch van der Hoogte, Arjo; Pieters, Toine


    The isolation of quinine from cinchona bark in 1820 opened new possibilities for the mass-production and consumption of a popular medicine that was suitable for the treatment of intermittent (malarial) fevers and other diseases. As the 19th century European empires expanded in Africa and Asia, contr

  11. Theoretical study on the mechanism and stereochemistry of the cinchona-thiourea organocatalytic hydrophosphonylation of an α-ketoester. (United States)

    Li, Weiyi; Huang, Dongfeng; Lv, Yajing


    The mechanism and stereochemistry of the hydrophosphonylation of an α-ketoester with dimethylphosphonate (DMHP) catalyzed by a thiourea-cinchona organocatalyst have been studied by the ONIOM method. The calculations show that the catalytic cycle is a three-step process, including the deprotonation of DMHP, C-P bond formation via nucleophilic addition and proton transfer with the regeneration of the catalyst. The deprotonation of DMHP mediated by the basicity of the quinuclidine nitrogen atom is the rate-determining step for the entire reaction. The activation of the α-ketoester by the thiourea or protonated cinchona moiety of the bifunctional catalyst is comparatively investigated, and the former is energy-preferred. AIM combined with NBO analysis indicate that the multiple hydrogen bonds play essential roles in activating substrates, facilitating charge transfer and stabilizing transition states and intermediates. The stereochemistry of the reaction is controlled by the C-P bond formation step and originated from the chiral induction of the multiple hydrogen-bonding interactions. The bulkier substituent groups on the chiral scaffold of the catalyst may increase rigidity of the catalyst and the asymmetric induction to the substrates. The calculations predict that alkyl substituted α-ketoesters might also be converted to chiral α-hydroxyl phosphonates with high enantioselectivity.

  12. Insights into the dual activation mechanism involving bifunctional cinchona alkaloid thiourea organocatalysts: an NMR and DFT study. (United States)

    Zhu, Jun-Ling; Zhang, Yong; Liu, Chong; Zheng, An-Min; Wang, Wei


    In-depth understanding of the activation mechanism in asymmetric organocatalysis is of great importance for rational development of highly efficient catalytic systems. In this Article, the mechanism for the direct vinylogous Michael reaction of α,β-unsaturated γ-butyrolactam (Nu) and chalcone (EI) catalyzed by the bifunctional cinchona alkaloid thiourea organocatalyst (Cat) was studied with a combination of experimental (NMR) and theoretical (DFT) approaches, through which a new dual activation pathway was found. The key feature of this new dual activation mechanism (Pathway C) is that one N-H(A) of the thiourea moiety and the N-H of the protonated amine in Cat simultaneously activate Nu, while the other N-H(B) of the thiourea moiety activates EI. Both the NMR measurement and the DFT calculation identified that the interaction of Cat with Nu is stronger than that with EI in the catalyst-substrate complexes. Kinetic studies via variable-temperature NMR measurements indicated that, with the experimental activation energy E(a) of 10.2 kcal/mol, the reaction is all first-order in Nu, EI, and Cat. The DFT calculation further revealed that the C-C bond formation is both the rate-determining and the stereoselectivity-controlling steps. In agreement with the experimental data, the energy barrier for the rate-determining step along Pathway C was calculated as 8.8 kcal/mol. The validity of Pathway C was further evidenced by the calculated enantioselectivity (100% ee) and diastereoselectivity (60:1 dr), which are in excellent match with the experimental data (98% ee and >30:1 dr, respectively). Mechanistic study on the Michael addition of nitromethane to chalcone catalyzed by the Catalyst I further identified the generality of this new dual activation mechanism in cinchona alkaloid thiourea organocatalysis.

  13. Rapid and Green Analytical Method for the Determination of Quinoline Alkaloids from Cinchona succirubra Based on Microwave-Integrated Extraction and Leaching (MIEL Prior to High Performance Liquid Chromatography

    Directory of Open Access Journals (Sweden)

    Farid Chemat


    Full Text Available Quinas contains several compounds, such as quinoline alkaloids, principally quinine, quinidine, cinchonine and cichonidine. Identified from barks of Cinchona, quinine is still commonly used to treat human malaria. Microwave-Integrated Extraction and Leaching (MIEL is proposed for the extraction of quinoline alkaloids from bark of Cinchona succirubra. The process is performed in four steps, which ensures complete, rapid and accurate extraction of the samples. Optimal conditions for extraction were obtained using a response surface methodology reached from a central composite design. The MIEL extraction has been compared with a conventional technique soxhlet extraction. The extracts of quinoline alkaloids from C. succirubra obtained by these two different methods were compared by HPLC. The extracts obtained by MIEL in 32 min were quantitatively (yield and qualitatively (quinine, quinidine, cinchonine, cinchonidine similar to those obtained by conventional Soxhlet extraction in 3 hours. MIEL is a green technology that serves as a good alternative for the extraction of Cinchona alkaloids.

  14. Regulación en el uso de la tierra con fines preventivos en los alrededores del cuadrante de la antigua comunidad de Cinchona, Alajuela, Costa Rica

    Directory of Open Access Journals (Sweden)

    Esquivel Valverde, Lidier


    Full Text Available La regulación del uso de la tierra permite establecer cuales lugares son aptas para el establecimiento de zonas habitacionales, comercios, industria, actividades agrícolas, actividades turísticas, entre otras, evitando incrementar la vulnerabilidad física o ambiental. El presente artículo se basa en un estudio realizado a la comunidad de Cinchona a raíz del sismo del año 2009, el cual, por las características topográficas y geológicas de la región, generó una cantidad alta de daños a la infraestructura y pérdida de vidas humanas, lo que propició la elaboración de una herramienta técnica normativa que regulara el uso de la tierra en esa zona. La investigación consideró aspectos como el uso de la tierra antes del sismo, tenencia de la tierra, producción agropecuaria, valor de la tierra, pendientes de terreno, geomorfología, capacidad de uso de la tierra, aguas subterráneas, zonas de vida y áreas silvestres y por último las amenazas más relevantes. Como resultado del estudio se presenta en el artículo un resumen de la regulación de tierra propuesta, la cual comprende el sector de Vieja Cinchona (zona devastada por el sismo y las microcuencas cercanas Land use regulations allow to identify suitable places to establish housing, commerce, industry, agricultural activities, and tourism, among others, avoiding to increase physical or environmental vulnerability. This article is based on a study developed at the Cinchona community after the 2009 earthquake, which due to the topographic and geological characteristics generated a lot of damages to infrastructures and losses of human lives. In this context, a normative technical tool was developed to regulate the land use in the zone. The investigation considered aspects such as land use before the earthquake, land possession, farming production, land value, land slopes, geomorphology, land use capacity, underground water, wild life areas and most relevant threats. As a result of

  15. Cinchona Alkaloid Derivative-Catalyzed Enantioselective Synthesis via a Mannich-Type Reaction and Antifungal Activity of β-Amino Esters Bearing Benzoheterocycle Moieties

    Directory of Open Access Journals (Sweden)

    Han Xiao


    Full Text Available An efficient synthesis of highly functionalized chiral β-amino ester derivatives containing benzothiophene and benzothiazole moieties is developed by a Mannich-type reaction using a cinchona alkaloid-derived thiourea catalyst. The desired products were obtained in good yields and high enantioselectivities (~86% yield, >99% ee using to the optimized reaction conditions. The synthesized compounds were characterized by 1H-NMR, 13C-NMR, IR, and HREI-MS analyses. The bioassays identified that compound 5dr has excellent antifungal activity, with a 60.53% inhibition rate against F. oxysporum, higher than that of the commercial agricultural fungicide hymexazol, whose inhibition rate was 56.12%.

  16. Procesos de ladera cosísmicos del terremoto de Cinchona (Costa Rica del 8 de enero de 2009 (Ms= 6,2

    Directory of Open Access Journals (Sweden)

    Adolfo Quesada Román


    Full Text Available The Cinchona earthquake of January 8, 2009, caused great physical impacts such as the destruction of the public and private infrastructure, including social, and left a total of 2,326 persons displaced, 91 injured, 7 missing, and 25 dead. Based on aerial photographs and the implementation of high resolution LiDAR, after the earthquake, 1,900 hillside processes were classified based on the Works of Alcántara- Ayala (2000, Cruden and Varnes (1996 and Highland y Bobrowsky (2008. The importance of this work for Costa Rica lies in the fact that it is the first time the international classification of hillside processes of the WP/WLI established in 1990 was used.

  17. [The complex travel of cinchona barks between Peru and Québec Hôtel-Dieu, in the middle of the eighteenth century]. (United States)

    Simon, Lorène; Lafont, Olivier


    Duplessis sisters, who were religious nuns in Hôtel-Dieu (Quebec hospital), were exchanging letters with a French apothecary from Dieppe in Normandy, named Jacques-Tranquilain Féret. They asked him to send them in Quebec the drugs and medicines their apothecary needed. Amongst these drugs were cinchona barks that came from Callao in Peru by boat, passed Cape Horn and then sailed to Cadiz, the great Spanish port. Then they embarked to Rouen, which was the French port for goods coming from overseas. The goods from Peru had then to be transported on little fishing boats to Dieppe, where Féret received the barks. The apothecary sent these drugs to Quebec by boats sailing either from Rouen or from La Rochelle. So these Peruvian drugs had to cross two times the Ocean before accessing to North America.

  18. Avaliação de parâmetros de extração da Cinchona Vahl por métodos farmacopéicos e não farmacopéicos Extraction parameters from Cinchona pubescens Vahl using pharmacopeia and no pharmacopeia methods

    Directory of Open Access Journals (Sweden)

    Iarah Daniela Dantas Silva


    Full Text Available O presente estudo teve como objetivo a otimização de parâmetros cinéticos de extração da Cinchona pubescens Vahl por ultra-som, usando métodos farmacopéicos e não farmacopéicos. Na extração por ultrasom variaram-se o tempo, a massa, a faixa granulométrica, o volume de solvente e o tipo de solvente. Na decocção, as extrações foram feitas no tempo e temperatura descrita na Farmacopéia Brasileira IV, variando-se o sistema solvente. Na extração por maceração variaram-se o tempo e o sistema solvente. O teor de alcalóides quinolínicos foi monitorado por espectrofotometria no UV a 325 nm. O método decocção foi o que apresentou o maior rendimento na extração dos alcalóides, dados equivalentes foram conseguidos com o método ultra-som, no tempo de 5 min e solvente acidificado pH 4, com um rendimento maior ao da maceração. Pela aplicação do planejamento fatorial para o método do ultra-som foi visto que há uma interação entre as variáveis, necessitando de um melhor ajuste entre elas a fim de melhorar a eficiência extrativa do método do ultra-som.The present study for ultrasound had as objective the optimization of kinetic parameters of extraction of the Cinchona pubescens Vahl, using pharmacopeia and no pharmacopeia methods. In the extraction for ultrasound they had varied the time, the solvent type, the mass, the volume of solvent and grain size of the sample. In the decoction, the extractions had been made according to the time and temperature described in Brazilian Pharmacopeia IV, varying the solvent system. In the extraction for maceration the time and the solvent system had varied. The alkali of the Cinchona pubescens Vahl, was monitored by spectrophotometry in UV 325 nm. The method decoction was the one that presented the biggest income in the alkaloids extraction, given equivalent data had been obtained with the method ultrasound, in the solvent acidified pH 4 and time of 5 min, with a bigger income than the

  19. High-performance liquid chromatographic enantioseparation of cyclic β-aminohydroxamic acids on zwitterionic chiral stationary phases based on Cinchona alkaloids

    Energy Technology Data Exchange (ETDEWEB)

    Lajkó, Gyula [Department of Inorganic and Analytical Chemistry, University of Szeged, H-6720 Szeged, Dóm tér 7 (Hungary); Institute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös u. 6 (Hungary); Orosz, Tímea [Department of Inorganic and Analytical Chemistry, University of Szeged, H-6720 Szeged, Dóm tér 7 (Hungary); Grecsó, Nóra [Department of Inorganic and Analytical Chemistry, University of Szeged, H-6720 Szeged, Dóm tér 7 (Hungary); Institute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös u. 6 (Hungary); Fekete, Beáta; Palkó, Márta; Fülöp, Ferenc [Institute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös u. 6 (Hungary); Lindner, Wolfgang [Department of Analytical Chemistry, University of Vienna, Währingerstrasse 38, A-1090 Vienna (Austria); Péter, Antal [Department of Inorganic and Analytical Chemistry, University of Szeged, H-6720 Szeged, Dóm tér 7 (Hungary); Ilisz, István, E-mail: [Department of Inorganic and Analytical Chemistry, University of Szeged, H-6720 Szeged, Dóm tér 7 (Hungary)


    Cyclic β-aminohydroxamic acid enantiomer pairs were stereoselectively separated by high-performance liquid chromatography on the recently developed Cinchona alkaloid-based zwitterionic chiral stationary phases Chiralpak ZWIX(+)™, ZWIX(−)™, ZWIX(+A) and ZWIX(−A). The results of variation of the applied chromatographic conditions, such as the bulk solvent composition, the concentrations and ratio of the acid and base additives, the presence of water as mobile phase additive and the counter-ion concentration furnished a better understanding of the retention mechanism. A thermodynamic study in the temperature range 5–50 °C revealed enthalpy-controlled enantiodiscrimination in all cases. The structure–selectivity relationships clearly indicated the importance of the strereochemistry of the functional groups. From an enantiorecognition aspect, the diexo position of the functional groups always proved more favorable than the diendo position. The elution sequence was determined in all cases and was found to reversed when ZWIX(+)™ was changed to ZWIX(−)™ or ZWIX(+A) to ZWIX(−A). - Highlights: • Zwitterionic columns were applied for the enantioseparation of cyclic β-aminohydroxamic acids. • Enthalpy controlled enantiodiscriminations were observed. • Enantiorecognition depended on the stereochemistry of the functional group.

  20. Selective binding of chiral molecules of cinchona alkaloid by beta- and gamma-cyclodextrins and organoselenium-bridged bis(beta-cyclodextrin)s. (United States)

    Liu, Yu; Li, Li; Zhang, Heng-Yi; Fan, Zhi; Guan, Xu-Dong


    The inclusion complexation behavior of chiral members of cinchona alkaloid with beta- and gamma-cyclodextrins (1 and 2) and 6,6(')-trimethylenediseleno-bridged bis(beta-cyclodextrin) (3) was assessed by means of fluorescence and 2D-NMR spectroscopy. The spectrofluorometric titrations have been performed in aqueous buffer solution (pH 7.20) at 25.0 degrees C to determine the stability constants of the inclusion complexation of 1-3 with guest molecules (i.e., cinchonine, cinchonidine, quinine, and quinidine) in order to quantitatively investigate the molecular selective binding ability. The stability constants of the resulting complexes of 2 with guest molecules are larger than that of 1. As a result of cooperative binding, the stability constants of inclusion complexation of dimeric beta-cyclodextrin 3 with cinchonidine and cinchonine are higher than that of parent 1 by factor of 4.5 and 2.4, respectively. These results are discussed from the viewpoint of the size-fit and geometric complementary relationship between the host and guest.

  1. Aspectos geohidrológicos y sedimentológicos de los flujos de lodo asociados al terremoto de Cinchona (Mw 6,2) del 8 de enero del 2009, Costa Rica


    Guillermo E. Alvarado


    The Cinchona earthquake (Mw 6.2) located 6.5 km east of the active crater of Poás, triggered several landslides (rock fall, rotational and translational slides), which in combination with existing pore water within the landslide mass in intense tropical weathering volcanic soils, local aquifers deformation, and mixing of fluvial waters into the moving sediment mass, produced high destructive debris flows along the Seco, María Aguilar, Cariblanco, Ángel, La Paz, Sarapiquí, Mataste and Tigre ri...

  2. Novel urea-linked cinchona-calixarene hybrid-type receptors for efficient chromatographic enantiomer separation of carbamate-protected cyclic amino acids. (United States)

    Krawinkler, Karl Heinz; Maier, Norbert M; Sajovic, Elisabeth; Lindner, Wolfgang


    Two novel diastereomeric cinchona-calixarene hybrid-type receptors (SOs) were synthesized by inter-linking 9-amino(9-deoxy)-quinine (AQN)/9-amino(9-deoxy)-epiquinine (eAQN) and a calix[4]arene scaffold via an urea functional unit. Silica-supported chiral stationary phases (CSPs) derived from these SOs revealed, for N-protected amino acids, complementary chiral recognition profiles in terms of elution order and substrate specificity. The AQN-derived CSP showed narrow-scoped enantioselectivity for open-chained amino acids bearing pi-acidic aromatic protecting groups, preferentially binding the (S)-enantiomers. In contrast, the eAQN congener exhibited broad chiral recognition capacity for open-chained as well as cyclic amino acids, and preferential binding of the (R)-enantiomers. Exceedingly strong retention due to nonenantioselective hydrophobic analyte-calixarene interactions observed with hydro-organic mobile phases could be largely suppressed with organic mobile phases containing small amounts of acetic acid as acidic modifier. With the eAQN-calixarene hybrid-type CSP particularly high levels of enantioselectivity could be achieved for tert-butoxycarbonyl (Boc)-, benzyloxycarbonyl (Z)- and fluorenylmethoxycarbonyl (Fmoc)-protected cyclic amino acids using chloroform as mobile phase, e.g. an enantioselectivty factor alpha >5.0 for Boc-proline. Increasing amounts of acetic acid compromised enantioselectivity, indicating the crucial contributions of hydrogen bonding to chiral recognition. Comparison of the performance characteristics of the urea-linked eAQN-calixarene hybrid-type CSP with those of structurally closely related mutants provided evidence for the active involvement of the urea and calixarene units in the chiral recognition process. The urea linker motif was shown to contribute to analyte binding via multiple hydrogen bonding interactions, while the calixarene module is believed to support stereodiscrimination by enhancing the shape complementarity of the

  3. 金鸡纳碱及其衍生物在不对称Mannich反应中的应用%Application of Cinchona Alkaloid and their Derivatives in Asymmetric Mannich Reactions

    Institute of Scientific and Technical Information of China (English)

    潘昭喜; 何永光; 刘浩


    Catalytic enantioselective Mannich reactions provided one of the most versatile approaches for the synthesis of optically active chiral amines.Recently,several organocatalytic protocols were developed by using the parent cinchona alkaloids or their derivatives.It was a focus of considerable attention in the domestic and foreign research.The recent progress of asymmetric Mannich reactions catalyzed by cinchona alkaloids or their derivatives was generally reviewed.%不对称Mannich反应是一种应用最广泛的合成光学活性的手性氨基酸衍生物的方法,近几年基于金鸡纳碱及其衍生物的有机小分子催化的不对称Mannich反应成为国内外研究的热点,本文简要介绍了金鸡纳碱及其衍生物在不对称Mannich反应中的应用。

  4. Antimalarial substances of an endophytic fungus isolated from cinchona tree%一株具有抗疟活性的金鸡纳树内生真菌的研究

    Institute of Scientific and Technical Information of China (English)

    周松林; 陈双林; 黄风迎; 王华; 赵焕阁


    为筛选具抗疟疾活性的的内生真菌,采用平板分离法对海南金鸡那树内生真菌进行分离纯化.利用“4日抑制疟疾”测试内生真菌发酵液的抗疟活性,采用TLC、HPLC等分析技术对内生菌发酵液等成分进行分析.从金鸡那树叶片分离到31种内生真菌,通过筛选找到了1株具有抗疟疾活性的产奎宁或奎宁类似物的内生真菌.从金鸡那树叶片中分离得到1株产奎宁的结实串孢霉属内生真菌,为奎宁的资源开发开辟了新途径.%Plate method was used to isolate and purify endophytic fungi from Cinchona sp. in Hainan Province. The anti-malaria activity of fermented liquid of the endophytic fungi was tested using "4 day inhibit malaria", and the components such as quinine or structural analogues were analysed using TLC and HPLC. Of the 31 endophytic species isolated from cinchona tree one strain producing quinine or quinine analogues with antimalarial activity was obtained. Morphological observation indicated that this endophytic fungus could be identified as Hormiscium sp.

  5. Mechanistic Study of the Gas-Phase In-Source Hofmann Elimination of Doubly Quaternized Cinchona-Alkaloid Based Phase-Transfer Catalysts by (+)-Electrospray Ionization/Tandem Mass Spectrometry (United States)

    Yang, Rong-Sheng; Sheng, Huaming; Lexa, Katrina W.; Sherer, Edward C.; Zhang, Li-Kang; Xiang, Bangping; Helmy, Roy; Mao, Bing


    An unusual in-source fragmentation pattern observed for 14 doubly quaternized cinchona alkaloid-based phase-transfer catalysts (PTC) was studied using (+)-ESI high resolution mass spectrometry. Loss of the substituted benzyl cation (R1 or R2) was found to be the major product ion [M2+ - R1 + or R2 +]+ in MS spectra of all PTC compounds. A Hofmann elimination product ion [M - H]+ was also observed. Only a small amount of the doubly charged M2+ ions were observed in the MS spectra, likely due to strong Columbic repulsion between the two quaternary ammonium cations in the gas phase. The positive voltage in the MS inlet but not the ESI probe was found to induce this extensive fragmentation for all PTC diboromo-salts. Compound 1 was used as an example to illustrate the proposed in-source fragmentation mechanism. The mechanism of formation of the Hofmann elimination product ion [M - H]+ was further investigated using HRMS/MS, H/D exchange, and DFT calculations. The proposed formation of 2b as the major Hofmann elimination product ion was supported both by HRMS/MS and DFT calculations. Formation of product ion 2b through a concerted unimolecular Ei elimination pathway is proposed rather than a bimolecular E2 elimination pathway for common solution Hofmann eliminations.

  6. 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

    Energy Technology Data Exchange (ETDEWEB)

    Wernisch, Stefanie, E-mail: [Institute for Analytical Chemistry, University of Vienna, Währinger Straße 38, A-1090 Vienna (Austria); Trapp, Oliver, E-mail: [Organisch-Chemisches Institut, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, D-69120 Heidelberg (Germany); Lindner, Wolfgang, E-mail: [Institute for Analytical Chemistry, University of Vienna, Währinger Straße 38, A-1090 Vienna (Austria)


    Graphical abstract: -- Highlights: •X-Pro peptides produce interconverting elution profiles on zwitterionic stationary phases. •The cis–trans isomerization rate in solution is lower than in the chromatographic system. •Cinchona-based zwitterionic selectors apparently lower the isomerization barrier. •Rotamer separation is feasible <0 °C, enantiomer separation above room temperature. -- Abstract: 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.

  7. Asymmetric Hydrogenation of Aromatic Ketones Catalyzed by Cinchona-Modified Ir/SiO2%金鸡纳碱衍生物修饰的负载铱催化剂催化芳香酮不对称加氢

    Institute of Scientific and Technical Information of China (English)

    蒋和雁; 吴志峰; 陈华


    The asymmetric hydrogenation of aromatic ketones catalyzed by cinchona-and triphenylphosphine (tpp)-modified Ir/SiO2 was studied.The heterogeneous enantioselective hydrogenation of heterocyclic ketones using a supported iridium catalyst was also investigated.Different analytical techniques,including inductively coupled plasma-atomic emission spectroscopy (ICP-AES),high resolution transmission electron microscopy (HRTEM),X-ray photoelectron spectroscopy (XPS),the Brunauer-Emmett-Teller (BET) method,infrared (IR) spectroscopy,31p solid state nuclear magnetic resonance (NMR)spectroscopy,homogeneous-heterogeneous comparison experiment,conventional filtering test,and mercury poisoning experiment,were used to characterize the catalytic system.HRTEM,XPS,and the BET method clearly characterized the catalytic system.IR and 31p solid state NMR spectra provided useful information about the interactions between modifier,metal,and stabilizer.The homogeneous-heterogeneous comparison experiment,conventional filtering test,and mercury poisoning experiment clearly showed the differences between supported,and homogeneous catalysts.In addition,the effects of different stabilizers,modifiers,iridium content,solvents,and base additives on the asymmetric hydrogenation of aromatic ketones were investigated in detail.The results showed that cinchona alkaloids positively modified the Ir/SiO2 catalyst.Under the optimum conditions,the hydrogenation enantioselectivities of acetophenone and its derivatives were 52%-96%.The enantioselectivities of the hydrogenation products of 4-acetopyridine,2-acetothiophene,and 2-acetofuran reached 74%,75%,and 63%,respectively.%以金鸡纳碱衍生物作为手性修饰剂,研究了三苯基膦稳定的Ir/SiO2催化剂催化芳香酮多相不对称加氢.通过电感耦合等离子体原子发射发谱(ICP-AES)、高分辨透射电镜(HRTEM)、X射线光电子能谱(XPS)、Brunauer-Emmett-Teller (BET)比表面积测试等固体表面分析手段对

  8. Excited state proton transfer in the Cinchona alkaloid cupreidine

    NARCIS (Netherlands)

    J. Qian; A.M. Brouwer


    Photophysical properties of the organocatalyst cupreidine (CPD) and its chromophoric building block 6-hydroxyquinoline (6HQ) in protic and nonprotic polar solvents (methanol and acetonitrile) were investigated by means of UV-vis absorption, and steady state and time resolved fluorescence spectroscop

  9. Drug: D08460 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available gif Cinchona [TAX:43462], Cinchona calisaya [TAX:153742], Cinchona succirubra, Cinchona calisaya Antiprotozoa...[BR:br08302] Antiparasitics Antiprotozoals Quinine D08460 Quinine (BAN) Antiinfectives [BR:br08307] Antipara

  10. An efficient, robust, and inexpensive grinding device for herbal samples like Cinchona bark

    DEFF Research Database (Denmark)

    Hansen, Steen Honoré; Holmfred, Else Skovgaard; Cornett, Claus;


    An effective, robust, and inexpensive grinding device for the grinding of herb samples like bark and roots was developed by rebuilding a commercially available coffee grinder. The grinder was constructed to be able to provide various particle sizes, to be easy to clean, and to have a minimum of d...

  11. Optimization of Extraction Conditions and HPTLC - UV Method for Determination of Quinine in Different Extracts of Cinchona species Bark

    Directory of Open Access Journals (Sweden)

    Dharam C. Jain


    Full Text Available A simple, precise and accurate high-performance thin-layer chromatographic method has been established for quantitative determination of quinine. Conditions were also optimized for best possible extraction of quinine via varying concentrations of diethyl amine in different solvents (n-hexane, chloroform, ethyl acetate and methanol for maximum recovery of quinine. Methanol modified with 20 % DEA found to be best for highest possible recovery of target analyte quinine. Chromatographic separation of quinine was performed on silica gel 60 F 254 HPTLC plates with ethyl acetate : diethyl amine in the proportion 88 : 12 (v/v, as mobile phase. The determination was carried out using the densitometric absorbance mode at 236 nm. Quinine response was found to be linear over the range 4–24 μg spot −1. The HPTLC method was evaluated in terms of specificity, precision, reproducibility, LOD – LOQ and robustness. Beside these parameters, number of theoretical plates and flow constant were also included as a part of validation

  12. Polymer-Supported Cinchona Alkaloid-Derived Ammonium Salts as Recoverable Phase-Transfer Catalysts for the Asymmetric Synthesis of α-Amino Acids

    Directory of Open Access Journals (Sweden)

    Carmen Nájera


    Full Text Available 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-(diphenylmethyleneglycine 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.

  13. Comparison of the Separation Performances of Cinchona Alkaloid-Based Zwitterionic Stationary Phases in the Enantioseparation of β2- and β3-Amino Acids

    Directory of Open Access Journals (Sweden)

    István Ilisz


    Full Text Available The enantiomers of twelve unusual β2- and β3-homoamino acids containing the same side-chains were separated on chiral stationary phases containing a quinine- or quinidine-based zwitterionic ion-exchanger as chiral selector. The effects of the mobile phase composition, the nature and concentration of the acid and base additives and temperature on the separations were investigated. The changes in standard enthalpy, ∆(∆H°, entropy, ∆(∆S°, and free energy, ∆(∆G°, were calculated from the linear van’t Hoff plots derived from the ln α vs. 1/T curves in the studied temperature range (10–50 °C. The values of the thermodynamic parameters depended on the nature of the selectors, the structures of the analytes, and the positions of the substituents on the analytes. A comparison of the zwitterionic stationary phases revealed that the quinidine-based ZWIX(−™ column exhibited much better selectivity for both β2- and β3-amino acids than the quinine-based ZWIX(+™ column, and the separation performances of both the ZWIX(+™ and ZWIX(−™ columns were better for β2-amino acids. The elution sequence was determined in some cases and was observed to be R < S and S < R on the ZWIX(+™ and ZWIX(−™ columns, respectively.

  14. Zwitterionic chiral stationary phases based on cinchona and chiral sulfonic acids for the direct stereoselective separation of amino acids and other amphoteric compounds. (United States)

    Zhang, Tong; Holder, Emilie; Franco, Pilar; Lindner, Wolfgang


    An extensive series of free amino acids and analogs were directly resolved into enantiomers (and stereoisomers where appropriate) by HPLC on zwitterionic chiral stationary phases (Chiralpak ZWIX(+) and Chiralpak ZWIX(-)). The interaction and chiral recognition mechanisms were based on the synergistic double ion-paring process between the analyte and the chiral selectors. The chiral separation and elution order were found to be predictable for primary α-amino acids with apolar aliphatic side chains. A systematic investigation was undertaken to gain an insight into the influence of the structural features on the enantiorecognition. The presence of polar and/or aromatic groups in the analyte structure is believed to tune the double ion-paring equilibrium by the involvement of the secondary interaction forces such as hydrogen bonding, Van der Waals forces and π-π stacking in concert with steric parameters. The ZWIX chiral columns were able to separate enantiomers and stereoisomers of various amphoteric compounds with no need for precolumn derivatization. Column switching between ZWIX(+) and ZWIX(-) is believed to be an instrumental tool to reverse or control the enantiomers elution order, due to the complementarity of the applied chiral selectors.

  15. Acylated mono-, bis- and tris- Cinchona-Based Amines Containing Ferrocene or Organic Residues: Synthesis, Structure and in Vitro Antitumor Activity on Selected Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Emese Gál


    Full Text Available A series of novel functionalized mono-, bis- and tris-(S-{[(2S,4R,8R-8-ethyl-quinuclidin-2-yl](6-methoxyquinolin-4-yl}methanamines including ferrocene-containing derivatives was obtained by the reaction of the precursor amine with a variety of acylation agents. Their in vitro antitumor activity was investigated against human leukemia (HL-60, human neuroblastoma (SH-SY5Y, human hepatoma (HepG2 and human breast cancer (MCF-7 cells by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT-assay and the 50% inhibitory concentration (IC50 values were determined. Our data indicate that the precursor amine has no antitumor activity in vitro, but the bis-methanamines with ureido-, thioureido and amide-type linkers display attractive in vitro cytotoxicity and cytostatic effects on HL-60, HepG2, MCF-7 and SH-SY5Y cells. Besides 1H- and 13C-NMR methods the structures of the new model compounds were also studied by DFT calculations.

  16. Comparison between 2 methods of solid-liquid extraction for the production of Cinchona calisaya elixir: an experimental kinetics and numerical modeling approach. (United States)

    Naviglio, Daniele; Formato, Andrea; Gallo, Monica


    The purpose of this study is to compare the extraction process for the production of China elixir starting from the same vegetable mixture, as performed by conventional maceration or a cyclically pressurized extraction process (rapid solid-liquid dynamic extraction) using the Naviglio Extractor. Dry residue was used as a marker for the kinetics of the extraction process because it was proportional to the amount of active principles extracted and, therefore, to their total concentration in the solution. UV spectra of the hydroalcoholic extracts allowed for the identification of the predominant chemical species in the extracts, while the organoleptic tests carried out on the final product provided an indication of the acceptance of the beverage and highlighted features that were not detectable by instrumental analytical techniques. In addition, a numerical simulation of the process has been performed, obtaining useful information about the timing of the process (time history) as well as its mathematical description.

  17. 48 CFR 25.104 - Nonavailable articles. (United States)


    .... Chalk, English. Chestnuts. Chicle. Chrome ore or chromite. Cinchona bark. Cobalt, in cathodes, rondelles..., blocks, and pigs. Triprolidine hydrochloride. Tungsten. Vanilla beans. Venom, cobra. Water chestnuts....

  18. 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. (United States)

    Wernisch, Stefanie; Trapp, Oliver; Lindner, Wolfgang


    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.

  19. 金鸡纳-铂催化2-氧代-4-苯基丁酸乙酯的不对称加氢%Enantioselective Hydrogenation of Ethyl 2-Oxo-4-phenylbutyrate on Cinchona-Platinum Catalysts

    Institute of Scientific and Technical Information of China (English)

    夏涛; 任其龙; 吴平东


    Enantioselective hydrogenation of ethyl 2-oxo-4-phenylbutyrate to ethyl (R)-2-hydroxy-4-phenyl- bu-tyrate on Pt/γ-Al2O3 modified by 10,11-dihydrocinchonidine was studied by investigating the influences of the amount of modifier, initial concentration of reactant, pressure and temperature on conversion and enantiometric excess in a stirred autoclave and the effects of the liquid velocity, gas velocity, modifier concentration and various catalytic beds in a trickle-bed reactor. The maximum optical yields were about 50% and 60% in the two types of reactors, respectively. It was assumed that the total hydrogenation rate included the reaction rates over the unmodified and modified active sites on platinum surface and a kinetic model, which fitted the experimental data well in autoclave, was obtained. A simplified plug-flow model was proposed to describe the bed average efficiency of trickle-bed reactor.

  20. Drug: D07153 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available amily) Cinchona bark Major component: Quinine [CPD:C06526] Therapeutic category of drugs... in Japan [BR:br08301] 5 Crude drugs and Chinese medicine formulations 51 Crude drugs 510 Crude drugs 5100 Crude drugs D07153 Cinchona bark PubChem: 51091492 ...

  1. Building the world's supply of quinine: Dutch colonialism and the origins of a global pharmaceutical industry. (United States)

    Goss, Andrew


    Quinine, a naturally occurring alkaloid from the Cinchona tree, was one of the first drugs produced and sold by a global pharmaceutical industry during the nineteenth century. Factories in Europe and North America dominated the manufacturing industry, and between 1890 and 1940, Cinchona plantations on Java supplied most of the bark for the quinine pharmaceutical business. At the end of the nineteenth century, the Dutch colonial state kept a hands-off approach to the Cinchona enterprises, in keeping with its liberal orientation. But the persistent low-price for bark, which led to the near ruin of the Cinchona planters, eventually pushed the colonial state to actively protect the Cinchona plantations. Colonial officials sought to stabilize the colonial Cinchona export-business by encouraging the integration of the quinine industry on a global scale. Most important was the colonial state's sponsorship in 1913 of the Quinine Agreement, establishing a set price for Cinchona bark, which created the world's first pharmaceutical cartel. In the interwar period, an alliance of Dutch government officials, planters, scientists, doctors and drug-makers, working in both the motherland and the colony, actively promoted the expansion of quinine consumption, as well as the merit of the Quinine Agreement, which they argued supplied guaranteed a steady supply of quinine, all for the wellbeing of global humanity.

  2. Preparation of Mesoporous SBA-16 Silica-Supported Biscinchona Alkaloid Ligand for the Asymmetric Dihydroxylation of Olefins

    Directory of Open Access Journals (Sweden)

    Shaheen M. Sarkar


    Full Text Available Optically active cinchona alkaloid was anchored onto mesoporous SBA-16 silica and the as-prepared complex was used as a heterogeneous chiral ligand of osmium tetraoxide for the asymmetric dihydroxylation of olefins. The prepared catalytic system provided 90–93% yield of vicinal diol with 92–99% enantioselectivity. The ordered mesoporous SBA-16 silica was found to be a valuable support for the cinchona alkaloid liganded osmium catalyst system which is frequently used in chemical industries and research laboratories for olefin functionalization.

  3. Drug: D08458 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available inchona calisaya [TAX:153742], Cinchona succirubra, Cinchona calisaya Antiarrhythmic; Antiprotozoal, Antimal...arial Same as: C06527 ATC code: C01BA01 Class I antiarrhythmic agent (Ia) voltage-gated sodium channel (SCN1...5244], SCL47A2 [HSA:146802], ABCB1 [HSA:5243] map07025 Quinolines map07037 Antiarrhythmic drugs map07231 Sod...br08303] C CARDIOVASCULAR SYSTEM C01 CARDIAC THERAPY C01B ANTIARRHYTHMICS, CLASS I AND III C01BA Antiarrhythmic...BR:br08302] Cardiovascular Agents Antiarrhythmics Quinidine D08458 Quinidine (BAN) Target-based classificati

  4. Catalytic Enantioselective Electrophilic Aminations of Acyclic α-Alkyl β-Carbonyl Nucleophilies. (United States)

    Liu, Xiaofeng; Sun, Bingfeng; Deng, Li


    Highly enantioselective aminations of acyclic α-alkyl β-keto thioesters and trifluoroethyl α-methyl α-cyanoacetate (12) with as low as 0.05 mol % of a bifunctional cinchona alkaloid catalyst were established. This ability to afford highly enantioselectivity for the amination of α-alkyl β-carbonyl compounds renders the 6'-OH cinchona alkaloid-catalyzed amination applicable for the enantioselective synthesis of acyclic chiral compounds bearing N-substituted quaternary stereocenters. The synthetic application of this reaction is illustrated in a concise asymmetric synthesis of α-methylserine, a key intermediate previously utilized in the total synthesis of a small molecule immunomodulator, conagenin.

  5. Extraction of alkaloids for NMR-based profiling

    DEFF Research Database (Denmark)

    Yilmaz, Ali; Nyberg, Nils; Jaroszewski, Jerzy W.


    A museum collection of Cinchona cortex samples (n = 117), from the period 1850–1950, were extracted with a mixture of chloroform-d1, methanol-d4, water-d2, and perchloric acid in the ratios 5:5:1:1. The extracts were directly analyzed using 1H NMR spectroscopy (600 MHz) and the spectra evaluated ...

  6. Lewis base catalyzed [4+2] annulation of electron-deficient chromone-derived heterodienes and acetylenes. (United States)

    Dückert, Heiko; Khedkar, Vivek; Waldmann, Herbert; Kumar, Kamal


    Lewis base catalyzed [4+2] annulation reactions between electron-deficient chromone oxa- and azadienes and acetylene carboxylates provide tricyclic benzopyrones inspired by natural products. An asymmetric synthesis of the tricyclic benzopyrones was developed by using modified cinchona alkaloids as enantiodifferentiating Lewis base catalysts.

  7. Historical Review: Problematic Malaria Prophylaxis with Quinine. (United States)

    Shanks, G Dennis


    Quinine, a bitter-tasting, short-acting alkaloid drug extracted from cinchona bark, was the first drug used widely for malaria chemoprophylaxis from the 19th century. Compliance was difficult to enforce even in organized groups such as the military, and its prophylaxis potential was often questioned. Severe adverse events such as blackwater fever occurred rarely, but its relationship to quinine remains uncertain. Quinine prophylaxis was often counterproductive from a public health viewpoint as it left large numbers of persons with suppressed infections producing gametocytes infective for mosquitoes. Quinine was supplied by the first global pharmaceutical cartel which discouraged competition resulting in a near monopoly of cinchona plantations on the island of Java which were closed to Allied use when the Japanese Imperial Army captured Indonesia in 1942. The problems with quinine as a chemoprophylactic drug illustrate the difficulties with medications used for prevention and the acute need for improved compounds.

  8. Highly enantio- and diastereoselective synthesis of β-methyl-γ- monofluoromethyl-substituted alcohols

    KAUST Repository

    Yang, Wenguo


    Enanatiopure β-methyl-γ-monofluoromethyl alcohols were prepared from the allylic alkylation between fluorobis(phenylsulfonyl)methane with Morita-Baylis-Hillman carbonates. The reaction was catalyzed by using the Cinchona alkaloid derivative, (DHQD)2AQN. The origin of the stereoselectivity was verified by DFT methods. Calculated geometries and relative energies of various transition states strongly support the observed stereoselectivity. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Synthesis of triazol derivatives of lupeol with potential antimalarial activity


    Tatiane Freitas Borgati; Guilherme Rocha Pereira; Geraldo Célio Brandão; Alaíde Braga Oliveira; José Dias Souza Filho


    The goal of this project is synthesize and characterization of derivatives of lupeol and evaluated antimalarial activity. Historically, plants are important source of antimalarial medicines, highlighting quinine (1) (Figure 1), an important      alkaloid from the Cinchona calisaya bark. This compound was an important model for cloroquine  synthesis, a drug that was widely used in malaria treatment. In addition, one of the principal medicines used today is artemisinine, isolated from the Chine...

  10. Chiral counteranion synergistic organocatalysis under high temperature: efficient construction of optically pure spiro[cyclohexanone-oxindole] backbone. (United States)

    Lan, Yu-Bao; Zhao, Hua; Liu, Zhao-Min; Liu, Guo-Gui; Tao, Jing-Chao; Wang, Xing-Wang


    The combination of a cinchona-based chiral primary amine and a BINOL-phosphoric acid has been demonstrated as a powerful and synergistic catalyst system for the double Michael addition of isatylidene malononitriles with α,β-unsaturated ketones, to provide the novel chiral spiro [cyclohexane-1,3'-indoline]-2',3-diones in high yields (88-99%) with excellent diastereo- and enantioselectivities (94:6-99:1 dr's, 95-99% ee's).

  11. Reconnaissance chirale dans des complexes moléculaires neutres et ioniques


    Sen, Ananya


    The main objective of this thesis is a spectroscopic study of molecules or complexes bearing multiple chiral centres in the gas phase, to understand the effects of stereochemistry on their structural properties. Neutral cinchona alkaloids have been introduced intact in gas phase by laser-ablation. They have been studied by combining supersonic expansion with laser spectroscopy. The two pseudo-enantiomers Quinine and Quinidine show similar electronic and vibrational spectra, in line with simil...

  12. Highly enantio- and diastereoselective allylic alkylation of Morita-Baylis-Hillman carbonates with allyl ketones

    KAUST Repository

    Tong, Guanghu


    The asymmetric allylic alkylation of Morita-Baylis-Hillman (MBH) carbonates with allyl ketones has been developed. The α-regioselective alkylation adducts, containing a hexa-1,5-diene framework with important synthetic value, were achieved in up to 83% yield, >99% ee, and 50:1 dr by using a commercially available Cinchona alkaloid as the catalyst. From the allylic alkylation adduct, a cyclohexene bearing two adjacent chiral centers was readily prepared. © 2013 American Chemical Society.

  13. Enantioselective Organocatalytic α-Fluorination of Cyclic Ketones


    Kwiatkowski, Piotr; Beeson, Teresa D.; Conrad, Jay C.; MacMillan, David W. C.


    The first highly enantioselective α-fluorination of ketones using organocatalysis has been accomplished. The long-standing problem of enantioselective ketone α-fluorination via enamine activation has been overcome via high-throughput evaluation of a new library of amine catalysts. The optimal system, a primary amine functionalized Cinchona alkaloid, allows the direct and asymmetric α-fluorination of a variety of carbo- and heterocyclic substrates. Furthermore, this protocol also provides dias...

  14. Origin of Stereodivergence in Cooperative Asymmetric Catalysis with Simultaneous Involvement of Two Chiral Catalysts. (United States)

    Bhaskararao, Bangaru; Sunoj, Raghavan B


    Accomplishing high diastereo- and enantioselectivities simultaneously is a persistent challenge in asymmetric catalysis. The use of two chiral catalysts in one-pot conditions might offer new avenues to this end. Chirality transfer from a catalyst to product gets increasingly complex due to potential chiral match-mismatch issues. The origin of high enantio- and diastereoselectivities in the reaction between a racemic aldehyde and an allyl alcohol, catalyzed by using axially chiral iridium phosphoramidites PR/S-Ir and cinchona amine is established through transition-state modeling. The multipoint contact analysis of the stereocontrolling transition state revealed how the stereodivergence could be achieved by inverting the configuration of the chiral catalysts that are involved in the activation of the reacting partners. While the enantiocontrol is identified as being decided in the generation of PR/S-Ir-π-allyl intermediate from the allyl alcohol, the diastereocontrol arises due to the differential stabilizations in the C-C bond formation transition states. The analysis of the weak interactions in the transition states responsible for chiral induction revealed that the geometric disposition of the quinoline ring at the C8 chiral carbon of cinchona-enamine plays an anchoring role. The quinolone ring is noted as participating in a π-stacking interaction with the phenyl ring of the Ir-π-allyl moiety in the case of PR with the (8R,9R)-cinchona catalyst combination, whereas a series of C-H···π interactions is identified as vital to the relative stabilization of the stereocontrolling transition states when PR is used with (8S,9S)-cinchona.

  15. Asymmetric Aldol Reaction Catalyzed by Modularly Designed Organocatalysts

    Institute of Scientific and Technical Information of China (English)

    Sinha, Debarshi; Mandal, Tanmay; Gogoi, Sanjib; Goldman, Joshua J.; 赵从贵


    The self-assembly of the precatalyst modules, which are amino acids and cinchona alkaloid derivatives, leads to the direct formation of the desired organocatalysts without any synthesis. These modularly designed organocatalysts (MDOs) may be used for catalyzed asymmetric aldol reaction the corresponding aldol products may be obtained in mediocre diastereoselectivities (up to 79 : 21 dr). Depending on structure of the aldehyde substrates, to excellent ee values (up to 92% ee) with moderate

  16. Enantioselective formal [3+3] cycloadditions of ketones and cyclic 1-azadienes by cascade enamine-enamine catalysis. (United States)

    He, Xiao-Long; Xiao, You-Cai; Du, Wei; Chen, Ying-Chun


    An asymmetric formal [3+3] cycloaddition process with diversely structured aliphatic ketones and electron-deficient cyclic 1-azadienes was developed by cascade enamine-enamine catalysis of a cinchona-based primary amine. This sequence involved a domino Michael addition-Mannich reaction to afford spirocyclic architectures in excellent diastereo- and enantioselectivity. Importantly, high regioselectivity was realized for a number of unsymmetrical aliphatic ketone substrates.

  17. Diastereodivergent and Enantioselective [4+2] Annulations of γ-Butenolides with Cyclic 1-Azadienes


    Chao Li; Kun Jiang; Ying-Chun Chen


    An asymmetric annulation reaction of γ-butenolides and cyclic 1-azadienes containing a 1,2-benzoisothiazole-1,1-dioxide motif has been studied, proceeding in a tandem Michael addition-aza-Michael addition sequence. Endo-type cycloadducts bearing fused tetracyclic skeletons were isolated in fair yields and with high enantioselectivity (up to >99% ee) under the catalysis of modified cinchona alkaloid (DHQD)2PHAL. Besides, exo-type diastereomers could be produced using β-isocupreidine (β-ICD...

  18. Asymmetric cyclopropanation of chalcones using chiral phase-transfer catalysts



    The first phase-transfer catalyzed cyclopropanation reaction of chalcones using bromomalonates as the nucleophiles in a Michael Initiated Ring Closing reaction (MIRC) was developed. Key to success was the use of a free OH-containing cinchona alkaloid ammonium salt catalyst and carefully optimized liquid/liquid reaction conditions. The reaction performed well for electron neutral and electron deficient chalcones giving the products in yields up to 98% and with enantiomeric ratios up to 91:9.

  19. Primary amine/CSA ion pair: A powerful catalytic system for the asymmetric enamine catalysis

    KAUST Repository

    Liu, Chen


    A novel ion pair catalyst containing a chiral counteranion can be readily derived by simply mixing cinchona alkaloid-derived diamine with chiral camphorsulfonic acid (CSA). A mixture of 9-amino(9-deoxy)epi-quinine 8 and (-)-CSA was found to be the best catalyst with matching chirality, enabling the direct amination of α-branched aldehydes to proceed in quantitative yields and with nearly perfect enantioselectivities. A 0.5 mol % catalyst loading was sufficient to catalyze the reaction, and a gram scale enantioselective synthesis of biologically important α-methyl phenylglycine has been successfully demonstrated. © 2011 American Chemical Society.

  20. An Economical, Highly Efficient and Recyclable Catalyst System for Asymmetric Dihydroxylation of Olefins

    Institute of Scientific and Technical Information of China (English)

    金瑛; 孙晓莉; 姜茹; 张生勇


    A reusable cinchona alkaloid derivative ligand, which could be easily synthesized by two step transformation with cheap 3,6-dichloropyridazine and quinine as materials, was applied to homogeneous asymmetric dihydroxylation of olefins with NMO as co-oxidant in Me2CO-H20 system and the products could be extracted with Et2O from the recyclable catalyst system. 80%---93% yield and 51%-99% ee have been obtained. When trans-stilbene was chosen as the substrate for recycling experiment, 88%-92% yield and >99% ee have been obtained for ten recycles.

  1. Direct asymmetric allylic alkenylation of N-itaconimides with Morita-Baylis-Hillman carbonates

    KAUST Repository

    Yang, Wenguo


    The asymmetric allylic alkenylation of Morita-Baylis-Hillman (MBH) carbonates with N-itaconimides as nucleophiles has been developed using a commercially available Cinchona alkaloid catalyst. A variety of multifunctional chiral α-methylene-β-maleimide esters were attained in moderate to excellent yields (up to 99%) and good to excellent enantioselectivities (up to 91% ee). The origin of the regio- and stereoselectivity was verified by DFT methods. Calculated geometries and relative energies of various transition states strongly support the observed regio- and enantioselectivity. © 2012 American Chemical Society.

  2. Isoindolinones as Michael Donors under Phase Transfer Catalysis: Enantioselective Synthesis of Phthalimidines Containing a Tetrasubstituted Carbon Stereocenter

    Directory of Open Access Journals (Sweden)

    Francesco Scorzelli


    Full Text Available Readily available chiral ammonium salts derived from cinchona alkaloids have proven to be effective phase transfer catalysts in the asymmetric Michael reaction of 3-substituted isoindolinones. This protocol provides a convenient method for the construction of valuable asymmetric 3,3-disubstituted isoindolinones in high yields and  moderate to good enantioselectivity. Diastereoselectivity was also investigated in the construction of contiguous tertiary and quaternary stereocenters. The use of acrolein as Michael acceptor led to an interesting tricyclic derivative, a pyrroloisoindolinone analogue, via a tandem conjugated addition/cyclization reaction.

  3. FT-Raman study of quinine aqueous solutions with varying pH: 2D correlation study (United States)

    Wesełucha-Birczyńska, Aleksandra


    Quinine (C 20H 24N 2O 2) is one of the best known, for its antimalarial activity, Cinchona alkaloid. In the current study 2D correlation method was applied to analyze FT-Raman spectra of quinine aqueous solutions with varying pH, which was regarded as an external perturbation. Protonation appears to be the main cause leading to the emergence of cross peaks in the synchronous and asynchronous correlation maps. One should know that protonation process is an important step associated with quinine antimalarial activity. Methoxy group manifests its presence by creation of the respective correlation peaks and seems to be significant for quinine mode of action.

  4. Organocatalyzed enantioselective synthesis of 6-amino-5-cyanodihydropyrano[2,3-c]pyrazoles (United States)

    Gogoi, Sanjib; Zhao, Cong-Gui


    The first enantioselective synthesis of biologically active 6-amino-5-cyanodihydropyrano[2,3-c]pyrazoles has been achieved through a cinchona alkaloid-catalyzed tandem Michael addition and Thorpe-Ziegler type reaction between 2-pyrazolin-5-ones and benzylidenemalononitriles. The reaction may also be carried out in a three-component or a four-component fashion via the in situ formation of these two components from simple and readily available starting materials. The desired products were obtained in excellent yields with mediocre to excellent enantioselectivities (up to >99% ee). PMID:19915654

  5. Diastereodivergent and Enantioselective [4+2] Annulations of γ-Butenolides with Cyclic 1-Azadienes

    Directory of Open Access Journals (Sweden)

    Chao Li


    Full Text Available An asymmetric annulation reaction of γ-butenolides and cyclic 1-azadienes containing a 1,2-benzoisothiazole-1,1-dioxide motif has been studied, proceeding in a tandem Michael addition-aza-Michael addition sequence. Endo-type cycloadducts bearing fused tetracyclic skeletons were isolated in fair yields and with high enantioselectivity (up to >99% ee under the catalysis of modified cinchona alkaloid (DHQD2PHAL. Besides, exo-type diastereomers could be produced using β-isocupreidine (β-ICD as the catalyst, though with moderate enantioselectivity.

  6. Diastereodivergent and Enantioselective [4+2] Annulations of γ-Butenolides with Cyclic 1-Azadienes. (United States)

    Li, Chao; Jiang, Kun; Chen, Ying-Chun


    An asymmetric annulation reaction of γ-butenolides and cyclic 1-azadienes containing a 1,2-benzoisothiazole-1,1-dioxide motif has been studied, proceeding in a tandem Michael addition-aza-Michael addition sequence. Endo-type cycloadducts bearing fused tetracyclic skeletons were isolated in fair yields and with high enantioselectivity (up to >99% ee) under the catalysis of modified cinchona alkaloid (DHQD)2PHAL. Besides, exo-type diastereomers could be produced using β-isocupreidine (β-ICD) as the catalyst, though with moderate enantioselectivity.

  7. α-Regioselective Asymmetric [3 + 2] Annulations of Morita-Baylis-Hillman Carbonates with Cyclic 1-Azadienes and Mechanism Elucidation. (United States)

    Wang, Kai-Kai; Jin, Tian; Huang, Xin; Ouyang, Qin; Du, Wei; Chen, Ying-Chun


    An α-regio-, diastereo-, and enantioselective [3 + 2] annulation reaction of Morita-Baylis-Hillman carbonates of isatins and activated alkenes with a bulky electron-withdrawing 1,2-benzoisothiazole 1,1-dioxide or 1,2,3-benzoxathiazine 2,2-dioxide motif is reported, furnishing an array of spirooxindoles (>19:1 dr, up to >99% ee) catalyzed by cinchona-derived tertiary amines. Density functional theory calculation studies have been conducted to elucidate the originality of the α-regioselective annulations.

  8. Novel chiral stationary phases based on peptoid combining a quinine/quinidine moiety through a C9-position carbamate group. (United States)

    Wu, Haibo; Wang, Dongqiang; Song, Guangjun; Ke, Yanxiong; Liang, Xinmiao


    By connecting a quinine or quinidine moiety to the peptoid chain through the C9-position carbamate group, we synthesized two new chiral selectors. After immobilizing them onto 3-mercaptopropyl-modified silica gel, two novel chiral stationary phases were prepared. With neutral, acid, and basic chiral compounds as analytes, we evaluated these two stationary phases and compared their chromatographic performance with chiral columns based on quinine tert-butyl carbamate and the previous peptoid. From the resolution of neutral and basic analytes under normal-phase mode, it was found that the new stationary phases exhibited much better enantioselectivity than the quinine tert-butyl carbamate column; the peptoid moiety played an important role in enantiorecognition, which controlled the elution orders of enantiomers; the assisting role of the cinchona alkaloid moieties was observed in some separations. Under acid polar organic phase mode, it was proved that cinchona alkaloid moieties introduced excellent enantiorecognitions for chiral acid compounds; in some separations, the peptoid moiety affected enantioseparations as well. Overall, chiral moieties with specific enantioselectivity were demonstrated to improve the performance of peptoid chiral stationary phase efficiently.

  9. Novel carbamoyl type quinine and quinidine based chiral anion exchangers implementing alkyne-azide cycloaddition immobilization chemistry. (United States)

    Hettegger, Hubert; Kohout, Michal; Mimini, Vebi; Lindner, Wolfgang


    The synthesis and chromatographic evaluation of a series of new Cinchona derived chiral weak anion exchangers is presented. Huisgen Cu(I) mediated alkyne-azide cycloaddition, so-called click chemistry, was used as an immobilization strategy. In this way it was possible to immobilize about 90% of offered selector via 1,2,3-triazole linker, which displays a more efficient way of binding the selector to modified silica compared to common radical mediated thiol-ene addition. Problems associated with potential radical scavenging properties of chiral selectors thereby could be circumvented. The evaluation of the synthesized chiral stationary phases regarding chromatographic behavior was carried out using polar organic mode mobile phase composition and a set of representative chiral organic acids. Different loading densities revealed an optimum selector density of about 310μmol/g chiral stationary phase with respect to resolution and selectivity. A decrease of performance was observed for higher loading, indicating mutual spatial influence of selector units leading to sterical hindrance. In addition, we observed that the effect of free azide groups on retention is negligible and the overall chromatographic behavior is comparable to other Cinchona derived chiral stationary phases.

  10. Antimalarial Drugs as Immune Modulators: New Mechanisms for Old Drugs. (United States)

    An, Jie; Minie, Mark; Sasaki, Tomikazu; Woodward, Joshua J; Elkon, Keith B


    The best known of the naturally occurring antimalarial compounds are quinine, extracted from cinchona bark, and artemisinin (qinghao), extracted from Artemisia annua in China. These and other derivatives are now chemically synthesized and remain the mainstay of therapy to treat malaria. The beneficial effects of several of the antimalarial drugs (AMDs) on clinical features of autoimmune disorders were discovered by chance during World War II. In this review, we discuss the chemistry of AMDs and their mechanisms of action, emphasizing how they may impact multiple pathways of innate immunity. These pathways include Toll-like receptors and the recently described cGAS-STING pathway. Finally, we discuss the current and future impact of AMDs on systemic lupus erythematosus, rheumatoid arthritis, and devastating monogenic disorders (interferonopathies) characterized by expression of type I interferon in the brain.

  11. Supramolecular tilt chirality in crystals of steroids and alkaloids. (United States)

    Hisaki, Ichiro; Tohnai, Norimitsu; Miyata, Mikiji


    The concept of supramolecular chirality has assumed increasing importance in association with the development of supramolecular chemistry over the last two decades. In chiral crystals, 2 1 helical molecular assemblies are frequently observed as key motifs. Helical handedness of the 2 1 assemblies, however, has not been determined from the mathematical or crystallographical viewpoints. In this context, we have proposed two new concepts, three-axial chirality and tilt chirality. On the basis of the concepts, we describe supramolecular chirality and determine the handedness of 2 1 assemblies that are composed of relatively complicated molecules with multiple stereogenic centers such as brucine, bile acids, and cinchona alkaloids as well as those of simple molecules.

  12. Molecular-level Design of Heterogeneous Chiral Catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Gellman, Andrew John [Carnegie Mellon University; Sholl, David S. [Georgia Institute of Technology; Tysoe, Wilfred T. [University of Wisconsin - Milwaukee; Zaera, Francisco [University of California at Riverside


    ) modified by a variety of chiral templates. • Demonstrated enantioselective separation of racemic PO on chemically synthesized chiral gold nanoparticles. • Discovery of zwitterionic adsorption states of amino acids on Pd(111). • First structure determinations of adsorbed amino acids and identification of tetrameric chiral template structures. • Exploration of the enantiospecific interaction of PO and R-3-MCHO adsorption on chirally modified Cu(100), Cu(110) and Cu(111). One-to-One Interactions • Determination of cinchona orientation on Pt surfaces in situ at the solid-liquid interface using FT-IRAS. • Systematic study of the influence of solution properties on the adsorption of modified cinchonas alkaloids onto Pt surfaces. • Correlation of cinchona adsorption with catalytic activity, as affected by concentration, the nature of the solvent, and dissolved gases in the liquid phase. • Measurement of enantioselective chemisorption on 1-(1-naphthyl) ethylamine (NEA) modified Pt(111) and Pd(111) surfaces. • Imaging of chiral docking complexes between NEA and methyl pyruvate on Pd(111). Chiral Catalyst Synthesis • Anchoring of cinchona alkaloid to surfaces • Synthesis of chiral Au nanoparticles and demonstration of their enantiospecific interactions with R- and S-PO. • Elucidation of the driving forces for chiral imprinting of Cu(100) by L- and D-lysine to form Cu(3,1,17)R&S facets.

  13. Direct Separation of Pregabalin Enantiomers Using a Zwitterionic Chiral Selector by High Performance Liquid Chromatography Coupled to Mass Spectrometry and Ultraviolet Detection

    Directory of Open Access Journals (Sweden)

    Lakshmi Narayana Chennuru


    Full Text Available The chromatographic resolution of pregabalin enantiomers has been often achieved by derivatization of the molecule, in order to reach enough sensitivity at low concentrations of the minor enantiomer present in the active principle. In the present article, the development and optimization of two liquid chromatographic methods are presented for the direct resolution of pregabalin enantiomers on a chiral stationary phase (CSP containing a zwitterionic selector derived from cinchona alkaloid and sulfonic acid (CHIRALPAK ZWIX. The key parameters for the separation as well as the compatibility of chromatographic conditions with different detection modes (ultraviolet and mass spectrometry were investigated. The resulting methods were found to be selective, of high performance and low limits of detection (2 µg/mL by UV and 1 ng/mL by MS, respectively and quantification (6 µg/mL by UV and 5 ng/mL by MS, respectively for the minor enantiomer which is considered as a chiral impurity.

  14. Tropical American plants in the treatment of infectious diseases. (United States)

    Dvorkin-Camiel, Lana; Whelan, Julia S


    The increasingly diverse U.S. immigrant populations and the growing use of medicinal herbs create a need for health care professionals to expand their knowledge in this area. This is a review of tropical plants, Annona Muricata, Artemisia absinthium, Cinchona officinalis, Illicium verum, Momordica charantia, Opuntia streptacantha, Schinus terebinthifolius, and Tabebuia avellanedae (impetiginosa), commonly used by Latino and Haitian populations for the treatment of infectious disease. All the eight plants discussed here have one or more of the following: antibacterial, antiviral, antifungal, or antiparasitic properties. All of these plants are primarily known and used in the tropical region, but they are also readily available for purchase in the United States, specifically in the ethnic markets. This review discusses their traditional uses, chemical constituents, proven scientific evidence, and toxicities.

  15. Simultaneous analysis of D-alanine, D-aspartic acid, and D-serine using chiral high-performance liquid chromatography-tandem mass spectrometry and its application to the rat plasma and tissues. (United States)

    Karakawa, Sachise; Shimbo, Kazutaka; Yamada, Naoyuki; Mizukoshi, Toshimi; Miyano, Hiroshi; Mita, Masashi; Lindner, Wolfgang; Hamase, Kenji


    A highly sensitive and selective chiral LC-MS/MS method for D-alanine, D-aspartic acid and D-serine has been developed using the precolumn derivatization reagents, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AccQ-Tag) or p-N,N,N-trimethylammonioanilyl N'-hydroxysuccinimidyl carbamate iodide (TAHS). The thus N-tagged enantiomers of the derivatized amino acids were nicely separated within 20min using the cinchona alkaloid-based zwittterionic ion-exchange type enantioselective column, Chiralpak ZWIX(+). The selected reaction monitoring was applied for detecting the target d-amino acids in biological matrices. By using the present chiral LC-MS/MS method, the three d-amino acids and their l-forms could be simultaneously determined in the range of 0.1-500nmol/mL. Finally, the technique was successfully applied to rat plasma and tissue samples.

  16. Asymmetric Desymmetrization via Metal-Free C-F Bond Activation: Synthesis of 3,5-Diaryl-5-fluoromethyloxazolidin-2-ones with Quaternary Carbon Centers. (United States)

    Tanaka, Junki; Suzuki, Satoru; Tokunaga, Etsuko; Haufe, Günter; Shibata, Norio


    We disclose the first asymmetric activation of a non-activated aliphatic C-F bond in which a conceptually new desymmetrization of 1,3-difluorides by silicon-induced selective C-F bond scission is a key step. The combination of a cinchona alkaloid based chiral ammonium bifluoride catalyst and N,O-bis(trimethylsilyl)acetoamide (BSA) as the silicon reagent enabled the efficient catalytic cycle of asymmetric Csp3 -F bond cleavage under mild conditions with high enantioselectivities. The ortho effect of the aryl group at the prostereogenic center is remarkable. This concept was applied for the asymmetric synthesis of promising agrochemical compounds, 3,5-diaryl-5-fluoromethyloxazolidin-2-ones bearing a quaternary carbon center.

  17. Solving a 3D structural puzzle

    DEFF Research Database (Denmark)

    Hoeck, Casper

    to spatial structural information using NMR spectroscopy. Experimental distances from nuclear Overhauser effect (NOE) correlations, and dihedral angles from 3JHH-coupling constants, were used to obtain 3D structural information for several natural and synthetic compounds. The stereochemistry of novel natural...... samples, which allows for RDCs to be extracted. The number of internuclear vectors for the correlation of RDCs to 3D structures is often limited for small molecules. Homonuclear RDCs were extracted by use of the homonuclear S3 HMBC that correlated well to alignment tensors from 1DCH-coupling constants......-calculation of RDCs from 3D structures was developed and tested, which copes better with multiple conformers than the commonly used SVD methodology. The approach thus resulted in good conformer populations for several small molecules, including multiple cinchona alkaloids....

  18. Unexpectedly high beta-diversity of root-associated fungal communities in the Bolivian Andes

    DEFF Research Database (Denmark)

    Barnes, Christopher James; Maldonado Goyzueta, Carla Brenda; Frøslev, Tobias Guldberg;


    variation respectively. Surprisingly, altitude does not influence community formation, and there is limited evidence that climate (precipitation and temperature) play a role. Our results suggest that sampling should be performed over a wide geographical and environmental range in order to capture the full......Bolivia is one of the most biologically diverse countries on the planet. Between the Andes and the Amazon drainage basin spans the Yungas, a vast forested region shown to be extremely species rich in macro-organisms. However, it remains unclear whether this high diversity is also reflected...... in microbial diversity. Here we assess the genetic, taxonomic and functional diversity of root-associated fungi surrounding Cinchona calisaya calisaya trees, a typical element of the intermediate altitudes of the Bolivian Yungas. We determine the relative effects of edaphic properties, climate, and geography...

  19. Unexpectedly high beta-diversity of root-associated fungal communities in the Bolivian Andes

    DEFF Research Database (Denmark)

    Barnes, Christopher James; Maldonado Goyzueta, Carla Brenda; Frøslev, Tobias Guldberg


    in microbial diversity. Here we assess the genetic, taxonomic and functional diversity of root-associated fungi surrounding Cinchona calisaya calisaya trees, a typical element of the intermediate altitudes of the Bolivian Yungas. We determine the relative effects of edaphic properties, climate, and geography...... in regulating fungal community assembly. We show that α-diversity for these fungal communities was similar to temperate and arid ecosystems, averaging 90.1 operational taxonomic units (OTUs) per sample, with reads predominantly assigned to the Ascomycota phylum and with a saprotrophic lifestyle. ß......-diversity was calculated as the distance-decay rate, and in contrast to α-diversity, was exceptionally high with a rate of -0.407. Soil properties (pH and P) principally regulated fungal community assembly in an analogous manner to temperate environments, with pH and phosphorus explaining 7.8 % and 7.2 % of community...

  20. Enantioselective Organocatalyzed Synthesis of 2-Amino-3-cyano-4H-chromene Derivatives

    Directory of Open Access Journals (Sweden)

    Isaac G. Sonsona


    Full Text Available The structural motif that results from the fusion of a benzene ring to a heterocyclic pyran ring, known as chromene, is broadly found in nature and it has been reported to be associated with a wide range of biological activity. Moreover, asymmetric organocatalysis is a discipline in expansion that is already recognized as a well-established tool for obtaining enantiomerically enriched compounds. This review covers the particular case of the asymmetric synthesis of 2-amino-3-cyano-4H-chromenes using organocatalysis. Herein, we show the most illustrative examples of the methods developed by diverse research groups, following a classification based on these five different approaches: (1 addition of naphthol compounds to substituted α,α-dicyanoolefins; (2 addition of malononitrile to substituted o-vinylphenols; (3 addition of malononitrile to N-protected o-iminophenols; (4 Michael addition of nucleophiles to 2-iminochromene derivatives; and (5 organocatalyzed formal [4+2] cycloaddition reaction. In most cases, chiral thioureas have been found to be effective catalysts to promote the synthetic processes, and generally a bifunctional mode of action has been envisioned for them. In addition, squaramides and cinchona derivatives have been occasionally used as suitable catalysts for the substrates activation.

  1. Organocatalytic aza-Michael/retro-aza-Michael reaction: pronounced chirality amplification in aza-Michael reaction and racemization via retro-aza-Michael reaction. (United States)

    Cai, Yong-Feng; Li, Li; Luo, Meng-Xian; Yang, Ke-Fang; Lai, Guo-Qiao; Jiang, Jian-Xiong; Xu, Li-Wen


    A detailed experimental investigation of an aza-Michael reaction of aniline and chalcone is presented. A series of Cinchona alkaloid-derived organocatalysts with different functional groups were prepared and used in the aza-Michael and retro-aza-Michael reaction. There was an interesting finding that a complete reversal of stereoselectivity when a benzoyl group was introduced to the cinchonine and cinchonidine. The chirality amplification vs. time proceeds in the quinine-derived organocatalyst containing silicon-based bulky group, QN-TBS, -catalyzed aza-Michael reaction under solvent-free conditions. In addition, we have demonstrated for the first time that racemization was occurred in suitable solvents under mild conditions due to retro-aza-Michael reaction of the Michael adduct of aniline with chalcone. These indicate the equilibrium of retro-aza-Michael reaction and aza-Michael reaction produce the happening of chirality amplification in aza-Michael reaction and racemization via retro-aza-Michael reaction under different conditions, which would be beneficial to the development of novel chiral catalysts for the aza-Michael reactions.

  2. Synthesis of triazol derivatives of lupeol with potential antimalarial activity

    Directory of Open Access Journals (Sweden)

    Tatiane Freitas Borgati


    Full Text Available The goal of this project is synthesize and characterization of derivatives of lupeol and evaluated antimalarial activity. Historically, plants are important source of antimalarial medicines, highlighting quinine (1 (Figure 1, an important      alkaloid from the Cinchona calisaya bark. This compound was an important model for cloroquine  synthesis, a drug that was widely used in malaria treatment. In addition, one of the principal medicines used today is artemisinine, isolated from the Chinese plant Artemisia annua L (2 (Figure 1, and their semi synthetic derivatives (artesunate, artemeter, arteter. However, the malaria parasite has already shown resistance    to most of these current drugs and  the search for new candidates is essential. Lupeol (3 (Figura 1 is a compound that occurs in many plant species and discloses antimalarial, antiinflamatoryl and antitumoral activities. Considering its potential as a lead antimalarial molecule, we focused our work in the synthesis of new lupeol derivatives with increased antimalarial activity(scheme 1.

  3. The Spread of Non-native Plant Species Collection of Cibodas Botanical Garden into Mt. Gede Pangrango National Park

    Directory of Open Access Journals (Sweden)

    Musyarofah Zuhri


    Full Text Available The role of botanic garden in spread of non-native plant species has concerned of international worldwide. This study aimed to study the extent of non-native plant species from Cibodas Botanical Garden (CBG which invades into natural rainforest. A line transect was made edge-to-interior with 1,600 m in distance from CBG boundary. Result showed that distance from CBG was not significant in correlation with non-native tree and treelet density. Furthermore, presence of existing CBG’s plant collection was not a single aspect which influenced presence and abundance. Three invasive species possibly was escape from CBG and it showed edge-to-interior in stems density, i.e. Cinchona pubescens, Calliandra calothyrsus and Cestrum aurantiacum. The patterns of non-native species were influenced by presence of ditch across transect, existence of human trail, and the other non-native species did not have general pattern of spread distribution. Overall, botanical gardens should minimize the risk of unintentional introduced plant by perform site-specific risk assessment.

  4. Study on the Asymmetric Aminohydroxylation of Olefins Catalyzed by a Free Recoverable and Reusable Ligand%可回收手性配体催化烯烃不对称氨羟化反应研究

    Institute of Scientific and Technical Information of China (English)

    南鹏娟; 陈晶; 孙晓莉


    A reusable free cinchona alkaloid derivative ligand was applied to asymmetric aminohydroxylation (AA) of 5 five methyl cinnamates with 91%-96% e.e. and 52%-72% yields. In the AA reaction of methyl cinnamates,this ligand can be easily recovered and reused without any significant loss in its catalytic efficiency by two defferent methods. this ligand was applied to the catalytic asymmetric aminohydroxylation to produce enantioselective α-aminoacid esters.%一种可重复使用的非支载型金鸡纳生物碱衍生物配体与金属锇形成原位催化剂用于催化5种肉桂酸甲酯类烯烃的不对称氨羟化(AA)反应,表现了好的对映选择性(91%~96%)和反应活性(52%~72%).在以对甲基肉桂酸甲酯为底物的AA反应中,采用了两种不同的回收方法,均能有效地进行配体的回收和再利用,配体的催化活性和对映选择性基本保持不变.该手性配体用于催化AA反应,可以制备光学活性的α-氨基酸酯类化合物.

  5. Separation of drug stereoisomers by the formation of. beta. -cyclodextrin inclusion complexes

    Energy Technology Data Exchange (ETDEWEB)

    Armstrong, D.W.; Ward, T.J.; Armstrong, R.D.; Beesley, T.E.


    For many drugs, only racemic mixtures are available for clinical use. Because different stereoisomers of drugs often cause different physiological responses, the use of pure isomers could elicit more exact therapeutic effects. Differential complexation of a variety of drug stereoisomers by immobilized ..beta..-cyclodextrin was investigated. Chiral recognition and racemic resolution were observed with a number of compounds from such clinically useful classes as ..beta..-blockers, calcium-channel blockers, sedative hypnotics, antihistamines, anticonvulsants, diuretics, and synthetic opiates. Separation of the diastereomers of the cardioactive and antimalarial cinchona alkaloids and of two antiestrogens was demonstrated as well. Three dimensional projections of ..beta..-cyclodextrin complexes of propanol, which is resolved by this technique, and warfarin, which is not, are compared. These studies have improved the understanding and application of the chiral interactions of ..beta..-cyclodextrin, and they have demonstrated a means to measure optical purity and to isolate or produce pure enantiomers of drugs. In addition, this highly specific technique could also be used in the pharmacological evaluation of enantiometric drugs. 27 references, 3 figures, 2 tables.

  6. Some Topics in Relation to José Celestino Mutis and Medicine

    Directory of Open Access Journals (Sweden)

    Leonardo Palacios Sánchez


    Full Text Available José Celestino Mutis showed different interestareas of study and worked in multipleknowledge fields: mathematics, mineralogy, astronomy,zoology and botanic, the one in whichis best known. However, he was a medical doctor,whit profound an up to date knowledge. Hestudied at Sevilla University, and in the RoyalCollege of Cadiz. He arrived to the “NuevoReino de Granada” as personal medical doctorof the the viceroy Pedro Messía de la Cerda andduring 47 years, period of time he lived there,he always exercised his profession. We showeda special interest in the study of cinchona andthe only work he published was El Arcano dela quina. He advised in public health manyviceroys and he contributed in different fieldsbut particularly in the prevention of smallpoxby inoculation. He played a decisive role in thereopening of the medical school of the ColegioMayor de Nuestra Señora del Rosario. Someof his achievements justifies the appellative“Father of the Medicine in Colombia”.

  7. Asymmetric hydrogenation on chirally modified Pt: origin of hydrogen in the N-H-O interaction between cinchonidine and ketone. (United States)

    Maeda, Nobutaka; Hungerbühler, Konrad; Baiker, Alfons


    An understanding of the chiral site-substrate interaction is a necessary prerequisite for the rational design and development of efficient heterogeneous asymmetric catalysts. For the enantioselective hydrogenation of α-ketoesters on cinchona-modified platinum, it has earlier been proposed that the crucial interaction is an N-H-O type hydrogen bonding between the quinuclidine N atom of cinchonidine and the α-carbonyl O atom of the substrate. The involved hydrogen atom has been proposed to originate either from protonation (in protic solvent) or from dissociatively adsorbed hydrogen (in aprotic solvent), but experimental evidence for the latter was lacking so far. In this study, in situ attenuated total reflection infrared spectroscopy combined with modulation excitation spectroscopy and phase sensitive detection provides clear evidence that in aprotic media, hydrogen dissociated on Pt is involved in the N-H-O interaction between the chiral modifier, cinchonidine, and the ketone. In the absence of Pt (pure alumina support), no such interaction occurs, indicating the crucial role of dissociated hydrogen in the formation of the diastereomeric transition complex.

  8. Alkoxide coordination of iron(III) protoporphyrin IX by antimalarial quinoline methanols: a key interaction observed in the solid-state and solution. (United States)

    Gildenhuys, Johandie; Sammy, Chandre J; Müller, Ronel; Streltsov, Victor A; le Roex, Tanya; Kuter, David; de Villiers, Katherine A


    The quinoline methanol antimalarial drug mefloquine is a structural analogue of the Cinchona alkaloids, quinine and quinidine. We have elucidated the single crystal X-ray diffraction structure of the complexes formed between racemic erythro mefloquine and ferriprotoporphyrin IX (Fe(iii)PPIX) and show that alkoxide coordination is a key interaction in the solid-state. Mass spectrometry confirms the existence of coordination complexes of quinine, quinidine and mefloquine to Fe(iii)PPIX in acetonitrile. The length of the iron(iii)-O bond in the quinine and quinidine complexes as determined by Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy unequivocally confirms that coordination of the quinoline methanol compounds to Fe(iii)PPIX occurs in non-aqueous aprotic solution via their benzylic alkoxide functional group. UV-visible spectrophotometric titrations of the low-spin bis-pyridyl-Fe(iii)PPIX complex with each of the quinoline methanol compounds results in the displacement of a single pyridine molecule and subsequent formation of a six-coordinate pyridine-Fe(iii)PPIX-drug complex. We propose that formation of the drug-Fe(iii)PPIX coordination complexes is favoured in a non-aqueous environment, such as that found in lipid bodies or membranes in the malaria parasite, and that their existence may contribute to the mechanism of haemozoin inhibition or other toxicity effects that lead ultimately to parasite death. In either case, coordination is a key interaction to be considered in the design of novel antimalarial drug candidates.

  9. Analysis on the Application and Development of Antimalarials Drugs%抗疟药物的应用与发展

    Institute of Scientific and Technical Information of China (English)



    人类在抗疟药物的应用过程中,先后经历了蚊帐、纱窗、巫术、中草药等传统办法,由金鸡纳树皮的疗效促使了奎宁、氯喹的产生,以及DDT杀虫剂和青蒿素类药物的使用,上述治疗手段和方法都对控制疟疾的传播扩散发挥了重要作用。本文通过回顾这些抗疟药物应用历程的同时,以期展望该领域的发展前景和未来趋势。%In the history, human used several ways, such as mosquito nets, screens, witchcraft, Chinese herbal medicine and other traditional ways, and due to the curative effect of cinchona bark, human find quinine and chloroquine, later, the pesticide DDT and arte-misinin drugs also can be found.All of them played an important role to control the spread of malaria.This paper is overviewed how many treatments and methods which by human used and found, and its development is also prospected.

  10. New insight into the stereoselective interactions of quinine and quinidine, with bovine serum albumin. (United States)

    Liu, Yan; Chen, Mingmao; Wang, Shuaihua; Lin, Jingjing; Cai, Lizhen; Song, Ling


    Quinine (QN) and quinidine (QD), the chief quinoline alkaloids of various species of cinchona bark, are stereoisomers to each other. In this study, a series of appropriate and efficient methods have been applied to compare the binding modes of QN and QD with bovine serum albumin (BSA). The isothermal titration calorimetry and room temperature phosphorescence results show that both QN and QD can interact with BSA at one binding site to form drug-protein complexes, mainly through enthalpic driving force with the binding affinity order: QN > QD. The fluorescence resonance energy transfer and time-resolved fluorescence spectroscopy exhibits that QN has a larger energy transfer and more intensified binding capacity for BSA than QD. Data of dynamic light scattering reveal that the aggregate state of BSA is changed during this binding process, and the particle size distribution of QN-BSA bioconjugate is larger than that of QD. Nuclear magnetic resonance analysis indicates that aromatic protons make more contribution during ligand-protein complexation than that of aliphatic protons. The circular dichroism spectra exhibit different degrees of changes in BSA secondary structures in the presence of QN and QD, respectively.

  11. Electrochemical studies of quinine in surfactant media using hanging mercury drop electrode: a cyclic voltammetric study. (United States)

    Dar, Riyaz Ahmad; Brahman, Pradeep Kumar; Tiwari, Sweety; Pitre, Krishna Sadashiv


    The electrochemical behavior of quinine was investigated by cyclic voltammetry (CV) and square wave voltammetry (SWV) using surfactant. The reduction peak current of quinine increases remarkably in presence of 1% CTAB. Its electrochemical behavior is quasi-reversible in the Britton-Robinson buffers of pH 10.38 by exhibiting the well-defined single cathodic and anodic waves and the ratio of I(p)(a)/I(p)(c) approaching one at the scan rate of 500 mVs(-1). On the basis of CV, SWV and Coulometry, electrochemical reduction mechanism of quinine has been proposed which has shown that protonation occurs on the nitrogen of the quinoline moiety. Linearity was obtained when the peak currents (I(p)) were plotted against concentrations of quinine in the range of 30.0-230.0 ng mL(-1) with a detection limit of 0.132 ng mL(-1) in SWV and 90.0-630.0 ng mL(-1) with a detection limit of 0.238 ng mL(-1) in DPV. Fast and sensitive SWV has been applied for the quantitative analysis of quinine in bark of Cinchona sp. and in soft drinks and a good recovery was obtained. The accuracy and precision of the method are determined and validated statistically. No interferences from other food additives were observed. The relative standard deviation for intraday and interday assay was 0.89 and 0.73% (n=3) respectively.

  12. Mechanistic insights on organocatalytic enantioselective decarboxylative protonation by epicinchona-thiourea hybrid derivatives. (United States)

    Sengupta, Arkajyoti; Sunoj, Raghavan B


    Mechanism and the origin of enantioselectivity in the decarboxylative protonation of α-amino malonate hemiester promoted by epicinchona-thiourea hybrid organocatalyst is established by using the DFT(M06-2X/6-311+G**//ONIOM2) computational methods. The origin of stereoselectivity rendered by this hybrid bifunctional catalyst in asymmetric protonation is investigated for the first time using suitable transition-state models. A detailed conformational analysis of N-[3,5-bis(trifluoromethyl)]phenylthiourea-based epicinchonidine reveals the potential for a bifunctional mode of activation of the substrate α-amino malonate hemiester through hydrogen bonding. Six different conformer families differing in characteristic dihedral angles are identified within a range of 16 kcal/mol with respect to the lowest energy conformer. Different likely mechanistic pathways obtained through detailed analysis of the transition states and intermediates are compared. It is identified that in the preferred pathway, the decarboxylation is followed by a direct proton transfer from the chiral quinuclidinium moiety to the enolate carbon as opposed to a conventional protonation at the enolate oxygen followed by a keto-enol tautomerization. The factors responsible for high levels of observed stereoselectivity are traced to interesting hydrogen-bonding interactions offered by the thiourea-cinchona bifunctional framework. The predicted stereoselectivities using computed Gibbs free energies of diastereomeric transition states are in fair agreement with the experimental stereoselectivities.

  13. The Stereoselective Epoxidation by a New Type of Soluble Polymer-Supported Catalysts

    Institute of Scientific and Technical Information of China (English)

    Wang Yongmei; Wang Xin; Liu Juyan


    As the phase transfer catalyst (PTC) is one of most important catalysts in organic synthesis. Here, we represent initial results of a research program aimed at the rational design of a variety of new two centers, soluble polyethylene glycol (PEG) supported catalysts based on the cinchona alkaloid system and their application in asymmetric expoxidation process.Table 1 and Table 2 summarized the results of epoxidation of substituted chalcone As shown in Table 1 and Table 2, chalcone derivatives as reactive olefins afforded the corresponding epoxided with modest to good enantiomeric excesses. In contrast, a definite trend to higher ee value is displayed by solvent effect. It was found that enantioselectivity becomes higher with the polarity increases(Table 1, Table 2). Changing catalyst 1 to catalyst 2, ee value was increased (entry 6 in Table 1) as well. Compared with Me, NO2 groups, substitution on the aromatic ring of the enone carbonyl function by OMe group increased the enantioselectivity(entry 3 in Table 1 and entry 3' in Table 2).

  14. Penerapan Logika Fuzzy pada Penilaian Mutu Teh Hitam Orthodox

    Directory of Open Access Journals (Sweden)

    Roni Kastaman


    Full Text Available In testing quality process of the orthodox black tea by using tea organoleptic expert, there is often found a problem of tester sensoric restriction. Based on this conditon the research has been carried out by using fuzzy modelling technique, which aimed to explore ruther more about how fuzzy method can concordance with fuzzy range value on black olthodox tea assesment. So that, it could be more objective on quality evalualion. The research has beld on May to June 2005 in tea plantation facility of PTPN Vlll Malabar. Pangalengan, and Tea and Cinchona Research Center (Pusat Penelitian Ten dan Kina -PPTK Gembung, Cieidey, West Java. This fuzzy method can keep a record experience of the orthodox black tea tester and also correct the result of the determination done by the tester, Based on the parametrik LSD test and non-parametrik Mann-Whitney, there is no significant value diference In the result of the determination done by the tester and by using the fuzzy logic. So that the fuzzy logic method can be used as a method in orthodox black tea quality determination. But The method can not be used if there is a far diference in the tea determination between one tester to the others. Tbe best defuzzification method for tea quality detemination in this occasion is Smallest of Maximum (SOM method.

  15. 用不对称二羟基化反应合成(S)-美托洛尔%Synthesis of (S)-metoprolol by Asymmetric Dihydroxylation

    Institute of Scientific and Technical Information of China (English)

    向顺; 匡永清; 邓宝玲; 谢斌; 杨昊宇; 姜茹


    Allyl 4- (2-methoxyethyl) phenyl ether ( 2 ) was prepared from 4 - ( 2 -methoxyethyl) phenol and allyl bromide in the presence of K2 CO3. (S) -3- [ 4 - ( 2 -methoxyethyl) phenoxy ] -1,2 -propanediol (3, 86% ee) was obtained by asymmetric dihydroxylation of 2 with the readily accessible bis-cinchona alkaloid derivative 1,4-bis(9-O-quinidine) phthalazine as the chiral ligand. 3 converted into (S)-[4-(2 -methoxyethyl) phenoxy ] methyloxiriane (4) by one-pot method. ( S ) -metoprolol in overall yield of 46% (from 2) was synthesized by nucleophilic ring-opening reaction of 4 with isopropylamine. The structures were characterized by 1H NMR.%在K2CO3存在下,4-(2-甲氧乙基)苯酚与烯丙基溴反应制得烯丙基[4-(2-甲氧乙基)苯基]醚(2);以廉价易得的双金鸡纳碱衍生物1,4-双(9-O-奎尼定)-2,3-二氮杂萘为手性配体催化2的不对称二羟基化反应制得(S)-3-[4-(2-甲氧乙基)苯氧基]-1,2-丙二醇(3,86%ee); 3经"一锅法"转化为(S)-3-[4-(2-甲氧乙基)苯氧基]-1,2-环氧丙烷(4); 4与异丙胺发生亲核开环反应合成了选择性β1-受体阻滞剂--(S)-美托洛尔,总产率46%(以2计算),其结构经1H NMR表征.

  16. Whole plant extracts versus single compounds for the treatment of malaria: synergy and positive interactions

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    Wright Colin W


    Full Text Available Abstract Background In traditional medicine whole plants or mixtures of plants are used rather than isolated compounds. There is evidence that crude plant extracts often have greater in vitro or/and in vivo antiplasmodial activity than isolated constituents at an equivalent dose. The aim of this paper is to review positive interactions between components of whole plant extracts, which may explain this. Methods Narrative review. Results There is evidence for several different types of positive interactions between different components of medicinal plants used in the treatment of malaria. Pharmacodynamic synergy has been demonstrated between the Cinchona alkaloids and between various plant extracts traditionally combined. Pharmacokinetic interactions occur, for example between constituents of Artemisia annua tea so that its artemisinin is more rapidly absorbed than the pure drug. Some plant extracts may have an immunomodulatory effect as well as a direct antiplasmodial effect. Several extracts contain multidrug resistance inhibitors, although none of these has been tested clinically in malaria. Some plant constituents are added mainly to attenuate the side-effects of others, for example ginger to prevent nausea. Conclusions More clinical research is needed on all types of interaction between plant constituents. This could include clinical trials of combinations of pure compounds (such as artemisinin + curcumin + piperine and of combinations of herbal remedies (such as Artemisia annua leaves + Curcuma longa root + Piper nigum seeds. The former may enhance the activity of existing pharmaceutical preparations, and the latter may improve the effectiveness of existing herbal remedies for use in remote areas where modern drugs are unavailable.

  17. Transits of Venus and Colonial India (United States)

    Kochhar, Rajesh


    Astronomical expeditions during the colonial period had a political and national significance also. Measuring the earth and mapping the sky were activities worthy of powerful and power- seeking nations. Such was the sanctity of global astronomical activity that many other agendas could be hidden under it. An early astronomy-related expedition turned out to be extremely beneficial, to botany. The expedition sent by the French Government in 1735 to South America under the leadership of Charles Marie de la Condamine (1701--1774) ostensibly for the measurement of an arc of the meridian at Quito in Ecuador surreptitiously collected data that enabled Linnaeus to describe the genus cinchona in 1742. When the pair of transits of Venus occurred in 1761 and 1769, France and England were engaged in a bitter rivalry for control of India. The observation of the transits became a part of the rivalry. A telescope presented by the British to a South Indian King as a decorative toy was borrowed back for actual use. Scientifically the transit observations were a wash out, but the exercise introduced Europe to details of living Indian tradition of eclipse calculations. More significantly, it led to the institutionalization of modern astronomy in India under the auspices of the English East India Company (1787). The transits of Venus of 1874 and 1882 were important not so much for the study of the events as for initiating systematic photography of the Sun. By this, Britain owned most of the world's sunshine, and was expected to help European solar physicists get data from its vast Empire on a regular basis. This and the then genuinely held belief that a study of the sun would help predict failure of monsoons led to the institutionalization of solar physics studies in India (1899). Of course, when the solar physicists learnt that solar activity did not quite determine rainfall in India, they forgot to inform the Government.

  18. Unexpectedly High Beta-Diversity of Root-Associated Fungal Communities in the Bolivian Andes (United States)

    Barnes, Christopher J.; Maldonado, Carla; Frøslev, Tobias G.; Antonelli, Alexandre; Rønsted, Nina


    Bolivia is one of the most biologically diverse countries on the planet. Between the Andes and the Amazon drainage basin spans the Yungas, a vast forested region shown to be extremely species rich in macro-organisms. However, it remains unclear whether this high diversity is also reflected in microbial diversity. Here we assess the genetic, taxonomic and functional diversity of root-associated fungi surrounding Cinchona calisaya trees, a typical element of the intermediate altitudes of the Bolivian Yungas. We determine the relative effects of edaphic properties, climate, and geography in regulating fungal community assembly. We show that α-diversity for these fungal communities was similar to temperate and arid ecosystems, averaging 90.1 operational taxonomic units (OTUs) per sample, with reads predominantly assigned to the Ascomycota phylum and with a saprotrophic lifestyle. ß-diversity was calculated as the distance-decay rate, and in contrast to α-diversity, was exceptionally high with a rate of −0.407. Soil properties (pH and P) principally regulated fungal community assembly in an analogous manner to temperate environments, with pH and phosphorus explaining 7.8 and 7.2% of community variation respectively. Surprisingly, altitude does not influence community formation, and there is limited evidence that climate (precipitation and temperature) play a role. Our results suggest that sampling should be performed over a wide geographical and environmental range in order to capture the full root-associated fungal diversity in subtropical regions. This study sheds further light on the diversity and distribution of the world's “hidden biodiversity.” PMID:27630629

  19. Organocatalysis: Fundamentals and Comparisons to Metal and Enzyme Catalysis

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    Pierre Vogel


    Full Text Available Catalysis fulfills the promise that high-yielding chemical transformations will require little energy and produce no toxic waste. This message is carried by the study of the evolution of molecular catalysis of some of the most important reactions in organic chemistry. After reviewing the conceptual underpinnings of catalysis, we discuss the applications of different catalysts according to the mechanism of the reactions that they catalyze, including acyl group transfers, nucleophilic additions and substitutions, and C–C bond forming reactions that employ umpolung by nucleophilic additions to C=O and C=C double bonds. We highlight the utility of a broad range of organocatalysts other than compounds based on proline, the cinchona alkaloids and binaphthyls, which have been abundantly reviewed elsewhere. The focus is on organocatalysts, although a few examples employing metal complexes and enzymes are also included due to their significance. Classical Brønsted acids have evolved into electrophilic hands, the fingers of which are hydrogen donors (like enzymes or other electrophilic moieties. Classical Lewis base catalysts have evolved into tridimensional, chiral nucleophiles that are N- (e.g., tertiary amines, P- (e.g., tertiary phosphines and C-nucleophiles (e.g., N-heterocyclic carbenes. Many efficient organocatalysts bear electrophilic and nucleophilic moieties that interact simultaneously or not with both the electrophilic and nucleophilic reactants. A detailed understanding of the reaction mechanisms permits the design of better catalysts. Their construction represents a molecular science in itself, suggesting that sooner or later chemists will not only imitate Nature but be able to catalyze a much wider range of reactions with high chemo-, regio-, stereo- and enantioselectivity. Man-made organocatalysts are much smaller, cheaper and more stable than enzymes.

  20. Five prevalent antiprotozoal herbal drugs

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    Mohammad Azadbakht1


    Full Text Available , (Received 21 Jun, 2008 ; Accepted 12 Nov, 2008 AbstractAccording to the statistics provided by the World Health Organization (WHO, about 80% of the world population nowadays uses herbal drugs for treatment of diseases. Natural products obtained from medicinal plants, serve as a great source for drug production and are the main basis of new drug compounds. Unicellular organisms (Protozoa are the cause of deaths and spread of diseases in various societies, especially in developing countries. There are anti-malaria herbal dugs produced from various medicinal plants, some of which are used for treatment of the disease and some under study. The first anti-malaria drug was quinine, produced from bark of the Cinchona tree. Recently, the drug artemisinin has been introduced by Chinese scientists for the treatment of malaria and is currently used extensively. Coetaneous leishmaniosis (salak is one of the endemic diseases in most parts of Iran. Common drugs used against leishmaniosis (such as glucantim, have severe side-effects and in 10 to 25% of cases, there is a recurrence of the disease. Emetine is one of the drugs obtained from a root of the plant Ipecac, which is used for treatment of the disease sub-cutaneously. Giardiasis is an acute protozoan infection usually with no clinical symptoms, however, may appear as acute or chronic diarrhea. According to the announcement of WHO, more than 2/3 of the world’s population is infected with intestinal parasites and the prevalence of giardia is higher than other intestinal parasites. Herbal drugs, such as wild garlic, eucalyptus and thyme, are some of the major plants which can annihilate the giarda cysts. Annually, 75000 to 100000 people die of amebiasis (dysentery worldwide. Due to the motility of the organism, it causes sever pathological changes and sometimes colon ulcers, and if entered into the blood stream, it may appear as liver or brain abscess. Medicinal plants such as ipecac, mango, and papaya

  1. Bosques montanos-relictos en Kañaris (Lambayeque, Perú

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    Santos Llatas-Quiroz


    Full Text Available En Kañaris (Lambayeque se encuentran grandes bosques relictos, probablemente los mayores de la vertiente occidental de los Andes peruanos. Actualmente están muy bien conservados, pero al mismo tiempo es la zona botánicamente menos estudiada de todos los bosques relictos de la zona. Estos bosques se ubican en las alturas de Upaypiteq y adyacentes a los flancos de la cordillera occidental de los Andes en la vertiente del Atlántico: Shin Shin, San Lorenzo, Huacapampa, Pandachí, Gramalote, Walte, Mollepampa; entre los 1500 a 3000 m sobre el nivel del mar, en el distrito de Kañaris (2300 m y los bosques de Chiñama y Luto en la vertiente del Pacífico. La presente investigación se emprendió con el objeto de estudiar científicamente, mediante muestreos florísticos, la vida y estructura de los componentes de los bosques de Upaypiteq. Las muestras conducen a un avance de la investigación, determinando que los principales componentes arbóreos corresponden a las Lauráceas: Persea, Ocotea y Nectandra, Cunoniáceas: Weinmannia, Podocarpáceas: Podocarpus, Cecropiáceas: Cecropia, Mirtáceas: Myrcianthes, Moráceas: Ficus, Rubiáceas: Cinchona, Bignoniáceas: Tabebuia, Arecáceas: Ceroxylon y, helechos arborescentes del género Nephelea. Circundantes a la masa boscosa se encuentran varias especies de arbustos, de los géneros Miconia, Munnozia, Baccharis, Senna, Colignonia, Gaiadendron, Oreopanax, etc.; también en la estructura es muy frecuente las epífitas y lianas ascendentes: Bromeliáceas, Orquídeas, Heliconias, Aráceas, musgos. Los helechos herbáceos, hongos, líquenes gelatinosos, hepáticas, Balanoforáceas y Begonias, tapizan por completo el piso boscoso. La composición florística es similar al bosque de Cutervo y los bosques de la Vertiente Oriental de los Andes, que a los demás bosques relictos en la Vertiente Occidental. La presencia de estos bosques se debe preservar, por su importancia en los procesos ecológicos para la

  2. Screening for antimicrobial activity of ten medicinal plants used in Colombian folkloric medicine: A possible alternative in the treatment of non-nosocomial infections

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    Ocampo Saul A


    Full Text Available Abstract Background The antimicrobial activity and Minimal Inhibitory Concentration (MIC of the extracts of Bidens pilosa L., Bixa orellana L., Cecropia peltata L., Cinchona officinalis L., Gliricidia sepium H.B. & K, Jacaranda mimosifolia D.Don, Justicia secunda Vahl., Piper pulchrum C.DC, P. paniculata L. and Spilanthes americana Hieron were evaluated against five bacteria (Staphylococcus aureus, Streptococcus β hemolític, Bacillus cereus, Pseudomonas aeruginosa, and Escherichia coli, and one yeast (Candida albicans. These plants are used in Colombian folk medicine to treat infections of microbial origin. Methods Plants were collected by farmers and traditional healers. The ethanol, hexane and water extracts were obtained by standard methods. The antimicrobial activity was found by using a modified agar well diffusion method. All microorganisms were obtained from the American Type Culture Collection (ATCC. MIC was determined in the plant extracts that showed some efficacy against the tested microorganisms. Gentamycin sulfate (1.0 μg/ml, clindamycin (0.3 μg/ml and nystatin (1.0 μg/ml were used as positive controls. Results The water extracts of Bidens pilosa L., Jacaranda mimosifolia D.Don, and Piper pulchrum C.DC showed a higher activity against Bacillus cereus and Escherichia coli than gentamycin sulfate. Similarly, the ethanol extracts of all species were active against Staphylococcus aureus except for Justicia secunda. Furthermore, Bixa orellana L, Justicia secunda Vahl. and Piper pulchrum C.DC presented the lowest MICs against Escherichia coli (0.8, 0.6 and 0.6 μg/ml, respectively compared to gentamycin sulfate (0.9 8g/ml. Likewise, Justicia secunda and Piper pulchrum C.DC showed an analogous MIC against Candida albicans (0.5 and 0.6 μg/ml, respectively compared to nystatin (0.6 μg/ml. Bixa orellana L, exhibited a better MIC against Bacillus cereus (0.2 μg/ml than gentamycin sulfate (0.5 μg/ml. Conclusion This in vitro study

  3. [Alexandre Yersin (1863-1943), explorer and a founding scientist of the Pasteur Institutes]. (United States)

    Milleliri, J M


    2013 was the year to celebrate Yersin: the 150th anniversary of his birth and the 70th anniversary of his death. Beyond the images usually attached to the memory of this doctor who discovered the bubonic plague bacillus (in Hong Kong in 1894), the author seeks to introduce Yersin, the man, as an explorer curious about his environment rather than a scientist concerned with honors and public recognition. Alexandre Yersin is an atypical figure in the universe of Pasteur, his collaborators, students, and followers. Although he began his career working with Louis Pasteur following the development of the vaccine against rabies, in 1885, the call of the sea led him to quit the laboratory on rue Ulm to, he said, "explore new lands". He worked for the Messageries maritimes merchant shipping company. In Saigon, he met Albert Calmette, who convinced him to join the newly created Colonial Army Medical Corps. In 1892 in Nha-Trang, Yersin set up a bacteriology laboratory in a straw hut; it subsequently became the first Pasteur Institute in Indochina, the starting point of a network of research laboratories. During the bubonic plague epidemic that raged in Hong Kong, Yersin succeeded in isolating its causal agent, surprising even himself by the ease with which he did so. He was 30 years old then, but what could have been the start of a prestigious career, crowned with honors, was spent instead at the service of the local populations. His exploration of the Vietnam highlands gave Yersin the occasion to cultivate and reveal a prodigious eclecticism and his profound humanism. He led three explorations in unknown regions of Annam and contributed to the development of this country by his social, educational, medical, and economic approach, entirely dedicated to aiding the indigenous populations. Yersin never left Vietnam again. He worked as an astronomer and agronomist (introducing the cultivation of cinchona (source of quinine) and rubber trees in the country) - always close to the

  4. Large-scale deforestation for plantation agriculture in the hill country of Sri Lanka and its impacts (United States)

    Wickramagamage, P.


    The forest cover in the hill country river catchment areas of Sri Lanka has been reduced to isolated patches on hilltops and a handful of reserves above the 1524 m (5000 ft) contour. Most of the land that was under forest cover at the turn of the nineteenth century is now covered with plantation crops. The districts of Kandy, Matale, Nuwara Eliya, Badulla, Ratnapura and Kegalle are the main hill country plantation areas. Within a period of less than half a century most of the forests in the hill country were cleared for plantation crops. Shifting cultivation was responsible for deforestation in the drier parts of the hill country. At the time of the British conquest of the hill country, the population of the whole island was not more than 3/4 to 1 million and they had settled in isolated villages at elevations below 1066 m. Subsistence agriculture was the main occupation of this predominantly rural population.During the first phase (1830-1880) of the plantation industry, large tracts of mostly forest land were cleared for coffee cultivation. By 1878, the extent of the coffee plantations reached its maximum of 111 336 ha most of which was situated in the wet zone hill country. The second phase of plantation agriculture began as the coffee industry was completely wiped out by a leaf disease. Most of the abandoned coffee plantations and the remaining forests were converted to tea, rubber and cinchona estates. The first two crops managed to survive price fluctuations in the world market, while the latter collapsed because of over production.During the period of large-scale deforestation in the hill country, the climate also underwent changes as exemplified by rainfall and temperature trends. However, these trends are not uniform everywhere in the plantation areas of the hill country. The temperature has risen a few degrees over a period of about a century and quarter in the hill country stations, while rainfall has declined significantly at some stations. These changes

  5. Utilization of N-X bonds in the synthesis of N-heterocycles. (United States)

    Minakata, Satoshi


    -deficient olefins in the presence of a phase transfer catalyst to give the corresponding aziridines. We also used this method to synthesize asymmetric aziridines using quaternary cinchona alkaloid catalysts. We also developed a facile synthetic method for preparing N-heterocycles that involves the in situ generation of an N-X bond using tert-butyl hypochlorite or tert-butyl hypoiodite (tert-BuOI). Treatment of alkenylamides containing an active hydrogen on the nitrogen with tert-BuOI led to the production of various N-heterocycles via intramolecular cyclization. Iodination of readily available sulfonamides or carboxamides with tert-BuOI generated reactive N-iodinated amides, which smoothly reacted with olefins to give aziridines or oxazolines. The reaction of fullerene, C(60), with CT also led to aziridination: the resulting aziridinofullerene underwent a unique rearrangement to an azafulleroid. Chlorination of readily available amide derivatives with tert-BuOCl, followed by a reaction with C(60) in the presence of an organic base, afforded aziridinofullerenes with various substituents on the nitrogen. The results in this Account contribute to the development of convenient methods for constructing simple and useful heterocycles.

  6. Asymmetric Hydrogenation of Ethyl 2-Oxo-4-Phenylbutyrate on Pt-Ir/Al2O3 Catalysts%Pt-Ir/Al2O3催化剂催化2-氧-4-苯基丁酸乙酯不对称加氢

    Institute of Scientific and Technical Information of China (English)

    张学勤; 何年志; 肖美添; 刘勇军; 叶静


    A series of Pt/γ-Al2O3 、Ir/γ-Al2O3 and Pt-Ir/γ-Al2O3 catalysts with different ratios of Pt and Ir were prepared by impregnation methods.The catalytic performance for asymmetric hydrogenation of ethyl 2-oxo-4-phenylbutyrate to ethyl (R)-2-hydroxy-4-phenylbutyrate was tested.The mechanism of chiral induction on cinchona-modified platinum and iridium catalysts and their physical and chemical properties were investigated by X-ray diffraction (XRD),transmission electron microscopy(TEM),H2-temperature programmed reduction (H2-TPR),X-ray photoelectron spectroscopy(XPS) and ultraviolet-visible spectroscopy(UV-Vis).The average metal particles size for Pt/γ-Al2O3 and Pt-Ir/γ-Al2O3 catalγsts were 3-4 nm; Pt and Ir existed as Pt(0) and Ir(0) for Pt-Ir/γ-Al2O3 ; Ir acted as an inactive species,covering and diluting the Pt active site in the surface.The results showed that a small amount of Ir obviously suppressed the hydrogenation activity and selectivity of Pt/γ-Al2O3.The notable differences in reaction rate and enantioselectivity of platinum and iridium attributed to different behaviour adsorption (adsorption strength,mode and conformation) of chiral modifier on the metal surface.%用浸渍法制备了一系列γ-Al2O3负载的Pt、Ir单金属及不同Pt/Ir比例的双金属催化剂,在辛可尼定修饰下用于对2-氧-4-苯基丁酸乙酯不对称加氢合成(R)-2-羟基-4-苯基丁酸乙酯反应.运用XRD、TEM、TPR、XPS、UV-Vis等表征手段,对催化剂的物化性质进行了研究,并对Pt、Ir金属表面辛可尼定手性诱导机理进行了初步探讨.结果表明,金属组分在催化剂上分散均匀,无团聚现象,平均粒径为3 ~4 nm; Pt-Ir/γ-Al2O3上Pt、Ir组分以单质形式存在;Ir作为低活性物种,在Pt/γ-Al2O3催化剂掺杂Ir组分遮盖和稀释了催化剂表面总体Pt活性位点数目,降低了Pt-Ir/γ-Al2O3催化剂加氢性能.辛可尼定在Pt、Ir表面的不同吸附行为(吸附方式、吸附强度、吸附

  7. Vladimir Prelog i Zavod za organsku kemiju

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    Jakopčić, K.


    -operation from the small but prosperous pharmaceutical company "Kaštel" in Zagreb. On behalf of the agreement, Prelog and his department obtained funds to fit up the laboratory and to start very prosperous research in the synthesis and studies of pharmaceutically interesting compounds. With his assistants, students and other collaborators, Prelog started research of cinchona bark alkaloids, preferentially oriented to the synthesis of quinine. For example, Prelog's method of double intramolecular alkylation to synthetize the quinuclidine moiety of quinine was patented by "Kaštel". With R. Seiwerth he developed the first useful synthesis of adamantane. Prelog's group started research in the field of sulphonamides and commercial success of "Streptazole" stimulated the development of the research laboratories within "Kaštel". The collaboration in the research continued in fields of other chemotherapeutics, analeptics, spasmolitics, barbiturates etc. Within the period 1935-1941, Prelog published 48 scientific papers and 8 patents. In less than seven years, his results enormously influenced the entire organic chemistry in Zagreb till nowadays. Under the confused and uncertain circumstances caused by the beginning of World War II, Prelog left Zagreb in 1941 and continued his extraordinary scientific career at the ETH in Zürich.During the war (1942-1945 the tuition and the Department were run by Dr. Rativoj Seiwerth, former collaborator and first assistant to V. Prelog. In almost unbelievable conditions, the young assistant, then assistant professor (since January 1943, R. Seiwerth fully succeeded in continuing most activities founded by Professor Prelog. After the war (1945, R. Seiwerth was forced to resign. Nevertheless, soon after R. Seiwerth continued his research work, firstly in the Institute for Industrial Research in Zagreb (1946-1952, and later in the Research Institute of "Pliva" in Zagreb. He retired in 1980.In post-war conditions (1945/46, the activity of the Technical