epicinchonine and cinchonidine

The organo-catalyzed enantioselective benzylation reaction of α-trifluoromethoxy indanones afforded α-benzyl-α-trifluoromethoxy indanones with a tetrasubstituted stereogenic carbon center in excellent yield with moderate enantioselectivity (up to 57% ee). Cinchona alkaloid-based chiral phase transfer catalysts were found to be effective for this transformation, and both enantiomers of α-benzyl-α-trifluoromethoxy indanones were accessed, depended on the use of cinchonidine and cinchonine-derived catalyst. The method was extended to the enantioselective allylation reaction of α-trifluoromethoxy indanones to give the allylation products in moderate yield with good enantioselectivity (up to 76% ee).

Topics: Allylbenzene Derivatives; Catalysis; Cinchona Alkaloids; Fluorides; Indans; Molecular Structure; Stereoisomerism

Topics: Alkaloids; Chromatography, Supercritical Fluid; Cinchona; Cinchona Alkaloids; Limit of Detection; Plant Bark; Plant Extracts; Quinidine; Quinine

In the crystal structures of the diastereoisomers of O-tosylcinchonidine [(9R)-cinchon-9-yl 4-methylbenzenesulfonate], (I), and O-tosylcinchonine [(9S)-cinchon-9-yl 4-methylbenzenesulfonate], (II), both C(26)H(28)N(2)O(3)S, both molecules are in an anti-closed conformation and, in each case, the position of the aryl ring of the tosylate system is influenced by an intramolecular C-H···O hydrogen bond. The molecular packing in (I) is influenced by weak intermolecular C-H···O and C-H···π interactions. The crystal structure of (II) features C-H···π interactions and van der Waals forces only. The computational investigations using RHF/6-31G** ab initio and AM1 semi-empirical methods performed for (I) and (II) and their protonated species show that the conformational and energetic parameters of the molecules are correlated with differences in their reactivity in hydrolysis to the corresponding 9-epibases.

Topics: Alkaloids; Benzenesulfonates; Cinchona Alkaloids; Crystallography, X-Ray; Esters; Hydrogen Bonding; Hydrolysis; Molecular Structure; Tosyl Compounds

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.

Topics: Antimalarials; Chromatography, High Pressure Liquid; Cinchona; Cinchona Alkaloids; Green Chemistry Technology; Microwaves; Plant Bark; Plant Extracts; Quinidine; Quinine; Quinolines

Three monodispersed, molecularly imprinted polymers (MIPs) for cinchonidine (CD) have been synthesized by precipitation polymerization. MIP1 was prepared using methacrylic acid (MAA) as a functional monomer and divinylbenzene (DVB) as a cross-linker and MIP2 was prepared with further addition of 2-hydroxyethyl methacrylate (HEMA) as a co-monomer. For the preparation of MIP3, core-shell type MIP, monodispersed DVB homopolymers, which are prepared by precipitation polymerization, were used as a core and CD-imprinted MAA-DVB copolymer phases were coated onto the core. Three MIPs synthesized gave monodispersed, spherical beads in micrometer sizes. The binding characteristics and molecular recognition properties of MIP1-3 were examined by Scatchard analysis and chromatographic studies. The association constant of CD with MIP1 was the highest among MIPs prepared, while that with MIP3 was the lowest. The template molecule, CD, was more retained than its stereoisomer, cinchonine, on the three MIPs, and the stereoseparation factor of 38 was obtained with MIP3.

Topics: Antimalarials; Chemical Precipitation; Chromatography, High Pressure Liquid; Cinchona Alkaloids; Molecular Imprinting; Particle Size; Polymers; Stereoisomerism; Temperature

While it is not uncommon to form chiral crystals during crystallization, the formation of bulk porous homochiral materials from achiral building units is rare. Reported here is the homochiral crystallization of microporous materials through the chirality induction effect of natural alkaloids. The resulting material possesses permanent microporosity and has a uniform pore size of 9.3 A.

Topics: Catalysis; Cinchona Alkaloids; Crystallization; Dimethylamines; Dimethylformamide; Indium; Models, Molecular; Organometallic Compounds; Solvents; Stereoisomerism; Thiophenes

A revised procedure for the conversion of the four major Cinchona alkaloids (quinine, quinidine, cinchonidine, and cinchonine) into their respective 10,11-didehydro derivatives is described. The reported protocol offers several advantages over a recently published synthetic route. These include (i) enhanced robustness (ii) ready scalability (iii) reduced operational complexity and number of steps (iv) chromatography-free work-up. In addition, toxic solvents were replaced by environmentally less problematic alternatives.

Topics: Cinchona Alkaloids; Magnetic Resonance Spectroscopy; Methods; Molecular Structure; Quinidine; Quinine; Stereoisomerism

A synthetic procedure for the preparation of 4-cyclohexyl-2-methyl-buta-2,3-dienoic acid in the two optically active forms has been developed. Synthesis of the racemic allenoic acid was made by an efficient route with good overall yield. Resolution of the enantiomers was achieved by forming the cinchonidine and cinchonine diastereomeric salt, respectively, and the enantiomers were isolated in up to 95% enantiomeric excess. The absolute configuration of the allenoic acid was determined by X-ray crystallography.

Topics: 4-Butyrolactone; Acids; Alkaloids; Cinchona Alkaloids; Crystallography, X-Ray; Optics and Photonics; Phosphoranes; Salts; Stereoisomerism

Scanning tunneling microscopy (STM) combined with cyclic voltammetry has been employed to investigate the adsorption of cinchonine on Cu(111). Similar to cinchonidine, cinchonine forms a long-range ordered adlayer with (4 x 4) symmetry on the substrate. The structural details on molecular adsorption were obtained by high-resolution STM images. On the basis of the previous results and obtained STM images, the quinoline ring is proposed to lie parallel to Cu(111) and serve as an anchoring group. The chiral quinuclidine moiety extends out of the surface to facilitate the interaction with the prochiral reactants.

Topics: Adsorption; Catalysis; Cinchona Alkaloids; Copper; Electrodes; Microscopy, Scanning Tunneling; Molecular Structure; Stereoisomerism

Highly stereoselective, uniformly sized molecularly imprinted polymers (MIPs) for cinchona alkaloids, cinchonine (CN) and cinchonidine (CD), were prepared using methacrylic acid (MAA) as a functional monomer and ethylene glycol dimethacrylate (EDMA) as a cross-linker. The MIPs were evaluated using a mixture of phosphate buffer and acetonitrile as the mobile phase. The CN- and CD-imprinted MAA-co-EDMA polymers can recognize the respective template molecule more than the other diastereomer, and afford an excellent diastereomer separation of CN and CD. In addition, the MIPs gave diastereomer separations of structurally related compounds, quinidine and quinine. The retentive and stereoselective properties of those compounds on the MIPs suggest that electrostatic and hydrophobic interactions can work to recognize these compounds. Furthermore, thermodynamic studies reveal that the entropy-driven effect is significant at mobile-phase pH 5.4, while the enthalpy-driven interactions seem to be dominant at mobile-phase pH 9.6.

Topics: Chromatography, High Pressure Liquid; Cinchona Alkaloids; Polymers; Quinidine; Quinine; Thermodynamics

Solvolysis of C9 mesylated cinchonidine 1-OMs and cinchonine 2-OMs in solvent MeOH, EtOH, and CF(3)CH(2)OH affords ring-expanded 1-azabicyclo[3.2.2]nonanes oxygenated at carbon C3 ("second Cinchona rearrangement"). The newly introduced substituents at C3 and the neighboring quinolyl group Q' at C2 adopt quasiequatorial positions. The derived 1-azabicyclo[3.2.2]nonan-3-ones 5 and 6 are easily equilibrated. On contact with MeOD uptake of deuterium takes place at room temperature.

Topics: Alkanes; Aza Compounds; Bridged Bicyclo Compounds, Heterocyclic; Cinchona Alkaloids; Ketones; Molecular Structure; Oxidation-Reduction; Temperature

Beaded molecule imprinted polymer (MIP) was made by suspension polymerization. Particles with the size of 50-70 microns in diameter were collected and evaluated in HPLC mode to separate stereo isomers. Stereo isomers cinchonine and cinchonidine were successfully discriminated with selectivity factor of 2.89 and resolution factor of 0.76. Stereo selectivity of the MIP was found to come from both the interaction between the analyte and carboxyl group on the MIP and the similarity between the stereo structure of imprinted molecule and the MIP. The thermal analysis results showed that the MIP had high thermal stability with initial thermal decomposition temperature of 320 degrees C. The pore volume of the MIP was 0.1849 mL/g, the specific surface area was 126.84 sqm/g and the average pore diameter was 5.8 nanometer. Scanning electron microscopy showed that MIP had perfect spherical morphology.

Topics: Chromatography, High Pressure Liquid; Cinchona Alkaloids; Polymers; Stereoisomerism

The use of a novel chiral functional monomer system in molecular imprinting protocols is described. The monomer, dibenzyl (2R,3R)-O-monoacryloyl tartrate, possesses a hydroxyl moiety which can be used to direct template-functional monomer interactions during molecular imprinting polymerization. This system simultaneously positions benzyl ester-protected carboxyl groups in close proximity to the template, which upon deprotection yield recognition sites with stronger ligand-binding capacities. Furthermore, the inherent chirality of the monomer engenders the polymer with an inbuilt preference for a given stereoisomer. Application of the system to the molecular imprinting of the cinchonidine alkaloids (+)-cinchonine and (-)-cinchonidine yielded stereoselective polymers. The effect of imprinting (+)-cinchonine produced a polymer which more than reversed the inherent chiral selectivity of the chiral monomer residues present in the matrix.

Topics: Binding Sites; Cinchona Alkaloids; Ligands; Molecular Mimicry; Polymers; Stereoisomerism

Lambda-carrageenan, a linear high molecular weight sulfated polysaccharide, has been employed as a chiral selector in capillary electrophoresis for the separation of enantiomers of weakly basic pharmaceutical compounds. The racemic compounds that were enantioresolved included propranolol, pindolol, tryptophanol, laudanosine and laudanosoline. In addition, the diastereomeric pair of cinchonine and cinchonidine were also resolved. Method conditions such as buffer pH, electrolyte concentration, column temperature, and chiral selector concentration were found to be important for improvement of enantioselectivity.

Topics: Adrenergic beta-Antagonists; Carrageenan; Cinchona Alkaloids; Electrophoresis, Capillary; Isoquinolines; Molecular Structure; Pharmaceutical Preparations; Pindolol; Propranolol; Stereoisomerism; Tryptophan

Previously described were three patients with quinine-dependent antibodies to neutrophils, platelets, and red cells who had episodic pancytopenia and renal failure. The nature of the antibody-drug-neutrophil interactions was investigated with sera from these patients.. Sera from all three patients were tested against neutrophils in flow cytometry in the presence of several compounds related to quinine. IgG and Fab and F(ab')2 fragments were prepared from the serum of one patient and tested against neutrophils in flow cytometry and immunoprecipitation in the presence of quinine and related compounds.. In flow cytometry, sera from all three patients plus quinidine reacted with neutrophils. Sera from Patients 1 and 3 reacted with neutrophils in the presence of cinchonidine (desmethoxy-quinine) and serum from Patient 3 also reacted with neutrophils in the presence of cinchonine (desmethoxy-quinidine). None of the sera reacted with neutrophils in the presence of chloroquine or primaquine. Serum from Patient 3 plus quinolinic acid, a tryptophan metabolite, reacted with neutrophils, but sera from the other two patients did not. Patient 3 serum plus tryptophan or another tryptophan metabolite, quinalidic acid, did not react with neutrophils. IgG from Patient 3 serum reacted with neutrophils in flow cytometry in the presence of quinine, quinidine, cinchonidine, cinchonine, and quinolinic acid. F(ab')2 fragments plus quinine or cinchonidine also reacted with neutrophils, but Fab fragments plus quinine did not. In the presence of quinine, Patient 3 IgG immunoprecipitated the 85- and 60-kDa molecules and F(ab')2 fragments immunoprecipitated the 85-kDa molecule. Patient 3 serum plus quinidine, cinchonidine, cinchonine, and quinolinic acid immunoprecipitated the 130- and 85-kDa molecules, but not the 60-kDa molecule.. Quinine-dependent neutrophil antibodies often react with neutrophils in the presence of quinidine and related compounds. These reactions were mediated by the F(ab')2 domain of IgG.

Topics: Autoantibodies; Cinchona Alkaloids; Flow Cytometry; Humans; Immunoglobulin Fab Fragments; Immunoglobulin G; Immunosorbent Techniques; Neutrophils; Quinidine; Quinine; Quinolinic Acid

In vitro studies with quinine, quinidine, cinchonine, and cinchonidine showed that despite a similarity of chemical structure, the effectiveness of these cinchona bark alkaloids against several culture lines of Plasmodium falciparum varied widely. Depending on the strain tested, quinidine and cinchonine were 1 to 10 and 1 to 5 times, respectively, more active than quinine. A combination made of equal parts of quinine, quinidine, and cinchonine was found to have several interesting features; it had activity similar to that of quinine against quinine-susceptible strains but was found to be 2 to 10 times more effective against strains resistant to quinine and had a more consistent effect than any of the alkaloids used singly. The potentiation was found to depend mainly on the presence of cinchonine in the mixtures studied. Synergism was also confirmed in a study of 25 P. falciparum strains isolated from Thai patients. Combinations of cinchona bark alkaloids could thus be of interest in areas where P. falciparum is becoming less susceptible to quinine.

Topics: Animals; Cinchona Alkaloids; Drug Resistance; Drug Synergism; Humans; Plasmodium falciparum; Quinidine; Quinine

The comparative disposition kinetics of quinidine, quinine, cinchonine , and cinchonidine were investigated in five male, mongrel dogs after intravenous bolus injections of a 9.2-mmol/kg dose of each alkaloid base. Blood and plasma specimens were obtained at various times up to 6 h postdose and assayed for quinidine and quinine with a TLC-fluorometric procedure and for cinchonine and cinchonidine by HPLC. The plasma alkaloid concentration-time data were analyzed by weighted, nonlinear least-squares regression analysis to obtain the central compartment volume (Vc), disposition rate constants (alpha and beta), and corresponding half-life values (t1/2). Total body clearance (CL) and apparent volume of distribution (Vd) were estimated by nonparametric analysis. In this study, the highest plasma alkaloid concentrations were reached with quinidine and the lowest concentrations with the quinidine congener, cinchonine . The other congeneric pair, quinine and cinchonidine , exhibited plasma alkaloid concentrations that were comparable and intermediate to those of quinidine and cinchonine . With cinchonine and cinchonidine , the plasma and blood concentration-time curves were virtually superimposable. However, with quinidine and quinine, the plasma alkaloid concentrations of these diastereomers were approximately twice the corresponding blood concentrations. The total body clearance rate of quinidine was significantly slower than quinine and cinchonine clearance. No difference in clearance was observed between cinchonine and cinchonidine . The beta and t1/2 beta for quinidine were significantly smaller and larger, respectively, than the corresponding values obtained with the other alkaloids. No significant differences in alpha or Vc and Vd were found between and within the two diastereomeric pairs of alkaloids. The differences in disposition kinetics observed in this study were attributable to an interaction of stereochemical and 6'-methoxy group substitution effects.

Topics: Animals; Cinchona Alkaloids; Dogs; Injections, Intravenous; Kinetics; Male; Plasma; Quinidine; Quinine; Stereoisomerism

Topics: Animals; Cinchona Alkaloids; Liver; Quinidine; Quinine; Sheep; Sheep, Domestic

Topics: Alcohols; Cinchona; Cinchona Alkaloids; Solubility; Water