ZHONG Shi-an; HUANG Ke-long; LEI Qi-fu; XIANG Hai-yan
A molecularly imprinting polymer (MIP) was synthesized via bulk polymerization under different conditions using anti-ague drug cinchonine (CN) as template. Infrared spectra (IR) results show that the template CNand functional monomer α-methyl acrylic acid (MAA) formed complexes before polymerization and the structure of complexes was simulated by Hyperchem. The results indicate that there are hydrogen bond or ionic bond between functional monomer and template molecule in acetonitrile solution. The MIP made in cold-initiated photo-polymerization has higher separation performance than that in the therm-initiated polymerization. The separation of the isomers CN and cinchonidine (CD) can be successfully obtained when its separate factor α reaches 1.82. Scatchard analysis suggests that the MIP recognizing CN with two classes of binding sites. The partition coefficient Kd, 1 and apparent maximum number nmax, 1 of binding sites with high affinity are 131.43 μmol/L and 58. 90 μmol/g, respectively,while Kd, 2 and nmax, 2 of binding sites with low affinity are 2.32 mmol/L and 169.08 mmol/g, respectively.
张海丽; 叶永康; 徐斌
A method for the determination of bismuth is reported with self _ made carbon paste electrode modified by cinchonine. After bismuth ions are accumulated under the applied potential of －1.00 V for 120 s on the chemical modified electrode in 1 mol/L H2SO4 solution, there is a sensitive oxidation peak of Bi at －0.022 V(vs SCE) in the determination by anodic stripping voltammetry(ASV). Dependence of current on concentration is linear from 1.0×10－8 to 1.0×10－4 mol/L of Bi3＋. The detection limit is 5.0×10－9 mol/L. Other metal ions do not interfere in the determination.%报道了利用辛可宁修饰碳糊电极测定铋的方法，在1 mol/L H2SO4溶液中，通过在－1.00 V电位下富集Bi3＋后，在－0.20 ～＋0.15 V电位范围内作阳极溶出伏安法测定。在－0.022 V处有一灵敏的氧化峰，峰电流与Bi3＋浓度在1.0×10－8 ～1.0×10－4 mol/L范围内成良好的线性关系，检出限为5.0×10－9 mol/L。其他金属离子不干扰测定。
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…
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.
ZHANGZhengpu; HUANGJinxia; 等
In this paper,two kinds of PS-PTCs were synthesized using different methods by introducing cinchonine and quinine to the polymer support.Their catalytic properties for the alkylation of N-diphenylmethylene glycine t-butyl ester were also compared.
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...
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.
Jakubec, Pavol; Farley, Alistair J M
Summary The enantio- and diastereoselective Michael addition of a δ-valerolactone-derived pronucleophile to a substituted furanyl nitroolefin catalysed by a bifunctional cinchonine-derived thiourea has been used as the key stereocontrolling step in a new synthetic strategy to the heavily functionalised piperidine core of keramaphidin B. PMID:27340496
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
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.
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.
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...
The optical α-amino acids were synthesized under room temperature by alkylation of N-(diphenyl methylene) glycine t-butyl ester under polymer-supported phase transfer conditions using polymer-supported cinchonine (or quinine) alkaloids as chiral phase transfer catalysts and dichloromethane as solvent, followed by hydrolysis of the above intermediates introduced to the final products-optical α-amino acids. This is a new method for the asymmetric synthesis of α-amino acids. The influences of catalyst,temperature, substrates, and organic solvents on the chemical yield and optical purities of products were studied.
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.
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.
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.
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.
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.
许卓; 于健; 马建学
试样经碱熔分解，水提取，铁、锰、铺、镍元素量氢氧化物沉淀与钨、钼分离。在0．34moL／L硫酸-2g／L苯羟乙酸-24g／L氯酸钠-0．08g／L辛兜宁体系中，钨和锢均能产生灵敏的极谱催化波，峰电位约为-0．70V和-0．07V（对饱和日‘汞电极）。方法检出限为WO．29蚓g、Mo0．26μg／g，精密度（RSD，n=12）为W1．21％-10．1％、Mo2.7％～12．4％，准确度（RE，n=12）为W-3．7％-2．33％、Mo-4．79％～3．17％。适用于化探样品中钨钿厄索的连续测定。%The sample was melted with potassium hydroxide and extracted with water. Tungsten and molybdenum were separated from iron, manganese, cobalt and nickel with their hydroxides. In 0.34 moL/L sulfuric acid-2 g/L hydroxyphenylacetic acid-24 g/L sodium chlorate -0.08 g/L cinchonine system, tungsten and molybdenum were produced sensitive polarographic catalytic waves with peak potentials (with a saturated calomel electrode) at -0.70 V and-0.07 V, respectively. The detection limit of tungsten and molybdenum were 0.29/ag/g and 0.26μg/g, respectively. The RSD (n=12) of method were 1.21%-10.1% for W, 2.7 %~12.4 % for Mo. The RE (n=12) of method were -3.7 %-2.33 % for W,-4.79 %-3.17% for Mo. The method has been applied to the continuous determination of tungsten and molybdenum in geochemical exploration samples.
Rushton, Gregory T.
Three distinct research goals governed the work presented herein. First, methods for characterizing the binding properties of molecularly imprinted polymers (MIPs) were investigated and reported upon. We found that although the heterogeneous nature of these materials produced highly concentration-dependent adsorption behavior, there was a dearth of analytical methods that had been previously applied that accommodated this feature. The merits of the Freundlich Isotherm in describing MIP binding properties was evaluated and found to be useful under most conditions tested. Based on this and other previous work, we also presented a more qualitative approach to analyzing MIPs using log-log isotherms. The advantage of this method was that the most important properties to a researcher, the polymer's capacity and selectivity, were easily evaluated through a visual inspection of the log-log isotherm. This approach avoided the necessity of assuming and applying a particular binding model to the isotherm before a determination of the material's utility could be assessed. When this analysis was applied to a MIP for (+)-cinchonine in aqueous and organic media, the results indicated that diastereoselectivity was achieved under both conditions. Second, host-guest interactions between a N,N'-diaryl naphthalene diimide atropisomer and a variety of organic molecules were investigated to determine the relationship between the strength of the complex formed and the rotational barrier about a Caryl-Nimide bond. We found that the barrier was sensitive to both the identity and the concentration of guest which afforded fine control over the rotational freedom of the system. This control was exploited in the design of a reversible molecular brake. Finally, two laboratory investigations based upon the these research projects were developed for use in undergraduate chemistry courses. The first was designed for a polymer course where the students investigate the binding properties of an ethyl