Transformation of the Iboga alkaloid voacangine into voaketone, a derivative of beta-carboline (author's transl)]

Transformation of the Iboga alkaloid voacangine into voaketone, a derivative of β-carboline. The reduction product voacanginol ( 2 ), obtained from the indole alkaloid (?)-voacangine ( 1 ), gave, by treatment of its tosylate 3 with methanolic pyridine in the presence of air, the rearrangement product (?)- 5 (voaketone). Its structure was derived from spectroscopic evidence (mainly NMR. and mass spectra) and some chemical transformation reaction, especially deuterium labelling. A possible mechanism for the formation of 5 from 3 is given in Scheme 6. The absolute configuration of 5 was deduced by comparison with yohimbine derivatives.     

Sub-nanogram analysis of yohimbine and related compounds by high-performance liquid chromatography

A sensitive (50 pg/ml) method is described for the analysis of yohimbine in blood by high-performance liquid chromatography with fluorescence detection. The chromatographic behaviour of eserine (employed as internal standard), reserpine, corynanthine, yohimbinic acid, and yohimbine are examined on a series of reversed-phase and normal-phase chromatographic columns with methanol-water mobile phases.     

PEEK tube‐based online solid‐phase microextraction–high‐performance liquid chromatography for the determination of yohimbine in rat plasma and its application in pharmacokinetics study

Yohimbine is a novel compound for the treatment of erectile dysfunction derived from natural products, and pharmacokinetic study is important for its further development as a new medicine. In this work, we developed a novel PEEK tube‐based solid‐phase microextraction (SPME)–HPLC method for analysis of yohimbine in plasma and further for pharmacokinetic study. Poly (AA‐EGDMA) was synthesized inside a PEEK tube as the sorbent for microextraction of yohimbine, and parameters that could influence extraction efficiency were systematically investigated. Under optimum conditions, the PEEK tube‐based SPME method exhibits excellent enrichment efficiency towards yohimbine. By using berberine as internal standard, an online SPME‐HPLC method was developed for analysis of yohimbine in human plasma sample. The method has wide linear range (2–1000 ng/mL) with an R ² of 0.9962; the limit of detection was determined and was as low as 0.1 ng/mL using UV detection. Finally, a pharmacokinetic study of yohimbine was carried out by the online SPME‐HPLC method and the results have been compared with those of reported methods.     

Structural motifs of diiodine complexes with amides and thioamides

The reaction of 2-pyrimidone hydrochloride ([C(4)H(5)N(2)O](+)[Cl](-) or [PMOH(2)](+)[Cl](-)) with diiodine in a dichloromethane-methanol solution resulted in the formation of ([C(4)H(5)N(2)O](+))(2)[I(2)Cl(2)](2-) (1) complex. The compound was characterized by elemental analysis, FT-IR, DTA-TG and conductivity titrations. The crystal structure of 1 was also determined by X-ray diffraction at 294(1) K. Compound 1 is monoclinic, space group P2(1)/n, consisting of two cationic [PMOH(2)](+) species and a [I(2)Cl(2)](2-) counter dianion. The cation is in its keto form. Direct reaction of thiazolidine-2-thione (tzdtH), with diiodine in dichloromethane solution, on the other hand, led to the formation of a crystalline solid which contained two complexes of formulae [(tzdtH)(2)I](+)[I(3)](-).2I(2) (2) and [(tzdtH)I(2)](2).I(2) (2a) in a ratio of 90 to 10%. Complex 2a was characterized by X-ray analysis at 180(2) K. Compound is monoclinic, space group C2/c and contains two units of [(tzdtH)I(2)] "spoke" structures. Compound 1, as well as the known species iodonium salt [(tzdtH)(2)I](+)[I(3)](-).2I(2) (2) and the charge transfer (CT) iodine complexes of formulae [(bztzdtH)I(2)] (3) and [(bztzdtH)I(2)].I(2) (4) (bztzdtH = 2-mercaptobenzothiazole) with "spoke" and extended "spoke" structures respectively, were tested for their oxidizing activity towards 3,5-di-tert-butylcatechol to 3,5-di-tert-butyl-o-benzoquinone.     

Optically active tricarbonyl(cyclohexadienyl)iron(1+) salts: Synthetic equivalents to spatially directed organic cations

Optically active tricarbonyl (cyclohexdienyl)iron(1+) salts I, II and III are examples of olefin complexes with moleoular asymmetry due to coordination uith a transition metal. Their reactions serve to direct the eventual specific formation of a new chiral centre of known absolute configuration. The absolute configuration of the 2-methoxy-5-methyl salt I is defined its application to the asymmetric synthesis of λ-disubstituted cyclohexenones is described.     

Analysis of yohimbine alkaloid from Pausinystalia yohimbe by non-aqueous capillary electrophoresis and gas chromatography-mass spectrometry

In the present work, the qualitative and quantitative analysis of Pausinystalia yohimbe-type alkaloids in the barks of Rubiaceae species is presented using different analytical approaches. Extracts of P. yohimbe were first examined by GC-MS and the major alkaloids were identified. The quantitation of yohimbine was then accomplished by non-aqueous CE (NACE) with diode array detection. This approach was selected in order to use a running buffer fully compatible with samples in organic solvent. In particular, a mixture of methanol containing ammonium acetate (20 mM) and glacial acetic acid was used as a BGE. The same analytical sample was subjected to GC-MS and NACE analysis; the different selectivity displayed by these techniques allowed different separation profiles that can be useful in phytochemical characterization of the extracts. The linear calibration ranges were all 10-1000 microg/mL for yohimbine by GC-MS and NACE analysis. The recovery of yohimbine was 91.2-94.0% with RSD 1.4-4.3%. The LOD for yohimbine were 0.6 microg/mL by GC-MS and 1.0 microg/mL by NACE, respectively. The GC-MS and NACE methods were successfully validated and applied to the quantitation of yohimbine.     

Assay of Yohimbine in Human Plasma Using High Performance Liquid Chromatography with Electrochemical Detection

Abstract

Yohimbine is a selective α₂ adrenoreceptor antagonist used in the study of α₂ adrenoreceptors in man. In order to better improve administration regimens for the study of yohimbine in man, we have developed an assay for the determination of yohimbine in plasma utilizing reverse phase high performance liquid chromatography with electrochemical detection. Using a C₁₈ column and a methanol:acetate (60:40) mobile phase, we detected yohimbine in plasma following a simple chloroform extraction. Reserpiline was used as an internal standard. The assay was linear over a concentration range of 50–250 ng/ml in spiked plasma and had a lower limit of sensitivity of 10 ng/ml. It was used to detect yohimbine in plasma sampled from 4 volunteers during an infusion of the alkaloid.     

A fast determination of yohimbine in pharmaceuticals by micellar electrokinetic chromatography

A method for the fast determination of yohimbine, a potent adrenoreceptor antagonist used for the treatment of sexual dysfunctions, is proposed in this article. MEKC under basic and acidic conditions (sodium borate, pH 9.5 and sodium phosphate, pH 2.5) with SDS was developed. The effect of the experimental parameters, e.g. pH, SDS concentration and injection time, on yohimbine migration was also studied. Both methods were validated in terms of linearity, limits of detection and quantification, accuracy, and precision using caffeine as an internal standard. The application for the determination of yohimbine in hand-made medicaments is also investigated in this study.      

Estimation of absorbed dose in 131I therapy of metastasis of thyroid cancer

The radiation absorbed dose was estimated for 131I therapy of metastatic lesions of thyroid cancer, by the quantitative gamma-camera imaging. Uptake for eleven lesions in five cases (out of four patients) was measured for two times after 131I administration. Activities were calculated from opposed images with corrections for distance and depth using empirical formulae. An activity time curve was assumed as a reminder of two exponentials and fitted to measured values. The sizes of lesions were evaluated using the multi-slice CT images. An increase of frequency of activity measurement, particularly within a few days after 131I administration is desirable, for the purpose of an improvement of accuracy of dosimetry.     

Sensitive determination of yohimbine in plasma by micropipette tip-based poly(methacrylic acid-co-ethylene glycol dimethacrylate) monolith SPME coupled with HPLC method

A simple, miniaturized micropipette tip-based poly(MAA-co-EGDMA) monolith was prepared by in situ polymerization for sensitive micro-extraction of yohimbine in aqueous and plasma samples. Several parameters for monolith preparation were systematically optimized to obtain monolith with better permeability and absorption property. Methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) were selected as monomer and crosslinker and the ratio of MAA and EGDMA was 1:6. Methanol containing 30% dimethyl sulfoxide was selected as porogens. The prepared micropipette tip-based poly (MAA-co-EGDMA) monolith could be easily connected with a syringe infusion pump for loading solutions. Several factors such as washing solvents, flow rate of sampling, sample volume, and pH of sample solutions which affect enrichment efficiency of yohimbine were also evaluated in this work. Under optimized conditions, good enrichment capacity and stability of poly(MAA-co-EGDMA) monolith were obtained. Finally, the prepared micropipette tip-based poly(MAA-co-EGDMA) monolith solid phase micro-extraction combined with high-performance liquid chromatography was also used to analyze yohimbine in plasma samples. The developed method exhibited good sensitivity with limit of detection as low as 0.5?ng/mL, and also showed wide linearity in the range of 1.0–2000 ng/mL with R²?≥?0.998, excellent reproducibility with relative standard deviation (RSD) ≤?2.5%, and good recoveries in the range of 97.9–103.8% of yohimbine in human plasma.     

Absolute configuration and conformation analysis of 1-phenylethanol by matrix-isolation infrared and vibrational circular dichroism spectroscopy combined with density functional theory calculation

The absolute configuration and conformation of 1-phenylethanol (1-PhEtOH) have been determined by matrix-isolation infrared (IR) and vibrational circular dichroism (VCD) spectroscopy combined with quantum chemical calculations. Quantum chemical calculations have identified that there are three conformers, namely, I, II, and III, in which characteristic intramolecular interactions are found. The IR spectrum-conformation correlation for 1-PhEtOH has been developed by the Ar matrix-isolation IR measurement and used for the assignments of the observed IR bands. In a dilute CCl(4) solution, 1-PhEtOH exists predominantly as conformer I along with a trace amount of conformer II. By considering conformations and intermolecular hydrogen-bonding in the spectral simulation for (S)-1-PhEtOH, we have successfully reproduced the VCD spectrum of (-)-1-PhEtOH observed in a dilute CS(2) solution. Thus, (-)-1-PhEtOH is of S-configuration and conformer I in the dilute solution. The same method has been applied to analyze the VCD spectra measured in the liquid state of (-)-1-PhEtOH. The absolute configuration of 1-PhEtOH in the condensed phase is enabled by identifying VCD bands that are insensitive to conformational changes and intermolecular interactions. The present work provides a combinatorial procedure for determination of both the absolute configuration and the conformation of chiral molecules in a dilute solution and condensed phase.     

Characteristic absolute efficiency response curves of a high purity germanium detector in the energy range 50–1500 keV

The characteristic absolute efficiency response curves of a high purity germanium detector (HPGe) for different counting geometries have been established in the energy range 50–1500 keV by measuring the absolute efficiencies using both mono-energetic and multi-gamma emitting radionuclide point calibrated sources supplied by IAEA. Several fitting functions proposed in the literature were assessed for interpolation within the intermediate energy range of interest. The values of the function parameters have been determined by using the linear least square methods. The problems associated with the measurements of experimental efficiency data at small source–detector distances and the importance of the correlation matrix in the estimation of precise uncertainties have been shown. It was found that the inclusion of correlation matrices in the propagation of error formulae plays a significant role up to 450 keV gamma-ray energy and results in a drastic reduction of errors associated with the predicted efficiencies. The discrepancy at closer counting geometries in the absence of true gamma-gamma coincidence corrections is found to reach to about 30%.     

Spectrophotometric study of the reaction of Hg(II) with cadion A and cadion 2B

The reaction between Hg(II) and Cadion A and Cadion 2B has been studied. Methods are suggested for the determination of Hg(II) in the 0.1-4 ppm range with Cadion A and in the 0.2-8 ppm range with Cadion 2B. Of the 49 ions studied only Hg(I), Sn(II), Br(-), I(-), MnO(-)(4), EDTA, SCN(-), CN(-) and S(2-) interfere. The combination ratios and instability constants of the Hg-Cadion complexes were determined. The structural formulae of the complexes were deduced from the infrared spectra and elemental and thermogravimetric analyses.     

Rhodium(I) complexes with pyridazine, 4,6-dimethyl-pyrimidine, 4,6-bis(3,5-dimethylpyrazol-1-yl)pyrimidine, 3,6-bis(3,5-dimethylpyrazol-1-yl)pyridazine and 3-(3,5-dimethylpyrazol-1-yl)-6-chloropyridazine

The synthesis and properties of rhodium(I) complexes of formulae [“RhCl(diolefin)”₂(L)] (or [Rh(Cl(diolefin)(L)]), and [Rh(diolefin)(L)]_n(ClO₄)_n are reported. These complexes react with carbon monoxide to yield the related carbonyl derivatives. Ligands used were pyridazine, 4,6-dimethyl-pyrimidine, 4,6-bis(3,5-dimethylpyrazol-1-yl)pyrimidine, 3,6-bis(3,5-dimethylpyrazol-1-yl)pyridazine and 3-(3,5-dimethyl-pyrazol-1-yl)-6-chloropyridazine. Related iridium(I) and gold(I) compounds are also reported.     

Theory of GC2 — an unusual approach

In contrast to traditional theoretical approaches by calculation of (nonexistent) theoretical plates, a unified theory of gas chromatography as given by a definition of the resolution analogue to methods in signal processing or spectroscopy using the well-known Kovacz indices as fundamental scale. A derivation of the thusly defined resolution from basic physical principles yields very practical formulae for peak width, maximum load, substance flow in peak maximum, concentration of substance in the carrier gas and other interesting parameters in dependence of capillary diameter, capillary length, film thickness, carrier gas speed, viscosities etc. Diagrams show favourite conditions for detectors responding on absolute substance flow (e.g. FID) or on concentrations.     

Isolement et structure d'un nouveau diterpène: L'acide daniellique Stéréochimie de l'acide daniellique

A new diterpene acid, daniellic acid, has been isolated from the African copal tree, Daniellia oliveri (Caesalpineae). Structure (I) is demonstrated for daniellic acid; the stereochemistry implied (relative and absolute) is derived from a correlation with agathic acid.     

Prediction of endocrine disruptors based on a new structure-activity relationship for sex and environmental hormones using chemical hardness concept.

Classification of the relationship between electronic structures and biological activities of endocrine disruptors (so-called environmental hormones) was attempted using the parameters of absolute hardness (eta), absolute electronegativity (chi), and global softness (S), approximately defined as eta=1/2(epsilonLUMO-epsilonHOMO), chi=-1/2(epsilonHOMO+ epsilonLUMO), and S=1/eta, respectively, based on the hardness concept. The strength of binding affinity and toxicity of the chemicals were approximately proportional to the absolute hardness, and laterally toxic chlorinated PCDDs, PCBs, and DDTs are classified as chemically soft. Here we found that the electronic structures of environmental hormones can be classified into four main groups: 17beta-estradiol type (group I), testosterone type (group II), thyroxine type (group III), and HCH (hexachlorocyclohexane) type (group IV). Therefore, if we can predict the coordinate (chi, eta) of the electronic structure of one chemical on the eta-chi activity diagram, we would be able to predict the receptor with which the chemicals (environmental hormones) interact. For instance, 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) is classified in group II, therefore, it would bind with the thyroid receptor more than the estrogen receptor (group I). It appears that dibutyl phthalate would not interact with estrogen receptor because it does not belong to group I. In addition, the coordinates of these four groups do not complementarily overlap with the electronic structures of 20 natural amino acid residues. The eta-chi activity diagram is a new tool for the prediction of the toxicity and biological activity of environmental hormones.     

昆虫信息素的结构鉴定和合成XXIV: (TR,8S)-(+)-和(7S,8R)-(-)-午毒蛾性信息素的合成及β-羟基硅烷的立体化学

从Sharpless不对称环氧化反应所得的光学活性环氧醛(e.e.96-97%)与三甲基硅锂试剂反应,得到β-羟基硅烷.它们经转化成乙酰氧基化合物后,再通过β-乙酰氧基硅烷的消除反应和均相催化氢化即得到两个标题化合物.对β-羟基硅烷的各非对映异构体的构型进行了测定.