含四氢噻吩类生物素杂质的合成

d-生物素(d-Biotin)又称维生素H、辅酶R,其已广泛应用于医药、家禽、家畜的营养和饲料添加剂方面[1-4].目前比较权威的质量标准是欧洲药典[5],其在美国药典[6]的基础上提出了5个有关物质(杂质A,B,C,D,E)的TLC控制.     

Synthesis and X‐ray analysis of 7‐bromoarbidol,an impurity standard of arbidol

For the first time, synthesis and X‐ray analysis of 7‐bromoarbidol hydrochloride is reported. The latter is a proven impurity of Arbidol which is an antiviral drug marketed in Russia and China. J. Heterocyclic Chem., (2011).     

Electron density near an impurity

The behavior of the electron density n(r) [and potential energy V(r)] near an impurity of charge Z is studied by using the linear response theory of an electron gas at finite temperature and with exchange and correlation effects included. The odd powers series in the expansion of n(r) [and V(r)] are calculated exactly by using asymptotic methods, and the coefficients in the series are given in terms of moments taken over the Fermi–Dirac distribution function. In all linear response theories and at all temperatures, the derivative n'(0) = -2Zn₀/a₀, where n₀ is the unperturbed electron density and a₀ is the Bohr radius. The effects of exchange and correlation appear in the fifth- and higher-order terms in n_odd(r).     

Electronic energy transfer in an impurity band

In this paper we explore the dynamics of triplet electronic energy transfer in an impurity band of a substitutionally-disordered material. The general characteristics of the solutions of the master equation in the strong scattering regime have been studied, leading to a generalized diffusion equation that contains a memory term, which results in a time-dependent diffusion coefficient. Approximate results for the average density of excitation were derived within the framework of the pair-approximation, resulting in explicit expressions for the time-resolved spectral diffusion, the mean-square displacement, as well as the time-dependent diffusion coefficient for electronic transfer processes induced by exchange interactions.     

Behavior of the electron density near an impurity

The behavior of the electron density n(r) and potential energy V(r) near the origin, where an impurity of charge Z is located, is studied using the Lindhard dielectric theory of the free-electron gas. The leading odd terms in the power-series expansion of n(r) and V(r) are obtained. It is shown that the derivative n′(0) = ?2Zn₀/a₀, where n₀ is the free-electron gas density and a₀ is the Bohr radius.     

Structural analysis of an impurity of the drug landiolol

In a course of development and preparation of landiolol (1a), a known ultra‐short‐acting β‐blocker, process quality control by HPLC and LC‐MS analysis consistently showed an impurity peak ranging from 0.05% to 0.15 % and exhibiting a molecular mass m/z 887. To identify the hitherto unknown impurity, we prepared one of the possible landiolol derivatives with the same molecular mass for proper spectral characterization (NMR and MS). Its equivalence with the unknown impurity was then confirmed by LC‐MS analysis. Ultimately, using fragmentation patterns in LC‐MS and selective two‐dimensional NMR experiments, the structure of the impurity was assigned as [(4S)‐2,2‐dimethyl‐1,3‐dioxolan‐4‐yl]methyl 3‐{4‐[(2S)‐2‐hydroxy‐3‐(3‐{4‐[(2S)‐2‐hydroxy‐3‐[(2‐{[(morpholin‐4‐yl)carbonyl]amino}ethyl)amino]propoxy]phenyl}‐N‐(2‐{[(morpholin‐4‐yl)carbonyl]amino}ethyl)propanamido)propoxy]phenyl}propanoate (2). It was found that the impurity was present in two rotameric forms at room temperature. The synthesis and NMR characterization of (2) are discussed. Copyright © 2014 John Wiley & Sons, Ltd.     

RP–LC Simultaneous Determination of Aconitine,Solanine and Piperine in an Ayurvedic Medicine

By optimizing the extraction, separation and analytical conditions, a reliable, rapid, simple and accurate liquid chromatography method with UV detection was developed for the simultaneous quantitative determination of aconitine, solanine and piperine in an ayurvedic preparation prepared from Aconitum ferox, Solanum indicum, Piper nigrum and Piper longum. The separation of these alkaloids was achieved on an reversed phase C-18 column (250 mm × 4.6 mm ID, 5 μm particle size), with isocratic elution using a mixture of acetonitrile–potassium hydrogen phosphate buffer (10 mM, pH 7.5)–methanol (60:25:15, v/v) at a flow rate of 1 mL min⁻¹ with UV detection at 227 nm for aconitine and solanine while 343 nm for piperine. The calibration curves were linear with correlation coefficients of 0.9990, 0.9942, 0.9989 for solanine, piperine and aconitine, respectively. The % Relative standard deviation (%RSD) values were less than 2% in the concentration range of 10–100 μg mL⁻¹ for all the three alkaloids. Intra-day assay and inter-day assay precision of the analytes were less than 2%, and the average recovery rates obtained were in the range of 98–102% for all with %RSD below 2%. Quantitative analysis of the alkaloids in the laboratory and marketed formulations showed that the contents of the alkaloids varied significantly. This method can provide a scientific and technical platform to the product manufacturers for setting up a quality control standard as well as to the public for quality and safety assurance of the proprietary ayurvedic formulations.

     

Identification of an isomer impurity in piperaquine drug substance

A significant contaminant of the antimalarial drug piperaquine (1,3-bis-[4-(7-chloroquinolyl-4)-piperazinyl-1]propane) has been identified using liquid chromatography-mass spectrometry (LC-MS) and 2D NMR spectroscopy (1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC). The impurity was identified as the positional isomer 1-[(5-chloroquinolin-4)-piperazinyl]-3-[(7-chloroquinolin-4)-piperazinyl]propane. The impurity is formed because of contamination of batches of 4,7-dichloroquinoline (a precursor in the synthesis of piperaquine) with 4,5-dichloroquinoline. The amount of impurity (peak area impurity/peak area piperaquine using LC-UV at 347 nm) in old batches of piperaquine and in Artekin (the combination of dihydroartemisinin-piperaquine) ranged from 1.5 to 5%.     

Synthesis and identification of 4-methyl-N-(4H-1,2,4-triazol-4-yl)-2-benzothiazolamine,an impurity in the synthesis of tricyclazole

The synthesis of 4-methyl-N-(4H-1,2,4-triazol-4-yl)-2-benzothiazolamine, 4 , a by-product in the synthesis of tricyclazole, 1 , by oxidative cyclization of the corresponding thiourea, 12 , with thionyl chloride, is described.     

Electronic structure of long polyene chains with an impurity atom

The influence of an impurity atom on the -electronic structure of long polyenes is considered using the unrestricted Hartree-Fock (UHF) method. It is shown that the substitution of a carbon atom in a long polyene chain is a local perturbation in spite of the nonlinearity of the UHF Hamiltonian. The conditions under which the local states appear in the forbidden zone of long polyenes are stated. Some experiments are proposed to elucidate the nature of the forbidden zone in the -electron spectra of long polyene chains.

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Zusammenfassung Der Einfluß eines Fremdatoms auf die -Elektronenstruktur langer Polyene wird mit Hilfe der uneingeschränkten Hartree-Fock-Methode (UHF) untersucht. Es wird gezeigt, daß die Substitution eines C-Atoms in einer langen Polyenkette eine lokale Störung darstellt, obwohl der UHF-Hamiltonoperator nicht linear ist. Die Bedingungen, unter denen die lokalen Zustände in der verbotenen Zone für die langen Polyene erscheinen, werden dargestellt. Einige Experimente zur Aufklärung der Natur der verbotenen Zonen in den -Elektronen-Spektren langer Polyenketten werden vorgeschlagen.

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Résumé La méthode Hartree-Fock sans restrictions (UHF) est utilisée pour étudier l'influence d'une impureté atomique sur la structure électronique des grands polyénes. On montre que la substitution d'un atome de carbone dans une longue chaîne polyénique est une perturbation locale en dépit de la non linéarité de l'hamiltonien UHF. On énonce les conditions d'apparition des états locaux dans la zone interdite des longs polyènes. Certaines expériences sont proposées pour élucider la nature de la zone interdite dans le spectre d'électrons des longues chaînes polyéniques.

     

Electronic structure of carbon nanotubes with an impurity point defect

A method for calculating the electronic structure of point defects in nanotubes is developed on the basis of the linear augmented cylindrical wave (LACW) method. The Green function of a defect nanotube is calculated using the Dyson matrix equation. The consideration is carried out in terms of the local density functional theory and the muffin-tin approximation for the electronic potential. Local densities of state are calculated for boron and nitrogen dopants in metal, semimetal, and semiconductor and chiral and nonchiral nanotubes. An increased density of states at the Fermi level is the most significant effect of boron and nitrogen dopants in metal nanotubes. In all semiconductor nanotubes, localized boron states close the optical band-gap. The effect of nitrogen atoms is restricted to a small rise in local densities of state at the Fermi level.     

Synthesis and characterization of Rosuvastatin calcium impurity A; a HMG-CoA reductase inhibitor

During the process development for multistep synthesis of Rosuvastatin calcium several impurities were obtained along with the final Rosuvastatin calcium. Out of this; synthesis of impurity A (acetone adduct) a minor impurity of Rosuvastatin calcium (3R,5S,6E)-7-[4-(4-fluorophenyl)-2-[[(2-hydroxy-2-methylpropyl)sulfonyl(methyl)amino]-6-(1-methylethyl)-pyrimidin-5-yl]-3,5-dihydroxyheptenoicacid hemicalcium salt, is described. The synthesis of impurity A has been accomplished in 6 steps; starting from formation of β-hydroxy sulfonamide as the key intermediate and followed by using convenient routes with overall yield of 13.5%. The target compound can be used as the reference substance of impurity of the Rosuvastatin calcium.     

Synthesis of silenosterone, an insect-molting hormone

Silenosterone is synthesized in five steps: acetylation of 2-desoxy-α-ecdysone (1), saponification of 2-desoxy-α-ecdysone-3,22-diacetate (2) to the 22-monoacetate (3), and oxidation of the latter to a ketone (4) and its base hydrolysis (5). The structures of the compounds are confirmed by PMR, IR spectroscopy, and mass spectrometry. Academician S. Yu. Yunusov Institute of the Chemistry of Plant Substances. Academy of Sciences of the Republic of Uzbekistan, Tashkent, fax (99871) 120 64 75. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 767–770, November–December, 1999.     

Experimental observation of Wannier-Mott impurity ground states in an amorphous medium

The experimental observation of Wannier-Mott impurity ground states in an amorphous material is reported.     

Synthesis, characterization, and isomerization of an iridabenzvalene

Metal- halogen exchange of vinylcyclopropene 4 followed by addition of [(Me3P)2Ir(CO)Cl] produced iridabenzvalene 5. The metallabenzene valence isomer was characterized by NMR and IR spectroscopy and by X-ray crystallography. Isomerization of complex 5 to iridabenzene derivatives 6 and 13 was accomplished by thermolysis and by Ag+ ions, respectively. The former transformation was a clean and quantitative process that displayed first-order kinetics.     

Quantification of an intact monoclonal antibody, rituximab, by (RP)HPLC/DAD in compliance with ICH guidelines

We studied the quantification of an intact therapeutic monoclonal antibody (mAb), rituximab (RTX), using (reverse-phase) high-performance liquid chromatography with diode array detection ((RP)HPLC/DAD). To this end, we developed a chromatographic method and validated it as stability-indicating in accordance with the International Conference on Harmonization guidelines (ICH). A 300-Å C8 column (250 mm?×?4.6 mm, 5 μm) was used to perform the analysis, and the temperature was maintained at 70 °C. Although only one mAb was analyzed, it was necessary to apply a gradient to elute it with a complex organic mixture. Chromatograms were registered at several wavelengths, with λ?=?214 nm employed for quantification purposes. The method was developed to quantify marketed RTX under typical hospital administration conditions. Further dilution was avoided in order to prevent additional mAb modification, and in this way the method was shown to be linear from 60 to 5000 mg/L. The precision of the method (repeatability and intermediate precision, estimated as the relative standard deviation, RSD %), was less than 1.0 %. Accuracy, specificity, robustness, and system suitability were also evaluated as specified in the ICH guidelines. We conducted a comprehensive chromatographic analysis by submitting RTX to several informative stress conditions. These forced degradation studies were conducted for two reasons: to estimate the specificity of the method, and to evaluate the robustness of the mAb formulation against external stress factors when handling it in preparation for administration. Thus, we investigated the effects of acid, base, oxidation, ionic strength, temperature, and UV light. Although a slight modification to the intact mAb could not be distinguished chromatographically in the stress studies we conducted, the procedure proposed here to evaluate peak purity enabled us to detect it with a satisfactory level of confidence. The proposed method could therefore be considered stability-indicating for quantyfying the intact mAb since it is qualified to detect its degradation/modification. Finally, the method was used to evaluate RTX in a long-term stability study performed under hospital conditions of use.     

Synthesis of isocryptolepine,an alkaloid fromCryptolepis sanguinolenta

Isocryptolepine, an alkaloid recently isolated from the roots ofCryptolepis sanguinotenta, was synthesized by selective methylation at the N(5) atom of 11H-indolo(3,2-c]quinoline with excess Mel in toluene.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp.2795–2796, November,1996     

On the windows in the absorption spectrum of an ensemble of oscillators embedding an impurity oscillator

The windows in the absorption spectrum of a harmonic oscillator coupled to a bath can be given a two-parameter form identical to the Fano windows in the absorption cross section of an atom with an autoionizing state.