刺乌头碱氢溴酸盐的合成及晶体结构

报道了以双溴代烷烃和刺乌头碱合成刺乌头碱氢溴酸盐的方法. 用元素分析、红外光谱、高分辨质谱和核磁共振进行了表征. 并用X射线单晶衍射确定了标题化合物的绝对构型. 晶体结构表明, 该化合物通过分子间氢键形成了网状类似超分子结构. 晶体属于单斜晶系, P2₁空间群, 晶胞参数: a＝1.0619(2) nm, b＝1.2196(3) nm, c＝1.2282(2) nm, β＝90.87(1)°, V＝1.59037(54) nm³, Z＝2, D_m＝1.428 g/cm^－3, F(000)＝720.0, µ＝1.349 mm^－1. 环 A, B, C, D, E和F分别呈船式、椅式、信封式、船式、船式和信封式. 其绝对构型被确定为1S,4S,5S,7S,8S,9S,10S,11S,13R,14S,16S,17R.     

刺乌头碱的提取与其氢溴酸盐的合成及表征

刺乌头碱;刺乌头碱氢溴酸盐;合成;提取;表征     

Secokaraconitine, A New Diterpenoid Alkaloid from Aconitum karacolicum

The known diterpenoid alkaloids karacoline, karakanine, songorine, napelline, 12-acetylnapelline, cammaconine, and a new 7,17-secoalkaloid of the lycoctonine type, secokaraconitine, were isolated from tubers of Aconitum karacolicum. An x-ray structure analysis of the new alkaloid was performed.     

Crystal Structure of Akuammigine Picrate Hydrate

The single‐crystal X‐ray data of akuammigine picrate hydrate ( 1 ?Picr?H₂O) confirm the relative configuration of the indole alkaloid akuammigine ( 1 ) as epiallo (Fig. 1). With reference to the known (15S)‐configuration due to biosynthesis, the absolute configuration of the other stereogenic centers is thus given by (3R,19S,20S). Four crystallographically independent molecules are observed in the asymmetric unit (Fig. 2). Each of the alkaloid cations forms H‐bonds to a H₂O and a picrate anion (Fig. 3). The H₂O molecules are further associated by a H‐bond as indicated by the short O???O distance (Table 2). The conformation in the solid state of the picrate hydrate is now firmly established, and a cute H‐bonding motif is observed.     

Hybrides of Alkaloid Lappaconitine with Pyrimidine Motif on the Anthranilic Acid Moiety: Design,Synthesis, and Investigation of Antinociceptive Potency

Convenient and efficient routes to construct hybrid molecules containing diterpene alkaloid lappaconitine and pyrimidine fragments are reported. One route takes place via first converting of lappaconitine to 1-ethynyl-lappaconitine, followed by the Sonogashira cross-coupling-cyclocondensation sequences. The other involves the palladium-catalyzed carbonylative Sonogashira reaction of 5′-iodolappaconitine with aryl acetylene and Mo (CO)₆ as the CO source in acetonitrile and subsequent cyclocondensation reaction of the generated alkynone with amidines. The reaction proceeded cleanly in the presence of the PdCl₂-(1-Ad)₂PBn∙HBr catalytic system. The protocol provides mild reaction conditions, high yields, and high atom and step-economy. Pharmacological screening of lappaconitine-pyrimidine hybrids for antinociceptive activity in vivo revealed that these compounds possessed high activity in experimental pain models, which was dependent on the nature of the substituent in the 2 and 6 positions of the pyrimidine nucleus. Docking studies were undertaken to gain insight into the possible binding mode of these compounds with the voltage-gated sodium channel 1.7. The moderate toxicity of the leading compound 12 (50% lethal dose (LD₅₀) value was more than 600 mg/kg in vivo) and cytotoxicity to cancer cell lines in vitro encouraged the further design of therapeutically relevant analogues based on this novel type of lappaconitine–pyrimidine hybrids.     

NaIO_4-Catalyzed Bromination of the Aromatic Ring of Lappaconitine

Lappaconitine 1, a bisnorditerpenoid alkaloid, was isolated from many plants of Aconitum species such as A. barbatum var. pulerulum and A. sinomontanum (Ranunculaceae)1-3, and used clinically for treatment of analgic disease as a nonaddicted drug in China4, and as an antiarrythmic in Uzbekistan5. In order to search for high activity, low toxicity compounds, we have carried out the structure modifications of lappaconitine. In this case, an attempt to induce the oxygenated group at C-10 in 1 b…     

Novel Product and Its Derivatives from the Reaction of Lappaconitine with HIO_4

Lappaconitine l, a bisnorditerpenoid alkaloid, was isolated from many plants ofAconitum and Delphinium species such as A. barbatum var. puberulum, A.sinomontanuml' 2. It is now used in the clinical practice as an analgesic in China', andantiarrhythmic drugs in Uzbekistan4' 5. In our attempts to prepare the 10-oxygenatedderivatives by treating lappaconitine I with HIO. followed by bromination, unexpectedby-products were obtained in modest yields. This communication described the isolationan…     

Resonance electron capture mass spectra of some diterpenoid alkaloids

Formation of negative ions from molecules of some diterpenoid alkaloids under conditions of resonance electron capture was studied. Ions formed by capturing low-energy electrons in the lowest unoccupied molecular orbital similar to the *-C=O or *-Ph—CO₂ orbitals contribute predominantly to the mass spectra.     

Alkaloids of Aconitum tuberosum. Structure of Tuberaconitine and Tubermesaconitine

Total alkaloids ofAconitum tuberosumroots afforded neoline and two new alkaloids, tuberaconitine and tubermesaconitine. The structures of the new alkaloids were proved based on spectral data and chemical transformations from aconitine and mesaconitine     

DSC and NMR Study on the Inclusion Complex of Lappaconitine with β—Cyclodextrin

The inclusion complex of lappaconitine(Lap) with β-cyclodextrin (β-CD) has been studied by the differential scanning calorimetry (DSC) and ^1H-NMR,2D-NMR spectroscopy. The structure of the complex has been deduced.     

Crystal and Molecular Structure of the Isoflavones Irilin B and Betavulgarin

The molecular structures of the isoflavones irilin B and betavulgarin, which were isolated for the first time from the aerial part of Iris tenuiflorita, were solved by x-ray structure analyses. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 319–321, July–August, 2005.     

DSC and NMR Study on the Inclusion Complex of Lappaconitine with b-Cyclodextrin

Lappaconitine (Figure 1) is a diterpenoid alkaloid, naturally occurring in roots and rhizomes of Aconitum and delphinium1. Lap reveals bradycardic and hypotensive activity2. But its application is restrained owing to its poor water solubility, toxicity and side effects on humans. In a number of pharmaceutical studies, b-CD has been reported to interact with many drug molecules to form inclusion complexes for improving the water solubility of drugs, and reducing their toxicity3. We have p…     

Crystal Structure Prediction and Isostructurality of Three Small Molecules

A crystal structure prediction (CSP) study of three small, rigid and structurally related organic compounds (differing only in the position and number of methyl groups) is presented. A tailor‐made force field (TMFF; a non‐transferable force field specific for each molecule) was constructed with the aid of a dispersion‐corrected density functional theory method (the hybrid method). Parameters for all energy terms in each TMFF were fitted to reference data generated by the hybrid method. Each force field was then employed during structure generation. The experimentally observed crystal structures of two of the three molecules were found as the most stable crystal packings in the lists of their force‐field‐optimised structures. A number of the most stable crystal structures were re‐optimised with the hybrid method. One experimental crystal structure was still calculated to be the most stable structure, whereas for another compound the experimental structure became the third most stable structure according to the hybrid method. For the third molecule, the experimentally observed polymorph, which was found to be the fourth most stable form using its TMFF, became the second most stable form. Good geometrical agreements were observed between the experimental structures and those calculated by both methods. The average structural deviation achieved by the TMFFs was almost twice that obtained with the hybrid method. The TMFF approach was extended by exploring the accuracy of a more general TMFF (GTMFF), which involved fitting the force‐field parameters to the reference data for all three molecules simultaneously. This GTMFF was slightly less accurate than the individual TMFFs but still of sufficient accuracy to be used in CSP. A study of the isostructural relationships between these molecules and their crystal lattices revealed a potential polymorph of one of the compounds that has not been observed experimentally and that may be accessible in a thorough polymorph screen, through seeding, or through the use of a suitable tailor‐made additive.     

Study of alkaloids of the Siberian and Altai flora. 10. Synthesis of N(20)-deethyllappaconitine derivatives

Efficient procedures were developed for N-deethylation of lappaconitine to give N(20)-deethyllappaconitine. Alkyl derivatives of N(20)-deethyllappaconitine, including labeled lappaconitine, and N(20)-acetoxy-N(20)-deethyllappaconitine were prepared for the first time. The assignments of the signals for the carbon atoms in the ¹³C NMR spectra of lappaconitine and related lappaconine were refined using ¹³C—¹³C 2D INADEQUATE and 2D ¹³C—¹H correlation experiments.     

Classification of diterpenoid alkaloids from Aconitum kusnezoffii Reichb. by liquid chromatography-tandem mass spectrometry-based on molecular networking

Trace amounts of components in traditional Chinese medicine are considered pharmacological active substances used for treating many serious diseases. However, purifying all the trace substances and making clear their structures are not easy. In this context, high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry based molecular networking was applied to investigate the chemical constituents of the roots of Aconitum kusnezoffii Reichb., which led to the identification of 33 nodes in different groups ( N1 – N33 ). Based on the excremental fragmentation pathway of known diterpenoid alkaloids ( 1 – 9 ) and comparisons of characteristic ions and characteristic loss of analogs in literature, the structures of unknown ions were deduced. This work lays a foundation for the evaluation of the clinical basis and mechanism of traditional Chinese medicine from the aspects of chemistry. In this paper, the method speculation of unknown natural products by means of molecular network method is expected to be applied in the discovery and change law of relevant active components in clinical pharmacology and the change of complex systems caused by trace active compounds.     

Diterpenoid alkaloids of Delphinium schmalhausenii

From the aerial parts of Delphinium schmalhausenii six norditerpenoid alkaloids gigactonine, lycoctonine, anthranoyllycoctonine, delsemine A, delsemine B, N-acetyldelectine and a diterpenoid alkaloid septatisine were isolated. Published in Khimiya Prirodnykh Soedinenii, No. 1, pp. 60–61, January–February, 2006.     

Molecular Structure of γ-Apienes. Crystal and Molecular Structure of Ferocin

The molecular structure of the sesquiterpene humulene ester ferocin isolated from plants of the Ferula genus was determined by x-ray structure analysis. The conformation of the 11-membered γ-humulene ring was analyzed by molecular mechanics. It was found that four energetically similar macrocycle conformations are characteristic of γ-apienes.__________Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 125–128, March–April, 2005.     

X-ray Crystal Structure and Molecular Mechanics Calculations of (2,6-iso-dipropyl-phenylamide) Dimethyl ( tetra-methylcyclopenta-dienyl ) Silane Titanium Dichloride

Crystal and molecular structure of (2,6-dipropylphenylamide) dimethyl (tetra-methyl cyclopentadienyl) silane titanium dichloride (I) was fully characterized by X-ray diffraction. The crystal is obtained from a mixture of ether/hexane as orthorhombic, with a = 12.658 (3) (A), b = 16.62 (3)(A), c = 11.760 (2)(A), V = 2474.2 (9)(A) 3, Z = 4, space group Pnma, R = 0.0399. Componud I compose of the π-bounded ring with its dimethylsilyl-dipropyl phenyl amido group and the two terminal chloride atoms coordinated to central metal to form a so-called constrained geometry catalyst (CGC) structure. The result of molecular mechanics (MM) calculations on compound I shows that bond lengths and bond angles from the MM calculation are comparable to the data obtained from the X-ray diffraction study. The relation of the structure of CGCs and their catalytic activity by MM calculations is also discussed.