强镇痛活性生物碱Epibatidine及其类似物的构效关系研究

强镇痛活性生物碱Ｅｐｉｂａｔｉｄｉｎｅ及其类似物的构效关系研究徐建平，何东，王志中，沈家骢，高连勋，宋雅茹（吉林大学化学系理论化学研究所，长春，１３００２３）（中国科学院长春应用化学研究所）（北京师范大学化学系）关键词Ｅｐｉｂａｔｉｄｉｎｅ，ＡＭ１，...     

聚醚醚酮酮结晶度研究

聚醚醚酮酮结晶度研究刘天西，王尚尔，张宏放，莫志深（中国科学院长春应用化学研究所高分子物理联合开放研究实验室长春１３００２２）那辉，王军佐，吴忠文（吉林大学化学系长春）关键词聚醚醚酮酮，广角Ｘ射线衍射，结晶度新型特种工程塑料聚醚醚酮酮（ＰＥＥＫＫ）具...     

PES／PC共混体系的相容性与力学性能

ＰＥＳ／ＰＣ共混体系的相容性与力学性能姜振华，马荣堂，寇喜春，安立佳（吉林大学化学系长春）（中国科学院长春应用化学研究所长春１３００２２）关键词聚醚砜，聚碳酸酯，共混物，力学性能聚醚砜（ＰＥＳ）是一种性能优异的特种工程塑料，它具有强度高、刚性大、耐热...     

Epibatidine的全合成研究进展

概述了Ｅｐｉｂａｔｉｄｉｎｅ全合成研究的进展,全文分四部分：（１）Ｅｐｉｂａｔｉｄｉｎｅ的发现和结构的确定。（２）Ｅｐｉｂａｔｉｄｉｎｅ的全合成研究;（３）氮杂双环的合成,（４）Ｅｐｉｂａｔｉｄｉｎｅ的全合成研究进展,参考文献３４篇。     

有限线性扩散区域内EC＇反应催化电流

有限线性扩散区域内ＥＣ＇反应催化电流吴志斌，董绍俊，吴浩青（同济大学化学系，上海，２０００９２）（中国科学院长春应用化学研究所）（复旦大学化学系）关键词有限线性扩散空间，ＥＣ＇反应，催化电流化学修饰电极等有关膜电极及薄层池的电极过程动力学问题均涉及到...     

聚醚砜／聚酚氧共混体系相容性与力学性能

聚醚砜／聚酚氧共混体系相容性与力学性能姜振华，马荣堂，寇喜春，安立佳（吉林大学化学系长春）（中国科学院长春应用化学研究所长春１３００２２）关键词聚醚砜，聚酚氧，共混物，相容性，力学性能，熔体粘度聚醚砜（ＰＥＳ）是一种耐热特种工程塑料，但韧性差、熔体粘...     

酚类在聚醚醚酮上的分离行为研究

酚类在聚醚醚酮上的分离行为研究于剑锋，吴通好，孙家（吉林大学化学系，理论化学研究所，长春，１３００２３）关键词：气相色谱固定相，聚醚醚酮，分离，酚类化合物聚醚醚酮［Ｐｏｌｙ（ｅｔｈｅｒ－ｅｔｈｅｒ－ｋｅｔｏｎｅ），简称ＰＥＥＫ］是近年来推出的一种新型...     

电解液添加成份对贮氢电极性能影响的初步研究

电解液添加成份对贮氢电极性能影响的初步研究蔡称心，黄翠虹（南京大学化学系，南京，２１０００８）王宝忱（中国科学院长春应用化学研究所，长春１３００２２）关键词：贮氢电极，ＭＨ／Ｎｉ电池，添加剂自从Ｊｕｓｔｉ和Ｅｗｅ￣［１，２］发现贮氢合金能够用电化学方...     

发光体YAG的软化学方法合成

发光体ＹＡＧ的软化学方法合成石士考刘行仁（河北师范大学化学系石家庄０５００９１）（中国科学院长春物理研究所１３００２１）ＹＡＧ（Ｙ３Ａｌ５Ｏ１２）不仅具有优良的光学和机械性质，还是极好的阴极射线发光（ＣＬ）、电致发光（ＥＬ）和光致发光（ＰＬ）材料［１...     

两步法提取笼内金属富勒烯

两步法提取笼内金属富勒烯郝春雁，刘子阳，徐文国，郭兴华，刘淑莹（中国科学院长春应用化学研究所，吉林大学化学系，长春，１３００２２）关键词金属富勒烯，索氏提取，ＤＥＩ－ＭＳ，ＬＤＩ－ＭＳ目前笼内包含金属的富勒烯化合物以其新颖独特的结构和性质而格外引人注...     

Medicinal Chemical Studies of Anti-Inflammatory and Analgesic Natural Products

Following the discovery of salicylates and its conversion to aspirin, natural products research has provided many promising leads for further modification as anti-inflammatory and analgesic agents. Recent studies have focused on biosynthesis inhibitors of eicosanoids and receptor antagonists of the platelet activating factor, including a new class of dual functional inhibitors derived from neolignans. The highly potent analgesic alkaloid epibatidine from the frog skin has been synthesized and recharacterized as a very strong acetylcholine nicotinic receptor agonist. Some novel epibatidine analogs have shown promise as potential CNS drugs and research probes for clarifying the anti-addictive property of the African alkaloid ibogaine.     

Structural features and protonation site of epibatidine in the gas phase: an investigation through infrared multiphoton dissociation spectroscopy and computational chemistry

The gas phase structures of epibatidine, one of the most potent agonists of nicotinic acetylcholine receptors (nAChRs), are determined by means of infrared multiphoton dissociation (IRMPD) spectroscopy and quantum chemistry calculations. Comparison of the experimental and theoretical spectra provides evidence that about 15% of epibatidine is protonated on the Nsp(2) nitrogen in the gas phase. In contrast, the computational study of deschloroepibatidine shows that in the gas phase, the molecule is present only protonated on the Nsp(2) nitrogen. The main minima of the Nsp(2) protonated forms of the two molecules are strongly stabilized by intramolecular CH···Nsp(3) hydrogen bonds. The fundamental insights obtained in the present study on these two important nAChRs agonists show how subtle chemical modifications can have a deep impact on important physicochemical properties.     

Synthesis of heterocyclic analogues of epibatidine via 7-azabicyclo[2.2.1]hept-2-yl radical intermediates. 1. Intermolecular reactions

The synthesis and reactivity of the 7-azabicyclo[2.2.1]hept-2-yl radical has been extensively investigated in inter- and intramolecular reaction processes for the first time. In this work we will present the preparation of the radical and its successful intermolecular reaction with radical acceptors such as tert-butylisocyanide and acrylonitrile. Computational analyses have been carried out to show and explain the mechanisms and stereochemical outcome of these transformations. Overall and from the chemical point of view, a new and convenient synthetic approach has been developed for the synthesis of exo-2-(cyano)alkyl substituted 7-azabicyclo[2.2.1]heptane derivatives, a series of compounds of wide interest for the synthesis of heterocyclic analogues of epibatidine. As a result, we describe here the synthesis of the tetrazoloepibatidines (8 and 15) and the oxadiazoloepibatidine (10).     

Determination of the in vitro metabolism of (+)- and (-)-epibatidine

The oxidative in vitro metabolism of epibatidine was investigated using liver microsomes from rat, dog, rhesus monkey and human. Analysis was performed using liquid chromatography-mass spectrometry (LC-MS) using both achiral and chiral stationary phases. Comparison of the metabolism of the (+)- and (-)-enantiomers revealed species differences in the extent of metabolism, with rhesus monkey>dog>rat=human. Furthermore, differences in the routes of metabolism for epibatidine enantiomers were also observed, with mass spectra consistent with hydroxylation of the azabicycle for (-)-epibatidine and with the formation of diastereomeric N-oxides for (+)-epibatidine being obtained. For chiral LC-MS, a volatile ion-pair reagent of heptafluorobutyric acid was used in place of pentanesulphonic acid with no deterioration in chiral selectivity. Analysis of the same samples by chiral LC-MS revealed no evidence for metabolic chiral interconversion and chiral analysis from a metabolic time course of racemic material revealed enantiomers to be metabolised to approximately the same extent. Such findings may be important particularly should epibatidine be investigated in non-rodent species.     

Nicotin

Tobacco and its main alkaloid nicotine have been of superior importance with relation to the history of many civilizations. Predominately it has been used for human consumption. However, nicotine was also one of the first highly efficient insecticides, already used for agricultural purposes more than one hundred years ago. Biosynthetically nicotine derives from several amino acids. It is related to a variety of other natural products, like anabasine, epibatidine, cytosine and anatoxin A, with similar pharmacological properties. Since elucidation of the correct chemical structure of nicotine by Adolf Pinner and Paul Karrer several smart syntheses of racemic as well as enantiopure nicotine have been published.     

Using physical chemistry to differentiate nicotinic from cholinergic agonists at the nicotinic acetylcholine receptor

The binding of three distinct agonists-acetylcholine (ACh), nicotine, and epibatidine-to the nicotinic acetylcholine receptor has been probed using unnatural amino acid mutagenesis. ACh makes a cation-pi interaction with Trp alpha149, while nicotine employs a hydrogen bond to a backbone carbonyl in the same region of the agonist binding site. The nicotine analogue epibatidine achieves its high potency by taking advantage of both the cation-pi interaction and the backbone hydrogen bond. A simple structural model that considers only possible interactions with Trp alpha149 suggests that a novel aromatic C-H...O=C hydrogen bond further augments the binding of epibatidine. These studies illustrate the subtleties and complexities of the interactions between drugs and membrane receptors and establish a paradigm for obtaining detailed structural information.     

Die Neonicotinoide. Nicotin und die Neonicotinoide – Teil 2

The cholinergic synapse is an important target for many highly selective insecticides. Nicotine and the neonicotinoids bind to the postsynaptical nicotinic acetylcholine receptor. The neonicotinoids did not derive of lead‐optimisation of natural products, e.g. nicotine or epibatidine, but from artificial nitro‐substituted ketene aminales. Today, the neonicotinoids are attributed as the most important group of insecticides on the crop protection market. Many smart syntheses have been published.     

Functionalization of the alicyclic skeleton of epibatidine: synthesis and nicotinic acetylcholine receptor binding affinities of epibatidine analogues

A novel method for the epimerization of endo-2-(6-chloro-3-pyridyl)-7-azabicyclo[2.2.1]heptan-3-one (12) on silica gel was developed and used as the key step to synthesize functionalized analogues of epibatidine which were evaluated for their nicotine receptor subtype selectivity in binding studies.