脱水芽子碱盐酸盐 | 74242-55-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: 脱水芽子碱盐酸盐
• 英文名称: anhydroecgonine hydrochloride
• 英文别名: (1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylic acid;hydrochloride
• CAS: 74242-55-0
• 化学式: C₉H₁₃NO₂*ClH
• 分子量: 203.669
• InChiKey: SLTJQTJRCKGLGT-CIRBGYJCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.29
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  脱水芽子碱盐酸盐 在 palladium on activated charcoal 1-氧化-2-巯基吡啶 、 4-二甲氨基吡啶 、 sodium hydroxide 、 sodium periodate 、 草酰氯 、 氢气 、 双氧水 、 sodium cyanoborohydride 、 sodium carbonate 、 三乙胺 、 N,N-二甲基甲酰胺 、 三氟乙酸 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 乙酸酐 、 溶剂黄146 、 甲苯 、 乙腈 为溶剂， 110.0 ℃ 、413.69 kPa 条件下， 反应 146.17h， 生成 古卡因
  参考文献：
  名称：

  Enantiospecific Synthesis of Natural (−)-Cocaine and Unnatural (+)-Cocaine from d- and l-Glutamic Acid

  摘要：

  Natural (-)-cocaine and unnatural (+)-cocaine have been synthesized enantiospecifically from D- and L-glutamic acid, respectively. The axial-equatorial substitutents were introduced by a stereo- and regiospecific dipolar cycloaddition to the corresponding (LR,5S)- and (1S,5R)-N-BOC-nortropenes with (ethoxycarbonyl)formonitrile N-oxide. A sequence of subsequent stereochemically controlled transformations converted the fused isoxazoline to the requisite P-hydroxy ester. Synthesis of the key intermediate N-BOC-nortropenes involved construction of the 8-azabicyclo[3.2.1]octane framework by Dieckmann condensation of cis-5-substituted D-and L-proline esters. For comparison, (1R,SS)-N-BOC-nortropene also was derived by degradation from natural cocaine. The cis-5-substituted D-and L-proline esters were obtained by sulfide contraction and subsequent catalytic hydrogenation to induce stereospecifically the C-5 stereochemistry from D-and L-thiopyroglutamate, which in turn were prepared from D-and L-glutamic acids, respectively.

  DOI：

  10.1021/jo980153t
• 作为产物：
  描述：

  古卡因 在 盐酸 、 水 作用下， 反应 24.0h， 生成 脱水芽子碱盐酸盐
  参考文献：
  名称：

  可卡因裂解产物脱水芽子碱甲酯以协同和时间依赖性方式促进可卡因诱导的大鼠原发性海马神经元死亡

  摘要：

  快克可卡因使用者同时暴露于挥发的可卡因及其主要热解产物，脱水芽子碱甲酯 (AEME)。尽管可卡因的神经毒性作用已被广泛研究，但对 AEME 或其组合知之甚少。我们使用暴露于可卡因 (2 mM)、AEME (1 mM) 及其组合 (C + A) 的大鼠原代海马细胞在 1、3、6 和 12 小时后研究细胞死亡过程。可卡因在 6 小时后增加 LC3 I，在 12 小时后增加 LC3 II，但降低了具有酸性囊泡的细胞百分比，表明自噬通量失败，这在 12 小时后激活了外在凋亡途径。AEME 神经毒性不涉及自噬过程；相反，它在 6 小时后激活 caspase-9，在 12 小时后激活 caspase-8，导致早期细胞凋亡的百分比很高。C + A 逐渐减少未损坏细胞的百分比，从 3 小时后开始；它在 6 小时后激活了两种凋亡途径，并且比单独的可卡因和 AEME 更具神经毒性。此外，C + A 在 12 小时后增加了

  DOI：

  10.1007/s00204-021-03017-z

文献信息

• [EN] METHODS FOR PRODUCING HYDROXYALKYL TROPANE ESTERS<br/>[FR] PROCÉDÉS DE PRODUCTION D'HYDROXYALKYL TROPANE ESTERS
  申请人：ENTROPIN INC

  公开号：WO2004018464A1

  公开（公告）日：2004-03-04

  This invention provides a method for preparing a hydroxyalkyl tropane ester, comprising: (a) contacting a tropane and 1,1'-carbonyldiimidazole to produce an activated tropane ester; (b) contacting the activated tropane ester with an excess of an alkanediol to form a reaction mixture; and (c) maintaining the reaction mixture at a temperature and for a sufficient time for the activated tropane ester to react with the alkanediol to form the corresponding hydroxyalkyl tropane ester. This method may be used to produce hydroxyalkyl derivatives of tropanes such as benzoylecgonine, ecgonine and ecgonidine.

  本发明提供了一种制备羟基烷基曲柳酯的方法，包括：（a）将曲柳和1,1'-羰基二咪唑接触以产生活化的曲柳酯；（b）将活化的曲柳酯与过量的脂肪二醇接触以形成反应混合物；并且（c）在足够的时间内将反应混合物保持在一定的温度下，使活化的曲柳酯与脂肪二醇反应形成相应的羟基烷基曲柳酯。该方法可用于生产苯甲酰异可卡因、异可卡因和异可吡啶等曲柳酯的羟基烷基衍生物。
• Novel tropane esters and methods for producing and using them
  申请人：——

  公开号：US20040171635A1

  公开（公告）日：2004-09-02

  This invention relates to novel primary diol tropane esters and related compounds, including methods for making and using those compounds. The compounds of this invention are those of formula (I), (II) or (III): 1 wherein A, B and R 1 are as defined herein. These compounds may be used as therapeutic and prophylactic agents against diseases such as immunoregulatory disorders, neuromuscular disorders, joint disorders, connective tissue disorders, circulatory disorders and pain.

  本发明涉及新型伯二醇托烷酯及相关化合物，包括制造和使用这些化合物的方法。本发明的化合物为式（I）、（II）或（III）的化合物： 1 其中 A、B 和 R 1 如本文所定义。这些化合物可用作免疫调节紊乱、神经肌肉紊乱、关节紊乱、结缔组织紊乱、循环系统紊乱和疼痛等疾病的治疗剂和预防剂。
• Methods for producing hydroxyalkyl tropane esters
  申请人：——

  公开号：US20040171834A1

  公开（公告）日：2004-09-02

  This invention provides a method for preparing a hydroxyalkyl tropane ester, comprising: (a) contacting a tropane and 1,1′-carbonyldiimidazole to produce an activated tropane ester; (b) contacting the activated tropane ester with an excess of an alkanediol to form a reaction mixture; and (c) maintaining the reaction mixture at a temperature and for a sufficient time for the activated tropane ester to react with the alkanediol to form the corresponding hydroxyalkyl tropane ester. This method may be used to produce hydroxyalkyl derivatives of tropanes such as benzoylecgonine, ecgonine and ecgonidine.

  本发明提供了一种制备羟基烷基托烷酯的方法，包括：(a)将托烷和1,1′-羰基二咪唑接触，生成活化的托烷酯;(b)将活化的托烷酯与过量的烷二醇接触，形成反应混合物;(c)将反应混合物保持在一定的温度和足够的时间，使活化的托烷酯与烷二醇反应，形成相应的羟基烷基托烷酯。这种方法可用于生产托烷的羟烷基衍生物，如苯甲酰可可碱、埃可宁和埃可尼丁。
• 3D QSAR Analyses-Guided Rational Design of Novel Ligands for the (α4)₂(β2)₃ Nicotinic Acetylcholine Receptor
  作者：Holger Gohlke、Simone Schwarz、Daniela Gündisch、Maria Cristina Tilotta、Alexander Weber、Thomas Wegge、Gunther Seitz

  DOI：10.1021/jm020859m

  日期：2003.5.1

  Three-dimensional quantitative structure-activity relationship methods, the comparative molecular field analysis (CoMFA) and the comparative molecular similarity indices analysis (CoMSIA), were applied using a training set of 45 ligands of the (alpha4)(2)(beta2)(3) nicotinic acetylcholine receptor (nAChR). All compounds are related to (-)-epibatidine, (-)-cytisine, (+)-anatoxin-a, and (-)-ferruginine, and additionally, novel diazabicyclo[4.2.1]nonane- and quinuclidin-2-ene-based structures were included. Their biological data have been determined by utilizing the same experimental protocol. Statistically reliable models of good predictive power (CoMFA r(2) = 0.928, q(2) = 0.692, no. of components = 3; CoMSIA r(2) = 0.899, q(2) = 0.701, no. of components = 3) were achieved. The results obtained were graphically interpreted in terms of field contribution maps. Hence, physicochemical. determinants of binding, such as steric and electrostatic and, for the first time, hydrophobic, hydrogen bond donor, and hydrogen bond acceptor properties, were mapped back onto the molecular structures of a set of nAChR modulators. In particular, changes in the binding affinity of the modulators as a result of modifications in the aromatic ring systems could be rationalized by the steric, electrostatic, hydrophobic, and hydrogen bond acceptor properties. These results were used to guide the rational design of new nAChR ligands such as 48-52 and 54, which were subsequently synthesized for the first time and tested. Key steps of our synthetic approaches were successfully applied Stille and Suzuki cross-coupling reactions. Predictive r(2) values of 0.614 and 0.660 for CoMFA and CoMSIA, respectively, obtained for 22 in part previously unknown ligands for the (alpha4)(2)(beta2)(3) subtype, demonstrate the high quality of the 3D QSAR models.
• AN IMPROVED PROCEDURE FOR THE SYNTHESIS OF ANHYDROECGONINE METHYL ESTER
  作者：C. R. Holmquist、K. R. Parham、J. A. Holleman、F. I. Carroll

  DOI：10.1080/00304949709355202

  日期：1997.6