(+/-)-3α-hydroxy-6β-acetoxytropane

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: (+/-)-3α-hydroxy-6β-acetoxytropane
• 英文别名: (+/-)-6β-acetoxytropan-3α-ol；[(1S,3S,5R,6S)-3-hydroxy-8-methyl-8-azabicyclo[3.2.1]octan-6-yl] acetate
• 化学式: C₁₀H₁₇NO₃
• 分子量: 199.25
• InChiKey: AEVQETQLKSVJET-QEYWKRMJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+/-)-3α-hydroxy-6β-acetoxytropane 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.25h， 生成 (1R,3R,5S)-3-[Bis-(4-fluoro-phenyl)-methoxy]-8-methyl-8-aza-bicyclo[3.2.1]octan-6-one
  参考文献：
  名称：

  The effect of 6-substituted-4′,4″-difluorobenztropines on monoamine transporters and the muscarinic M1 receptor

  摘要：

  A series of racemic 6-hydroxy and carboalkoxy substituted-4',4"-difluorobenztropines was synthesized and evaluated for binding at the dopamine (DAT), the serotonin (SERT), the norepinephrine (NET) transporters, and the muscarinic M1 receptor. Each of the analogues displaced [H-3]WIN 35,428 (DAT) with a range of affinities from 5.81 to 175 nM and [H-3]pirenzepine (M1), with a range of affinities (K-i = 27.0-8430 nM). Binding affinities at the SERT and the NET were generally low. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2004.03.075
• 作为产物：
  描述：

  (1R,5R,6S)-6-羟基-8-甲基-8-氮杂双环[3.2.1]辛烷-3-酮 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 7.0h， 生成 (+/-)-3α-hydroxy-6β-acetoxytropane
  参考文献：
  名称：

  金丝桃叶生物碱

  摘要：

  摘要 从金丝桃(Erythroxylum hypericifolium) 的叶子中表征了15 种生物碱；大多数是肉桂酸酯和苯甲酸酯。3α-Cinnamoyloxytropan-6β-ol 是主要碱。报道的新生物碱是 3β-cinnamoyloxytropane、3α, 6β-dicinnamoyloxytropane、3-cinnamoyloxynortropan-6-ol、6β-acetoxy-3α-cinnamoyl-oxytropane 和暂定的 6-phenylacetoxytropan-3-ol。还发现了两种混合的肉桂酸二聚体。报告了一些合成，并讨论了结果的化学分类学意义。

  DOI：

  10.1016/0031-9422(89)80309-7

文献信息

• The effect of absolute configuration on activity, subtype selectivity (M3/M2) of 3α-acyloxy-6β-acetoxyltropane derivatives as muscarinic M3 receptor antagonists
  作者：Zhi-Peng Wang、Hui-Zhong Liu、Liang Zhu、You-Min Hu、Yong-Yao Cui、Yin-Yao Niu、Yang Lu、Hong-Zhuan Chen

  DOI：10.1016/j.bmc.2012.12.052

  日期：2013.3

  muscarinic M3 or M2 receptors and elicited antagonistic activity. Furthermore, the muscarinic M3 activity and subtype selectivity (M3/M2) of 6S enantiomers could be improved by increasing the electron density of carbonyl oxygen or introducing methylene group between the carbonyl and phenyl ring in C-3α position. Understanding the effect of absolute configuration on activity, subtype selectivity (M3/M2)

  3α酰氧基6β-acetoxyltropane衍生物的两种对映体1 - 4分别和后行制备功能性研究和放射性受体结合测定。通过功能研究，6 S对映异构体显示出明显的毒蕈碱M3，M2拮抗活性，而6 R对映异构体几乎没有毒蕈碱活性。此外，6 S对映体与大鼠下颌腺的毒蕈碱M3受体，大鼠左心房的M2受体的亲和力远大于相应的6 R对映体。所有这些药理结果表明6 S构型有利于3α-酰氧基-6β-乙酰氧基托环烷衍生物与毒蕈碱型M3或M2受体结合并引起拮抗活性。此外，可以通过增加羰基氧的电子密度或在C-3α位置的羰基和苯环之间引入亚甲基来提高6 S对映异构体的毒蕈碱M3活性和亚型选择性（M3 / M2）。了解绝对构型对活性的影响，3α-酰氧基-6β-乙酰氧基托烷衍生物的亚型选择性（M3 / M2）将为设计具有高活性，低副作用或低毒性的毒蕈碱M3拮抗剂提供线索。
• The absolute configuration plays an important role in muscarinic activity of BGT-A and its analogs
  作者：Yin-Yao Niu、Liang Zhu、Yong-Yao Cui、Hui-Zhong Liu、Hong-Zhuan Chen、Yang Lu

  DOI：10.1016/j.bmc.2008.10.047

  日期：2008.12.15

  Both enantiomers of 2, 3, and 4, three bioactive analogs of muscarinic agonist BGT-A were prepared respectively and underwent functional studies and radioreceptor binding assays. 6S enantiomers of 2, 3, and 4 showed obvious muscarinic activity, while 6R ones elicited little muscarinic activity by functional studies. Besides, the affinity of 6S enantiomers of 2, 3, and 4 was greatly larger than that of their 6R enantiomers respectively. All these pharmalogical results indicated the 6S configuration was beneficial for the active BGT-A analogs to bind with the muscarinic receptors. The finding was in good agreement with our previous SAR study to BGT-A and its active analogs by computational approach. The understanding to the relationship between muscarinic activity and absolute configuration will provide the basis for successive screening of BGT-A analogs as effective muscarinic agonists or antagonists in clinical use. (C) 2008 Elsevier Ltd. All rights reserved.