甲基8-甲基-3-苯基-8-氮杂双环[3.2.1]辛烷-2-羧酸酯 | 50370-54-2

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 中文名称: 甲基8-甲基-3-苯基-8-氮杂双环[3.2.1]辛烷-2-羧酸酯
• 英文名称: Win 35140
• 英文别名: methyl 3β-phenyltropane-2α-carboxylate；2α-carbomethoxy-3β-phenyltropane；α-CPT；(1R,2R,3S,5S)-8-Methyl-3-phenyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid methyl ester；methyl (1R,2R,3S,5S)-8-methyl-3-phenyl-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 50370-54-2
• 化学式: C₁₆H₂₁NO₂
• 分子量: 259.348
• InChiKey: OMBOXYLBBHNWHL-GBJTYRQASA-N

物化性质

• 熔点：
  63-65oC
• 溶解度：
  可溶于氯仿（少许）、DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  甲基8-甲基-3-苯基-8-氮杂双环[3.2.1]辛烷-2-羧酸酯 在 硫酸 、 碘 、 硝酸 作用下， 以39%的产率得到RTI 258
  参考文献：
  名称：

  [123I] -2β-羰甲氧基-3β-（4-碘苯基）托烷：脑中单胺再摄取位点的高亲和力SPECT放射性示踪剂。

  摘要：

  DOI：

  10.1021/jm00114a027
• 作为产物：
  描述：

  脱水芽子碱甲基酯甲磺酸盐 、 phenylmagnesium bromide 生成 甲基8-甲基-3-苯基-8-氮杂双环[3.2.1]辛烷-2-羧酸酯
  参考文献：
  名称：

  KLINE, RICHARD H. (JR);WRIGHT, JEREMY;FOX, KRISTINE M.;ELDEFRAWI, MOHYEE +, J. MED. CHEM., 33,(1990) N, C. 2024-2027

  摘要：

  DOI：

文献信息

• 3-Aryl-2-(3'-substituted-1',2',4'-oxadiazol-5'-yl)tropane analogs of cocaine: affinities at the cocaine binding site at the dopamine, serotonin, and norepinephrine transporters
  作者：F. Ivy Carroll、Jeffrey L. Gray、Philip Abraham、Michael A. Kuzemko、Anita H. Lewin、John W. Boja、Michael J. Kuhar

  DOI：10.1021/jm00072a007

  日期：1993.10

  Previous studies have shown that 3 beta-(substituted phenyl)tropan-2 beta-carboxylic acid esters possess high affinity for the cocaine binding site on the dopamine transporter both in vitro and in vivo and inhibit dopamine uptake in vitro. Since 1,2,4-oxadiazoles are excellent bioisosteres of ester groups, we have prepared several 3 beta-(substituted phenyl)-2 beta-(3-substituted 1',2',4'-oxadiazol-5'-yl)tropanes

  先前的研究表明，3种β-（取代的苯基）tropan-2β-羧酸酯在体外和体内对多巴胺转运蛋白上的可卡因结合位点均具有高亲和力，并在体外抑制多巴胺的摄取。由于1,2,4-恶二唑是优异的酯基生物等排体，我们制备了3个3-β-（取代的苯基）-2β-（3-取代的1'，2'，4'-恶二唑-5'-基）托烷（5b-h）和（1R，5S）-3苯基-2-（3-甲基-1'，2'，4'-恶二唑-5'-基）托烷的所有四个立体异构体（5a和6-8 ）。3苯基苯基-2-α-（3'-甲基-1'，2'，4'-恶二唑）异构体7是通过向（1R，5S）-2-（3'-甲基-1′，2′，4′-恶二唑-5-基）-8-甲基-8-氮杂双环[3.2.1]辛-2-烯（11）。获得了在多巴胺，5-羟色胺和去甲肾上腺素转运蛋白上5a-h和6-8的结合亲和力。通常，这些生物甾体对多巴胺转运蛋白的效力与其母体酯相似。3 beta-（4'-氯苯基）-2
• Synthesis and cocaine receptor affinities of 3-phenyl-2-(3′-methyl-1,2,4-oxadiazole-5′-yl)tropane isomers
  作者：F. Ivy Carroll、Philip Abraham、Michael A. Kuzemko、Jeffrey L. Gray、Anita H. Lewin、John W. Boja、Michael J. Kuhar

  DOI：10.1039/c39930000044

  日期：——

  This study reports the synthesis and binding affinities at the cocaine receptor of all four isomers of 3-phenyl-2-(3-methyl-1,2,4-oxadiazole-5-yl)tropane derivable from natural (–)-cocaine

  本研究报告了从天然（−）可卡因衍生的所有四个异构体3-苯基-2-(3-甲基-1,2,4-噻唑-5-基)托烷的合成及其在可卡因受体的结合亲和力。
• Stereoselective synthesis of 2β-carbomethoxy-3β-phenyltropane derivatives. Enhanced stereoselectivity observed for the conjugate addition reaction of phenylmagnesium bromide derivatives with anhydro dichloromethane
  作者：Lifen Xu、Mark L. Trudell

  DOI：10.1002/jhet.5570330676

  日期：1996.11

  The use of dichloromethane as a solvent for the conjugate addition reaction of preformed etheral solutions of phenylmagnesium bromide derivatives with anhydroecgonine methyl ester (2) was found to enhance the stereoselectivity of the reaction and provide the 2β-carbomethoxy-3β-phenyltropane derivatives 3a-d in high yield.

  发现使用二氯甲烷作为溶剂使溴化镁镁衍生物的预先形成的醚溶液与脱水电子精氨酸甲酯（2）进行共轭加成反应，可增强反应的立体选择性并提供2β-羰甲氧基-3β-苯环戊烷衍生物3a-d高产。
• Alternative labelling of the cocaine analogue isomers α-CIT and β-CIT by direct iodination with no-carrier-added Na125I
  作者：Lars Müller、Christer Halldin、Carl-Gunnar Swahn、Christian Foged

  DOI：10.1002/jlcr.2580341105

  日期：1994.11

  An alternative labelling of the cocaine analogue isomers α-CIT and β-CIT with no-carrier-added 125I by direct iodination of 2α- and 2β-carbomethoxy-3β-phenyltropane with Na125I / sulfuric acid / nitric acid / acetic acid and peracetic acid under different reaction conditions, is described. The maximum radiolabelling yield obtained with the two isomers was 48% for [125I]α-CIT and 28% for [125I]β-CIT.

  本文介绍了在不同的反应条件下，用 Na125I/硫酸/硝酸/乙酸和过乙酸直接碘化 2α- 和 2β- 碳甲氧基-3β-苯基丙烷，用不添加载体的 125I 对可卡因类似物异构体 α-CIT 和 β-CIT 进行标记的替代方法。两种异构体的最大放射性标记率分别为：[125I]α-CIT 48%，[125I]β-CIT 28%。
• Base-catalyzed C-2 exchange and epimerization of cocaine analogs: methyl 3.beta.-substituted 8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylates
  作者：John F. Casale、Anita H. Lewin、J. Phillip Bowen、F. I. Carroll

  DOI：10.1021/jo00044a028

  日期：1992.8

  The kinetic and thermodynamic parameters associated with epimeric 2-carbomethoxy-3-beta-substituted tropanes have been investigated by means of base-catalyzed deuterium incorporation, epimerization, and by molecular modeling. The equilibration results, as well as the molecular mechanics calculations, showed the 2-alpha-epimers to be more stable than the 2-beta-epimers. However, it was found that the energies of the transitions states for deprotonation at C-2 from the beta-face were higher than those for deprotonation from the alpha-face. These results are contrary to what would have been predicted based on the assumption that the more exothermic reaction pathway would involve a more stabilized transition state.