(-)-methyl (1R,2R,3S,5S)-3-(benzoyloxy)-1,8-dimethyl-8-azabicyclo[3.2.1]octane-2-carboxylate | 1243634-58-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (-)-methyl (1R,2R,3S,5S)-3-(benzoyloxy)-1,8-dimethyl-8-azabicyclo[3.2.1]octane-2-carboxylate
• 英文别名: methyl (1R,2R,3S,5S)-(-)-3-(benzoyloxy)-1,8-dimethyl-8-azabicyclo[3.2.1]octane-2-carboxylate；(1R,2R,3S,5S)-methyl 3-(benzoyloxy)-1,8-dimethyl-8-azabicyclo[3.2.1]octane-2-carboxylate；1-methyl-cocaine；methyI (1R,2R,3S,5S)-(-)-3-(benzoyloxy)-1,8-dimethyl-8-azabicyclo[3.2.1]octane-2-carboxylate；methyl (1R,2R,3S,5S)-3-benzoyloxy-1,8-dimethyl-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 1243634-58-3
• 化学式: C₁₈H₂₃NO₄
• 分子量: 317.385
• InChiKey: GCVRHQXJBWNGEP-OIPACUDHSA-N

物化性质

• 沸点：
  396.7±42.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-甲基-1,3-二氧戊环-2-丙酸乙酯 在 盐酸 、 三乙基硅烷 、 4-二甲氨基吡啶 、 manganese(IV) oxide 、 lithium aluminium tetrahydride 、 草酰氯 、 (2R)-2-[二苯基[(三甲基硅酯)氧基]甲基]-吡咯烷 、 palladium 10% on activated carbon 、 水 、 氢气 、 二异丁基氢化铝 、 aluminum tri-tert-butoxide 、 二甲基亚砜 、 三乙胺 、 palladium dichloride 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 氯仿 、 甲苯 、 苯 为溶剂， -78.0~150.0 ℃ 、482.64 kPa 条件下， 反应 230.25h， 生成 (-)-methyl (1R,2R,3S,5S)-3-(benzoyloxy)-1,8-dimethyl-8-azabicyclo[3.2.1]octane-2-carboxylate
  参考文献：
  名称：

  简洁催化不对称全合成生物活性Tropane生物碱

  摘要：

  公开了通过催化立体选择性转化完全不对称合成有价值的托烷生物碱的一般策略。（+）-甲基芽子碱，（-）-可卡因和（+）-可卡因的简洁催化对映选择性总合成以及可卡因C-1衍生物和（ +）-ferruginine分别仅使用两步和三步色谱纯化步骤从5-氧代保护的α，β-不饱和烯醛开始。

  DOI：

  10.1002/adsc.201100917

文献信息

• Asymmetric Total Synthesis of (<i>S</i>)-(+)-Cocaine and the First Synthesis of Cocaine C-1 Analogs from <i>N</i>-Sulfinyl β-Amino Ester Ketals
  作者：Franklin A. Davis、Naresh Theddu、Ram Edupuganti

  DOI：10.1021/ol1017118

  日期：2010.9.17

  Sulfinimine-derived α,β-unsaturated pyrrolidine nitrones, on heating with Al(O-t-Bu)3, undergo a highly stereoselective intramolecular [3 + 2] cycloaddition to give tricyclic isoxazolidines, which are transformed in three-steps to give C-1 substituted cocaine analogs.

  亚砜胺衍生的α，β-不饱和吡咯烷腈与Al（O- t- Bu）3加热时，经历高度立体选择性的分子内[3 + 2]环加成反应，得到三环异恶唑烷，将其分三步转化为C -1个取代的可卡因类似物。
• [EN] COCAINE ANALOGS AND METHODS OF PREPARATION AND USES THEREOF<br/>[FR] ANALOGUES DE COCAÏNE ET LEURS PROCÉDÉS DE PRÉPARATION ET D'UTILISATION
  申请人：UNIV TEMPLE

  公开号：WO2012009263A1

  公开（公告）日：2012-01-19

  The invention provides novel cocaine analogs. The invention also provides a method of preparing cocaine analogs with control over the substituents installed at the C-1, C-2, C-3, C-4 and N-8 positions of the tropane bicyclic scaffold. The invention further provides a method of providing anesthesia to a subject in need thereof comprising administering to the subject a pharmaceutical composition comprising a compound of the invention. The invention also provides a method of blocking reuptake of a monoamine neurotransmitter in a subject in need thereof, to a subject in need thereof comprising administering to the subject a pharmaceutical composition comprising a compound of the invention.

  该发明提供了新型可卡因类似物。该发明还提供了一种制备可卡因类似物的方法，该方法可以控制在Tropane双环支架的C-1、C-2、C-3、C-4和N-8位置安装的取代基。该发明还提供了一种给需要麻醉的受试者提供麻醉的方法，包括向受试者注射包含该发明化合物的药物组合物。该发明还提供了一种阻止需要单胺神经递质再摄取的受试者的方法，包括向受试者注射包含该发明化合物的药物组合物。
• Enantioselective Synthesis of Cocaine C-1 Analogues using Sulfinimines (<i>N</i>-Sulfinyl Imines)
  作者：Franklin A. Davis、Narendra V. Gaddiraju、Naresh Theddu、Joshua R. Hummel、Sandeep K. Kondaveeti、Michael J. Zdilla

  DOI：10.1021/jo202652f

  日期：2012.3.2

  The first examples of cocaine analogues having substituents (methyl, ethyl, n-propyl, n-pentyl, and phenyl) at the C-1 position of the cocaine tropane skeleton were prepared by heating sulfinimine-derived alpha,beta-unsaturated pyrrolidine nitrones. In the presence of the Lewis acid Al((OBu)-Bu-t)(3) the nitrones undergo an intramolecular [3 + 2] cycloaddition to give tricyclic isoxazolidines that were transformed in three steps to the cocaine analogues. In the absence of the Lewis acid, lactams were formed resulting from rearrangement of the nitrone to an oxaziridine. A novel Pd-and base-promoted rearrangement of methanesulfonate salts of isoxazolidine to bridge bicyclic[4.2.1]isoxazolidines was discovered.
• Concise Catalytic Asymmetric Total Synthesis of Biologically Active Tropane Alkaloids
  作者：Armando Córdova、Shuangzheng Lin、Abrehet Tseggai

  DOI：10.1002/adsc.201100917

  日期：2012.5.7

  the total asymmetric synthesis of valuable tropane alkaloids by catalytic stereoselective transformations is disclosed. The power of this approach is exemplified by the concise catalytic enantioselective total syntheses of (+)‐methylecgonine, (−)‐cocaine and (+)‐cocaine as well as the first catalytic asymmetric total syntheses of a cocaine C‐1 derivative and (+)‐ferruginine starting from 5‐oxo‐protected‐α

  公开了通过催化立体选择性转化完全不对称合成有价值的托烷生物碱的一般策略。（+）-甲基芽子碱，（-）-可卡因和（+）-可卡因的简洁催化对映选择性总合成以及可卡因C-1衍生物和（ +）-ferruginine分别仅使用两步和三步色谱纯化步骤从5-氧代保护的α，β-不饱和烯醛开始。