(1R,2S,3S,4S)-2-(Methoxycarbonyl)bicyclo<2.2.1>heptane-3-carboxylic Acid | 116404-48-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (1R,2S,3S,4S)-2-(Methoxycarbonyl)bicyclo<2.2.1>heptane-3-carboxylic Acid
• 英文别名: (1R,2S,3S,4S)-3-carboxy-2-methoxycarbonylbicyclo(2.2.1)heptane；(1R,2S,3S,4S)-3-Carboxy-2-(methoxycarbonyl)bicyclo<2.2.1>heptane；(1R,2S,3S,4S)-2-methoxycarbonyl-3-carboxybicyclo[2.2.1]heptane；(1R,2S,3S,4S)-2-carbomethoxy-3-carboxybicyclo [2.2.1]heptane；(1S,2S,3S,4R)-3-methoxycarbonylbicyclo[2.2.1]heptane-2-carboxylic acid
• CAS: 116404-48-9
• 化学式: C₁₀H₁₄O₄
• 分子量: 198.219
• InChiKey: AIMKQBORRFFXGP-YWIQKCBGSA-N

物化性质

• 熔点：
  59-60 °C
• 沸点：
  323.6±25.0 °C(Predicted)
• 密度：
  1.278±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1R,2S,3S,4S)-2-(Methoxycarbonyl)bicyclo<2.2.1>heptane-3-carboxylic Acid 在 氢氧化钾 、 ammonium hydroxide 、 氯甲酸乙酯 、 三乙胺 作用下， 反应 1.0h， 生成 (1R,2S,3S,4S)-3-Carbamoyl-2-carboxybicyclo<2.2.1>heptane
  参考文献：
  名称：

  Enantioselective synthesis of S-1452, an orally active potent thromboxane A2 receptor antagonist

  摘要：

  An efficient and extremely practical enantioselective fission of pro-chiral bicyclo[2.2.1]heptane-2,3-dicarboxylic anhydride was applied to the asymmetric synthesis of the potent and orally active thromboxane A2 (TXA2) receptor antagonist, S-1452. The lithium salt of (R)-(-)-benzylmandelate was employed as a chiral ligand, giving a crystalline key intermediate 3 of which the chemical purity was 100.0% after crystallization. Epimerization and the methanolysis process of 3 afforded the half ester 4, which was transformed into S-1452.

  DOI：

  10.1021/jo00006a030
• 作为产物：
  描述：

  3,6-endomethylene-1,2,3,6-tetrahydrophthalic anhydride 在 盐酸 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 0.2h， 生成 (1R,2S,3S,4S)-2-(Methoxycarbonyl)bicyclo<2.2.1>heptane-3-carboxylic Acid
  参考文献：
  名称：

  Enantioselective synthesis of S-1452, an orally active potent thromboxane A2 receptor antagonist

  摘要：

  An efficient and extremely practical enantioselective fission of pro-chiral bicyclo[2.2.1]heptane-2,3-dicarboxylic anhydride was applied to the asymmetric synthesis of the potent and orally active thromboxane A2 (TXA2) receptor antagonist, S-1452. The lithium salt of (R)-(-)-benzylmandelate was employed as a chiral ligand, giving a crystalline key intermediate 3 of which the chemical purity was 100.0% after crystallization. Epimerization and the methanolysis process of 3 afforded the half ester 4, which was transformed into S-1452.

  DOI：

  10.1021/jo00006a030

文献信息

• Structural requirements in the enzymic optical resolution of bicyclic esters using pig liver esterase
  作者：A.J.H Klunder、F.J.C van Gastel、B Zwanenburg

  DOI：10.1016/0040-4039(88)85263-8

  日期：——

  The PLE-catalyzed hydrolysis of bicyclic mono- and diesters 4–15 have been studied. Structural features such as bridge size and relative configuration of the ester functions have found to be essential for effective hydrolysis. A high degree of stereo- and enantioselectivity was observed for -bicyclo-12.2.1]heptane-2,3-diesters 4, 5 and 6.

  已经研究了PLE催化的双环单酯和双酯4-15的水解。已经发现结构特征例如桥的大小和酯官能团的相对构型对于有效水解是必不可少的。观察到高度的立体和对映体选择性-二环-12.2.1]庚烷-2,3-二酯4，5和6。
• Enantioselective production of homochiral (+)-(1R,2S,3S,4S)- and (−)-(1S,2R,3R,4R)-bicyclo(2.2.1)heptane-2,3-dicarboxylic acid, 2-methyl esters. Formal synthesis of the TXA2 antagonist S-1452.
  作者：Ramon Casas、Rosa M. Oituõ

  DOI：10.1016/s0957-4166(00)82106-0

  日期：1992.9

  Both enantiomers of the title half ester have been synthesized from -mannitol as single chiral precursor. The -enantiomer is the key intermediate in the synthesis of the TXA2 antagonistic drug S-1452.

  标题半酯的两种对映体均由-甘露醇合成为单一手性前体。所述对映体是在TXA的合成中的关键中间体2拮抗药物S-1452。
• Alkenyltetrazole derivatives, their preparation and use
  申请人：SHIONOGI SEIYAKU KABUSHIKI KAISHA trading under the name of SHIONOGI & CO. LTD.

  公开号：EP0352083A2

  公开（公告）日：1990-01-24

  Tetrazole derivatives represented by the formula are provided. wherein R is naphthyl or phenyl optionally substituted by phenyl, lower alkyl, halogen, lower alkoxy, hydroxy or acetoxy; X is methylene, dimethylmethylene or oxygen; n is an integer of 0 or 1; and p and r each is an integer of 0 or 1 and q is an integer of 1 or 2 provided that p + q + r = 2; or tautomers thereof in the tetrazole ring; or salts thereof; are useful as TXA2 receptor antagonist.

  提供了由式表示的四唑衍生物。 其中 R 是萘基或苯基，任选被苯基、低级烷基、卤素、低级烷氧基、羟基或乙酰氧基取代；X 是亚甲基、二甲基亚甲基或氧；n 是 0 或 1 的整数；p 和 r 分别是 0 或 1 的整数，q 是 1 或 2 的整数，条件是 p + q + r = 2；或其在四唑环上的同系物；或其盐；可用作 TXA2 受体拮抗剂。
• Pharmaceutical or veterinary preparations of substituted hexenoic acid derivatives
  申请人：SHIONOGI SEIYAKU KABUSHIKI KAISHA trading under the name of SHIONOGI & CO. LTD.

  公开号：EP0384747A1

  公开（公告）日：1990-08-29

  Pharmaceutical or veterinary preparations for use in the treatment of thromboxane A₂ mediating diseases, comprising a pharmacologically effective amount of at least one compound of the formula: wherein R¹ is carboxyl or 5-tetrazolyl, R² is hydrogen, methyl, hydroxy, chloro, or bromo, or a pharmaceutically acceptable ester or salt thereof, formulated for such use with one or more non-toxic pharmaceutically or veterinarily acceptable carrier and optionally in unit dosage form.

  用于治疗血栓素 A₂介导疾病的药物或兽药制剂，包含药理有效量的至少一种式化合物： 其中 R¹ 为羧基或 5-四唑基，R² 为氢、甲基、羟基、氯基或溴基，或其药学上可接受的酯或盐，与一种或多种无毒的药学上或兽医学上可接受的载体配制成用于上述用途的制剂，可选单位剂型。
• OHTANI, MITSUAKI;MATSUURA, TAKAHARU;WATANABE, FUMIHIKO;NARISADA, MASAYUKI, J. ORG. CHEM., 56,(1991) N3, C. 4120-4123
  作者：OHTANI, MITSUAKI、MATSUURA, TAKAHARU、WATANABE, FUMIHIKO、NARISADA, MASAYUKI

  DOI：——

  日期：——