(2R,3S)-3-<(2-amino-1-naphthalenyl)thio>-2-hydroxy-3-(4-methoxyphenyl)propanoic acid (1R,2S)-2-phenylcyclohexyl ester hydrochloride | 128232-04-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (2R,3S)-3-<(2-amino-1-naphthalenyl)thio>-2-hydroxy-3-(4-methoxyphenyl)propanoic acid (1R,2S)-2-phenylcyclohexyl ester hydrochloride
• 英文别名: (2S,3S)-3-[(2-amino-1-naphthalenyl)thio]-2-hydroxy-3-(4-methoxyphenyl) propanoic acid (1R,2S)-2-phenylcyclohexyl ester hydrochloride；[(1R,2S)-2-phenylcyclohexyl] (2S,3S)-3-(2-aminonaphthalen-1-yl)sulfanyl-2-hydroxy-3-(4-methoxyphenyl)propanoate;hydrochloride
• CAS: 128232-04-2
• 化学式: C₃₂H₃₃NO₄S*ClH
• 分子量: 564.145
• InChiKey: JTCOEDLXLIEWQV-KYNVTRJBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.32
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,3S)-3-<(2-amino-1-naphthalenyl)thio>-2-hydroxy-3-(4-methoxyphenyl)propanoic acid (1R,2S)-2-phenylcyclohexyl ester hydrochloride 在 sodium hydroxide 、 potassium carbonate 、 对甲苯磺酸 作用下， 以 乙醇 、 水 、 乙酸乙酯 、 xylene 为溶剂， 反应 39.0h， 生成 (+)-cis-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-naphtho<1,2-b><1,4>thiazepin-4(5H)-one
  参考文献：
  名称：

  Enantioselective synthesis of calcium channel blockers of the diltiazem group

  摘要：

  A lipase-catalyzed kinetic resolution of racemic trans-2-phenylcyclohexanol readily provides the (-)-1R,2S enantiomer. This alcohol is employed as its chloroacetate 10a in a chiral auxiliary-induced asymmetric Darzens glycidic ester condensation with p-anisaldehyde (9). Crystallization of the Darzens product affords enantiomerically pure (1R,2S)-2-phenylcyclohexyl (1R,2S)-2-(p-methoxyphenyl)glycidate (11), the structure of which was established by X-ray crystallography. The use of this glycidic ester in syntheses of diltiazem (1) and naltiazem (8), members of the diltiazem group of calcium channel blockers, provides these drug substances directly in enantiomerically pure form.

  DOI：

  10.1021/jo00029a013
• 作为产物：
  描述：

  2-aminonaphthalene-1-thiol 、 (2R,3S)-3-(4-methoxyphenyl)oxirane-2-carboxylic acid (1R,2S)-2-phenylcyclohexyl ester 以 甲苯 为溶剂， 反应 20.0h， 生成 (2R,3S)-3-<(2-amino-1-naphthalenyl)thio>-2-hydroxy-3-(4-methoxyphenyl)propanoic acid (1R,2S)-2-phenylcyclohexyl ester hydrochloride
  参考文献：
  名称：

  Enantioselective synthesis of calcium channel blockers of the diltiazem group

  摘要：

  A lipase-catalyzed kinetic resolution of racemic trans-2-phenylcyclohexanol readily provides the (-)-1R,2S enantiomer. This alcohol is employed as its chloroacetate 10a in a chiral auxiliary-induced asymmetric Darzens glycidic ester condensation with p-anisaldehyde (9). Crystallization of the Darzens product affords enantiomerically pure (1R,2S)-2-phenylcyclohexyl (1R,2S)-2-(p-methoxyphenyl)glycidate (11), the structure of which was established by X-ray crystallography. The use of this glycidic ester in syntheses of diltiazem (1) and naltiazem (8), members of the diltiazem group of calcium channel blockers, provides these drug substances directly in enantiomerically pure form.

  DOI：

  10.1021/jo00029a013

文献信息

• Glycidic acid ester and process of preparation
  申请人：Hoffmann-La Roche Inc.

  公开号：US05008411A1

  公开（公告）日：1991-04-16

  A process for the preparing a compound of the formula ##STR1## wherein R.sub.1 and R.sub.2 are each independently hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, halogen, trifluoromethyl or nitro; or R.sub.1 and R.sub.2 taken together with the benzene ring to which they are attached are naphthalene, and Ar is p-lower alkoxy phenyl. which comprises reacting ##STR2## wherein R.sub.1 and R.sub.2 are as described above with the compound of the formula ##STR3## wherein Ar is as described above, in an aromatic organic compound. The intermediates formed by the process of the invention are useful in the production of thiazepin-4(5H)-ones which have activity as calcium channel blockers and accordingly are useful as agents for lowering blood pressure and agents for treating ischemia.

  一种制备式为 ##STR1## 的化合物的方法，其中R.sub.1和R.sub.2各自独立地为氢，1至4个碳原子的烷基，1至4个碳原子的烷氧基，卤素，三氟甲基或亚硝基；或R.sub.1和R.sub.2与它们连接的苯环一起为萘基，而Ar为p-低烷氧基苯基。该方法包括在芳香有机化合物中反应式为 ##STR2## 的化合物（其中R.sub.1和R.sub.2如上所述）和式为 ##STR3## 的化合物（其中Ar如上所述）以制备中间体。该发明所制备的中间体在制备噻唑啉-4（5H）-酮方面有用，其具有作为钙通道阻滞剂的活性，因此可用作降低血压和治疗缺血的药物。
• Enantioselective synthesis of calcium channel blockers of the diltiazem group
  作者：Alan Schwartz、Pradeep B. Madan、Erno Mohacsi、Jay P. O'Brien、Louis J. Todaro、David L. Coffen

  DOI：10.1021/jo00029a013

  日期：1992.1

  A lipase-catalyzed kinetic resolution of racemic trans-2-phenylcyclohexanol readily provides the (-)-1R,2S enantiomer. This alcohol is employed as its chloroacetate 10a in a chiral auxiliary-induced asymmetric Darzens glycidic ester condensation with p-anisaldehyde (9). Crystallization of the Darzens product affords enantiomerically pure (1R,2S)-2-phenylcyclohexyl (1R,2S)-2-(p-methoxyphenyl)glycidate (11), the structure of which was established by X-ray crystallography. The use of this glycidic ester in syntheses of diltiazem (1) and naltiazem (8), members of the diltiazem group of calcium channel blockers, provides these drug substances directly in enantiomerically pure form.