(+)-3-<(2-amino-1-naphthalenyl)thio>-2-hydroxy-3-(4-methoxyphenyl)propanoic acid | 125226-69-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: (+)-3-<(2-amino-1-naphthalenyl)thio>-2-hydroxy-3-(4-methoxyphenyl)propanoic acid
• 英文别名: (+)-3-[(2-amino-1-naphthalenyl)thio]-2-hydroxy-3-(4-methoxyphenyl)propanoic acid；(2S,3S)-3-(2-aminonaphthalen-1-yl)sulfanyl-2-hydroxy-3-(4-methoxyphenyl)propanoic acid
• CAS: 125226-69-9
• 化学式: C₂₀H₁₉NO₄S
• 分子量: 369.441
• InChiKey: UIOJTIUAGAWMDP-MSOLQXFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+)-3-<(2-amino-1-naphthalenyl)thio>-2-hydroxy-3-(4-methoxyphenyl)propanoic acid 在 potassium carbonate 、 对甲苯磺酸 作用下， 以 水 、 乙酸乙酯 、 xylene 为溶剂， 反应 35.0h， 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 在 sodium hydroxide 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 24.0h， 生成 (+)-3-<(2-amino-1-naphthalenyl)thio>-2-hydroxy-3-(4-methoxyphenyl)propanoic acid
  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

• Process for the preparation of optically pure aminophenylthio- and aminoaphthalenylthio-propanoic acids
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0343474A2

  公开（公告）日：1989-11-29

  A process for preparing an acid of the general formula wherein R₁ and R₂ are each, independently, hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, halogen, trifluoromethyl or nitro or R₁ and R₂, taken together with the benzene ring to which they are attached, are naphthalene and Ar is phenyl which is unsubstituted or substituted by one to three substituents selected from the group consisting of alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms and halogen, by hydrolyzing a compound of the formula The compounds of formula I formed by the process of the invention are useful in the production of thiazepin-4(5H)-ones of the formula and anaogs thereof which have activity as calcium channel blockers and accordingly are useful as agents for lowering blood pressure and as agents for treating ischemia.

  一种制备通式如下的酸的工艺 其中 R₁ 和 R₂ 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、三氟甲基或硝基，或 R₁ 和 R₂ 与它们所连接的苯环一起为萘，Ar 为未被取代或被 1 至 3 个选自 1 至 4 个碳原子的烷基、1 至 4 个碳原子的烷氧基和卤素的取代基取代的苯基、 水解式如下的化合物 通过本发明工艺形成的式 I 化合物可用于生产式中的硫氮杂卓-4(5H)-酮及其类似物。 及其类似物，它们具有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。
• US5008411A
  申请人：——

  公开号：US5008411A

  公开（公告）日：1991-04-16
• 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.