Ethyl (3S,4aR,8aR)-6-methylidene-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate | 157006-68-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Ethyl (3S,4aR,8aR)-6-methylidene-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate
• 英文别名: ethyl-(3S,4aR,8aR)-6-methylenyl-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,82-decahydroisoquinoline-3-carboxylate；3-O-ethyl 2-O-methyl (3S,4aR,8aR)-6-methylidene-1,3,4,4a,5,7,8,8a-octahydroisoquinoline-2,3-dicarboxylate
• CAS: 157006-68-3
• 化学式: C₁₅H₂₃NO₄
• 分子量: 281.352
• InChiKey: VHJIUFOZJUTRKM-XQQFMLRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Ethyl (3S,4aR,8aR)-6-methylidene-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate 在 sodium hydroxide 、 草酰氯 、 dimethyl sulfide borane 、 双氧水 、 sodium hydride 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 9.25h， 生成 替占帕奈
  参考文献：
  名称：

  Stereoselective Synthesis of 6-Substituted Decahydroisoquinoline-3-carboxylates: Intermediates for the Preparation of Conformationally Constrained Acidic Amino Acids

  摘要：

  In this article we describe the stereoselective preparation of two 6-(hydroxymethyl) substituted decahydroisoquinoline-3-carboxylates, which are useful in the synthesis of a number of excitatory amino acid antagonists, e.g., (-)-1a (LY235959), (-)-2a (LY202157) and (-)-3a(LY293558). For example, the known ketone 4 was converted to either the (3SR,4aRS,6SR,8aRS)-alcohol 18 or the (3SR,4aRS,6RS,8aRS)-alcohol 21, the former via a stereoselective hydroboration reaction, the latter via a stereoselective enol ether hydrolysis followed by reduction. These C-6 epimeric alcohols were easily converted to a number of useful intermediates, e.g., aldehydes, bromides and iodides. If we used resolved ketone 4, then these intermediates could be obtained in optically active form. In either racemic or non-racemic form, these intermediates provided access to a number of diastereomerically pure amino acids that were difficult to obtain by earlier routes.

  DOI：

  10.1021/jo00104a051
• 作为产物：
  描述：

  Ethyl (3SR,4aRS,6RS,8aRS)-6-(hydroxymethyl)-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate 在 咪唑 、 碘 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 2.75h， 生成 Ethyl (3S,4aR,8aR)-6-methylidene-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate
  参考文献：
  名称：

  Stereoselective Synthesis of 6-Substituted Decahydroisoquinoline-3-carboxylates: Intermediates for the Preparation of Conformationally Constrained Acidic Amino Acids

  摘要：

  In this article we describe the stereoselective preparation of two 6-(hydroxymethyl) substituted decahydroisoquinoline-3-carboxylates, which are useful in the synthesis of a number of excitatory amino acid antagonists, e.g., (-)-1a (LY235959), (-)-2a (LY202157) and (-)-3a(LY293558). For example, the known ketone 4 was converted to either the (3SR,4aRS,6SR,8aRS)-alcohol 18 or the (3SR,4aRS,6RS,8aRS)-alcohol 21, the former via a stereoselective hydroboration reaction, the latter via a stereoselective enol ether hydrolysis followed by reduction. These C-6 epimeric alcohols were easily converted to a number of useful intermediates, e.g., aldehydes, bromides and iodides. If we used resolved ketone 4, then these intermediates could be obtained in optically active form. In either racemic or non-racemic form, these intermediates provided access to a number of diastereomerically pure amino acids that were difficult to obtain by earlier routes.

  DOI：

  10.1021/jo00104a051

文献信息

• [Tetrazoyl-11C]LY202157 synthesis forin vivo studies of the NMDA receptor channel complex
  作者：M. Ponchant、H. Galéa、M. Bottlaender、C. Coulon、C. Fuseau、M. Ottaviani、C. Crouzel

  DOI：10.1002/1099-1344(200011)43:13<1311::aid-jlcr422>3.0.co;2-b

  日期：2000.11

  [Tetrazoyl-C-11]LY202157 8 was prepared via a three step synthesis from ethyl (3S,4aR,6S,8aR)-6-bromomethyl-2-methoxycarbonyl 1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinol This bromo precursor was reacted with [C-11]hydrogen cyanide affording the corresponding [C-11]nitrile. Conversion to the tetrazole was achieved by treatment with azidotributyltin followed by hydrolysis with 6N hydrochloric acid at 200 degreesC. After HPLC purification and analytical HPLC control, more than 370 MBq (10 mCi) of [tetrazoyl-C-11] LY202157 were obtained after an overall 60 minute synthesis time with 38% yield (EOB) and specific activity of 25.9 GBq/mu mol (700 mCi/mu mol). Ex vivo biological studies showed that the [tetrazoyl-C-11] LY202157 did not cross the brain blood barrier.
• Synthesis and Characterization of Phosphonic Acid-Substituted Amino Acids as Excitatory Amino Acid Receptor Antagonists
  作者：Paul Ornstein、M. Brian Arnold、Nancy Allen、Darryle Schoepp

  DOI：10.1080/10426509608545152

  日期：——
• (3SR,4aRS,6RS,8aRS)-6-[2-(1H-Tetrazol-5-yl)ethyl]decahydroisoquinoline-3-carboxylic acid: a structurally novel, systemically active, competitive AMPA receptor antagonist
  作者：Paul L. Ornstein、M. Brian Arnold、Nancy K. Augenstein、David Lodge、J. David Leander、Darryle D. Schoepp

  DOI：10.1021/jm00066a016

  日期：1993.7
• Stereoselective Synthesis of 6-Substituted Decahydroisoquinoline-3-carboxylates: Intermediates for the Preparation of Conformationally Constrained Acidic Amino Acids
  作者：Paul L. Ornstein、Nancy K. Augenstein、M. Brian Arnold

  DOI：10.1021/jo00104a051

  日期：1994.12

  In this article we describe the stereoselective preparation of two 6-(hydroxymethyl) substituted decahydroisoquinoline-3-carboxylates, which are useful in the synthesis of a number of excitatory amino acid antagonists, e.g., (-)-1a (LY235959), (-)-2a (LY202157) and (-)-3a(LY293558). For example, the known ketone 4 was converted to either the (3SR,4aRS,6SR,8aRS)-alcohol 18 or the (3SR,4aRS,6RS,8aRS)-alcohol 21, the former via a stereoselective hydroboration reaction, the latter via a stereoselective enol ether hydrolysis followed by reduction. These C-6 epimeric alcohols were easily converted to a number of useful intermediates, e.g., aldehydes, bromides and iodides. If we used resolved ketone 4, then these intermediates could be obtained in optically active form. In either racemic or non-racemic form, these intermediates provided access to a number of diastereomerically pure amino acids that were difficult to obtain by earlier routes.