benzyl (2S,3aR,7aR)-1-benzyl-6-oxooctahydroindole-2-carboxylate | 181649-49-0

• 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: benzyl (2S,3aR,7aR)-1-benzyl-6-oxooctahydroindole-2-carboxylate
• 英文别名: (2S,3aR,7aR)-1-benzyl-6-oxo-octahydroindole-2-carboxylic acid benzyl ester；benzyl (2S,3aR,7aR)-1-benzyl-6-oxo-3,3a,4,5,7,7a-hexahydro-2H-indole-2-carboxylate
• CAS: 181649-49-0
• 化学式: C₂₃H₂₅NO₃
• 分子量: 363.456
• InChiKey: NZZOYIBQDBXYNF-FCEUIQTBSA-N

物化性质

• 沸点：
  503.6±40.0 °C(Predicted)
• 密度：
  1.192±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl (2S,3aR,7aR)-1-benzyl-6-oxooctahydroindole-2-carboxylate 在 palladium dihydroxide Dowex 1XB 、 氢气 、 L-Selectride 作用下， 以 四氢呋喃 为溶剂， 生成 methyl (2S,3aR,6S,7aR)-1-acetyl-6-hydroxy-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylate
  参考文献：
  名称：

  Synthesis of the octahydroindole core of aeruginosins: a new bicyclic α-amino acid

  摘要：

  The first synthesis of 6-hydroxyoctahydroindole-2-carboxylic acid derivatives with a cis fusion in the azabicyclic nucleus is described. The synthesis involves a Birch reduction of O-methyl-L-tyrosine followed by an aminocyclization in acid medium to give a mixture of 6-oxo-octahydroindole-2-carboxylic acids 3 and 4, which could be separated after dibenzylation. Transesterification, hydrogenolysis in the presence of acetic anhydride and reduction of the amido ketones 9 and 10 provides the four stereoisomeric alcohols from which alcohol 14 showed nmr data very close to the aeruginosin 298-A core. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0957-4166(96)00225-x
• 作为产物：
  描述：

  lithium 2-amino-3-(4-methoxycyclohexa-1,4-dienyl)propanoate 、 溴甲苯 在 盐酸 、 碳酸氢钠 作用下， 以 水 、 乙醇 为溶剂， 反应 15.0h， 以27%的产率得到benzyl (2S,3aR,7aR)-1-benzyl-6-oxooctahydroindole-2-carboxylate
  参考文献：
  名称：

  [EN] [B]-FUSED BICYCLIC PROLINE DERIVATIVES AND THEIR USE FOR TREATING ARTHRITIC CONDITIONS
  [FR] DERIVES BICYCLIQUES [B]-FUSIONNES DE PROLINE ET LEUR UTILISATION POUR TRAITER DES ETATS ARTHRITIQUES

  摘要：

  该发明涉及一种[b]-融合双环脯氨酸衍生物，或其药用盐；包括该化合物或其盐的药物组合物；以及治疗疾病的方法，包括但不限于预防或抑制关节软骨损伤，预防或治疗以关节软骨损伤、关节炎或关节疼痛为特征的疾病的方法。[b]-融合双环脯氨酸衍生物是上述化合物的I式化合物。以关节软骨损伤或关节疼痛为特征的疾病包括骨关节炎和类风湿性关节炎。类风湿性关节炎也以关节炎为特征。该发明还涉及合成和制备[b]-融合双环脯氨酸衍生物或其药用盐的方法。

  公开号：

  WO2004092132A1

文献信息

• Synthesis of the octahydroindole unit of aeruginosins via asymmetric hydrogenation of the Diels–Alder adducts of 2-amido-2,4-pentadienoate
  作者：Yoichiro Hoshina、Takayuki Doi、Takashi Takahashi

  DOI：10.1016/j.tet.2007.09.078

  日期：2007.12

  An optically active octahydroindole, the core unit of aeruginosins (Choi) was synthesized. The Diels–Alder reaction of Danishefsky's diene with methyl (Z)-2-acetamido-2,4-pentadienoates provided the adducts regioselectively in good yield. The adducts were converted to the l-Choi precursor by asymmetric hydrogenation, followed by acid cyclization.

  合成了一种光学活性的八氢吲哚，它是铜绿素酶（Choi）的核心单元。Danishefsky的二烯与（Z）-2-乙酰氨基-2,4-戊二烯酸甲酯的Diels-Alder反应提供了良好的区域选择性加合物。通过不对称氢化，然后酸环化，将加合物转化为1-Choi前体。
• First Total Syntheses of Aeruginosin 298-A and Aeruginosin 298-B, Based on a Stereocontrolled Route to the New Amino Acid 6-Hydroxyoctahydroindole-2-carboxylic Acid
  作者：Nativitat Valls、Meritxell López-Canet、Mercè Vallribera、Josep Bonjoch

  DOI：10.1002/1521-3765(20010817)7:16<3446::aid-chem3446>3.0.co;2-0

  日期：2001.8.17

  The first total syntheses of aeruginosin 298-A (1) and aeruginosin 298-B (3) are described. The syntheses of the alternative putative structures 2 and 4 were also accomplished. The key common strategic element is the stereo-controlled synthesis of (2S,3aS,6R,7aS)-6-hydroxyoctahydroindole-2-carboxylic acid (L-Choi, 5) from L-tyrosine. The synthesis of this new bicyclic alpha-amino acid, which is the core

  描述了铜绿素298-A（1）和铜绿素298-B（3）的第一批合成。还完成了备选推定结构2和4的合成。关键的共同战略要素是从L-酪氨酸立体控制合成（2S，3aS，6R，7aS）-6-羟基八氢吲哚-2-羧酸（L-Choi，5）。作为铜绿素酶的核心，这种新的双环α-氨基酸的合成涉及桦木还原O-甲基-L-酪氨酸（6）和在酸性介质中将所得的二氢茴香醚7进行氨基环化，然后进行N-苄基化，得到非对映异构体12和13。用HCl-MeOH酸处理后，最后两个产生平衡混合物，其中内异构体13明显占优势。在（Boc）2O存在下加氢13得到16，经LS-Selectride还原后，可提供醇22（一种受保护的L-Choi）。22与D-亮氨酸，受保护的（R）-（4-羟苯基）乳酸和L-精氨酸片段的连续偶联，然后降低至精氨酸水平和脱保护的最终步骤完成了合成序列，产生了铜绿素酶298-A （1）。光谱比较显示，肽2具有先前针
• [B]-fused bicyclic proline derivatives and their use for treating arthritic conditions
  申请人：Barvian C. Nicole

  公开号：US20050143427A1

  公开（公告）日：2005-06-30

  This invention relates to a compound which is [b]-fused bicyclic proline derivative, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition comprising the compound or the salt thereof, and methods of treating diseases, including, but not limited to, methods of preventing or inhibiting joint cartilage damage and preventing or treating diseases characterized by joint cartilage damage, joint inflammation, or joint pain. The [b]-fused bicyclic proline derivatives are compounds of Formula I as described above. Diseases characterized by joint cartilage damage or joint pain include, for example, osteoarthritis and rheumatoid arthritis. Rheumatoid arthritis is also characterized by joint inflammation. This invention also relates to methods of synthesizing and preparing the [b]-fused bicyclic proline derivatives, or a pharmaceutically acceptable salt thereof.

  本发明涉及一种[b]-融合的双环脯氨酸衍生物，或其药学上可接受的盐；包括该化合物或其盐的制药组合物，以及治疗疾病的方法，包括但不限于预防或抑制关节软骨损伤和预防或治疗以关节软骨损伤、关节炎或关节疼痛为特征的疾病的方法。[b]-融合的双环脯氨酸衍生物是如上所述的式I的化合物。以关节软骨损伤或关节疼痛为特征的疾病包括骨关节炎和类风湿性关节炎等。类风湿性关节炎也以关节炎为特征。本发明还涉及合成和制备[b]-融合的双环脯氨酸衍生物或其药学上可接受的盐的方法。
• [EN] [B]-FUSED BICYCLIC PROLINE DERIVATIVES AND THEIR USE FOR TREATING ARTHRITIC CONDITIONS<br/>[FR] DERIVES BICYCLIQUES [B]-FUSIONNES DE PROLINE ET LEUR UTILISATION POUR TRAITER DES ETATS ARTHRITIQUES
  申请人：WARNER LAMBERT CO

  公开号：WO2004092132A1

  公开（公告）日：2004-10-28

  The invention relates to a compound which is [b]-fused bicyclic proline derivative, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition comprising the compound or the salt thereof, and methods of treating diseases, including, but not limited to, methods of preventing or inhibiting joint cartilage damage and preventing or treating diseases characterized by joint cartilage damage, joint inflammation, or joint pain. The [b]-fused bicyclic proline derivatives are compounds of Formula I as described above. Diseases characterized by joint cartilage damage or joint pain include, for example, osteoarthritis and rheumatoid arthritis. Rheumatoid arthritis is also characterized by joint inflammation. This invention also relates to methods of synthesizing and preparing the [b]-fused bicyclic proline derivatives, or a pharmaceutically acceptable salt thereof.

  该发明涉及一种[b]-融合双环脯氨酸衍生物，或其药用盐；包括该化合物或其盐的药物组合物；以及治疗疾病的方法，包括但不限于预防或抑制关节软骨损伤，预防或治疗以关节软骨损伤、关节炎或关节疼痛为特征的疾病的方法。[b]-融合双环脯氨酸衍生物是上述化合物的I式化合物。以关节软骨损伤或关节疼痛为特征的疾病包括骨关节炎和类风湿性关节炎。类风湿性关节炎也以关节炎为特征。该发明还涉及合成和制备[b]-融合双环脯氨酸衍生物或其药用盐的方法。
• Synthesis of the octahydroindole core of aeruginosins: a new bicyclic α-amino acid
  作者：Josep Bonjoch、Juanlo Catena、Esther Isábal、Meritxell López-Canet、Nativitat Valls

  DOI：10.1016/0957-4166(96)00225-x

  日期：1996.7

  The first synthesis of 6-hydroxyoctahydroindole-2-carboxylic acid derivatives with a cis fusion in the azabicyclic nucleus is described. The synthesis involves a Birch reduction of O-methyl-L-tyrosine followed by an aminocyclization in acid medium to give a mixture of 6-oxo-octahydroindole-2-carboxylic acids 3 and 4, which could be separated after dibenzylation. Transesterification, hydrogenolysis in the presence of acetic anhydride and reduction of the amido ketones 9 and 10 provides the four stereoisomeric alcohols from which alcohol 14 showed nmr data very close to the aeruginosin 298-A core. Copyright (C) 1996 Elsevier Science Ltd