(-)-(3S,4aS,8aS,2'R,3'R)-2-[3'-amino-2'-hydroxy-4'-phenylbutyl]-N-tert-butyldecahydroisoquinoline-3-carboxamide | 737767-64-5

• 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: (-)-(3S,4aS,8aS,2'R,3'R)-2-[3'-amino-2'-hydroxy-4'-phenylbutyl]-N-tert-butyldecahydroisoquinoline-3-carboxamide
• 英文别名: (3S,4aS,8aS)-2-[(2R,3R)-3-amino-2-hydroxy-4-phenylbutyl]-N-tert-butyl-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinoline-3-carboxamide
• CAS: 737767-64-5
• 化学式: C₂₄H₃₉N₃O₂
• 分子量: 401.593
• InChiKey: YJRJYYPXNAHNMD-AHJNKEMKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  78.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-喹啉基羰基)-L-天冬氨酰胺 、 (-)-(3S,4aS,8aS,2'R,3'R)-2-[3'-amino-2'-hydroxy-4'-phenylbutyl]-N-tert-butyldecahydroisoquinoline-3-carboxamide 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以72%的产率得到(2S)-N-[(2R,3R)-4-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-(quinoline-2-carbonylamino)butanediamide
  参考文献：
  名称：

  Stereocontrolled synthesis and biological activity of two diastereoisomers of the potent HIV-1 protease inhibitor saquinavir

  摘要：

  A general enantioselective synthesis of new syn-hydroxyethylamine isosteres has been developed. The approach, based on the controlled opening of functionalized optically active 2,3-epoxy amines, can be conveniently used for the preparation of new peptidomimetics with various residues. Finally the total synthesis of two diastereoisomer analogues of HIV-Protease inhibitor Saquinavir has been achieved and their biological activity evaluated. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.10.020
• 作为产物：
  描述：

  N-叔丁基-十氢异喹啉-3(S)-甲酰胺 在 2,4,6-三甲基吡啶 、 氢氧化钾 、 三氟乙酸酐 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 乙腈 为溶剂， 反应 60.0h， 生成 (-)-(3S,4aS,8aS,2'R,3'R)-2-[3'-amino-2'-hydroxy-4'-phenylbutyl]-N-tert-butyldecahydroisoquinoline-3-carboxamide
  参考文献：
  名称：

  Stereocontrolled synthesis of hydroxyethylamine isosteres via chiral sulfoxide chemistry

  摘要：

  A novel synthesis of enantiopure hydroxyethylamine isosteres has been developed. Reaction of lithiated beta-sulfinyl-ethylamines 3 with N-Cbz-irnines generated in situ from alpha-amino-sulfones 4 afforded in good to excellent yields and moderate stereocontrol the 2-sulfinyl-1,3-diamines 2. The latter were submitted to the nonoxidative Pummerer reaction (NOPR) in CH2Cl2, that produced the target compounds 1 in very good yields with inversion Of Configuration. In some cases, the use of acetonitrile as solvent resulted in a double-inversion pathway, leading for example to the oxazolidinone 5. The total synthesis of an epimer of Saquinavir has been achieved by this method. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2004.04.160

文献信息

• Stereocontrolled synthesis of hydroxyethylamine isosteres via chiral sulfoxide chemistry
  作者：Cristina Pesenti、Alberto Arnone、Paolo Arosio、Massimo Frigerio、Stefano V. Meille、Walter Panzeri、Fiorenza Viani、Matteo Zanda

  DOI：10.1016/j.tetlet.2004.04.160

  日期：2004.6

  A novel synthesis of enantiopure hydroxyethylamine isosteres has been developed. Reaction of lithiated beta-sulfinyl-ethylamines 3 with N-Cbz-irnines generated in situ from alpha-amino-sulfones 4 afforded in good to excellent yields and moderate stereocontrol the 2-sulfinyl-1,3-diamines 2. The latter were submitted to the nonoxidative Pummerer reaction (NOPR) in CH2Cl2, that produced the target compounds 1 in very good yields with inversion Of Configuration. In some cases, the use of acetonitrile as solvent resulted in a double-inversion pathway, leading for example to the oxazolidinone 5. The total synthesis of an epimer of Saquinavir has been achieved by this method. (C) 2004 Elsevier Ltd. All rights reserved.
• Stereocontrolled synthesis and biological activity of two diastereoisomers of the potent HIV-1 protease inhibitor saquinavir
  作者：Giuliana Righi、Simona Ciambrone、Carlo Bonini、Pietro Campaner

  DOI：10.1016/j.bmc.2007.10.020

  日期：2008.1

  A general enantioselective synthesis of new syn-hydroxyethylamine isosteres has been developed. The approach, based on the controlled opening of functionalized optically active 2,3-epoxy amines, can be conveniently used for the preparation of new peptidomimetics with various residues. Finally the total synthesis of two diastereoisomer analogues of HIV-Protease inhibitor Saquinavir has been achieved and their biological activity evaluated. (C) 2007 Elsevier Ltd. All rights reserved.