2-[(2S)-4-(oxan-2-yloxy)-3-oxo-1-phenylbutan-2-yl]isoindole-1,3-dione | 1026632-96-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-[(2S)-4-(oxan-2-yloxy)-3-oxo-1-phenylbutan-2-yl]isoindole-1,3-dione
• CAS: 1026632-96-1
• 化学式: C₂₃H₂₃NO₅
• 分子量: 393.439
• InChiKey: GWDZGIIJHPUIEU-ZQRQZVKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[(2S)-4-(oxan-2-yloxy)-3-oxo-1-phenylbutan-2-yl]isoindole-1,3-dione 在 palladium on activated charcoal N-乙基吗啉 、 吡啶 、 盐酸 、 sodium tetrahydroborate 、 potassium tert-butylate 、 氢气 、 对甲苯磺酸 、 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 、 甲胺 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 123.75h， 生成 沙喹那韦
  参考文献：
  名称：

  Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959

  摘要：

  Ro 31-8959 (1), a potent and selective inhibitor of HIV proteinase, is currently in phase III clinical trials. Six approaches for the large-scale synthesis of this compound have been studied. All routes employ an initial disconnection to an electrophilic L-phenylalanine homologue equivalent 13 and the decahydroisoquinoline derivative 5. They differ in adopting either an epoxide, a cyclic sulfate, or an aldehyde as the electrophilic entity and develop chirality from L-phenylalanine, dimethyl D-tartrate, or a Sharpless epoxidation. The preferred route starts from N-phthaloyl-L-phenylalaninyl chloride and uses tris((trimethylsilyl)oxy)ethene to effect homologation to hydroxy ketone 30, which is elaborated in a five-step two-pot procedure to N-phthaloyl epoxide 33 and hence 1. Kilogram quantities of Ro 31-8959 have been prepared using this route.

  DOI：

  10.1021/jo00092a026
• 作为产物：
  描述：

  phthaloyl-L-phenylalanyl chloride 在 盐酸 、 对甲苯磺酸 作用下， 以 二氯甲烷 为溶剂， 反应 20.5h， 生成 2-[(2S)-4-(oxan-2-yloxy)-3-oxo-1-phenylbutan-2-yl]isoindole-1,3-dione
  参考文献：
  名称：

  Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959

  摘要：

  Ro 31-8959 (1), a potent and selective inhibitor of HIV proteinase, is currently in phase III clinical trials. Six approaches for the large-scale synthesis of this compound have been studied. All routes employ an initial disconnection to an electrophilic L-phenylalanine homologue equivalent 13 and the decahydroisoquinoline derivative 5. They differ in adopting either an epoxide, a cyclic sulfate, or an aldehyde as the electrophilic entity and develop chirality from L-phenylalanine, dimethyl D-tartrate, or a Sharpless epoxidation. The preferred route starts from N-phthaloyl-L-phenylalaninyl chloride and uses tris((trimethylsilyl)oxy)ethene to effect homologation to hydroxy ketone 30, which is elaborated in a five-step two-pot procedure to N-phthaloyl epoxide 33 and hence 1. Kilogram quantities of Ro 31-8959 have been prepared using this route.

  DOI：

  10.1021/jo00092a026

文献信息

• Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959
  作者：Kevin E. B. Parkes、David J. Bushnell、Peter H. Crackett、Stephen J. Dunsdon、Andrew C. Freeman、Michelle P. Gunn、Richard A. Hopkins、Robert W. Lambert、Joseph A. Martin

  DOI：10.1021/jo00092a026

  日期：1994.7

  Ro 31-8959 (1), a potent and selective inhibitor of HIV proteinase, is currently in phase III clinical trials. Six approaches for the large-scale synthesis of this compound have been studied. All routes employ an initial disconnection to an electrophilic L-phenylalanine homologue equivalent 13 and the decahydroisoquinoline derivative 5. They differ in adopting either an epoxide, a cyclic sulfate, or an aldehyde as the electrophilic entity and develop chirality from L-phenylalanine, dimethyl D-tartrate, or a Sharpless epoxidation. The preferred route starts from N-phthaloyl-L-phenylalaninyl chloride and uses tris((trimethylsilyl)oxy)ethene to effect homologation to hydroxy ketone 30, which is elaborated in a five-step two-pot procedure to N-phthaloyl epoxide 33 and hence 1. Kilogram quantities of Ro 31-8959 have been prepared using this route.