(7S,5R)-methyl 3-benzyl-1,2,3,4,5,6,7,8-octahydro-5-((2S)-2-ethyl-2,3-epoxypropyl)-7-(15-vindolinyl)azonino[5,4-b]indole-7-carboxylate | 131703-73-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: (7S,5R)-methyl 3-benzyl-1,2,3,4,5,6,7,8-octahydro-5-((2S)-2-ethyl-2,3-epoxypropyl)-7-(15-vindolinyl)azonino[5,4-b]indole-7-carboxylate
• 英文别名: methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-4-[(5R,7S)-3-benzyl-5-[[(2S)-2-ethyloxiran-2-yl]methyl]-7-methoxycarbonyl-1,2,4,5,6,8-hexahydroazonino[5,4-b]indol-7-yl]-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraene-10-carboxylate
• CAS: 131703-73-6
• 化学式: C₅₃H₆₄N₄O₉
• 分子量: 901.113
• InChiKey: LDARYMNUOPZUBO-LPUQXOQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.22
• 重原子数：
  66.0
• 可旋转键数：
  11.0
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  146.4
• 氢给体数：
  2.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  (7S,5R)-methyl 3-benzyl-1,2,3,4,5,6,7,8-octahydro-5-((2S)-2-ethyl-2,3-epoxypropyl)-7-(15-vindolinyl)azonino[5,4-b]indole-7-carboxylate 生成 vinblastine
  参考文献：
  名称：

  Enantioselective syntheses of vinblastine, leurosidine, vincovaline and 20'-epi-vincovaline

  摘要：

  The binary indole-indoline alkaloids vinblastine (1), leurosidine (13), 20'-epi-vincovaline (14a), and vincovaline (14b) were obtained by coupling of vindoline (3) to the tetracyclic intermediates 7a, 7b or 22a, 22b, followed by reduction and cyclization steps (60% overall yield for these reactions). The intermediates were obtained by enantioselective establishment of C20' through a first-step Sharpless oxidation (10a,b) and followed by a subsequent diastereomeric separation (20a,b or 21a,b). Alternatively, enantioselective control of the key secodine-type cyclization in the reaction sequence provided the tetracyclic intermediates 54 and 60 for coupling to vindoline. Selective generation of the natural (1, 13, 14a,b) or unnatural (30, 34, 35a,b) atropisomeric forms of the alkaloids was achieved through alternative closures of ring D'. The natural products were also obtained from the higher energy atropisomers by conformational inversion on heating. For the vinblastine synthesis, the overall yield was 22%.

  DOI：

  10.1021/jo00002a008
• 作为产物：
  描述：

  (R)-(2-ethoxyoxiran-2-yl)methanol 在 盐酸 、 四氟硼酸-二乙醚络合物 、 copper(l) iodide 、 silver tetrafluoroborate 、 钾硼氢 、 次氯酸叔丁酯 、 四丁基氟化铵 、 对甲苯磺酸 、 臭氧 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 81.5h， 生成 (7S,5R)-methyl 3-benzyl-1,2,3,4,5,6,7,8-octahydro-5-((2S)-2-ethyl-2,3-epoxypropyl)-7-(15-vindolinyl)azonino[5,4-b]indole-7-carboxylate
  参考文献：
  名称：

  Enantioselective syntheses of vinblastine, leurosidine, vincovaline and 20'-epi-vincovaline

  摘要：

  The binary indole-indoline alkaloids vinblastine (1), leurosidine (13), 20'-epi-vincovaline (14a), and vincovaline (14b) were obtained by coupling of vindoline (3) to the tetracyclic intermediates 7a, 7b or 22a, 22b, followed by reduction and cyclization steps (60% overall yield for these reactions). The intermediates were obtained by enantioselective establishment of C20' through a first-step Sharpless oxidation (10a,b) and followed by a subsequent diastereomeric separation (20a,b or 21a,b). Alternatively, enantioselective control of the key secodine-type cyclization in the reaction sequence provided the tetracyclic intermediates 54 and 60 for coupling to vindoline. Selective generation of the natural (1, 13, 14a,b) or unnatural (30, 34, 35a,b) atropisomeric forms of the alkaloids was achieved through alternative closures of ring D'. The natural products were also obtained from the higher energy atropisomers by conformational inversion on heating. For the vinblastine synthesis, the overall yield was 22%.

  DOI：

  10.1021/jo00002a008

文献信息

• KUEHNE, MARTIN
  作者：KUEHNE, MARTIN

  DOI：——

  日期：——