(8S,9R,11R)-2,8-dimethyl-9-hydroxy-9-methoxycarbonyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo[a,g]cycloocta[cde]trinden-1-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (8S,9R,11R)-2,8-dimethyl-9-hydroxy-9-methoxycarbonyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo[a,g]cycloocta[cde]trinden-1-one
• 英文别名: methyl (15S,16R,18R)-16-hydroxy-4,15-dimethyl-3-oxo-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaene-16-carboxylate
• 化学式: C₂₈H₂₃N₃O₅
• 分子量: 481.508
• InChiKey: DRIRPEIGDLTAFJ-KEFSCGHKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  36
• 可旋转键数：
  2
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  85.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (+)-抗生素K252A 、 碘甲烷 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以74%的产率得到(8S,9R,11R)-9-methoxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo[a,g]cycloocta[cde]trinden-1-one
  参考文献：
  名称：

  Synthetic Process Development of Antitumor Agent KT6587, an Indolocarbazole Alkaloid K252a Derivative

  摘要：

  A facile and large-scale preparation process of an antitumor. agent KT6587 (2), derived from an indolocarbazole alkaloid K252a (1), has been developed, The new synthetic process requires four steps: (i) selective N-silylation of the amide group of 1 with tert-butyldimethylsilyl chloride, (ii) methylation of the hydroxy group, (iii) deprotection under aqueous acidic conditions to afford 3, and (iv) reduction of the methoxycarbonyl group to obtain 2, The key strategic improvement is to obtain fine quality of the intermediate 3 in a reasonable yield with reproducibility. This new process improves the overall yield from 33% to 70% without tedious chromatographic separations and hazardous conditions, Multikilogram quantities of KT6587 (2) for early clinical evaluation have been obtained by this method.

  DOI：

  10.1021/op980087x