(20S)-9,10-ethylenedioxy-7-(4-methylpyrazinomethyl)camptothecin

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: (20S)-9,10-ethylenedioxy-7-(4-methylpyrazinomethyl)camptothecin
• 英文别名: (18S)-18-ethyl-18-hydroxy-2-[(4-methylpiperazin-1-yl)methyl]-5,8,20-trioxa-13,24-diazahexacyclo[12.11.0.03,12.04,9.015,24.017,22]pentacosa-1,3(12),4(9),10,13,15,17(22)-heptaene-19,23-dione
• 化学式: C₂₈H₃₀N₄O₆
• 分子量: 518.569
• InChiKey: CQUSOQYBOCTTRK-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  38
• 可旋转键数：
  3
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-Ethyl-8-methoxy-6-trimethylsilanyl-1H-pyrano[3,4-c]pyridine 在 四氧化锇 、 hydroquinindine-2,5-diphenyl-4,6-pyrimidinediyl diether 、 氢碘酸 、 碘 、 一氯化碘 、 calcium carbonate 作用下， 生成 (20S)-9,10-ethylenedioxy-7-(4-methylpyrazinomethyl)camptothecin
  参考文献：
  名称：

  Curran, Dennis P.; Ko, Sung-Bo; Josien, Hubert, Angewandte Chemie, 1995, vol. 107, # 23/24, p. 2948 - 2950

  摘要：

  DOI：

文献信息

• A General Synthetic Approach to the (20S)-Camptothecin Family of Antitumor Agents by a Regiocontrolled Cascade Radical Cyclization of Aryl Isonitriles
  作者：Hubert Josien、Sung-Bo Ko、David Bom、Dennis P. Curran

  DOI：10.1002/(sici)1521-3765(199801)4:1<67::aid-chem67>3.0.co;2-f

  日期：1998.1

  A general and efficient synthesis of (20S)-camptothecin (1a) is reported. A key common intermediate containing the pyridone and lactone (DE) rings of camptothecin and most derivatives was constructed from 2-trimethylsilyl-6-methoxypyridine by a series of metalation reactions and a Heck cyclization to provide an achiral bicyclic enol ether. Sharpless asymmetric dihydroxylation followed by lactol oxidation and iododesilylation produced the key intermediate in 94% enantiomeric excess. Alkylation with propargyl bromide and a cascade radical reaction with phenyl isonitrile then produced 1a. About 20 other penta- and hexacyclic analogues of camptothecin with differing single or multiple substituents at C7, C9, C10, C11, and/or C12 were made by changing the propargylating agent and the isonitrile. Included among these are several drug candidates and the approved drugs topotecan and irinotecan. The synthesis of the prodrug irinotecan is direct one that does not pass through the active metabolite. The use of ortho-trimethylsilyl-substituted isonitriles allows the regioselective synthesis of camptothecin analogues in cases where isomeric mixtures are formed from the parent isonitriles. The synthesis of the derivatives relies on the broad scope and functional group tolerance of the key cascade radical reaction.