(S)-(+)-4-ethyl-4-hydroxy-8-methoxy-6-(trimethylsilyl)-1,4-dihydro-3H-pyrano[3,4-c]pyridin-3-one | 174092-78-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃吡啶类
• 英文名称: (S)-(+)-4-ethyl-4-hydroxy-8-methoxy-6-(trimethylsilyl)-1,4-dihydro-3H-pyrano[3,4-c]pyridin-3-one
• 英文别名: (S)-4-ethyl-3,4-dihydro-4-hydroxy-8-methoxy-6-trimethylsilyl-3-oxo-1H-pyrano[3,4-c] pyridine；(S)-4-Ethyl-4-hydroxy-8-methoxy-6-trimethylsilanyl-1,4-dihydro-pyrano[3,4-c]pyridin-3-one；(4S)-4-ethyl-4-hydroxy-8-methoxy-6-trimethylsilyl-1H-pyrano[3,4-c]pyridin-3-one
• CAS: 174092-78-5
• 化学式: C₁₄H₂₁NO₄Si
• 分子量: 295.411
• InChiKey: LDHXQUYWUFVOBW-AWEZNQCLSA-N

物化性质

• 沸点：
  392.9±42.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.29
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  68.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-(+)-4-ethyl-4-hydroxy-8-methoxy-6-(trimethylsilyl)-1,4-dihydro-3H-pyrano[3,4-c]pyridin-3-one 在 氢碘酸 、 六甲基二锡 、 一氯化碘 、 sodium hydride 、 lithium bromide 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 生成 喜树碱
  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：
• 作为产物：
  描述：

  2-溴-6-甲氧基吡啶 在 palladium diacetate 三乙基硅烷 、 四氧化锇 、 正丁基锂 、 hydroquinindine-2,5-diphenyl-4,6-pyrimidinediyl diether 、 甲基磺酰胺 、 四丁基溴化铵 、 碘 、 potassium carbonate 、 三氟乙酸 、 calcium carbonate 、 potassium hexacyanoferrate(III) 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 73.0h， 生成 (S)-(+)-4-ethyl-4-hydroxy-8-methoxy-6-(trimethylsilyl)-1,4-dihydro-3H-pyrano[3,4-c]pyridin-3-one
  参考文献：
  名称：

  A General Synthetic Approach to the (20S)-Camptothecin Family of Antitumor Agents by a Regiocontrolled Cascade Radical Cyclization of Aryl Isonitriles

  摘要：

  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.

  DOI：

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

文献信息

• Total and semisynthesis and in vitro studies of both enantiomers of 20-fluorocamptothecin
  作者：Raghuram S. Tangirala、Rachel Dixon、Danzhou Yang、Attila Ambrus、Smitha Antony、Keli Agama、Yves Pommier、Dennis P. Curran

  DOI：10.1016/j.bmcl.2005.07.074

  日期：2005.11

  Both enantiomers of 20-fluorocamptothecin and the racemate have been prepared by total synthesis. The (R)-enantiomer is essentially inactive in a topoisomerase-I/DNA assay, while the (S)-enantiomer is much less active than (20S)-camptothecin. The lactone ring of 20-fluorocamptothecin hydrolyzes more rapidly than that of camptothecin in PBS. The results provide insight into the role of the 20-hydroxy

  通过全合成制备了20-氟喜树碱的对映体和外消旋体。（R）-对映体在拓扑异构酶-I / DNA分析中基本上是无活性的，而（S）-对映体的活性远低于（20S）-喜树碱。20-氟喜树碱的内酯环比喜树碱在PBS中的内酯环水解得更快。该结果提供了关于20-羟基在喜树碱与拓扑异构酶-I和DNA结合中的作用的见解。
• METHOD OF SYNTHESIZING CAMPTOTHECIN-RELATING COMPOUNDS
  申请人：KABUSHIKI KAISHA YAKULT HONSHA

  公开号：EP1378505B1

  公开（公告）日：2014-11-05