N-methoxycarbonyl-20-hydroxy-19-oxocatharanthine | 1313860-86-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 依波格型生物碱
• 英文名称: N-methoxycarbonyl-20-hydroxy-19-oxocatharanthine
• 英文别名: dimethyl (6R,9R)-7-(1-hydroxyethyl)-10-oxo-9,10,12,13-tetrahydro-5H-6,9-methanopyrido[1',2':1,2]azepino[4,5-b]indole-5,6(6aH)-dicarboxylate；Na-methoxycarbonyl-20-hydroxy-19-oxocatharanthine
• CAS: 1313860-86-4
• 化学式: C₂₃H₂₄N₂O₆
• 分子量: 424.453
• InChiKey: ZQVWJAGAMYMFJL-WSZZGJJOSA-N

物化性质

• 沸点：
  621.5±65.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.76
• 重原子数：
  31.0
• 可旋转键数：
  2.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  98.07
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  N-methoxycarbonyl-20-hydroxy-19-oxocatharanthine 在 盐酸 、 4-二甲氨基吡啶 、 manganese(IV) oxide 、 sodium tetrahydroborate 、 四(三苯基膦)钯 、 硼氘化钠 、 氯仿 、 cerium(III) chloride heptahydrate 、 三氟化硼乙醚 、 氢氟酸 、 五氟化锑 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 51.59h， 生成 20',20'-difluoro-4'-deoxyvinblastine-4'-d1
  参考文献：
  名称：

  On the Elucidation of the Mechanism ofVincaAlkaloid Fluorination in Superacidic Medium

  摘要：

  Detailed investigations on one of the key steps of the superacidic fluorination of Vinca alkaloids that is the origin of C20' activation are reported. While two different pathways can be envisioned for the emergence of the transient secondary carbocationic intermediate, isotopic labeling experiments unambiguously revealed the involvement of a 1,2-hydride shift mechanism.

  DOI：

  10.1021/ol201637m
• 作为产物：
  描述：

  N-methoxycarbonyl-19-oxocatharanthine 在 selenium(IV) oxide 作用下， 以 乙醇 为溶剂， 反应 72.0h， 以61%的产率得到N-methoxycarbonyl-20-hydroxy-19-oxocatharanthine
  参考文献：
  名称：

  二氟金刚烷胺的合成及其与长春新碱的仿生偶联研究

  摘要：

  奇怪的一对：据报道从天然存在的catharanthine开始合成20,20-difluorocatharanthine。研究了氟化的长春花碱类似物作为长春氟宁家族二聚长春花生物碱的潜在前体。然而，二氟金刚烷胺与长春花碱的仿生偶联导致了意想不到的产物，其形成是合理的（参见方案）。

  DOI：

  10.1002/chem.201203577

文献信息

• Synthesis of fluorinated catharanthine analogues and investigation of their biomimetic coupling with vindoline
  作者：Emerson Giovanelli、Lionel Moisan、Sébastien Comesse、Sébastien Leroux、Bernard Rousseau、Paul Hellier、Marc Nicolas、Eric Doris

  DOI：10.1039/c3ob41170b

  日期：——

  The syntheses of 20,20-difluorocatharanthine and congeners, starting from the naturally occurring catharanthine, are reported. The fluorinated catharanthine analogues were investigated as potential precursors to dimeric Vinca alkaloids of the vinflunine family. However, the biomimetic coupling of the fluorinated catharanthine derivatives with vindoline led to unexpected alkaloid structures, the formation

  从天然存在开始，合成20,20-二氟金刚烷胺和同类物 黄hara素，均已报告。研究了氟化长春花碱类似物作为长春氟宁家族二聚长春花生物碱的潜在前体。然而，氟化的Catharanthine衍生物与长春花碱 导致出人意料的生物碱结构，其形成是合理的。
• Synthesis of a Potent Vinblastine: Rationally Designed Added Benign Complexity
  作者：Oliver Allemann、Manuela Brutsch、John C. Lukesh、Daniel M. Brody、Dale L. Boger

  DOI：10.1021/jacs.6b04330

  日期：2016.7.13

  Many natural products, including vinblastine, have not been easily subjected to simplifications in their structures by synthetic means or modifications by late-stage semisynthetic derivatization in ways that enhance their biological potency. Herein, we detail a synthetic vinblastine that incorporates added benign complexity (ABC), which improves activity 10-fold, and is now accessible as a result of advances in the total synthesis of the natural product. The compound incorporates designed added molecular complexity but no new functional groups and maintains all existing structural and conformational features of the natural product. It constitutes a member of an analogue class presently inaccessible by semisynthetic derivatization of the natural product, by its late-stage functionalization, or by biosynthetic means. Rather, it was accessed by synthetic means, using an appropriately modified powerful penultimate single-step vindoline-catharanthine coupling strategy that proceeds with a higher diastereoselectivity than found for the natural product itself.