anhydrovinblastine | 38390-45-3

• 物质功能分类: 原料药 - 抗肿瘤药 - 其它抗肿瘤药
• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 长春花生物碱
• 英文名称: anhydrovinblastine
• 英文别名: methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-4-[(13S,15S)-17-ethyl-13-methoxycarbonyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaen-13-yl]-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: 38390-45-3
• 化学式: C₄₆H₅₆N₄O₈
• 分子量: 792.973
• InChiKey: FFRFGVHNKJYNOV-DOVUUNBWSA-N

物化性质

• 密度：
  1.35±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO（少量）、甲醇（少量）、水（少量）

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  58
• 可旋转键数：
  10
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  134
• 氢给体数：
  2
• 氢受体数：
  11

制备方法与用途

产品描述

脱水长春碱是制备长春瑞滨及其可药用盐的重要原料，在酒石酸长春瑞滨的化学合成中具有重要意义。

产品用途

脱水长春碱是一种效果极佳的在研主流抗肿瘤药物，其主要通过与细胞有丝分裂G2期的微管蛋白单体结合来抑制微管形成，并促使肿瘤细胞凋亡。该药物常用于治疗非小细胞癌、乳腺癌、卵巢癌、软组织及内脏转移癌和淋巴癌。此外，脱水长春碱还可作为合成长春瑞滨的中间体。

反应信息

• 作为反应物：
  描述：

  anhydrovinblastine 在 氯仿 、 氢氟酸 、 五氟化锑 作用下， 反应 0.33h， 以40%的产率得到20',20'-difluoro-4'-deoxyvinblastine
  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：

  在 sodium hydroxide 、 sodium tetrahydroborate 作用下， 以415 mg的产率得到anhydrovinblastine
  参考文献：
  名称：

  Laccase-catalyzed coupling of catharanthine and vindoline: an efficient approach to the bisindole alkaloid anhydrovinblastine

  摘要：

  The efficient enzyme-catalyzed coupling of the indolic alkaloids catharanthine and vindoline was carried out by exploiting the oxidoreductases laccases and atmospheric oxygen. Following NaBH4 reduction of the eniminium cationic intermediate, the synthetically useful dimer anhydrovinblastine (AVBL) was isolated and characterized. Several reaction parameters were investigated in detail and, under the optimized reaction conditions, AVBL was isolated in 56% yield. The practicability of this bioconversion was further confirmed through the condensation of catharanthine with the vindoline analogue 11-methoxy-dihydrotabersonine. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2008.10.064

文献信息

• Mechanistic aspects of the formation of anhydrovinblastine by Potier-Polonovski oxidative coupling of catharanthine and vindoline. Spectroscopic observation and chemical reactions of intermediates
  作者：Richard J. Sundberg、Kumar G. Gadamasetti、Phyllis J. Hunt

  DOI：10.1016/s0040-4020(01)88140-0

  日期：——

  by trifluoroacetic anhydride has been carried out under conditions which allow observation of intermediates and comparison of reactivity by low temperature NMR. These studies have confirmed or revealed the following facets of the mechanism of the reaction: (1) fragmentation of an intermediate derived from catharanthine-N-oxide which otherwise is stable at −40°C occurs rapidly on addition of vindoline;

  三氟乙酸酐对金刚烷胺和长春新碱的断裂偶联反应是在允许观察中间体并通过低温NMR比较反应性的条件下进行的。这些研究已经证实或揭示了反应机理的以下几个方面：（1）加入长春花碱后，在-40°C时稳定的衍生自Catharanthine-N-氧化物的中间体发生断裂。（2）其他的碱，包括三- Ñ-丁胺，N，N-二甲基-3-甲氧基苯胺，N，N-二甲基-2-（2,4-二甲氧基苯基）乙胺和10-三氟乙酰基-长春花碱也促进了裂解; （3）偶合的立体选择性部分受长春花碱与脱水长春碱和16′-表-脱水长春碱的单独前体的不同反应速率控制；（4）N一个-methylcatharanthine-N b的方式类似于catharantine -N-氧化物-氧化物经受碎裂，但有不能在后者的情况下被检测到可观察到的中间体; （5）将N碎片的速率一个-methylcatharanthine-N b氧化物还受到碱的加速；（6）由最
• Biosynthesis of the antitumour catharanthus alkaloids: the fate of the 21′α-hydrogen of anhydrovinblastine
  作者：Robert L. Baxter、Mashooda Hasan、Neil E. Mackenzie、A. Ian Scott

  DOI：10.1039/c39820000791

  日期：——

  [21′α-3H,methyl-14C] Anhydrovinblastine is incorporated into vinblastine by cell-free preparation of Catharanthus roseus without loss of 3H.

  [21'α- 3 H，甲基- 14 C]脱水长春碱是通过无细胞制备物掺入到长春花碱长春花不损失3 H.
• Process for the preparation of binary indole alkaloids
  申请人：Mitsui Petrochemical Industries, Inc.

  公开号：US05432279A1

  公开（公告）日：1995-07-11

  The present invention relates to a process for the preparation, from e.g. anhydrovinblastine, of binary indole alkaloids effective as an anti-cancer drug, such as vinblastine, leurosidine, etc., wherein a trivalent iron source and hydride source are added in the presence of oxygen, thereby increasing a yield of an object compound. The yield of an object compound is improved still more by further addition, to the reaction system, of an oxalic acid ion source, malonic acid ion source, inorganic anion source, amino acid, etc.

  本发明涉及一种制备二元吲哚类生物碱的方法，所述生物碱可用作抗癌药物，例如长春新碱、龙葵碱等，其中在存在氧气的情况下添加三价铁源和氢化物源，从而提高目标化合物的产率。通过向反应体系进一步添加草酸离子源、丙二酸离子源、无机阴离子源、氨基酸等，可以进一步提高目标化合物的产率。
• Process for the preparation of alkaloids of the leurosine type
  申请人：Richter Gedeon Vegyeszeti Gyar Rt.

  公开号：US04199505A1

  公开（公告）日：1980-04-22

  A process for the preparation of alkaloids of the leurosine type having the formula I ##STR1## and the acid addition salts thereof. In the formula I R is hydrogen or methyl. The compounds prepared according to the invention are known compounds showing cytostatic activity.

  一种制备具有公式I的leurosine型生物碱及其酸盐的过程。在公式I中，R是氢或甲基。根据本发明制备的化合物是已知的具有细胞毒活性的化合物。
• Vinblastine synthesis
  申请人：Allelix, Inc.

  公开号：US05034320A1

  公开（公告）日：1991-07-23

  The reaction of 3',4'-anhydrovinblastine with a Catharanthus roseus-derived protein fraction to form vinblastine is improved by conducting the reaction in the presence of a reducing agent such as the enzyme cofactor NADH. A cationic species such as manganous ion may also be added to the reaction. Vinblastine yields are enhanced.

  在存在还原剂，如酶辅因子NADH的情况下，将3'，4'-去水乙万古霉素与长春花衍生的蛋白质分数反应以形成长春花碱，可以改善反应。也可以向反应中添加阳离子物种，如锰离子。这可以增强长春花碱的产量。