3-epi-desoxyepothilone A | 188259-95-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: 3-epi-desoxyepothilone A
• 英文别名: 3-Epi-dEpoA；(4R,7R,8S,9S,13Z,16S)-4,8-dihydroxy-5,5,7,9-tetramethyl-16-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-1-oxacyclohexadec-13-ene-2,6-dione
• CAS: 188259-95-2
• 化学式: C₂₆H₃₉NO₅S
• 分子量: 477.665
• InChiKey: BEFZAMRWPCMWFJ-VIBHQXHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  33
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-epi-desoxyepothilone A 在 二甲基二环氧乙烷 作用下， 生成 3-epi-epothilone A
  参考文献：
  名称：

  Remote Effects in Macrolide Formation through Ring-Forming Olefin Metathesis:  An Application to the Synthesis of Fully Active Epothilone Congeners

  摘要：

  DOI：

  10.1021/ja964275j
• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 3-epi-desoxyepothilone A
  参考文献：
  名称：

  Designed Epothilones: Combinatorial Synthesis, Tubulin Assembly Properties, abd Cytotoxic Action against Taxol-Resistant Tumor Cells

  摘要：

  A library of epothilone A and B analogues, which was constructed by solid‐phase combinatorial synthesis using SMART Microreactors and solution chemistry, was screened in two different tubulin binding assays. Selected compounds were subjected to cytotoxicity studies against a number of cell lines, including Taxol‐resistant cells. Important structure–activity relationship emerged from these studies, which sets the stage for further discoveries and developments in the anticancer field.

  DOI：

  10.1002/anie.199720971

文献信息

• Synthesis of epothilones, intermediates thereto, analogues and uses thereof
  申请人：Sloan-Kettering Institute For Cancer Research

  公开号：EP2186811A1

  公开（公告）日：2010-05-19

  The present invention provides compounds of formula (I): as described generally and in classes and subclasses herein. The present invention additionally provides pharmaceutical compositions comprising compounds of formula (I) and provides methods of treating cancer comprising administering a compound of formula (I).

  本发明提供了式（I）化合物：如一般所述 以及本文中的类和亚类。本发明还提供了包含式（I）化合物的药物组合物，并提供了通过施用式（I）化合物治疗癌症的方法。
• Total Syntheses of Epothilones A and B
  作者：Dongfang Meng、Peter Bertinato、Aaron Balog、Dai-Shi Su、Ted Kamenecka、Erik J. Sorensen、Samuel J. Danishefsky

  DOI：10.1021/ja971946k

  日期：1997.10.1

  Convergent, stereocontrolled total syntheses of the microtubule-stabilizing macrolides epothilones A (2) and B (3) have been achieved. Four distinct ring-forming strategies were pursued (see Scheme 1). Of these four, three were reduced to practice. In one approach, the action of a base on a substance possessing an acetate ester and a nonenolizable aldehyde brought about a remarkably effective macroaldolization see (89 --> 90 + 91; 99 --> 100 + 101), simultaneously creating the C2-C3 bond and the hydroxyl-bearing stereocenter at C-3. Alternatively, the 16-membered macrolide of the epothilones could be fashioned through a C12-C13 ring-closing olefin metathesis (e.g. see 111 --> 90 + 117; 122 --> 105 + 123) and through macrolactonization of the appropriate hydroxy acid (e.g. see 88 --> 93). The application of a stereospecific B-alkyl Suzuki coupling strategy permitted the establishment of a cis C12-C13 olefin, thus setting the stage for an eventual site-and diastereoselective epoxidation reaction (see 96 --> 2; 106 --> 3). The development of a novel cyclopropane solvolysis strategy for incorporating the geminal methyl groups of the epothilones (see 39 --> 40 --> 41), and the use of Lewis acid catalyzed diene-aldehyde cyclocondensation (LACDAC) (see 35 + 36 --> 37) and asymmetric allylation (see 10 --> 76) methodology are also noteworthy.