(E,2S)-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-1-[(2S,3R)-3-prop-2-enyloxiran-2-yl]but-3-en-2-ol | 184246-37-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (E,2S)-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-1-[(2S,3R)-3-prop-2-enyloxiran-2-yl]but-3-en-2-ol
• CAS: 184246-37-5
• 化学式: C₁₄H₁₉NO₂S
• 分子量: 265.376
• InChiKey: SDZSSTUZJQZLQH-JVGZMYSTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E,2S)-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-1-[(2S,3R)-3-prop-2-enyloxiran-2-yl]but-3-en-2-ol 在 4-二甲氨基吡啶 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Total Syntheses of Epothilones A and B

  摘要：

  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.

  DOI：

  10.1021/ja971946k
• 作为产物：
  描述：

  [(2S,4S)-2-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-3,4-dihydro-2H-pyran-4-yl] acetate 在 sodium periodate 、 二甲基二环氧乙烷 、 四氯化锡 、 sodium hydride 、 potassium carbonate 、 三乙胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 (E,2S)-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-1-[(2S,3R)-3-prop-2-enyloxiran-2-yl]but-3-en-2-ol
  参考文献：
  名称：

  Total Syntheses of Epothilones A and B

  摘要：

  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.

  DOI：

  10.1021/ja971946k

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：US06369234B1

  公开（公告）日：2002-04-09

  The present invention provides convergent processes for preparing epothilone A and B, desoxyepothilones A and B, and analogues thereof. Also provided are analogues related to epothilone A and B and intermediates useful for preparing same. The present invention further provides novel compositions based on analogues of the epothilones and methods for the treatment of cancer and cancer which has developed a multidrug-resistant phenotype.

  本发明提供了用于制备依托酮A和B、去氧依托酮A和B及其类似物的汇聚过程。还提供了与依托酮A和B相关的类似物以及用于制备它们的中间体。本发明还提供了基于依托酮类似物的新型组合物，以及用于治疗癌症和发展出多药耐药表型的癌症的方法。