(E)-(4S,8S,15S,16R,17S)-4-(tert-Butyl-dimethyl-silanyloxy)-16-hydroxy-15,17-dimethyl-8-[(E)-1-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-7-oxa-spiro[2.15]octadec-10-ene-6,18-dione | 202333-64-0

• 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: (E)-(4S,8S,15S,16R,17S)-4-(tert-Butyl-dimethyl-silanyloxy)-16-hydroxy-15,17-dimethyl-8-[(E)-1-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-7-oxa-spiro[2.15]octadec-10-ene-6,18-dione
• CAS: 202333-64-0
• 化学式: C₃₂H₅₁NO₅SSi
• 分子量: 589.912
• InChiKey: PLRNKQUKRNVEHR-RRHCSRSPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.66
• 重原子数：
  40.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  85.72
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (E)-(4S,8S,15S,16R,17S)-4-(tert-Butyl-dimethyl-silanyloxy)-16-hydroxy-15,17-dimethyl-8-[(E)-1-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-7-oxa-spiro[2.15]octadec-10-ene-6,18-dione 在 1,1,1-三氟丙酮 、 Oxone<*> 、 edetate disodium 、 碳酸氢钠 、 氟化氢吡啶 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 22.5h， 生成
  参考文献：
  名称：

  Total Synthesis of Oxazole- and Cyclopropane-Containing Epothilone A Analogues by the Olefin Metathesis Approach

  摘要：

  AbstractFor structure‐activity relationship studies, two series of epothilone A (1) analogues have been designed and synthesized, one containing an oxazole moiety instead of the thiazole heterocycle and the other containing a spirocyclopropane moiety in place of the gem‐dimethyl group at position C‐4 (4,4‐ethano‐epothilones). The olefin metathesis strategy in solution was utilized for the chemical synthesis of these compounds starting with key building blocks 7–9 for the oxazole series (compounds 2, 14–18, 21–26) and building blocks 8, 30, and 31 for the 4,4‐ethano series (compounds 3,39–43, 46–51). The convergent strategy towards the designed epothilone A series involved a) an aldol condensation reaction, b) an esterification reaction, c) an olefin metathesis reaction catalyzed by [RuCl2(=CHPh)‐(PCy3)2], and d) epoxidation of the macrocycle double bond.

  DOI：

  10.1002/chem.19970031211
• 作为产物：
  描述：

  (S)-3-(tert-Butyl-dimethyl-silanyloxy)-3-(1-propionyl-cyclopropyl)-propionic acid 在 Grubbs catalyst first generation 4-二甲氨基吡啶 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 (E)-(4S,8S,15S,16R,17S)-4-(tert-Butyl-dimethyl-silanyloxy)-16-hydroxy-15,17-dimethyl-8-[(E)-1-methyl-2-(2-methyl-thiazol-4-yl)-vinyl]-7-oxa-spiro[2.15]octadec-10-ene-6,18-dione
  参考文献：
  名称：

  Total Synthesis of Oxazole- and Cyclopropane-Containing Epothilone A Analogues by the Olefin Metathesis Approach

  摘要：

  AbstractFor structure‐activity relationship studies, two series of epothilone A (1) analogues have been designed and synthesized, one containing an oxazole moiety instead of the thiazole heterocycle and the other containing a spirocyclopropane moiety in place of the gem‐dimethyl group at position C‐4 (4,4‐ethano‐epothilones). The olefin metathesis strategy in solution was utilized for the chemical synthesis of these compounds starting with key building blocks 7–9 for the oxazole series (compounds 2, 14–18, 21–26) and building blocks 8, 30, and 31 for the 4,4‐ethano series (compounds 3,39–43, 46–51). The convergent strategy towards the designed epothilone A series involved a) an aldol condensation reaction, b) an esterification reaction, c) an olefin metathesis reaction catalyzed by [RuCl2(=CHPh)‐(PCy3)2], and d) epoxidation of the macrocycle double bond.

  DOI：

  10.1002/chem.19970031211

文献信息

• Designed Epothilones: Combinatorial Synthesis, Tubulin Assembly Properties, abd Cytotoxic Action against Taxol-Resistant Tumor Cells
  作者：K. C. Nicolaou、Dionisios Vourloumis、Tianhu Li、Joaquin Pastor、Nicolas Winssinger、Yun He、Sacha Ninkovic、Francisco Sarabia、Hans Vallberg、Frank Roschangar、N. Paul King、M. Ray V. Finlay、Pareskevi Giannakakou、Pascal Verdier-Pinard、Ernest Hamel

  DOI：10.1002/anie.199720971

  日期：1997.10.17

  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.