tert-butyl (2Z,6R,7S,8S,12Z,15S,16E)-15-amino-3-methoxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)heptadeca-2,12,16-trienoate | 350042-19-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: tert-butyl (2Z,6R,7S,8S,12Z,15S,16E)-15-amino-3-methoxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)heptadeca-2,12,16-trienoate
• CAS: 350042-19-2
• 化学式: C₃₅H₅₃Cl₃N₂O₇S
• 分子量: 752.24
• InChiKey: RLAORZNKGITITB-YOFYTEPTSA-N

物化性质

• 沸点：
  786.4±60.0 °C(Predicted)
• 密度：
  1.185±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.32
• 重原子数：
  48.0
• 可旋转键数：
  17.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  127.04
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (2Z,6R,7S,8S,12Z,15S,16E)-15-amino-3-methoxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)heptadeca-2,12,16-trienoate 在 盐酸 、 N-羟基-7-氮杂苯并三氮唑 、 Et₂NH₂[{((R)-BINAP)RuCl}2Cl₂] 、 对甲苯磺酸 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， -78.0~25.0 ℃ 、8.27 MPa 条件下， 反应 77.0h， 生成 伊沙匹隆
  参考文献：
  名称：

  On the Interactivity of Complex Synthesis and Tumor Pharmacology in the Drug Discovery Process:  Total Synthesis and Comparative in Vivo Evaluations of the 15-Aza Epothilones

  摘要：

  The total syntheses of 12,13,15-desoxy-15(S)-aza-epothilone B (aza-dEpoB; dEpoB-lactam) and 12,13, 15-desoxy-15(R)-aza-epothilone B (15-epi-aza-dEpoB; 15-epi-dEpoB-lactam) have been accomplished via a highly convergent strategy. We have also successfully oxidized 12,13,15-desoxy 15(S)-aza-epothilone B to aza-epothilone B (aza-EpoB; EpoB-lactam). Aza-epothilone B has been advanced to phase I clinical trials by the Bristol-Myers Squibb group. Our synthesis is efficient and was amenable to the production of significant quantities of these lactams. Using our fully synthetically derived lactams, in vitro and in vivo studies were conducted in comparison with advanced clinical candidates, 12,13-desoxyepothilone B and 12,13-desoxyepothilone F, also derived by total synthesis.

  DOI：

  10.1021/jo010275c
• 作为产物：
  描述：

  (5R)-5-hydroxy-2-iodo-6-methyl-7-(2-methylthiazol-4-yl)-2,6-heptadiene 在 9-borabicyclo[3.3.1]nonane dimer 、 三(2-氯乙基)胺 、 偶氮二甲酸二异丙酯 、 水 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 生成 tert-butyl (2Z,6R,7S,8S,12Z,15S,16E)-15-amino-3-methoxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)heptadeca-2,12,16-trienoate
  参考文献：
  名称：

  On the Total Synthesis and Preliminary Biological Evaluations of 15(R) and 15(S) Aza-dEpoB:  A Mitsunobu Inversion at C15 in Pre-Epothilone Fragments

  摘要：

  [GRAPHICS]The syntheses of two epothilone analogues, 15(S)-aza-12,13-desoxyepothilone B and the epimeric 15(R)-aza-12,13-desoxyepothitone B, are described. A Mitsunobu inversion was utilized for elaboration of pre epothilone fragments to the corresponding macrolactam. Tubulin binding and cytotoxicity profiles of these analogues are presented.

  DOI：

  10.1021/ol005932m