(12Z,16E)-(6R,7S,8S,15S)-15-Azido-7-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-thiazol-4-yl)-3,5-dioxo-heptadeca-12,16-dienoic acid tert-butyl ester | 350042-05-6

• 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: (12Z,16E)-(6R,7S,8S,15S)-15-Azido-7-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-thiazol-4-yl)-3,5-dioxo-heptadeca-12,16-dienoic acid tert-butyl ester
• CAS: 350042-05-6
• 化学式: C₃₁H₄₈N₄O₅S
• 分子量: 588.812
• InChiKey: PMCSPFZLAIZZJB-CQLANRJWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.57
• 重原子数：
  41.0
• 可旋转键数：
  16.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  142.32
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (12Z,16E)-(6R,7S,8S,15S)-15-Azido-7-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-thiazol-4-yl)-3,5-dioxo-heptadeca-12,16-dienoic acid tert-butyl ester 在 水 作用下， 以 四氢呋喃 为溶剂， 生成
  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：

  triethyl-[(1E,3R,5Z)-6-iodo-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)hepta-1,5-dien-3-yl]oxysilane 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 三苯胂 、 二苯基膦叠氮化物 、 caesium carbonate 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 10.0h， 生成 (12Z,16E)-(6R,7S,8S,15S)-15-Azido-7-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-thiazol-4-yl)-3,5-dioxo-heptadeca-12,16-dienoic acid tert-butyl ester
  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