tert-butyl (3S,6R,7S,8S,12Z,15S,16E)-3-hydroxy-4,4,6,8,12,16-hexamethyl-15-[(2-methylpropan-2-yl)oxycarbonylamino]-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)heptadeca-12,16-dienoate | 277749-42-5

• 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 (3S,6R,7S,8S,12Z,15S,16E)-3-hydroxy-4,4,6,8,12,16-hexamethyl-15-[(2-methylpropan-2-yl)oxycarbonylamino]-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)heptadeca-12,16-dienoate
• CAS: 277749-42-5
• 化学式: C₃₉H₆₁Cl₃N₂O₉S
• 分子量: 840.346
• InChiKey: GTPHTWZZZZPCAW-HIOYZYAKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.2
• 重原子数：
  54
• 可旋转键数：
  24
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  179
• 氢给体数：
  2
• 氢受体数：
  11

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(12Z,16E)-(6R,7S,8S,15S)-15-tert-Butoxycarbonylamino-4,4,6,8,12,16-hexamethyl-17-(2-methyl-thiazol-4-yl)-3,5-dioxo-7-(2,2,2-trichloro-ethoxycarbonyloxy)-heptadeca-12,16-dienoic acid tert-butyl ester	277749-41-4	C39H59Cl3N2O9S	838.33
  ——	tert-butyl (2Z,6R,7S,8S,12Z,15S,16E)-3-methoxy-4,4,6,8,12,16-hexamethyl-15-[(2-methylpropan-2-yl)oxycarbonylamino]-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)heptadeca-2,12,16-trienoate	350042-11-4	C40H61Cl3N2O9S	852.357
  ——	tert-butyl (2Z,6R,7S,8S,12Z,15S,16E)-15-azido-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	350042-09-0	C35H51Cl3N4O7S	778.238

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(3S,6R,7S,8S,12Z,15S,16E)-15-amino-3-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)heptadeca-12,16-dienoic acid	350042-12-5	C30H45Cl3N2O7S	684.122
  ——	[4S-[4R*,7S*,8R*,9R*,15R*(E)]]-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-1-aza-13(Z)-cyclohexadecene-2,6-dione	219989-87-4	C27H42N2O4S	490.707
  伊沙匹隆	ixabepilone	219989-84-1	C27H42N2O5S	506.707

反应信息

• 作为反应物：
  描述：

  tert-butyl (3S,6R,7S,8S,12Z,15S,16E)-3-hydroxy-4,4,6,8,12,16-hexamethyl-15-[(2-methylpropan-2-yl)oxycarbonylamino]-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)heptadeca-12,16-dienoate 在 N-羟基-7-氮杂苯并三氮唑 、 溶剂黄146 、 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 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 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：

  tert-butyl (2Z,6R,7S,8S)-3-methoxy-4,4,6,8-tetramethyl-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)undeca-2,10-dienoate 在 盐酸 、 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 、 Et₂NH₂[{((R)-BINAP)RuCl}2Cl₂] 、 水 、 caesium carbonate 、 对甲苯磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 20.0~65.0 ℃ 、8.27 MPa 条件下， 反应 82.0h， 生成 tert-butyl (3S,6R,7S,8S,12Z,15S,16E)-3-hydroxy-4,4,6,8,12,16-hexamethyl-15-[(2-methylpropan-2-yl)oxycarbonylamino]-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)heptadeca-12,16-dienoate
  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

文献信息

• On the Total Synthesis and Preliminary Biological Evaluations of 15(<i>R</i>) and 15(<i>S</i>) Aza-dEpoB:  A Mitsunobu Inversion at C15 in Pre-Epothilone Fragments
  作者：Shawn J. Stachel、Mark D. Chappell、Chul Bom Lee、Samuel J. Danishefsky、Ting-Chao Chou、Lifeng He、Susan B. Horwitz

  DOI：10.1021/ol005932m

  日期：2000.6.1

  [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.
• 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
  作者：Shawn J. Stachel、Chul Bom Lee、Maria Spassova、Mark D. Chappell、William G. Bornmann、Samuel J. Danishefsky、Ting-Chao Chou、Yongbiao Guan

  DOI：10.1021/jo010275c

  日期：2001.6.1

  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.