[(4S,7R,8S,9S,13Z,16R)-4-hydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-2,6-dioxo-1-azacyclohexadec-13-en-8-yl] 2,2,2-trichloroethyl carbonate | 350042-20-5

• 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: [(4S,7R,8S,9S,13Z,16R)-4-hydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-2,6-dioxo-1-azacyclohexadec-13-en-8-yl] 2,2,2-trichloroethyl carbonate
• CAS: 350042-20-5
• 化学式: C₃₀H₄₃Cl₃N₂O₆S
• 分子量: 666.106
• InChiKey: NGQBZYKYYKXHFS-KTLXQJKPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.37
• 重原子数：
  42.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  114.82
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  [(4S,7R,8S,9S,13Z,16R)-4-hydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-2,6-dioxo-1-azacyclohexadec-13-en-8-yl] 2,2,2-trichloroethyl carbonate 在 溶剂黄146 、 锌 作用下， 生成 15(R)-aza-12,13-desoxyepothilone B
  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
• 作为产物：
  描述：

  (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 在 盐酸 、 N-羟基-7-氮杂苯并三氮唑 、 Et₂NH₂[{((R)-BINAP)RuCl}2Cl₂] 、 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 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0~25.0 ℃ 、8.27 MPa 条件下， 反应 36.0h， 生成 [(4S,7R,8S,9S,13Z,16R)-4-hydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-2,6-dioxo-1-azacyclohexadec-13-en-8-yl] 2,2,2-trichloroethyl carbonate
  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