tert-butyl (6R,7S,8S)-7-hydroxy-4,4,6,8-tetramethyl-3,5-dioxoundec-10-enoate | 350041-92-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: tert-butyl (6R,7S,8S)-7-hydroxy-4,4,6,8-tetramethyl-3,5-dioxoundec-10-enoate
• CAS: 350041-92-8
• 化学式: C₁₉H₃₂O₅
• 分子量: 340.46
• InChiKey: RIRWUUZXWDDILS-ZENOOKHLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (6R,7S,8S)-7-hydroxy-4,4,6,8-tetramethyl-3,5-dioxoundec-10-enoate 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 、 caesium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 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：

  (S)-2-methyl-4-pentenal 、 tert-butyl 4,4-dimethyl-3,5-dioxoheptanoate 在 lithium diisopropyl amide 作用下， 生成 tert-butyl (6R,7S,8S)-7-hydroxy-4,4,6,8-tetramethyl-3,5-dioxoundec-10-enoate 、 tert-butyl 2-[(5R,6S)-2-hydroxy-3,3,5-trimethyl-4-oxo-6-[(2S)-pent-4-en-2-yl]oxan-2-yl]acetate
  参考文献：
  名称：

  Dianion equivalents corresponding to the polypropionate domain of epothilone B

  摘要：

  A modified synthesis of the polypropionate portion of epothilone, which utilizes a novel, diastereoselective aldol reaction of (S)-2-methyl-4-pentenal (4) and the Z-enolate of the tricarbonyl species (3) is reported. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)00221-x

文献信息

• Total Synthesis and Antitumor Activity of 12,13-Desoxyepothilone F:  An Unexpected Solvolysis Problem at C15, Mediated by Remote Substitution at C21
  作者：Chul Bom Lee、Ting-Chao Chou、Xiu-Guo Zhang、Zhi-Guang Wang、Scott D. Kuduk、Mark D. Chappell、Shawn J. Stachel、Samuel J. Danishefsky

  DOI：10.1021/jo000617z

  日期：2000.10.1

  A new epothilone analogue, 12,13-desoxyepothilone F (dEpoF, 21-hydroxy-12,13-desoxyepothilone B, 21-hydroxyepothilone D), was synthesized and evaluated for antitumor potential. A convergent strategy employed for the semipractical synthesis of 12,13-desoxyepothilone B (dEpoB) has been utilized to yield an amount of dEpoF sufficient for relevant biological studies. The results from an in vitro assay

  合成了新的埃博霉素类似物12,13-脱氧埃博霉素F（dEpoF，21-羟基-12,13-脱氧埃博霉素B，21-羟基埃博霉素D），并评估了其抗肿瘤潜力。用于12,13-脱氧埃博霉素B（dEpoB）的半实用合成的收敛策略已被用来产生足够的dEpoF量用于相关的生物学研究。体外测定的结果表明，这种新的类似物对各种肿瘤细胞系具有很高的活性，其功效与dEpoB相当。特别地，在紫杉醇（Taxol）基本上无效的浓度下，dEpoF抑制了抗性肿瘤细胞的生长。对其体内活性的初步评估也是有希望的。新的类似物在C21处含有一个额外的羟基，
• 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.
• Dianion equivalents corresponding to the polypropionate domain of epothilone B
  作者：Christina R. Harris、Scott D. Kuduk、Ken Savin、Aaron Balog、Samuel J. Danishefsky

  DOI：10.1016/s0040-4039(99)00221-x

  日期：1999.3

  A modified synthesis of the polypropionate portion of epothilone, which utilizes a novel, diastereoselective aldol reaction of (S)-2-methyl-4-pentenal (4) and the Z-enolate of the tricarbonyl species (3) is reported. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.