tert-butyl (2Z,6R,7S,8S)-3-methoxy-4,4,6,8-tetramethyl-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)undeca-2,10-dienoate | 224580-49-8

• 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 (2Z,6R,7S,8S)-3-methoxy-4,4,6,8-tetramethyl-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)undeca-2,10-dienoate
• CAS: 224580-49-8
• 化学式: C₂₃H₃₅Cl₃O₇
• 分子量: 529.886
• InChiKey: XBBWTNKFSHVWOR-DLJRHPOFSA-N

物化性质

• 沸点：
  588.4±50.0 °C(Predicted)
• 密度：
  1.180±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  33
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  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 、 N-羟基-7-氮杂苯并三氮唑 、 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 、 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 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， -78.0~65.0 ℃ 、8.27 MPa 条件下， 反应 103.0h， 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：

  (S)-2-methyl-4-pentenal 在 吡啶 、 lithium diisopropyl amide 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 生成 tert-butyl (2Z,6R,7S,8S)-3-methoxy-4,4,6,8-tetramethyl-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)undeca-2,10-dienoate
  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
• 作为试剂：
  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 、 (5S)-5-azido-2-iodo-6-methyl-7-(2-methylthiazol-4-yl)-2,6-heptadiene 在 tert-butyl (2Z,6R,7S,8S)-3-methoxy-4,4,6,8-tetramethyl-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)undeca-2,10-dienoate 作用下， 以70的产率得到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
  参考文献：
  名称：

  J. Org. Chem. 2001, 66, 4369-4378

  摘要：

  DOI：

文献信息

• New Chemical Synthesis of the Promising Cancer Chemotherapeutic Agent 12,13-Desoxyepothilone B: Discovery of a Surprising Long-Range Effect on the Diastereoselectivity of an Aldol Condensation
  作者：Christina R. Harris、Scott D. Kuduk、Aaron Balog、Ken Savin、Peter W. Glunz、Samuel J. Danishefsky

  DOI：10.1021/ja991189l

  日期：1999.8.1

  The epothilones are naturally occurring cytotoxic molecules that possess the remarkable ability to arrest cell division through the stabilization of microtubule assemblies. Our in vivo studies with 12,13-desoxyepothilone B (dEpoB), have established that the desoxy compound is well tolerated and virtually curative against a variety of sensitive and resistant xenograft tumors in animal models. In light of these discoveries, we sought a chemical synthesis of dEpoB that would be able to support a serious and substantial discovery research program directed toward the clinical development of this molecule. The overall strategy for this endeavor assumed the ability to synthesize dEpoB from three constructs which include an achiral beta,delta-diketo ester construct A, an (S)-2-methylpentenal moiety B, and the thiazoyl-containing vinyl iodide moiety C. We envisioned that a diastereoselective aldol condensation between an achiral C5-C6 (Z)-metalloenolate derived from construct A and an (S)-2-methylalkanal fragment, B, would generate the desired C6-C7 bond. Second, a B-alkyl Suzuki coupling between the vinyl iodide construct C and an alkyl borane would form the C11-C12 bond. Finally, a late-stage reduction of the C3 ketone to the requisite C3 alcohol with high asymmetric induction would permit us to introduce the beta,delta-diketo ester fragment A, into the synthesis as a readily accessible achiral building block. The governing concepts for our new synthesis are described herein.
• 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.
• 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.
• J. Org. Chem. 2001, 66, 4369-4378
  作者：

  DOI：——

  日期：——