tert-butyl (2Z,6R,7S,8S)-7-hydroxy-3-methoxy-4,4,6,8-tetramethyl-5-oxoundeca-2,10-dienoate | 224580-54-5

• 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)-7-hydroxy-3-methoxy-4,4,6,8-tetramethyl-5-oxoundeca-2,10-dienoate
• CAS: 224580-54-5
• 化学式: C₂₀H₃₄O₅
• 分子量: 354.487
• InChiKey: WEYLYPATCYSAMB-OKANTDCFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (2Z,6R,7S,8S)-7-hydroxy-3-methoxy-4,4,6,8-tetramethyl-5-oxoundeca-2,10-dienoate 在 吡啶 、 2,6-二甲基吡啶 、 nickel(II) iodide 、 盐酸 、 4-二甲氨基吡啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 samarium diiodide 、 三苯胂 、 [RuCl₂-((R)-binap)]*NEt₃ 、 BBN 、 2,4,6-三氯苯甲酰氯 、 水 、 氢气 、 caesium carbonate 、 对甲苯磺酸 、 氟化氢吡啶 、 三乙胺 、 丙酮 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， -78.0~25.0 ℃ 、8.27 MPa 条件下， 反应 35.25h， 生成 埃博霉素B
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/ja991189l
• 作为产物：
  描述：

  tert-butyl 4,4-dimethyl-3,5-dioxoheptanoate 在 N,N-二异丙基乙胺 、 lithium diisopropyl amide 作用下， 以 甲醇 、 乙腈 为溶剂， 生成 tert-butyl (2Z,6R,7S,8S)-7-hydroxy-3-methoxy-4,4,6,8-tetramethyl-5-oxoundeca-2,10-dienoate
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/ja991189l

文献信息

• 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.
• 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.