tert-butyl (Z)-3-methoxy-4,4-dimethyl-5-oxohept-2-enoate | 224580-53-4

• 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 (Z)-3-methoxy-4,4-dimethyl-5-oxohept-2-enoate
• CAS: 224580-53-4
• 化学式: C₁₄H₂₄O₄
• 分子量: 256.342
• InChiKey: PQISDEFVFHKVIV-LUAWRHEFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (Z)-3-methoxy-4,4-dimethyl-5-oxohept-2-enoate 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 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， -120.0~25.0 ℃ 、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 、 三甲基硅烷化重氮甲烷 在 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 以81%的产率得到tert-butyl (Z)-3-methoxy-4,4-dimethyl-5-oxohept-2-enoate
  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

• Synthesis of epothilones, intermediates thereto and analogues thereof
  申请人：——

  公开号：US20030208080A1

  公开（公告）日：2003-11-06

  The present invention provides convergent processes for preparing epothilone A and B, desoxyepothilones A and B, and analogues thereof, useful in the treatment of cancer and cancer which has developed a multidrug-resistant phenotype. Also provided are intermediates useful for preparing said epothilones.

  本发明提供了用于制备依托泊苷A和B、去氧依托泊苷A和B及其类似物的汇聚过程，这些化合物在治疗癌症和已经发展出多药耐药表型的癌症方面具有用途。同时还提供了用于制备上述依托泊苷的中间体。
• SYNTHESIS OF EPOTHILONES, INTERMEDIATES THERETO AND ANALOGUES THEROF
  申请人：Sloan-Kettering Institute For Cancer Research

  公开号：EP1058679B1

  公开（公告）日：2005-10-19
• US6204388B1
  申请人：——

  公开号：US6204388B1

  公开（公告）日：2001-03-20
• US6316630B1
  申请人：——

  公开号：US6316630B1

  公开（公告）日：2001-11-13
• US6603023B2
  申请人：——

  公开号：US6603023B2

  公开（公告）日：2003-08-05