(3Z,9E)-(1R,7S,11S,17R)-11-(tert-butyl-dimethyl-silanyloxy)-13-methylidene-5-oxo-6,21-dioxa-bicyclo[15.3.1]henicosa-3,9,19-triene-7-carbaldehyde | 688743-59-1

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: (3Z,9E)-(1R,7S,11S,17R)-11-(tert-butyl-dimethyl-silanyloxy)-13-methylidene-5-oxo-6,21-dioxa-bicyclo[15.3.1]henicosa-3,9,19-triene-7-carbaldehyde
• 英文别名: (3Z,9E)-(1R,7S,11S,17R)-11-(tert-butyl-dimethyl-silanyloxy)-13-methylene-5-oxo-6,21-dioxa-bicyclo[15.3.1]henicosa-3,9,19-triene-7-carbaldehyde；(1R,3Z,7S,9E,11S,17R)-11-[tert-butyl(dimethyl)silyl]oxy-13-methylidene-5-oxo-6,21-dioxabicyclo[15.3.1]henicosa-3,9,19-triene-7-carbaldehyde
• CAS: 688743-59-1
• 化学式: C₂₇H₄₂O₅Si
• 分子量: 474.713
• InChiKey: UZXDOPCVODHETP-BSUUAMMASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.22
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3Z,9E)-(1R,7S,11S,17R)-11-(tert-butyl-dimethyl-silanyloxy)-13-methylidene-5-oxo-6,21-dioxa-bicyclo[15.3.1]henicosa-3,9,19-triene-7-carbaldehyde 在 chromium dichloride 、 Proton Sponge 、 nickel dichloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (3Z,9E)-(1R,7S,11S,17R)-11-(tert-Butyl-dimethyl-silanyloxy)-7-[(E)-(S)-1-methoxy-3-((S)-4-methyl-3,6-dihydro-2H-pyran-2-yl)-allyl]-13-methylene-6,21-dioxa-bicyclo[15.3.1]henicosa-3,9,19-trien-5-one
  参考文献：
  名称：

  Synthesis of Novel 11-Desmethyl Analogues of Laulimalide by Nozaki−Kishi Coupling

  摘要：

  As a first entry into structurally simplified analogues of the anticancer agent laulimalide, 11-desmethyl compounds 2 and 3 were selected by molecular modeling. The unfavorable diastereoselectivity in the key synthetic step, a Nozaki-Kishi coupling between macrocyclic aldehyde 4 and vinyl iodide 5, was overcome either by use of catalytic amounts of DIANANE-type ligands or L-Selectride reduction of the derived enone. This methodology should allow modular introduction of other, unnatural, side chains.

  DOI：

  10.1021/ol049791q
• 作为产物：
  描述：

  (1R,3Z,7S,9E,11S,14E,17S)-11-[tert-butyl(dimethyl)silyl]oxy-7-[[tert-butyl(diphenyl)silyl]oxymethyl]-6,21-dioxabicyclo[15.3.1]henicosa-3,9,14,19-tetraene-5,13-dione 在 lead(II) iodide 三甲基氯硅烷 、 草酰氯 、 Stryker's reagent 、 四丁基氟化铵 、 四氯化钛 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 苯 为溶剂， 反应 72.0h， 生成 (3Z,9E)-(1R,7S,11S,17R)-11-(tert-butyl-dimethyl-silanyloxy)-13-methylidene-5-oxo-6,21-dioxa-bicyclo[15.3.1]henicosa-3,9,19-triene-7-carbaldehyde
  参考文献：
  名称：

  Synthesis of Novel 11-Desmethyl Analogues of Laulimalide by Nozaki−Kishi Coupling

  摘要：

  As a first entry into structurally simplified analogues of the anticancer agent laulimalide, 11-desmethyl compounds 2 and 3 were selected by molecular modeling. The unfavorable diastereoselectivity in the key synthetic step, a Nozaki-Kishi coupling between macrocyclic aldehyde 4 and vinyl iodide 5, was overcome either by use of catalytic amounts of DIANANE-type ligands or L-Selectride reduction of the derived enone. This methodology should allow modular introduction of other, unnatural, side chains.

  DOI：

  10.1021/ol049791q

文献信息

• Design, synthesis and biological evaluation of novel, simplified analogues of laulimalide: modification of the side chain
  作者：Ian Paterson、Dirk Menche、Anders E. Håkansson、Adrian Longstaff、David Wong、Isabel Barasoain、Rubén M. Buey、J. Fernando Díaz

  DOI：10.1016/j.bmcl.2005.03.018

  日期：2005.5

  Novel, simplified analogues of the microtubule-stabilizing anticancer agent laulimalide, including the first derivatives with unnatural side chains, were designed by molecular modelling, synthesized by a late-stage diversification strategy, and evaluated in vitro for growth inhibition of human ovarian carcinoma cell lines (A2780, A2780/AD10).

  通过分子模型设计，稳定化的微管稳定抗癌药laulimalide的新型简化类似物，包括具有不自然侧链的一阶衍生物，通过后期多样化策略合成，并在体外评估其对人卵巢癌细胞系生长的抑制作用（A2780，A2780 / AD10）。