ethyl (2R,3R)-3-(allyloxy)-3-<(2R)-1,4-dioxaspiro<4.5>decanyl>-2-fluoropropanoate

• 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: ethyl (2R,3R)-3-(allyloxy)-3-<(2R)-1,4-dioxaspiro<4.5>decanyl>-2-fluoropropanoate
• 英文别名: ethyl (2R,3R)-3-[(3R)-1,4-dioxaspiro[4.5]decan-3-yl]-2-fluoro-3-prop-2-enoxypropanoate
• 化学式: C₁₆H₂₅FO₅
• 分子量: 316.37
• InChiKey: AFIXOWQSFZEYFU-MGPQQGTHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,2,2-三氯乙酰胺烯丙酯 、 ethyl (2R/S,3R)-3-<(2R)-1,4-dioxaspiro<4.5>decanyl>-2-fluoro-3-hydroxypropanoate 在 三氟甲磺酸 作用下， 反应 70.0h， 以21%的产率得到ethyl (2S,3R)-3-(allyloxy)-3-<(2R)-1,4-dioxaspiro<4.5>decanyl>-2-fluoropropanoate
  参考文献：
  名称：

  Synthesis of Fluorinated Macrocyclic Bis(indolyl)maleimides as Potential ¹⁹F NMR Probes for Protein Kinase C

  摘要：

  Six macrocyclic bis(indolyl)maleimides 1-6 bearing a fluorine label on the aliphatic portion of the macrocycle have been prepared as potential fluorine NMR probes for the catalytic domain of protein kinase C. The macrocyclic bis(indolyl)maleimides such as LY333531 are reversible, ATP competitive, and isoform-selective inhibitors of protein kinase C and may thus serve to probe for subtle differences between protein kinase catalytic domains. The key stereochemical elements were put in place by a Welch aldol condensation between ethyl fluoroacetate and (R)-cyclohexylidene glyceraldehyde, which was followed, by allylation of the secondary alcohol, elaboration of the alkene and ester to alcohols, and mesylation. The macrocycle was formed by slow addition of a mixture of the fluorine-labeled aliphatic dimesylate and N-methyl 2,3-bis[1H-indol-3-yl]maleimide to a suspension of cesium carbonate. Adjusting the Functionality led to the six fluorine-labeled macrocyclic bis(indolyl)maleimides. These compounds retain the high potency of the parent compounds, with IC50 values below 5 nM for the 14-membered ring compounds 1-3 and 13-90 nM for the 15-membered ring compounds 5-6. Vicinal proton-fluorine coupling constants provide an experimental parameter for determining the local macrocycle conformation.

  DOI：

  10.1021/jo9808876

文献信息

• Synthesis of Fluorinated Macrocyclic Bis(indolyl)maleimides as Potential ¹⁹F NMR Probes for Protein Kinase C
  作者：Peter G. Goekjian、Guo-Zhang Wu、Shi Chen、Lanxin Zhou、Michael R. Jirousek、James R. Gillig、Lawrence M. Ballas、Jeffrey T. Dixon

  DOI：10.1021/jo9808876

  日期：1999.6.1

  Six macrocyclic bis(indolyl)maleimides 1-6 bearing a fluorine label on the aliphatic portion of the macrocycle have been prepared as potential fluorine NMR probes for the catalytic domain of protein kinase C. The macrocyclic bis(indolyl)maleimides such as LY333531 are reversible, ATP competitive, and isoform-selective inhibitors of protein kinase C and may thus serve to probe for subtle differences between protein kinase catalytic domains. The key stereochemical elements were put in place by a Welch aldol condensation between ethyl fluoroacetate and (R)-cyclohexylidene glyceraldehyde, which was followed, by allylation of the secondary alcohol, elaboration of the alkene and ester to alcohols, and mesylation. The macrocycle was formed by slow addition of a mixture of the fluorine-labeled aliphatic dimesylate and N-methyl 2,3-bis[1H-indol-3-yl]maleimide to a suspension of cesium carbonate. Adjusting the Functionality led to the six fluorine-labeled macrocyclic bis(indolyl)maleimides. These compounds retain the high potency of the parent compounds, with IC50 values below 5 nM for the 14-membered ring compounds 1-3 and 13-90 nM for the 15-membered ring compounds 5-6. Vicinal proton-fluorine coupling constants provide an experimental parameter for determining the local macrocycle conformation.