(2S,3R)-3-(allyloxy)-3-<(2R)-1,4-dioxaspiro<4.5>decanyl>-2-fluoropropan-1-ol | 198965-24-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,3R)-3-(allyloxy)-3-<(2R)-1,4-dioxaspiro<4.5>decanyl>-2-fluoropropan-1-ol
• 英文别名: (2S,3R)-3-[(3R)-1,4-dioxaspiro[4.5]decan-3-yl]-2-fluoro-3-prop-2-enoxypropan-1-ol
• CAS: 198965-24-1
• 化学式: C₁₄H₂₃FO₄
• 分子量: 274.333
• InChiKey: OIPMRGYHMWGRJL-XQQFMLRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,3R)-3-(allyloxy)-3-<(2R)-1,4-dioxaspiro<4.5>decanyl>-2-fluoropropan-1-ol 在 sodium hydroxide 、 9-borabicyclo[3.3.1]nonane dimer 、 双氧水 、 caesium carbonate 、 对甲苯磺酸 、 三乙胺 作用下， 以 甲醇 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 78.0h， 生成 C₂₉H₂₈FN₃O₅
  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
• 作为产物：
  描述：

  ethyl (2R/S,3R)-3-(allyloxy)-3-<(2R)-1,4-dioxaspiro<4.5>decanyl>-2-fluoropropanoate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以75%的产率得到(2S,3R)-3-(allyloxy)-3-<(2R)-1,4-dioxaspiro<4.5>decanyl>-2-fluoropropan-1-ol
  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.