| 198965-61-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• CAS: 198965-61-6
• 化学式: C₂₆H₂₁FN₂O₅
• 分子量: 460.462
• InChiKey: VIMIPHDZGZVXLA-DENIHFKCSA-N

反应信息

• 作为反应物：
  描述：

  在 六甲基二硅氮烷 作用下， 以 甲醇 为溶剂， 反应 36.0h， 生成 (18R,19R)-19-fluoro-18-(hydroxymethyl)-17-oxa-4,14,21-triazahexacyclo<19.6.1.1^7,14.0^2,6.0^8,13.0^22,27>nonacosa-1(28),2(6),7(29),8,10,12,22(27),23,25-nonaene-3,5-dione
  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：

  在 氢氧化钾 、 sodium tetrahydroborate 、 sodium periodate 作用下， 以 乙醇 为溶剂， 反应 23.17h， 生成
  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