11-hydroxymethyl-5-methyl-6H-pyrido<4,3-b>carbazole | 83329-79-7

• 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
• 英文名称: 11-hydroxymethyl-5-methyl-6H-pyrido<4,3-b>carbazole
• 英文别名: 5-methyl-11-methanol-6H-pyrido<4,3-b>carbazole；12-hydroxyellipticine；ellipticine；6H-Pyrido(4,3-b)carbazole-11-methanol, 5-methyl-；(5-methyl-6H-pyrido[4,3-b]carbazol-11-yl)methanol
• CAS: 83329-79-7
• 化学式: C₁₇H₁₄N₂O
• 分子量: 262.311
• InChiKey: BXYTXDGNFNTMLR-UHFFFAOYSA-N

物化性质

• 沸点：
  574.5±45.0 °C(Predicted)
• 密度：
  1.356±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  48.9
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  indolo<1,2-b><2,7>naphthyridine-5,12-quinone 在 sodium tetrahydroborate 、 三氟乙酸 、 [双(三氟乙酰氧基)碘]苯 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 1.5h， 生成 11-hydroxymethyl-5-methyl-6H-pyrido<4,3-b>carbazole
  参考文献：
  名称：

  有效合成C-11取代的6H-吡啶并[4,3-b]咔唑

  摘要：

  描述了由酮内酰胺7合成天然产物5-甲基-6H-吡啶并[4，3-b]咔唑-11-甲醇5。化合物7用一当量的MeLi处理，然后将反应混合物用水淬灭以得到内酯19。化合物19用多种有机锂试剂例如甲基锂处理。正丁基锂，锂乙氧基乙烯基和甲醛的锂衍生物二乙基缩硫给，之后硼氢化物还原钠，1，15，30，和31分别。将化合物30和31水解，然后还原，得到化合物5和6的总产率分别为21％。化合物16和22被确定为玫瑰树碱的Saulnier-Gribble合成的中间体。

  DOI：

  10.1016/s0040-4020(01)82308-5

文献信息

• Synthesis of 5-methyl-6h-pyrido[4,3-b]carbazole-11-methanol
  作者：Sandeep P. Modi、James J. Carey、Sydney Archer

  DOI：10.1016/s0040-4039(00)97974-7

  日期：1990.1
• Cytochrome <i>b</i>₅ Increases Cytochrome P450 3A4-Mediated Activation of Anticancer Drug Ellipticine to 13-Hydroxyellipticine Whose Covalent Binding to DNA Is Elevated by Sulfotransferases and <i>N</i>,<i>O</i>-Acetyltransferases
  作者：Marie Stiborová、Radek Indra、Michaela Moserová、Věra Černá、Martina Rupertová、Václav Martínek、Tomáš Eckschlager、René Kizek、Eva Frei

  DOI：10.1021/tx3000335

  日期：2012.5.21

  The antineoplastic alkaloid ellipticine is a prodrug, whose pharmacological efficiency is dependent on its cytochrome P450 (P450)- and/or peroxidase-mediated activation in target tissues. The P450 3A4 enzyme oxidizes ellipticine to five 3 metabolites, mainly to 13-hydroxy- and 12-hydroxyellipticine, the metabolites responsible for the formation of ellipticine-13-ylium and ellipticine-12-ylium ions that generate covalent DNA adducts. Cytochrome b(5) alters the ratio of ellipticine p metabolites formed by P450 3A4. While the amounts of the detoxication metabolites (7-hydroxy- and 9-hydroxyellipticine) were not changed with added cytochrome b(5), 12-hydroxy- and 13-hydroxyellipticine, and ellipticine N-2-oxide increased considerably. The P450 3A4-mediated oxidation of ellipticine was significantly changed only by holo-cytochrome 65, while apo-cytochrome b(5) without heme or Mn-cytochrome b(5) had no such effect. The change in amounts of metabolites resulted in an increased formation of covalent ellipticine-DNA adducts, one of the DNA-damaging mechanisms of ellipticine antitumor action. The amounts of 13-hydroxy- and 12-hydroxyellipticine formed by P450 3A4 were similar, but more than 7-fold higher levels of the adduct. were formed by 13-hydrox-yellipticine than by 12-hydroxyellipticine. The higher susceptibility of 13-hydroxyellipticine toward heterolytic dissociation to ellipticine-13-ylium in comparison to dissociation of 12-hydroxyellipticine to ellipticine-12ylium, determined by quantum chemical calculations, explains this phenomenon. The amounts of the 13-hydroxyellipticinederived DNA adduct significantly increased upon reaction of 13-hydroxyellipticine with either 3'-phosphoadenosine-5'phosphosulfate or acetyl-CoA catalyzed by human sulfotransferases 1A1, 1A2, 1A3, and 2A1, or N,O-acetyltransferases 1 and 2. The calculated reaction free energies of heterolysis of the sulfate and acetate esters are by 10-17 kcal/mol more favorable than the energy of hydrolysis of 13-hydroxyellipticine, which could explain the experimental data.
• MODI, SANDEEP P.;CAREY, JAMES J.;ARCHER, SYDNEY, TETRAHEDRON LETT., 31,(1990) N1, C. 5815-5818
  作者：MODI, SANDEEP P.、CAREY, JAMES J.、ARCHER, SYDNEY

  DOI：——

  日期：——
• An efficient synthesis of C-11 substituted 6H-pyrido[4,3-b]carbazoles
  作者：Sandeep P. Modi、Meged A. Michael、Sydney Archer、James J. Carey

  DOI：10.1016/s0040-4020(01)82308-5

  日期：1991.8

  treated with one equivalent of MeLi followed by quenching of the reaction mixture with water to give the lactone 19 Compound 19 was treated with a number of organolithium reagents such as methyllithium. n-butyllithium, ethoxyvinyl lithium and the lithio derivative of formaldehyde diethyl mercaptal to give, after sodium borohydride reduction, 1, 15, 30, and 31 respectively. Compounds 30 and 31 were hydrolyzed

  描述了由酮内酰胺7合成天然产物5-甲基-6H-吡啶并[4，3-b]咔唑-11-甲醇5。化合物7用一当量的MeLi处理，然后将反应混合物用水淬灭以得到内酯19。化合物19用多种有机锂试剂例如甲基锂处理。正丁基锂，锂乙氧基乙烯基和甲醛的锂衍生物二乙基缩硫给，之后硼氢化物还原钠，1，15，30，和31分别。将化合物30和31水解，然后还原，得到化合物5和6的总产率分别为21％。化合物16和22被确定为玫瑰树碱的Saulnier-Gribble合成的中间体。