12-carbaeudistomin

• 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: 12-carbaeudistomin
• 英文别名: (2S,3R)-7-oxa-8,18-diazatetracyclo[9.7.0.02,8.012,17]octadeca-1(11),12,14,16-tetraen-3-amine
• 化学式: C₁₅H₁₉N₃O
• 分子量: 257.335
• InChiKey: GSBPCFNXHOYSTE-DOMZBBRYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  54.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  D-谷氨酸 在 盐酸 、 potassium fluoride 、 lithium aluminium tetrahydride 、 三甲基氯硅烷 、 氯化亚砜 、 四丁基氯化铵 、 sodium hydride 、 二异丁基氢化铝 、 三乙胺 、 三氟乙酸 、 sodium iodide 作用下， 以 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 18.5h， 生成 12-carbaeudistomin
  参考文献：
  名称：

  Antiviral and tumor cell antiproliferative SAR studies on tetracyclic eudistomins—II

  摘要：

  In a search for the minimum pharmacophore of the naturally occurring tetracyclic eudistomins, five structural analogues (4-8) were evaluated for their in vitro antiviral and tumor cell antiproliferative activities. For the synthesis of these derivatives both intra- and intermolecular Pictet-Spengler reactions have been used. Opening of the beta-carboline annulated 7-membered D-ring in 6 and 7 resulted in a complete loss of activity. On the other rand, replacement of either the oxygen atom or the sulfur atom in the 7-membered ring by a methylene group in 5 and 8, respectively, is allowed. These results combined with previous SAR data underline the crucial importance of the D-ring in eudistomins as a scaffold for the correct positioning of both basic nitrogen atoms. Also bioisosteric replacement of the bicyclic indole system with a dimethoxyphenyl group, to give the isoquinoline skeleton, is allowed. The tricyclic isoquinoline derivative 4 is, so far, the most promising antiviral analogue; it combines a high potency (MIG at 100 ng/mL (340 nM)) with high MCC/MIC ratios (ranging from 1000 to 5000 against HSV-1, HSV-2, vaccinia virus, and vesicular stomatitis virus). (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00034-5

文献信息

• Meisenheimer Rearrangement of Azetopyridoindoles. VI. Synthesis of 12-Carbaeudistomin and Related Compounds.
  作者：Takushi KURIHARA、Yasuhiko SAKAMOTO、Hiromi MATSUMOTO、Natsuki KAWABATA、Shinya HARUSAWA、Ryuji YONEDA

  DOI：10.1248/cpb.42.475

  日期：——

  N-oxide of the 2-vinylazetopyridoindole 12a bearing a benzenesulfonyl group as a protective group of the indole nitrogen atom afforded the oxazepino ester 14, which was easily isomerized to 20a. Compounds 3 and 4 were synthesized from 14 and 20a, respectively, according to the following reaction sequences [hydrogenation of the double bond (Pd-C/H2), desulfonylation (Mg in MeOH), hydrolysis (AlBr3-EtSH)

  为了研究大黄菌素1、12-十二碳半胱氨酸3，其1,10-反式异构体4和11,12-二氢十二碳十二碳半乳糖苷5的结构-活性关系，已进行了合成。带有苯磺酰基作为吲哚氮原子保护基的2-乙烯基吡咯并吲哚吲哚12a的相应N-氧化物的[2，3] -Meisenheimer重排提供了氧杂庚酸酯14，其易于异构化为20a。根据以下反应顺序，分别从14a和20a合成化合物3和4 [双键氢化（Pd-C / H2），脱磺酰化（Mg在MeOH中），水解（AlBr3-EtSH）和Curtius重排（使用NaN3的混合酸酐法），然后进行脱苄基作用（Pd-C / H2）。使用DPPA对羧酸27进行Curtius反应，得到氨基甲酸酯29，
• Antiviral and tumor cell antiproliferative SAR studies on tetracyclic eudistomins—II
  作者：Jan H. van Maarseveen、Hans W. Scheeren、Erik De Clercq、Jan Balzarini、Chris G. Kruse

  DOI：10.1016/s0968-0896(97)00034-5

  日期：1997.5

  In a search for the minimum pharmacophore of the naturally occurring tetracyclic eudistomins, five structural analogues (4-8) were evaluated for their in vitro antiviral and tumor cell antiproliferative activities. For the synthesis of these derivatives both intra- and intermolecular Pictet-Spengler reactions have been used. Opening of the beta-carboline annulated 7-membered D-ring in 6 and 7 resulted in a complete loss of activity. On the other rand, replacement of either the oxygen atom or the sulfur atom in the 7-membered ring by a methylene group in 5 and 8, respectively, is allowed. These results combined with previous SAR data underline the crucial importance of the D-ring in eudistomins as a scaffold for the correct positioning of both basic nitrogen atoms. Also bioisosteric replacement of the bicyclic indole system with a dimethoxyphenyl group, to give the isoquinoline skeleton, is allowed. The tricyclic isoquinoline derivative 4 is, so far, the most promising antiviral analogue; it combines a high potency (MIG at 100 ng/mL (340 nM)) with high MCC/MIC ratios (ranging from 1000 to 5000 against HSV-1, HSV-2, vaccinia virus, and vesicular stomatitis virus). (C) 1997 Elsevier Science Ltd.