bouchardatine | 623903-29-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: bouchardatine
• 英文别名: 2-(4-oxo-3,4-dihydroquinazolin-2-yl)-1H-indole-3-carbaldehyde；Bouchardatine；2-(4-oxo-3H-quinazolin-2-yl)-1H-indole-3-carbaldehyde
• CAS: 623903-29-7
• 化学式: C₁₇H₁₁N₃O₂
• 分子量: 289.293
• InChiKey: ZDTNFKKWSCJPNF-UHFFFAOYSA-N

物化性质

• 熔点：
  >260 °C(Solv: ethanol (64-17-5))
• 沸点：
  588.4±60.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  bouchardatine 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 生成 2-(3-(hydroxymethyl)-1H-indol-2-yl)quinazolin-4(3H)-one
  参考文献：
  名称：

  无催化剂的快速，实用和常规合成方法，用于合成2个取代的喹唑啉-4（3 H）-酮，从而生成褪黑素B和E，布加达汀和8-去甲芸香碱†

  摘要：

  已经开发出一种非常快速但无微波/超声波/无催化剂的方法，用于使用甲酰胺作为有效的氨前体和PEG-400作为有效的溶剂来构建喹唑啉-4（3 H）-环。该方法通过在空气中通过等角酸酐，醛和甲酰胺的三组分反应，以高收率获得了各种2-取代的喹唑啉-4（3 H）-一衍生物。该单一方法成功地扩展到了几种生物碱的合成，例如，白蛋白B和E，布加达汀和8-去甲太卡品。

  DOI：

  10.1039/c5ra10928k
• 作为产物：
  描述：

  2-氰基吲哚 在 iron(III) chloride 、 羟胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 14.25h， 生成 bouchardatine
  参考文献：
  名称：

  氯化铁（III）催化取代喹唑啉-4（3 H）-天然产物的一种简捷方法

  摘要：

  利用氯化铁（III）催化反应作为关键步骤，开发了一种新颖高效的合成各种喹唑啉-4（3 H）-天然产物的方法。Circumdatin H，Bouchardatine，8-Norrutaecarpine以及Luotonin B和E很少是通过这种方法合成的天然产物。

  DOI：

  10.1016/j.tetlet.2016.02.030

文献信息

• <i>ortho</i>-Naphthoquinone-catalyzed aerobic oxidation of amines to fused pyrimidin-4(3<i>H</i>)-ones: a convergent synthetic route to bouchardatine and sildenafil
  作者：Kyeongha Kim、Hun Young Kim、Kyungsoo Oh

  DOI：10.1039/d0ra06820a

  日期：——

  A facile access to fused pyrimidin-4(3H)-one derivatives has been established by using the metal-free ortho-naphthoquinone-catalyzed aerobic cross-coupling reactions of amines. The utilization of two readily available amines allowed a direct coupling strategy to quinazolinone natural product, bouchardatine, as well as sildenafil (Viagra™) in a highly convergent manner.

  通过使用无金属邻萘醌催化的胺有氧交叉偶联反应，已经建立了一种容易获得稠合 pyrimidin-4(3 H )-one 衍生物的方法。利用两种容易获得的胺，可以以高度收敛的方式直接偶联喹唑啉酮天然产物布沙达汀和西地那非 (Viagra™)。
• Total Synthesis of Bouchardatine
  作者：Nilesh H. Naik、Tukaram D. Urmode、Arun K. Sikder、Radhika S. Kusurkar

  DOI：10.1071/ch13331

  日期：——

  Two new, efficient and simple routes using Heck-type reaction and intramolecular cyclization were developed for the synthesis of the naturally occurring cytotoxic alkaloid 2-(4-oxo-3,4-dihydroquinazolin-2-yl)-1H-indole-3-carbaldehyde (bouchardatine).

  利用赫克型反应和分子内环化技术，开发了两条高效、简单的新路线，用于合成天然细胞毒性生物碱 2-(4-氧代-3,4-二氢喹唑啉-2-基)-1H-吲哚-3-甲醛（布沙丁）。
• Copper catalysed synthesis of indolylquinazolinone alkaloid bouchardatine
  作者：MAYAVAN VIJI、RAJAGOPAL NAGARAJAN

  DOI：10.1007/s12039-014-0637-5

  日期：2014.7

  the quinazolinone derivatives. The aerobic oxidation induced by copper(I) bromide, followed by Vilsmeier-Haack formylation gives the natural product bouchardatine alkaloid in good yield. 2,3-Dihydroquinazolin-4(1H)-ones are an important class of privileged compounds which have a range of applications in many areas of chemistry and frequently found in many natural products. The aerobic oxidation induced

  我们描述了吲哚基喹唑啉酮生物碱布加达汀和一些喹唑啉酮衍生物的总合成。溴化铜（I）诱导的需氧氧化，然后进行Vilsmeier-Haack甲酰化反应，可以高收率获得天然产物布沙达汀生物碱。 2,3-二氢喹唑啉-4（1 H）-1是一类重要的特权化合物，在许多化学领域中都有广泛的应用，并且经常在许多天然产物中发现。溴化铜（I）诱导的需氧氧化，然后进行Vilsmeier-Haack甲酰化反应，可以高收率获得天然产物布沙达汀生物碱。
• Synthesis of hybrids between the alkaloids rutaecarpine and luotonins A, B
  作者：Máté Bubenyák、Melinda Pálfi、Mária Takács、Szabolcs Béni、Éva Szökő、Béla Noszál、József Kökösi

  DOI：10.1016/j.tetlet.2008.05.141

  日期：2008.8

  The synthesis of 7,12-dihydroindolo[2′,3′:3,4]pyrrolo[2,1-b]quinazolin-5-one, a hybrid compound containing common structural features of the natural alkaloids rutaecarpine (Evodia rutaecarpa) and luotonin A (Peganum nigellastrum), was performed by active methylene group transformations of deoxyvasicinone. The synthesis of 7-hydroxy-8-norrutaecarpine was accomplished via the first total synthesis of

  7,12-二氢吲哚的合成[2'，3'：3,4]吡咯并[2,1- b ]喹唑啉-5-酮，含有天然生物碱的共同的结构特征的混合化合物吴茱萸次碱（吴茱萸）和褪黑素A（Peganum nigellastrum）是通过脱氧维西酮的活性亚甲基转化而进行的。7-羟基-8-去甲rutacarcarpine的合成是通过第一次全合成布查达汀（bouchardatia neurococca）及其酸催化的闭环反应。合成的生物碱类似物是新的杂环系统的第一个代表。对合成化合物的初步测试显示，在与对照药物依托泊苷相当的浓度下，其对HeLa细胞具有细胞毒活性，并诱导了凋亡。
• Discovery of natural alkaloid bouchardatine as a novel inhibitor of adipogenesis/lipogenesis in 3T3-L1 adipocytes
  作者：Yong Rao、Hong Liu、Lin Gao、Hong Yu、Jia-Heng Tan、Tian-Miao Ou、Shi-Liang Huang、Lian-Quan Gu、Ji-Ming Ye、Zhi-Shu Huang

  DOI：10.1016/j.bmc.2015.05.057

  日期：2015.8

  Bouchardatine (1), a naturally occurring beta-indoloquinazoline alkaloid, was synthesized. For the first time, the lipid-lowering effect and mechanism of 1 was investigated in 3T3-L1 adipocytes. Our study showed that 1 could significantly reduce lipid accumulation without cytotoxicity and mainly inhibited early differentiation of adipocyte through proliferation inhibition and cell cycle arrested in dose-dependent manner. Furthermore, the inhibition of early differentiation was reflected by down-regulation of key regulators of adipogenesis/lipogenesis, including CCAAT enhancer binding proteins (C/EBPb, C/EBPd, C/EBP alpha), peroxisome proliferator-activated receptors gamma (PPAR gamma) and sterol-regulatory element binding protein-1c (SREBP-1c), in both of mRNA and protein levels. Subsequently decreasing the protein levels of acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), and stearyl coenzyme A desaturated enzyme 1 (SCD-1), the rate-limited metabolic enzymes of fatty acid synthesis, were also observed. Further studies revealed that 1 persistently activated adenosine 5 '-monophosphate (AMP)-activated protein kinase (AMPK) during differentiation, suggesting that the AMPK may be an upstream mechanism for the effect of 1 on adipogenesis and lipogenesis. Our data suggest that 1 can be a candidate for the development of new therapeutic drugs against obesity and related metabolic disorders. (C) 2015 Elsevier Ltd. All rights reserved.