(2,4-dimethoxyphenyl)(9H-pyrido[3,4-b]indol-1-yl)methanone

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: (2,4-dimethoxyphenyl)(9H-pyrido[3,4-b]indol-1-yl)methanone
• 英文别名: (2,4-dimethoxyphenyl)-(9H-pyrido[3,4-b]indol-1-yl)methanone
• 化学式: C₂₀H₁₆N₂O₃
• 分子量: 332.359
• InChiKey: ANJRPXWIUGDSJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  64.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  色胺 、 1,3-二甲氧基-4-乙炔基苯 在 碘 、 二甲基亚砜 作用下， 反应 4.0h， 以90%的产率得到(2,4-dimethoxyphenyl)(9H-pyrido[3,4-b]indol-1-yl)methanone
  参考文献：
  名称：

  碘介导的Pictet-Spengler氧化反应，使用末端炔烃作为2-氧醛代用品来合成1-芳酰基-β-咔啉和稠合氮杂环

  摘要：

  一种有效的碘介导的二甲基亚砜（DMSO）中碘介导的氧化Pictet-Spengler反应，使用末端炔烃作为2-氧醛替代物来合成芳基（9 H-吡啶并[3,4- b ]吲哚-1-基）甲烷酮。描述。该方案的范围包括法西林蛋白酶，大黄素（Eusoditomins）Y 1和Y 2的总合成。该方法扩展了制备吡咯并[1,2- a ]-喹喔啉和吲哚并[1,5- a ]喹喔啉衍生物的方法。1-芳酰基-β-咔啉的实用性通过执行钯催化的β-咔啉直接邻位得到证明-C（sp2）-H使用DMSO作为来源和访问4-芳基-canthin-6-ones的硫代甲基（SMe）基团对苯环的官能化。

  DOI：

  10.1016/j.tet.2017.03.031

文献信息

• A Cascade Coupling Strategy for One-Pot Total Synthesis of β-Carboline and Isoquinoline-Containing Natural Products and Derivatives
  作者：Yan-Ping Zhu、Mei-Cai Liu、Qun Cai、Feng-Cheng Jia、An-Xin Wu

  DOI：10.1002/chem.201301734

  日期：2013.7.29

  Multi‐birds with one stone: A cascade coupling strategy was developed for the synthesis of β‐carbolines. The method can direct the synthesis of β‐carboline and isoquinoline‐containing natural products with high yields. Moreover, this protocol can also be further applied towards the total synthesis of natural products fascaplysin and papaverin (see scheme).

  一块石头的多鸟：开发了一种级联偶联策略来合成β-咔啉。该方法可以指导高产率合成含β-咔啉和异喹啉的天然产物。此外，该方案还可以进一步应用于天然产物fascaplysin和papaverin的全合成（参见方案）。
• Pd(OAc)₂-catalysed regioselective alkoxylation of aryl (β-carbolin-1-yl)methanones via β-carboline directed ortho-C(sp²)–H activation of an aryl ring
  作者：Shivalinga Kolle、Sanjay Batra

  DOI：10.1039/c5ob01500f

  日期：——

  Synthesis of (2-alkoxyphenyl)(9H-pyrido[3,4-b]indol-1-yl)methanoneviaPd(OAc)₂-catalyzed regioselective alkoxylation of aryl (β-carbolin-1-yl)methanones employing β-carboline directedortho-C(sp²)–H activation of an aryl ring under oxidative conditions is described.

  通过Pd(OAc)2催化的芳基(β-咔啉-1-基)甲酮的定向烷氧基化合成(2-烷氧基苯基)(9H-吡啶并[3,4-b]吲哚-1-基)甲酮，利用β-咔啉引导的芳基骨架在氧化条件下进行ortho-C(sp2)-H活化。
• Discovery of a marine-derived bis-indole alkaloid fascaplysin, as a new class of potent P-glycoprotein inducer and establishment of its structure–activity relationship
  作者：Sudhakar Manda、Sadhana Sharma、Abubakar Wani、Prashant Joshi、Vikas Kumar、Santosh K. Guru、Sonali S. Bharate、Shashi Bhushan、Ram A. Vishwakarma、Ajay Kumar、Sandip B. Bharate

  DOI：10.1016/j.ejmech.2015.10.049

  日期：2016.1

  The screening of IIIM natural products repository for P-gp modulatory activity in P-gp over-expressing human adenocarcinoma LS-180 cells led to the identification of 7 natural products viz. withaferin, podophyllotoxin, 3-demethylcolchicine, agnuside, reserpine, seseberecine and fascaplysin as P-gp inducers. Fascaplysin (6a), a marine-derived bis-indole alkaloid, was the most potent among all of them, showing induction of P-gp with EC50 value of 25 nM. P-gp induction is one of the recently targeted strategy to increase amyloid-beta clearance from Alzheimer brains. Thus, we pursued a medicinal chemistry of fascaplysin to establish its structure activity relationship for P-gp induction activity. Four series of analogs viz, substituted quaternary fascaplysin analogs, D-ring opened quaternary analogs, D-ring opened non-quaternary analogs, and beta-carbolinium analogs were synthesized and screened for P-gp induction activity. Among the total of 48 analogs screened, only quaternary nitrogen containing analogs 6a-g and 10a, 10h-1 displayed promising P-gp induction activity; whereas non-planar non-quaternary analogs 9a-m, 13a-n, 15a-h were devoid of this activity. The P-gp induction activity of best compounds was then confirmed by western-blot analysis, which indicated that fascaplysin (6a) along with 4,5-difluoro analog of fascaplysin 6f and D-ring opened analog 10j displayed 4-8 fold increase in P-gp expression in LS-180 cells at 1 mu M. Additionally, compounds 6a and 6f also showed inhibition of acetylcholinestease (AChE), an enzyme responsible for neuronal loss in Alzheimer's disease. Thus, fascaplysin and its analogs showing promising P-gp induction along with AChE inhibition at 1 mu M, with good safety window (LS-180: IC50 > 10 mu M, hGF: 4 mu M), clearly indicates their promise for development as an anti-Alzheimer agent. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles
  作者：Shashikant U. Dighe、Surya K. Samanta、Shivalinga Kolle、Sanjay Batra

  DOI：10.1016/j.tet.2017.03.031

  日期：2017.4

  iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y1 and Y2. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives

  一种有效的碘介导的二甲基亚砜（DMSO）中碘介导的氧化Pictet-Spengler反应，使用末端炔烃作为2-氧醛替代物来合成芳基（9 H-吡啶并[3,4- b ]吲哚-1-基）甲烷酮。描述。该方案的范围包括法西林蛋白酶，大黄素（Eusoditomins）Y 1和Y 2的总合成。该方法扩展了制备吡咯并[1,2- a ]-喹喔啉和吲哚并[1,5- a ]喹喔啉衍生物的方法。1-芳酰基-β-咔啉的实用性通过执行钯催化的β-咔啉直接邻位得到证明-C（sp2）-H使用DMSO作为来源和访问4-芳基-canthin-6-ones的硫代甲基（SMe）基团对苯环的官能化。