pityriacitrin | 244295-64-5

• 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: pityriacitrin
• 英文别名: (1H-indol-3-yl)(9H-pyrido[3,4-b]indol-1-yl)methanone；1H-indol-3-yl(9H-pyrido[3,4-b]indol-1-yl)methanone
• CAS: 244295-64-5
• 化学式: C₂₀H₁₃N₃O
• 分子量: 311.343
• InChiKey: BQTUGQOWZZUYIA-UHFFFAOYSA-N

物化性质

• 沸点：
  641.9±40.0 °C(Predicted)
• 密度：
  1.416±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  61.5
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 危险性防范说明：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319

反应信息

• 作为反应物：
  描述：

  pityriacitrin 、 碘甲烷 以 乙腈 为溶剂， 反应 12.0h， 以62%的产率得到1-(3-indoloyl)-2-methyl-beta-carbolinium iodide
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2015.10.049
• 作为产物：
  描述：

  吲哚-3-乙醛酰氯 在 三正丁基氢锡 、 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 反应 3.5h， 生成 pityriacitrin
  参考文献：
  名称：

  WO2019200232A5

  摘要：

  公开号：

  WO2019200232A5

文献信息

• Unexplored reactivity of 2-oxoaldehydes towards Pictet–Spengler conditions: concise approach to β-carboline based marine natural products
  作者：Narsaiah Battini、Anil K. Padala、Nagaraju Mupparapu、Ram A. Vishwakarma、Qazi Naveed Ahmed

  DOI：10.1039/c4ra01387e

  日期：——

  Novel reactions under Pictet–Spengler conditions between tryptophan methyl ester/tryptamine and 2-oxoaldehydes have been developed and successfully utilized for the total synthesis of Merinacarboline (A and B), Eudistomin Y1, Pityriacitrin B, Pityriacitrin, Fascaplysin and analogues.

  在Pictet–Spengler条件下，开发了色氨酸甲酯/色胺与2-氧代醛之间的新型反应，并成功应用于Merinacarboline（A和B）、Eudistomin Y1、Pityriacitrin B、Pityriacitrin、Fascaplysin及其类似物的全合成。
• Total synthesis and bioactivity of the marine alkaloid pityriacitrin and some of its derivatives
  作者：Puyong Zhang、Xiaofei Sun、Bin Xu、Krikor Bijian、Shengbiao Wan、Guigen Li、Moulay Alaoui-Jamali、Tao Jiang

  DOI：10.1016/j.ejmech.2011.10.036

  日期：2011.12

  We report herein the chemical synthesis and biological evaluation of β-carboline alkaloid pityriacitrin and some of its new derivatives. Using tryptophan or 5-hydroxytryptophan and 5-substituted indole-3-glyoxals as the starting materials, pityriacitrin and some of its derivatives were synthesized via the acid-catalyzed Pictet–Spengler reaction and fully characterized by 1H and 13C NMR, mass spectroscopy

  我们在此报告β-咔啉生物碱Pitriacitrin及其一些新衍生物的化学合成和生物学评估。以色氨酸或5-羟基色氨酸和5-取代的吲哚-3-乙二醛为起始原料，通过酸催化的Pictet-Spengler反应合成了糠硫胞苷及其衍生物，并通过1 H和13 C NMR，质谱进行了全面表征。和红外测定。生物学研究表明，苦参碱对一组乳腺癌和前列腺癌细胞系具有较弱的抗增殖活性，而其某些衍生物表现出更强而有力的活性，这与诱导细胞凋亡和坏死有关。
• 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）。
• First total synthesis of the β-carboline alkaloids trigonostemine A, trigonostemine B and a new synthesis of pityriacitrin and hyrtiosulawesine
  作者：Tímea Szabó、Viktor Hazai、Balázs Volk、Gyula Simig、Mátyás Milen

  DOI：10.1016/j.tetlet.2019.04.044

  日期：2019.5

  The total synthesis of four natural products, trigonostemine A, trigonostemine B, pityriacitrin, and hyrtiosulawesine was accomplished. The key intermediates, variously substituted 1-formyl-β-carbolines, were prepared in five steps via a novel synthetic approach using readily available starting materials. These formyl derivatives were then further transformed, providing a general route for the synthesis

  完成了四种天然产物，三角果糖胺A，三角果糖胺B，pityriacitrin和hyrtiosulawesine的总合成。通过新颖的合成方法，使用容易获得的起始原料，通过五个步骤制备了关键的中间体，即各种取代的1-甲酰基-β-咔啉。然后将这些甲酰基衍生物进一步转化，为合成四种标题生物碱提供了一条通用途径。本文报道的方法代表了两个三角骨素的第一个全合成，以及新的通往糠酸柠檬苦苷和hyrtiosulawesine的途径。
• (NH₄)₂S₂O₈-Mediated Metal-Free Decarboxylative Formylation/Acylation of α-Oxo/Ketoacids and Its Application to the Synthesis of Indole Alkaloids
  作者：Votarikari Dinesh、Rajagopal Nagarajan

  DOI：10.1021/acs.joc.2c00552

  日期：2022.8.5

  reaction occurs between ambient temperature and 40 °C under mild reaction conditions with commercially available starting materials. This methodology can be expanded to some biologically active indole alkaloids like pityriacitrins, eudistomins Y1 and Y3, and marinacarbolines A–D.

  描述了一种通过 α-氧代/酮酸的直接脱羧交叉偶联以中等至良好的产率将吲哚和 β-咔啉与 (NH 4 ) 2 S 2 O 8进行甲酰化/酰化的无金属方法。该反应在温和的反应条件下在环境温度和 40 °C 之间发生，使用市售的起始材料。这种方法可以扩展到一些具有生物活性的吲哚生物碱，如糠秕子苷、eudistomins Y 1和 Y 3以及 marinacarbolines A-D。