4-甲基白芷素 | 6457-92-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 中文名称: 4-甲基白芷素
• 英文名称: 4-methylangelicin
• 英文别名: 4-methyl-2H-furo[2,3-h]chromen-2-one；4-methylfuro[2,3-h]chromen-2-one
• CAS: 6457-92-7
• 化学式: C₁₂H₈O₃
• 分子量: 200.194
• InChiKey: HCYYGOURSFQHRV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  39.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  8-乙酰基-7-羟基-4-甲基-2H-1-苯并吡喃-2-酮 在 铜 sodium hydroxide 、 五氯化磷 、 sodium 作用下， 以 1,4-二氧六环 、 喹啉 、 四氯化碳 为溶剂， 反应 8.0h， 生成 4-甲基白芷素
  参考文献：
  名称：

  Bhayani; Thakor, Journal of the Indian Chemical Society, 1990, vol. 67, # 1, p. 71 - 72

  摘要：

  DOI：

文献信息

• Novel Furocoumarin Derivatives Stimulate Melanogenesis in B16 Melanoma Cells by Up-Regulation of MITF and TYR Family via Akt/GSK3β/β-Catenin Signaling Pathways
  作者：Chao Niu、Li Yin、Haji Aisa

  DOI：10.3390/ijms19030746

  日期：——

  The extracts of Ficuscarica L. and Psoralen corylifolia L. are traditional Uygur medicines for the treatment of vitiligo, and its active ingredients furocoumarins, were are found to be the most effective agents against this skin disorder nowadays. Therefore, a series of novel easter derivatives (8a–8p) of furocoumarin were designed and synthesized based on our previous research to improve this activity in the present study. The synthesized derivatives were biologically evaluated for melanin synthesis in murine B16 cells and the SAR (structure-activity relationship) was summarized. Eight derivatives were more potent than positive control (8-MOP, 8-methoxypsoralan), especially compounds 8n (200%) and 8o (197%), which were nearly 1.5-fold potency when compared with 8-MOP (136%). Furthermore, the signaling pathway by which 8n activates the melanin biosynthesis was defined. Our results showed that it not only elevated the melanin content, but also stimulated the activity of tyrosinasein a concentration-dependent manner. Increasing of phosphorylation of Akt (also named PKB, protein kinase B) and non-activated GSK3β (glycogen synthase kinase 3 beta), which inhibited the degradation of β-catenin were observed through Western blot analysis. The accumulation of β-catenin probably led to the activation of transcription of MITF (microphthalmia-associated transcription factor) and TYR (tyrosinase) family, as well as the subsequent induction of melanin synthesis.

  白玉盘提取物和补骨脂素是小叶白蜡树的传统维吾尔药材,用于治疗白癜风,其活性成分呋喃香豆素被发现是目前对该皮肤病最有效的药物。因此,根据我们以前的研究,设计并合成了一系列新的呋喃香豆素衍生物(8a-8p)以改善这种活性。合成的衍生物在鼠B16细胞中对黑色素合成的生物学评价和SAR(结构-活性关系)进行了总结。八种衍生物比阳性对照(8-MOP,8-甲氧基补骨脂素)更有效,特别是化合物8n(200%)和8o(197%),其效力几乎是8-MOP(136%)的1.5倍。此外,8n激活黑色素生物合成的信号途径被确定。我们的结果表明,它不仅提高了黑色素含量,而且刺激了酪氨酸酶的活性,呈浓度依赖性。通过Westernblot分析观察到磷酸化Akt(也称为PKB,蛋白激酶B)和非激活GSK3β(糖原合酶激酶3β)的增加,抑制了β-catenin的降解。β-catenin的积累可能导致MITF(小眼相关转录因子)和TYR(酪氨酸酶)家族的转录激活,以及随后诱导黑色素合成。
• Palladium-Catalyzed Intramolecular Hydroarylation of 4-Benzofuranyl Alkynoates. Approach to Angelicin Derivatives
  作者：Tsugio Kitamura、Kensuke Otsubo

  DOI：10.1021/jo300021a

  日期：2012.3.16

  Intramolecular hydroarylation of 4-benzofuranyl alkynoates using Pd(OAc)2 as catalyst took place selectively and efficiently, giving angular furocoumarin derivatives in high yields. The parent angelicin was obtained in 80% yield by this method. The starting 4-benzofuranyl alkynoates were easily accessible from readily available 4-hydroxybenzofurans and alkynoic acids.

  使用Pd（OAc）2作为催化剂的4-苯并呋喃基烷基炔烃分子内氢芳基化反应选择性且有效地进行，从而以高收率得到了角型呋喃香豆素衍生物。通过这种方法以80％的产率获得了当归素。起始的4-苯并呋喃基炔酸酯可容易地从容易获得的4-羟基苯并呋喃和炔酸获得。
• Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins
  作者：Christiane Schultze、Bernd Schmidt

  DOI：10.3762/bjoc.14.278

  日期：——

  conveniently accessible through a microwave-promoted tandem Claisen rearrangement/Wittig olefination/cyclization sequence. They serve as a versatile platform for the annellation of five- to seven-membered rings using ring-closing olefin metathesis (RCM). Furano-, pyrano-, oxepino- and azepinocoumarins were synthesized from the same set of precursors using Ru-catalyzed double bond isomerizations and RCM in a defined

  可通过微波促进的串联克莱森重排/维蒂希烯化/环化序列方便地获得8-烯丙基香豆素。它们是使用闭环烯烃复分解（RCM）进行五元至七元环环合的通用平台。使用Ru催化的双键异构化和RCM按定义的顺序，从同一组前体中合成呋喃并，吡喃并，氧杂环丁烷和氮杂环庚烷香豆素。一类产品吡喃并[2,3-f]亚甲基-2,8-二酮无法通过丙烯酸酯的直接RCM获得，但可通过辅助串联催化RCM /烯丙基氧化序列从类似的烯丙基醚获得。
• A convenient synthesis of psoralens
  作者：Stefano Chimichi、Marco Boccalini、Barbara Cosimelli、Giampietro Viola、Daniela Vedaldi、Francesco Dall'Acqua

  DOI：10.1016/s0040-4020(02)00441-6

  日期：2002.6

  An efficient synthesis (yields >70%) of linear 7H-furo[3,2-g]chromen-7-one derivatives (psoralens or furocoumarins) has been carried out starting from ring-substituted 2-(coumarin-7-yl)oxyaldehydes; moreover, the phototoxicity of these compounds has been tested on a cultured cell line of murine fibroblast.

  从环取代的2-（香豆素-7-基）开始，已经进行了线性7 H-呋喃[3,2 - g ] chromen-7-one衍生物（补骨脂素或呋喃香豆素）的有效合成（收率> 70％）。）乙醛; 此外，已经在鼠成纤维细胞的培养细胞系上测试了这些化合物的光毒性。
• A Coumarin−Donepezil Hybrid as a Blood−Brain Barrier Permeable Dual Cholinesterase Inhibitor: Isolation, Synthetic Modifications, and Biological Evaluation of Natural Coumarins
  作者：Ankita Sharma、Vijay K. Nuthakki、Sumeet Gairola、Bikarma Singh、Sandip B. Bharate

  DOI：10.1002/cmdc.202200300

  日期：2022.9.16

  The semisynthetic derivative 34, a coumarin−donepezil hybrid, exhibits dual inhibition of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 1.22 and 3.09 μM, respectively. Molecular modeling and enzyme kinetics studies revealed that 34 is a non-competitive inhibitor of AChE. It crosses the blood−brain barrier and inhibits β-amyloid self-aggregation. These results

  半合成衍生物 34是一种香豆素-多奈哌齐杂合体，对乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BChE) 具有双重抑制作用，IC 50值分别为 1.22 和 3.09 μM。分子建模和酶动力学研究表明，34是 AChE 的非竞争性抑制剂。它穿过血脑屏障并抑制β-淀粉样蛋白的自聚集。这些结果值得对阿尔茨海默病临床前模型中的34个进行详细调查。