(5R,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl isonicotinate

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素内酯
• 英文名称: (5R,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl isonicotinate
• 英文别名: 4-O-podophyllotoxinyl-isonicotinate；(5aR)-9t-isonicotinoyloxy-5t-(3,4,5-trimethoxy-phenyl)-(5ar,8at)-5,8,8a,9-tetrahydro-5aH-furo[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6-one；(5aR)-9t-Isonicotinoyloxy-5t-(3,4,5-trimethoxy-phenyl)-(5ar,8at)-5,8,8a,9-tetrahydro-5aH-furo[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6-on；[(5R,5aR,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-5-yl] pyridine-4-carboxylate
• 化学式: C₂₈H₂₅NO₉
• 分子量: 519.508
• InChiKey: XUNFTUNXEHEAOR-PVUOONDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  112
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  異菸鹼[酸]酐 、 鬼臼毒素 在 吡啶 作用下， 生成 (5R,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl isonicotinate
  参考文献：
  名称：

  Components of Podophyllin. XVII.² Ionic Derivatives of Podophyllotoxin and of the Peltatins³

  摘要：

  DOI：

  10.1021/ja01629a043

文献信息

• Stereoselective synthesis of 4β-acyloxypodophyllotoxin derivatives as insecticidal agents
  作者：Zhi-Ping Che、Yue-E Tian、Sheng-Ming Liu、Jia Jiang、Mei Hu、Gen-Qiang Chen

  DOI：10.1080/10286020.2018.1490275

  日期：2019.10.3

  4α/β-acyloxypodophyllotoxin derivatives were synthesized, and were evaluated against the pre-third-instar larvae of B. mori, A. dissimilis and M. separate in vivo at the concentration of 1 mg ml−1, respectively. Among all derivatives, compounds 2 g, h and 4c, d showed more promising insecticidal activities than their precursors – podophyllotoxin and epipodophyllotoxin. Furthermore, derivatives 2 g, h and 4c, d exhibited

  由于我们在基于天然产物杀虫剂的研究正在进行的工作，一些4α/β-acyloxypodophyllotoxin衍生物的合成，反对的预第三龄幼虫进行了评价家蚕，A. dissimilis和M.分开体内分别为1 mg ml -1的浓度。在所有衍生物中，化合物2 g，h和4c，d显示出比其前体鬼臼毒素和表鬼臼毒素更有希望的杀虫活性。此外，导数2 g，h和4c，d与前体鬼臼毒素和表鬼臼毒素相比，它们显示出更多的相对友好活性。该结果表明鬼臼毒素衍生物中的4β-酰氧基部分对于获得更有效的化合物是重要的。
• Synthesis of Novel 4α-(Acyloxy)-2′(2′,6′)-(di)halogenopodophyllotoxin Derivatives as Insecticidal Agents
  作者：Zhiping Che、Xiang Yu、Xiaoyan Zhi、Lingling Fan、Xiaojun Yao、Hui Xu

  DOI：10.1021/jf4025079

  日期：2013.8.28

  In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, we have prepared three series of novel 4α-(acyloxy)-2′(2′,6′)-(di)halogenopodophyllotoxin derivatives modified in the C and E rings of podophyllotoxin, which is a naturally occurring aryltetralin lignan isolated from the roots and rhizomes of Podophyllum hexandrum. Their structures were

  在继续旨在发现和开发基于天然产物的杀虫剂的程序的过程中，我们制备了3个系列的新型4α-（酰氧基）-2′（2′，6′）-（二）卤代鬼臼毒素衍生物鬼臼毒素的C和E环，鬼臼毒素是从鬼臼的根和根茎中分离出来的天然芳基四氢木脂素。通过1 H NMR，HRMS，ESI-MS，旋光度和mp很好地表征了它们的结构。化合物5s，6b，6d和7q的立体化学构型通过单晶X射线衍射明确证实。在体内浓度为1 mg / mL的条件下，针对东方粘虫Mythimna separata Walker的三龄前幼虫评估了它们的杀虫活性。这些衍生物可能显示出抗蜕皮激素的作用。在所有衍生物中，尤其是化合物5a，5n，7f，7n和7w表现出最强的杀虫活性，最终死亡率为70％左右。这表明在鬼臼毒素E环的C2'或C2'和C6'位置引入的氯或溴原子是获得有效化合物所必需的。这将为进一步设计，结构修饰和开发鬼臼毒素衍生物作为杀虫剂铺平道路。
• The ester derivatives obtained by C‐ring modification of podophyllotoxin‐induced apoptosis and inhibited proliferation in Hemangioma Endothelial Cells via downregulation of PI3K/Akt signaling pathway
  作者：Yan Zhao、Danyao Li、Yun Han、Haohao Wang、Rui Du、Zhaowei Yan

  DOI：10.1111/cbdd.14034

  日期：2022.6

  may develop into malignant tumors. Hemangioma endothelial cells (HemECs) are one of the main components of IH. Podophyllotoxin (PPT) has been reported to have many pharmacological activities, especially anti-tumor, but its high toxicity, poor water solubility, and serious gastrointestinal side effects limit its clinical application. In this study, we have designed and synthesized 20 ester derivatives

  婴儿血管瘤（infantile hemangioma，IH）是婴幼儿常见的良性内皮细胞肿瘤，有时伴有潜在的并发症，并可能发展为恶性肿瘤。血管瘤内皮细胞 (HemECs) 是 IH 的主要成分之一。据报道，鬼臼毒素（PPT）具有多种药理活性，尤其是抗肿瘤活性，但其毒性大、水溶性差、胃肠道副作用严重，限制了其临床应用。本研究通过酯化反应在鬼臼毒素C-4位引入Boc-氨基酸或有机酸，设计合成了20种酯类衍生物。这些化合物的细胞毒性在 HemEC 上进行了评估。通过 DAPI 染色、集落形成试验、迁移测定、活性氧 (ROS) 水平的测量流式细胞术和蛋白质印迹分析。我们发现其中八种化合物比 PPT 更有效。其中，化合物 V-31 是最活跃的（IC50  = 0.079 ± 0.0049 µM）。进一步的研究表明，化合物V-31通过下调p-PI3K、p-Akt和Bcl-2，上调cleaved casp
• Design, synthesis, and biological evaluation of novel pyridine acid esters of podophyllotoxin and esters of 4′-demethylepipodophyllotoxin
  作者：Ying-Qian Liu、Liu Yang、Xuan Tian

  DOI：10.1007/s00044-007-9010-2

  日期：2007.12

  Podophyllotoxin and related analogs present numerous challenges associated with optimal antitumor activity and severe unpredictable toxicity. In the course of our ongoing investigation of quantitative structure-activity relationships to find biorational antitumor drugs, two series of pyridine acid ester derivatives of podophyllotoxin and 4 '-demethylepipodophyllotoxin have been prepared by reacting the corresponding pyridine acids with the hydroxyl group of podophyllotoxin and 4 '-demethyl epipodophyllotoxin in the presence of dimethylaminopyridine (DMAP) and N, N-dicyclohexylcarbodiimde (DCC). The structures of the compounds were extensively characterized by using H-1-nuclear magnetic resonance, mass spectroscopy, infrared, and elemental analysis and evaluated for their in vitro cytotoxicity on two neoplastic cell lines (P-388 murine leukemia, A-549 human lung carcinoma) using a MTT-based assay, the results indicated significantly higher efficacy of these compounds in comparison with the prototypical inhibitor etoposide. On the basis of the preliminary biological testing results, it suggested that the cytotoxic activity of OCH3 at C-4 ' is more potent than that of its demethylated analogs and the podophyllotoxin substitution at C-4 may be optimal for synthesizing more potent cytotoxic compounds.
• The ester derivatives obtained by C-ring modification of podophyllotoxin induce apoptosis and inhibited proliferation in PC-3M cells via down-regulation of PI3K/Akt signaling pathway
  作者：Yan Zhao、Danyao Li、Minggang Wei、Rui Du、Zhaowei Yan

  DOI：10.1016/j.bmcl.2021.128174

  日期：2021.8