(S,E)-4-hydroxy-3-(2-((1S,2S,4aS,5R,6R,8aR)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyloctahydro-1H-spiro [naphthalene-2,2'-oxirane]-1-yl)ethylidene)dihydrofuran-2(3H)-one | 774581-28-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (S,E)-4-hydroxy-3-(2-((1S,2S,4aS,5R,6R,8aR)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyloctahydro-1H-spiro [naphthalene-2,2'-oxirane]-1-yl)ethylidene)dihydrofuran-2(3H)-one
• 英文别名: 8,17-epoxyandrographolide；(3E,4S)-3-[2-[(1S,2S,4aS,5R,6R,8aR)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethylspiro[3,4,4a,6,7,8-hexahydro-1H-naphthalene-2,2'-oxirane]-1-yl]ethylidene]-4-hydroxyoxolan-2-one
• CAS: 774581-28-1
• 化学式: C₂₀H₃₀O₆
• 分子量: 366.455
• InChiKey: YKPLIKPPBOCWOJ-RMHQAIMASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  99.5
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S,E)-4-hydroxy-3-(2-((1S,2S,4aS,5R,6R,8aR)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyloctahydro-1H-spiro [naphthalene-2,2'-oxirane]-1-yl)ethylidene)dihydrofuran-2(3H)-one 在 4-甲基苯磺酸吡啶 、 溶剂黄146 作用下， 以 二甲基亚砜 、 苯 为溶剂， 反应 9.25h， 生成 [(3S,4E)-4-[2-[(1S,2S,4aS,5R,6R,8aR)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethylspiro[3,4,4a,6,7,8-hexahydro-1H-naphthalene-2,2'-oxirane]-1-yl]ethylidene]-5-oxooxolan-3-yl] acetate
  参考文献：
  名称：

  Synthesis and structure–activity relationships of andrographolide analogues as novel cytotoxic agents

  摘要：

  Andrographolide 1, the cytotoxic agent of the plant Androgrophis paniculata was subjected to semi-synthetic studies leading to the preparation of a number of potent and novel analogues. Of the analogues synthesized, while 8,17-epoxy andrographolide 6 retained the cytotoxic activity of 1, ester derivatives of 6 exhibited considerable improvement in activity. Lower activity was observed when the epoxy moiety in the triacetate 9, derived from 6 was modified. Synthesis and structure-activity relationships are discussed. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.06.090
• 作为产物：
  描述：

  穿心莲内酯 在 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 19.0h， 以72%的产率得到(S,E)-4-hydroxy-3-(2-((1S,2S,4aS,5R,6R,8aR)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyloctahydro-1H-spiro [naphthalene-2,2'-oxirane]-1-yl)ethylidene)dihydrofuran-2(3H)-one
  参考文献：
  名称：

  Inhibition of topoisomerase II α activity and induction of apoptosis in mammalian cells by semi-synthetic andrographolide analogues

  摘要：

  拓扑异构酶 II α 在 DNA 复制过程中发挥着关键作用。它在转录过程中控制 DNA 的拓扑状态，对细胞增殖至关重要。人类DNA拓扑异构酶II α（hTopo II α）是一种很有前景的抗癌化疗靶点。本研究研究了穿心莲内酯及其结构修饰类似物对 hTopo II α 酶的抑制活性。九种穿心莲内酯类似物中有五种能有效降低 hTopo II α 的活性，并抑制四种哺乳动物细胞系（Hela、CHO、BCA-1 和 HepG2 细胞）的细胞增殖。类似物 3A.1、3A.2、3A.3、1B 和 2C 的细胞毒性 IC50 值为 4 至 7 μM。结构-活性关系研究表明，穿心莲内酯的核心结构和功能基团的硅基分子对抑制 hTopo II α 的活性非常重要，而类似物的 C-19 位则是抗增殖的必要条件。此外，类似物 2C 在 10 μM 浓度下可抑制 hTopo II α，并诱导 HepG2 细胞凋亡，使细胞核破碎并形成凋亡体。因此，类似物 2C 可能具有治疗潜力，可作为针对 hTopo II α 功能的有效抗癌剂。

  DOI：

  10.1007/s10637-012-9868-9

文献信息

• One-pot three steps cascade synthesis of novel isoandrographolide analogues and their cytotoxic activity
  作者：Teerapich Kasemsuk、Pawinee Piyachaturawat、Rada Bunthawong、Uthaiwan Sirion、Kanoknetr Suksen、Apichart Suksamrarn、Rungnapha Saeeng

  DOI：10.1016/j.ejmech.2017.07.035

  日期：2017.9

  andrographolide analogues is reported from a naturally occurring and abundant andrographolide isolated from aerial parts of Andrographis paniculata. Reactions in the one-pot proceed through a cascade epoxide ring opening by aniline derivatives/intramolecular ring closing and oxa-conjugate addition-elimination reactions. This methodology produces a new series of 17-amino-8-epi-isoandrographolide analogues in fair

  新颖穿心莲内酯类似物的有效一锅法合成是从的地上部分分离的天然存在的和丰富的穿心莲内酯报道穿心莲。一锅中的反应通过苯胺衍生物/分子内的闭环和氧杂-共轭加成-消除反应通过级联的环氧开环进行。该方法使用经济和环境方法，在室温下无需碱或催化剂的情况下，以高立体选择性公平，优异地产生了一系列新的17-氨基-8-表位异二十碳内酯类似物。获得了二十五个类似物，并针对六种癌细胞系评估了所有新类似物的细胞毒性，以寻找基于穿心莲内酯结构的新的先导化合物。
• Synthesis and Bioactivities of Andrographolide Derivatives: New (−)-Limonidilactone Analogues
  作者：Haiwei Xu、Pingjuan Jiang、Weiyi Li、Junfeng Wang、Hongmin Liu

  DOI：10.1002/cjoc.201180366

  日期：2011.10

  In this study, a novel route to (−)‐limonidilactone analogues 10, 11 by way of stereoselective reaction of andrographolide (5) from 8, 9 was reported. The anti‐tumor and α‐glucosidsae inhibition activities of some synthetic compounds were screened.

  在这项研究中，一种新的路线limonidilactone类似物- （ - ）10，11由穿心莲内酯（立体选择性反应的方式5从）8，9报道了。筛选了一些合成化合物的抗肿瘤和α-葡萄糖苷抑制活性。
• Synthesis of andrographolide derivatives: A new family of α-glucosidase inhibitors
  作者：Hai-Wei Xu、Gui-Fu Dai、Gai-Zhi Liu、Jun-Feng Wang、Hong-Min Liu

  DOI：10.1016/j.bmc.2007.03.063

  日期：2007.6

  Andrographolide (1), the cytotoxic agent of the plant Andrographis paniculata, was subjected to semi-synthetic studies leading to a series of new derivatives, a novel family of glucosidase inhibitors. Nicotination of 3,19-hydroxyls in 15-alkylidene andrographolide derivatives (9) was favorable to alpha-glucosidase inhibition activity. Among them, 15-p-chlorobenzylidene-14-deoxy-11,12-didehydro-3,19-dinicotinateandrographolide (11c) was a very potent inhibitor against alpha-glucosidase with an IC50 value of 6 mu M. However, all compounds concerned for beta-glucosidase showed no inhibition. All compounds synthesized were characterized by the analysis of NMR, IR, HRMS spectra and the stereochemistry of 2 was confirmed by X-ray analysis. (C) 2007 Published by Elsevier Ltd.
• Synthesis of new andrographolide derivatives and evaluation of their antidyslipidemic, LDL-oxidation and antioxidant activity
  作者：Sukanya Pandeti、Ravi Sonkar、Astha Shukla、Gitika Bhatia、Narender Tadigoppula

  DOI：10.1016/j.ejmech.2013.09.002

  日期：2013.11

  Andrographis paniculata, native to Taiwan, Mainland China and India, is a medicinal herb, which possesses various biological activities including anti-atherosclerosis. Andrographolide (1) has been identified as one of the active constituents against atherosclerosis. In continuation of our drug discovery program we synthesized few novel derivatives of 1 to improve their antidyslipidemic, LDL-oxidation and antioxidant activity. The tosylated derivative 7 has been turned out to be more potent than the parent compound and comparable activity with marketed antidyslipidemic drugs. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Synthesis and structure–activity relationships of andrographolide analogues as novel cytotoxic agents
  作者：Srinivas Nanduri、Vijay Kumar Nyavanandi、Siva Sanjeeva Rao Thunuguntla、Sridevi Kasu、Mahesh Kumar Pallerla、P. Sai Ram、Sriram Rajagopal、R. Ajaya Kumar、Rajagopalan Ramanujam、J. Moses Babu、Krishnamurthi Vyas、A. Sivalakshmi Devi、G. Om Reddy、Venkateswarlu Akella

  DOI：10.1016/j.bmcl.2004.06.090

  日期：2004.9

  Andrographolide 1, the cytotoxic agent of the plant Androgrophis paniculata was subjected to semi-synthetic studies leading to the preparation of a number of potent and novel analogues. Of the analogues synthesized, while 8,17-epoxy andrographolide 6 retained the cytotoxic activity of 1, ester derivatives of 6 exhibited considerable improvement in activity. Lower activity was observed when the epoxy moiety in the triacetate 9, derived from 6 was modified. Synthesis and structure-activity relationships are discussed. (C) 2004 Elsevier Ltd. All rights reserved.