(1R,4aS,5R,8aS)-5-((E)-2-((S)-4-hydroxy-2-oxodihydrofuran-3(2H)-ylidene)ethyl)-1,4a-dimethyl-6-methylene-2-oxodecahydronaphthalene-1-carbaldehyde

• 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: (1R,4aS,5R,8aS)-5-((E)-2-((S)-4-hydroxy-2-oxodihydrofuran-3(2H)-ylidene)ethyl)-1,4a-dimethyl-6-methylene-2-oxodecahydronaphthalene-1-carbaldehyde
• 英文别名: andrographolide-3,19-dione；3,19-didehydroandrographolide；(1R,4aS,5R,8aS)-5-[(2E)-2-[(4S)-4-hydroxy-2-oxooxolan-3-ylidene]ethyl]-1,4a-dimethyl-6-methylidene-2-oxo-3,4,5,7,8,8a-hexahydronaphthalene-1-carbaldehyde
• 化学式: C₂₀H₂₆O₅
• 分子量: 346.423
• InChiKey: YZKJGBDSKBLPHO-IZRDHSPGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.38
• 重原子数：
  25.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  80.67
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (1R,4aS,5R,8aS)-5-((E)-2-((S)-4-hydroxy-2-oxodihydrofuran-3(2H)-ylidene)ethyl)-1,4a-dimethyl-6-methylene-2-oxodecahydronaphthalene-1-carbaldehyde 在 吡啶 、 咪唑 、 氟化氢吡啶 、 lithium hexamethyldisilazane 、 (methoxymethyl)triphenylphosphonium chloride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 23.17h， 生成 (4S,E)-3-(2-((1R,4aR,5R,8aR)-5,8a-dimethyl-6-(methylamino)-2-methylenedecahydronaphthalen-1-yl)ethylidene)-4-hydroxydihydrofuran-2(3H)-one
  参考文献：
  名称：

  [EN] DITERPENOID DERIVATIVES AND METHODS OF USE THEREOF
  [FR] DÉRIVÉS DE DITERPÉNOÏDES ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  本文提供了公式（I）的化合物和含有这些化合物的组合物。这些化合物和组合物在治疗、改善或预防与Nrf2/NF-κΒ途径相关的疾病的方法中是有用的。相关的疾病包括但不限于纤维化疾病，如肺纤维化、肝纤维化、肾纤维化和硬皮病，或神经退行性疾病，如多发性硬化症、肌萎缩侧索硬化症、帕金森病、亨廷顿病和阿尔茨海默病，以及镰状细胞病。

  公开号：

  WO2016065264A1
• 作为产物：
  描述：

  穿心莲内酯 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 (1R,4aS,5R,8aS)-5-((E)-2-((S)-4-hydroxy-2-oxodihydrofuran-3(2H)-ylidene)ethyl)-1,4a-dimethyl-6-methylene-2-oxodecahydronaphthalene-1-carbaldehyde
  参考文献：
  名称：

  [EN] DITERPENOID DERIVATIVES AND METHODS OF USE THEREOF
  [FR] DÉRIVÉS DE DITERPÉNOÏDES ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  本文提供了公式（I）的化合物和含有这些化合物的组合物。这些化合物和组合物在治疗、改善或预防与Nrf2/NF-κΒ途径相关的疾病的方法中是有用的。相关的疾病包括但不限于纤维化疾病，如肺纤维化、肝纤维化、肾纤维化和硬皮病，或神经退行性疾病，如多发性硬化症、肌萎缩侧索硬化症、帕金森病、亨廷顿病和阿尔茨海默病，以及镰状细胞病。

  公开号：

  WO2016065264A1

文献信息

• Site-selective oxidation, amination and epimerization reactions of complex polyols enabled by transfer hydrogenation
  作者：Christopher K. Hill、John F. Hartwig

  DOI：10.1038/nchem.2835

  日期：2017.12

  for selective reactions of complex polyol structures. We present a new ruthenium catalyst with a unique efficacy for the selective oxidation of a single hydroxyl group among many in unprotected polyol natural products. This oxidation enables the introduction of nitrogen-based functional groups into such structures that lack nitrogen atoms and enables a selective alcohol epimerization by stepwise or

  带有一个或多个羟基的多氧化碳氢化合物包含大量天然和合成化合物，通常具有强大的生物活性。在合成化学中，醇是羰基的重要前体，然后可以将其转化为多种基于氧或氮的官能团。因此，将天然产物中的单个羟基选择性转化为酮将能够选择性引入非天然官能团。然而，已知的将简单的醇或什至在包含多个受保护的官能团的分子中的醇转化的方法不适用于复杂的多元醇结构的选择性反应。我们提出了一种新型的钌催化剂，该催化剂具有独特的功效，可以选择性氧化多个未保护的多元醇天然产物中的单个羟基。该氧化使得能够将氮基官能团引入缺乏氮原子的这种结构中，并能够通过逐步或可逆的氧化和还原来进行选择性醇差向异构化。
• De novo consecutive chemo/regioselective IBX mediated oxidation of andrographolide and its derivatives
  作者：Sudhakar Mokenapelli、Madhu Gutam、Ramana Govu、Vijay Kumar Pasala、Jayaprakash Rao Yerrabelly、Prasad Rao Chitneni

  DOI：10.1080/00397911.2019.1587775

  日期：2019.5.19

  Abstract A new IBX mediated protocol for regio/chemoselective oxidation of andrographolide (1), a labdane diterpenoid isolated from Andrographis paniculata, is developed. After the initial success of this protocol with andrographolide (1) to provide 19-dehydroandrographolide (5) or 3,19-didehydroandrographolide (6) as major products, the procedure was further applied for the oxidation of hydroxyl functionality

  摘要 开发了一种新的 IBX 介导的穿心莲内酯 (1) 区域/化学选择性氧化方案，穿心莲内酯是一种从穿心莲中分离出来的劳丹烷二萜。该协议与穿心莲内酯 (1) 初步成功以提供 19-脱氢穿心莲内酯 (5) 或 3,19-二脱氢穿心莲内酯 (6) 作为主要产品后，该程序进一步应用于穿心莲内酯衍生物中羟基官能团的氧化，即 2 、3、14 和 16。该过程同样适用于毫克到克的范围内。在乙腈-水 (8:2) 系统中使用 TBDMS-Cl 以良好的收率实现了化合物 15 和 18 中 C-19-OTBDMS 的脱保护。图形概要
• Synthesis, structure–activity relationships and biological evaluation of dehydroandrographolide and andrographolide derivatives as novel anti-hepatitis B virus agents
  作者：Hao Chen、Yun-Bao Ma、Xiao-Yan Huang、Chang-An Geng、Yong Zhao、Li-Jun Wang、Rui-Hua Guo、Wen-Juan Liang、Xue-Mei Zhang、Ji-Jun Chen

  DOI：10.1016/j.bmcl.2014.03.060

  日期：2014.5

  Dehydroandrographolide and andrographolide, two natural diterpenoids isolated from Andrographis paniculata possessed activity against HBV DNA replication with IC50 values of 22.58 and 54.07 mu M and low SI values of 8.7 and 3.7 in our random assay. Consequently, 48 derivatives of dehydroandrographolide and andrographolide were synthesized and evaluated for their anti-HBV properties to yield a series of active derivatives with lower cytotoxicity, including 14 derivatives against HBsAg secretion, 19 derivatives against HBeAg secretion and 38 derivatives against HBV DNA replication. Interestingly, compound 4e could inhibit not only HBsAg and HBeAg secretions but also HBV DNA replication with SI values of 20.3, 125.0 and 104.9. Furthermore, the most active compound 2c with SI value higher than 165.1 inhibiting HBV DNA replication was revealed with the optimal logP value of 1.78 and logD values. Structureactivity relationships (SARs) of the derivatives were disclosed for guiding the future research toward the discovery of new anti-HBV drugs. (C) 2014 Elsevier Ltd. All rights reserved.
• 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.
• DITERPENOID DERIVATIVES AND METHODS OF USE THEREOF
  申请人：Biogen MA Inc.

  公开号：US20170354639A1

  公开（公告）日：2017-12-14

  Provided herein are compounds of formula (I) and compositions containing the compounds. The compounds and compositions are useful in the methods of treating, amelioration or prophylaxix of diseases associated with Nrf2/NF- κ B pathways. The diseases associated include, but are not limited to a fibrotic disease such as lung fibrosis, liver fibrosis, kidney fibrosis, and scleroderma, or a neurodegenerative disease, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, and Alzheimer's disease, and sickle cell disease.