ingenol 20-acetate-3-angelate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: ingenol 20-acetate-3-angelate
• 英文别名: 20-O-Acetylingenol-3-angelate；[(1S,4S,5S,6R,9S,10R,12R,14R)-7-(acetyloxymethyl)-5,6-dihydroxy-3,11,11,14-tetramethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,7-dienyl] (Z)-2-methylbut-2-enoate
• 化学式: C₂₇H₃₆O₇
• 分子量: 472.579
• InChiKey: ZYCAGKYWXRKLSN-KLKWOBOISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ingenol 20-acetate-3-angelate 在 二乙胺基三氟化硫 、 sodium carbonate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 [(1S,4S,5R,8S,9S,10R,12R,14R)-8-fluoro-5-hydroxy-7-(hydroxymethyl)-3,11,11,14-tetramethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,6-dienyl] (Z)-2-methylbut-2-enoate
  参考文献：
  名称：

  Syntheses, biological evaluation and SAR of ingenol mebutate analogues for treatment of actinic keratosis and non-melanoma skin cancer

  摘要：

  Ingenol mebutate is the active ingredient in Picato (R) a new drug for the treatment of actinic keratosis. A number of derivatives related to ingenol mebutate were prepared by chemical synthesis from ingenol with the purpose of investigating the SAR and potency in assays relating to pro-inflammatory effects (induction of PMN oxidative burst and keratinocyte cytokine release), the potential of cell death induction, as well as the chemical stability. By modifications of the ingenol scaffold several prerequisites for activity were identified. The chemical stability of the compounds could be linked to an acyl migration mechanism. We were able to find analogues of ingenol mebutate with comparable in vitro properties. Some key features for potent and more stable ingenol derivatives have been identified. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.038
• 作为产物：
  描述：

  3-O-angeloyl-5,20-O-isopropylideneingenol 在 盐酸 、 三乙胺 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 ingenol 20-acetate-3-angelate
  参考文献：
  名称：

  Syntheses, biological evaluation and SAR of ingenol mebutate analogues for treatment of actinic keratosis and non-melanoma skin cancer

  摘要：

  Ingenol mebutate is the active ingredient in Picato (R) a new drug for the treatment of actinic keratosis. A number of derivatives related to ingenol mebutate were prepared by chemical synthesis from ingenol with the purpose of investigating the SAR and potency in assays relating to pro-inflammatory effects (induction of PMN oxidative burst and keratinocyte cytokine release), the potential of cell death induction, as well as the chemical stability. By modifications of the ingenol scaffold several prerequisites for activity were identified. The chemical stability of the compounds could be linked to an acyl migration mechanism. We were able to find analogues of ingenol mebutate with comparable in vitro properties. Some key features for potent and more stable ingenol derivatives have been identified. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.038

文献信息

• On the Active Principles of the Euphorbiaceae, IX^a Ingenane Type Diterpene Esters from Five Euphorbia Species
  作者：H. Gotta、W. Adolf、H. J. Opferkuch、E. Hecker

  DOI：10.1515/znb-1984-0525

  日期：1984.5.1

  Investigations of E. antiquorum, E. helioscopia, E. palustris, E. peplus and E. quadrialata for irritant and tumor promoting constituents afforded several new ingenane type diterpene esters derived from the parent alcohols ingenol and 20-deoxyingenol and from the hitherto unknown 20- deoxy-16-hydroxyingenol and 20-deoxy-13.16-dihydroxyingenol. The irritant activities of the natural compounds are reported together with some aspects on structure activity relationships

  对 E. antiquorum、E. helioscopia、E. palustris、E. peplus 和 E. quadrialata 进行的刺激和肿瘤促进成分的研究发现了几种新的因格诺醇和 20-去氧因格诺醇的二萜酯衍生物，以及迄今为止未知的 20-去氧-16-羟基因格诺醇和 20-去氧-13,16-二羟基因格诺醇。报道了这些天然化合物的刺激活性，以及一些关于结构活性关系的方面。
• PROCESS FOR THE PREPARATION OF INGENOL-3-ANGELATE
  申请人：LEO Laboratories Limited

  公开号：US20150024443A1

  公开（公告）日：2015-01-22

  The invention relates to methods for preparing ingenol-3-angelate from ingenol or ingenol derivatives.

  本发明涉及从英吉利醇或英吉利醇衍生物制备英吉利醇-3-安吉酯的方法。
• Ingenane and lathyrane diterpenes from the latex of Euphorbia canariensis
  作者：J.Alberto Marco、Juan F. Sanz-Cervera、Alberto Yuste

  DOI：10.1016/s0031-9422(97)00018-6

  日期：1997.6

  The latex of Euphorbia canariensis yielded, in addition to five known ingenol esters, the ingenane derivatives ingenol 3-angelate 5,20-diacetate and 5-deoxyingenol 3-angelate 20-acetate, and the lathyrane derivatives 2,3-diepiingol 7,12-diacetate 8-benzoate, 2,3-diepiingol 7,12-diacetate 8-isobutyrate and 2-epiingol 3,7,12-triacetate 8-benzoate. The structures were established with the aid of spectroscopic

  除了五种已知的大戟醇酯外，加那利大戟的胶乳还产生了大戟二萜醇 3-当归醇 5,20-二乙酸酯和 5-脱氧姜烯醇 3-当归醇 20-乙酸酯，以及二十四烷衍生物 2,3-二萜醇 7,12 -二乙酸酯 8-苯甲酸酯、2,3-二乙酸酯 7,12-二乙酸酯 8-异丁酸酯和 2-表烯醇酯 3,7,12-三乙酸酯 8-苯甲酸酯。结构是在光谱方法（主要是核磁共振）和分子力学计算的帮助下建立的。他们也得到了一些化学转化结果的支持。
• Regioselective acylation of 3-O-angeloylingenol by Candida antarctica Lipase B
  作者：R.W. Teng、D. McManus、J. Aylward、S. Ogbourne、J. Johns、P. Parsons、A. Bacic

  DOI：10.1016/j.fitote.2009.02.001

  日期：2009.6

  Acylation of 3-O-angeloylingenol (1) with vinyl acetate, vinyl decanoate and vinyl cinnamate, catalyzed by Candida antarctica Lipase 13, was investigated. In each case, compound 1 was quantitatively and regioselectively acylated to afford a single product, 3-O-angeloyl-20-O-acetylingenol (1a), 3-O-angeloyl-20-O-decanoylingenol (1b) and 3-O-angeloyl-20-O-cinnamoylingenol (1c), respectively. The structures of the novel compounds 1b-1c were determined by MS and NMR, and product la by comparison of RP-HPLC and TLC with a standard. Compounds 1b-1c induced a bipolar morphology of MM96L melanoma cells at a similar concentration as compound 1, as well as having activity in inhibiting the growth of MM96L melanoma cells. (C) 2009 Elsevier B.V. All rights reserved.
• METHOD FOR WOUND HEALING
  申请人：LEO Laboratories Limited

  公开号：US20160317486A1

  公开（公告）日：2016-11-03

  The present invention relates generally to methods and compositions for promoting wound healing in a subject. In particular, the invention relates to the use of ingenol compounds, particularly ingenol angelates, in wound healing and compositions thereof which contain such compounds.