9β-acetoxyparthenolide | 853130-17-3

• 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: 9β-acetoxyparthenolide
• 英文别名: 9α-Acetoxyparthenolid
• CAS: 853130-17-3
• 化学式: C₁₇H₂₂O₅
• 分子量: 306.359
• InChiKey: QMKVWBGFFNUWNW-AFTKUYHXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  65.13
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  parthenolide 在 4-二甲氨基吡啶 、 sodium phosphite 、 nicotinamide adenine dinucleotide phosphate 、 三乙胺 作用下， 以 aq. phosphate buffer 、 二氯甲烷 为溶剂， 反应 14.0h， 生成 9β-acetoxyparthenolide
  参考文献：
  名称：

  [EN] PARTHENOLIDE DERIVATIVES, METHODS FOR THEIR PREPARATION AND THEIR USE AS ANTICANCER AGENTS
  [FR] DÉRIVÉS DE PARTHÉNOLIDE, LEURS PROCÉDÉS DE PRÉPARATION ET LEUR UTILISATION EN TANT QU'AGENTS ANTICANCÉREUX

  摘要：

  公开号：

  WO2014197591A3

文献信息

• Synthetic Modification of 9α- and 9β-Hydroxyparthenolide by Heck or Acylation Reactions and Evaluation of Cytotoxic Activities
  作者：Abderrahman El Bouakher、Badr Jismy、Hassan Allouchi、Eric Duverger、Latifa Barkaoui、Ahmed El Hakmaoui、Richard Daniellou、Gérald Guillaumet、Mohamed Akssira

  DOI：10.1055/s-0042-119864

  日期：——

  anticancer activity of parthenolides and their derivatives, a series of new substituted parthenolides was efficiently synthesized. Structural modifications were performed at the C-9 and C-13 positions of 9α- and 9β-hydroxyparthenolide, which were isolated from the aerial parts of Anvillea radiata. Twenty-one derivatives were synthesized and evaluated for their in vitro cytotoxic activity against HS-683,

  受广泛报道的小白菊内酯及其衍生物的抗癌活性的影响，有效合成了一系列新的取代的小白菊内酯。结构修饰是在9α-和9β-羟基小白菊的C-9和C-13位置上进行的，这些位置是从辐射小牛的地上部分中分离出来的。合成了二十一种衍生物，并使用MTT比色测定法评估了它们对HS-683，SK-MEL-28，A549和MCF-7人癌细胞系的体外细胞毒活性。在这些衍生物中，有七个与5-氟尿嘧啶和依托泊苷相比，对四种测试细胞系表现出优异的活性，IC50值在1.1至9.4 µM之间。
• Discovery of Potent Parthenolide-Based Antileukemic Agents Enabled by Late-Stage P450-Mediated C—H Functionalization
  作者：Joshua N. Kolev、Kristen M. O’Dwyer、Craig T. Jordan、Rudi Fasan

  DOI：10.1021/cb400626w

  日期：2014.1.17

  The sesquiterpene lactone parthenolide has recently attracted considerable attention owing to its promising antitumor properties, in particular in the context of stem-cell cancers including leukemia. Yet, the lack of viable synthetic routes for re-elaborating this complex natural product has represented a fundamental obstacle toward further optimization of its pharmacological properties. Here, we demonstrate how this challenge could be addressed via selective, late-stage sp(3) C-H bond functionalization mediated by P450 catalysts with tailored site-selectivity. Taking advantage of our recently introduced tools for high-throughput P450 fingerprinting and fingerprint-driven P450 reactivity prediction, we evolved P450 variants useful for carrying out the highly regioselective hydroxylation of two aliphatic sites (C9 and C14) in parthenolide carbocyclic backbone. By chemoenzymatic synthesis, a panel of novel C9- and C14-modified parthenolide analogs were generated in order to gain initial structure-activity insights on these previously inaccessible sites of the molecule. Notably, some of these compounds were found to possess significantly improved antileukemic potency against primary acute myeloid leukemia cells, while exhibiting low toxicity against normal mature and progenitor hematopoietic cells. By identifying two 'hot spots' for improving the anticancer properties of parthenolide, this study highlights the potential of P450-mediated C-H functionalization as an enabling, new strategy for the late-stage manipulation of bioactive natural product scaffolds.
• [EN] PARTHENOLIDE DERIVATIVES, METHODS FOR THEIR PREPARATION AND THEIR USE AS ANTICANCER AGENTS<br/>[FR] DÉRIVÉS DE PARTHÉNOLIDE, LEURS PROCÉDÉS DE PRÉPARATION ET LEUR UTILISATION EN TANT QU'AGENTS ANTICANCÉREUX
  申请人：UNIV ROCHESTER

  公开号：WO2014197591A3

  公开（公告）日：2015-02-26
• 10.1021/cb400626
  作者：Kolev, Joshua N.、O'Dwyer, Kristen M.、Jordan, Craig T.、Fasan, Rudi

  DOI：10.1021/cb400626

  日期：——