首页> 外文OA文献 >Total synthesis of natural derivatives and artificial analogs of 13-oxyingenol and their biological evaluation
【2h】

Total synthesis of natural derivatives and artificial analogs of 13-oxyingenol and their biological evaluation

机译:13-氧化烯醇的天然衍生物和人工类似物的全合成及其生物学评价

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

We have established an efficient synthetic methodology for the 13-oxyingenol natural derivative (13-oxyingenol-13-dodecanoate-20-hexanoate), featuring a ring-closing olefin metathesis reaction for the “direct” construction of a highly strained inside–outside framework and a Mislow–Evans-type [2,3]-sigmatropic rearrangement for the stereoselective introduction of the hydroxy group at C5. We also synthesized artificial analogs of 13-oxyingenol and ingenol by using our synthetic strategy. In vitro activation assays of protein kinase C (PKC) α and δ revealed that the dodecanoyl group at O13 on 13-oxyingenol analogs had a significant role in PKCδ activation. The PKCα- or PKCδ-activating 13-oxyingenol and ingenol analogs induced both distinct morphological changes and increases of CD11b expression in HL-60 cells, which would be typical signs of HL-60 cell differentiation to macrophage-like cells, as expected by previous reports. Intriguingly, however, similar differentiation phenotypes were observed with the use of 13-oxyingenol natural derivatives and 13-oxyingenol-13-dodecanoate showing a remarkably less potent PKCα or PKCδ activation ability, which the PKC inhibitor Gö6983 diminished. This indicated the involvement of other PKC isozymes or related kinase activities. 13-Oxyingenol analogs, which induced HL-60 cell differentiation, also induced HL-60 cell death, similar to the action of a phorbol ester, a strong PKC activator.
机译:我们已经建立了一种有效的13-氧烯醇天然衍生物(13-氧烯醇-13-十二酸酯-20-己酸酯)的合成方法,其特征是通过一个闭环烯烃复分解反应来“直接”构建高度紧张的内外框架。和Mislow–Evans型[2,3]-σ重排用于C5处的羟基的立体选择性引入。我们还使用我们的合成策略合成了13-氧丁烯醇和丁香酚的人工类似物。蛋白激酶C(PKC)α和δ的体外活化试验表明,13-氧烯醇类似物在O13处的十二烷酰基在PKCδ活化中具有重要作用。 PKCα或PKCδ激活的13-氧丁烯醇和丁香酚类似物在HL-60细胞中诱导了明显的形态变化和CD11b表达的增加,这是HL-60细胞分化为巨噬细胞样细胞的典型标志。报告。然而,有趣的是,使用13-氧烯醇天然衍生物和13-氧烯醇-13-十二烷酸酯也观察到了相似的分化表型,表现出明显较弱的PKCα或PKCδ活化能力,而PKC抑制剂Gö6983减弱了。这表明其他PKC同工酶或相关的激酶活性也参与其中。诱导HL-60细胞分化的13-羟基烯醇类似物也诱导HL-60细胞死亡,类似于佛波酯(一种强的PKC激活剂)的作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号