利用氧化还原介导的伯格曼循环化,开发出双作用的金属二烯疗法
Sarah E Lindahl1, Hyunsoo Park, Maren Pink
1Department of Chemistry, Indiana University, Bloomington, Indiana 47405, USA.
Journal of the American Chemical Society
|February 26, 2013
概括
一个稳定的(0) 金属二烯复合物,Pt(dppeb) 2,经过氧化后经过高效的氧化还原介导的伯格曼循环. 这种反应产生一种类似于西斯的副产品,为双重作用的金属二烯疗法提供了一种新的策略.
科学领域:
- 有机金属化学 有机金属化学
- 材料科学 材料科学 材料科学
- 药用化学 医学化学
背景情况:
- 金属二烯是含有金属原子和二烯部分的化合物.
- 伯格曼循环化是enediynes的一个关键反应,形成反应性para-benzyne中间体.
- 复合物正在研究其治疗潜力,特别是在癌症治疗中 (例如,西斯).
研究的目的:
- 为了合成和表征一个稳定的(0) 金属二烯基复合物,Pt(dppeb) 2.2.
- 为了研究这个复杂的氧化还原介导的伯格曼循环.
- 探索这个系统的潜力,作为一种双重威胁的金属联合疗法.
主要方法:
- 从Pt(cod) Cl2和1,2-bis(((diphenylphosphino) ethynyl) benzene (dppeb) 中合成Pt(dppeb) 2的合成.
- 使用 (I2) 的氧化反应,有或没有基因陷 (1,4-环二烯).
- 使用NMR (31P) 和拉曼光谱进行表征.
- 计算分析以确定反应中间体的可信结构.
主要成果:
- 合成了稳定的Pt(0) 复合物Pt(dppeb) 2,并发现它对空气氧化和自发的伯格曼循环化具有抗性.
- 与I2和一个激素陷的反应迅速产生了cis-Bergman循环的二氧化物产物.
- 与多余I2的反应形成了一个转移稳定的Pt(dppeb) 2(2+) 中间体,随后经历了连接物交换和自发的伯格曼循环,形成Pt(dppnap-I2) I2.2.
结论:
- 稳定的Pt(0) 金属二烯 Pt(dppeb) 2可以通过氧化还原介导的伯格曼循环化有效地激活.
- 反应产生一种类似于西斯的副产品,表明潜在的双重治疗作用.
- 该系统代表了开发基于metalloenediyne的治疗方法的有希望的新策略.
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