总合成的epothilone B,epothilone D,以及 cis-和 trans-9,10-脱水roepothilone D 的总合成
J D White1, R G Carter, K F Sundermann
1Department of Chemistry, Oregon State University, Corvallis, OR 97331-4003, USA.
Journal of the American Chemical Society
|June 8, 2001
概括
研究人员合成了新型的epothilone类似物,cis-和trans-9,10-dehydroepothilone D.虽然不如天然的epothilones强,但这些合成化合物对抗性癌细胞表现出抗增殖活性.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 化学合成 化学合成
背景情况:
- 埃波提隆是强大的抗癌药物,可以稳定微管.
- 开发合成类型的epothilones对于药物发现至关重要.
- 了解结构-活性关系是提高治疗疗效的关键.
研究的目的:
- 为了合成新的cis-和trans-9,10-dehydroepothilone D类似物.
- 评估这些合成化合物的抗增殖活性和蛋白聚合.
- 为了比较它们的活性与天然的epothilones和paclitaxel.
主要方法:
- 涉及维蒂格,卡斯特罗-斯蒂芬斯和斯蒂尔合反应的多步合成.
- 准备关键中间体,如盐35和化物33的制备.
- 干酸的乳化,然后进行选择性还原和环氧化.
主要成果:
- 成功合成了 cis-9,10-脱水皮醇 D (43) 和 trans-9,10-脱水皮醇 D (54).
- 与天然的epothilones B和D相比,合成类似物表现出较低的效力.
- 这两种类似物都保留了对抗帕克利塔塞尔耐药细胞系的抗增殖活性.
结论:
- 合成的epotilone类似物显示出作为抗癌剂的潜力,特别是在耐药细胞系中.
- 结构-活性关系研究表明,修改可以影响功效,但不一定对抗抗性癌症的整体活性产生影响.
- 进一步的研究可能将重点放在优化这些类似物以提高治疗效益上.
相关概念视频
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