总合成和生物评估的pederin,psymberin,和高强度的类似物
Shuangyi Wan1, Fanghui Wu, Jason C Rech
1Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Journal of the American Chemical Society
|September 10, 2011
概括
研究人员使用高效的合成路径合成了强大的细胞毒素pederin和psymberin. 为了研究它们的生物活性,创造了类似物,从而在细胞毒素开发方面取得了新的发现.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 化学生物学 化学生物学
背景情况:
- 佩德林和psymberin是具有复杂结构的强大的细胞毒素.
- 了解它们的结构-活性关系对于开发新的治疗剂至关重要.
研究的目的:
- 使用简洁的合成路径合成pederin和psymberin.
- 准备和评估类似物,以了解生物活动的结构要求.
- 研究特定功能组和分子构成在细胞毒素疗效中的作用.
主要方法:
- 利用后期的多元组分反应来构建N-氨酸氨基连接.
- 合成了一种pederin和psymberin类型的库,包括一个神灵.
- 评估合成化合物的增长抑制作用.
- 为化合物-核糖体相互作用开发了基于结构的模型.
主要成果:
- 实现了对pederin (10个步骤) 和psymberin (14个步骤) 的简洁合成路径.
- 在合成的类似物中确定了几种新的强效细胞毒素.
- 建立了结构-活动关系,假定了活动的关键构造和结模式.
- 根据初步发现和计算模型准备的第二代类似物.
结论:
- 晚期的多元组分反应对于合成复杂的自然产品和类似物是有效的.
- 这项研究提供了关于pederin和psymberin细胞毒性的分子基础的见解.
- 这项工作强调了合成有机化学在发现和开发新型生物活性分子中的实用性.
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