哈利佩普丁A和D和类似物的总合成和生物评估
K C Nicolaou1, Dimitrios E Lizos, David W Kim
1Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA. kcn@scripps.edu
Journal of the American Chemical Society
|March 30, 2006
概括
合成和评估了海洋天然产品 - - 甲和甲. 一些类似物体表现出抗炎性质,但对结肠癌细胞没有毒性.
科学领域:
- 海洋天然产品化学 海洋天然产品化学
- 有机合成 有机合成
- 药品化学 药品化学 是一个
背景情况:
- 甲和甲是具有潜在生物活性的海洋衍生周期性.
- 复杂的天然产品的合成对于药物发现至关重要.
- 了解结构-活动关系需要对类型的合成.
研究的目的:
- 合成海洋衍生哈利佩A和D及其类似物.
- 评估合成化合物的抗炎和细胞毒性质.
- 探索合成策略来构建黄素核心结构.
主要方法:
- 多步骤的有机合成,利用巨乳化和 thiazoline 的形成.
- 从特定的构建块开始合成 (10,13,14a/14d,15,16).
- 生物评估包括抗炎试验和对HCT-116细胞的细胞毒性测试.
主要成果:
- 成功合成了哈利佩A (1a) 和D (1d) 以及类似物3a,3d,4a,4d.
- 采用了两种不同的合成策略,产生了不同的产品分布.
- 化合物1a,1d和氧沙类比物6d表现出抗炎活性.
- 针对人类结肠癌细胞 (HCT-116),没有观察到细胞毒性.
结论:
- 合成途径为生物评估提供了哈利佩和它们的类似物.
- 哈利佩A,D和类似物6d显示出有前途的抗炎作用.
- 合成的化合物代表了抗炎药物开发的潜在线索,具有有利的安全性.
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