甲 D D 的总合成
Akiyuki Hamasaki1, Jeffrey M Zimpleman, Inkyu Hwang
1Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|July 28, 2005
概括
这项研究简要介绍了九个步骤的Nalian D合成方法,实现了19%的总产量. 这种新的方法有效地构建了复杂的分子,并探索了它在逆转多药耐药性的潜力.
科学领域:
- 有机合成 有机合成
- 药用化学 医学化学
- 化学生物学 化学生物学
背景情况:
- 宁林D是一种复杂的天然产品,具有已证明的细胞毒性和多药耐药性 (MDR) 逆转活动.
- 有效的合成路径对于进一步的生物评估和模拟开发至关重要.
研究的目的:
- 披露一个简洁而有效的全合成 ningalin D.
- 为了研究看兰D,其衍生物和合成中间体的细胞毒性和MDR逆转活动.
主要方法:
- 一个由9个步骤组成的总合成,采用了1,2,4,5-四氨酸 --> 1,2-二氨酸 --> 醇迪尔斯-阿尔德策略.
- 关键反应包括双迪克曼凝结,苏苏基合,以及由库尔蒂斯重排序启动的氧化脱碳化级联.
主要成果:
- 实现了19%的总产量,用于全合成的目光D.
- 成功组装了完全替代的pyrrole核心,并引入了硬质要求高的aryl环.
- 证明了合成化合物的细胞毒性和MDR逆转活性.
结论:
- 开发的合成策略是高效的,并提供了对目安D及其类型的访问.
- 生物评估为细胞毒性和MDR逆转效应的结构-活性关系提供了洞察力.
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