生物模拟启发了1-O-methyllateriflorone的总合成和结构活性关系. 在有机合成中6 pi电循环
K C Nicolaou1, Pradip K Sasmal, Hao Xu
1Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. kcn@scripps.edu
Journal of the American Chemical Society
|April 29, 2004
概括
研究人员实现了1-O-methyllateriflorone的总合成,发现了一个潜在的生物合成途径. 这项工作还探索了新的复杂的二烯系统,并确定了强大的抗瘤化合物.
科学领域:
- 有机合成 有机合成
- 自然产品化学 自然产品化学
- 药用化学 医学化学
背景情况:
- 拉特里弗洛隆是一种复杂的天然产品,具有独特的形和螺旋拉顿框架.
- 了解其生物合成和开发合成路径对于探索其潜在应用至关重要.
- 关于后期iflorone类型的结构-活性关系 (SAR) 的信息有限.
研究的目的:
- 为了实现1-O-methyllateriflorone的总合成.
- 研究新的合成方法,包括级联反应,用于构建复杂的分子架构.
- 为了建立第一个结构-活性关系 (SAR) 对于针对瘤细胞的后期iflorone类似物.
主要方法:
- 生物模拟克莱森/迪尔斯-阿尔德级联,用于构建类似子的域.
- 内分子迈克尔反应用于生成螺旋拉克框架.
- 开发了一种涉及6pi电循环的级联序列,用于二烯合成.
- 对针对瘤细胞的合成化合物的生物评估.
主要成果:
- 成功完成了1-O-甲基后叶的总合成 (2).
- 合成策略为lateriflorone的潜在生物合成途径提供了洞察力.
- 强效抗瘤化合物的鉴定,包括2,16b,56,58和59,确定初始SAR.
结论:
- 开发的合成途径提供了对后期和相关复杂分子的高效访问.
- 这些发现表明,后的生物合成途径是合理的.
- 已识别的活性化合物代表了进一步抗癌药物开发的有希望的线索.
相关概念视频
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Electrocyclic reactions are reversible reactions. They involve an intramolecular cyclization or ring-opening of a conjugated polyene. Shown below are two examples of electrocyclic reactions. In the first reaction, the formation of the cyclic product is favored. In contrast, in the second reaction, ring-opening is favored due to the high ring strain associated with cyclobutene formation.
01:17Thermal Electrocyclic Reactions: Stereochemistry
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01:26Photochemical Electrocyclic Reactions: Stereochemistry
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Selection Rules: Photochemical Activation
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