总合成的拉莫普拉宁A2和拉莫普拉诺酸甘的总合成
Wanlong Jiang1, Jutta Wanner, Richard J Lee
1Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|May 9, 2002
概括
这项研究详细介绍了拉莫普拉宁A2及其亚格利康的融合总合成. 成功的合成为创造强大的抗微生物类似物提供了途径.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 合成化学 合成化学
背景情况:
- 拉莫普拉宁是一种复杂的糖抗生素.
- 拉莫普拉宁的亚格利康具有显著的抗菌活性.
- 总合成提供了一条通往具有潜在增强性质的新类型的途径.
研究的目的:
- 为了实现拉莫普拉宁A2及其亚格利康的融合总合成.
- 开发关键的合成方法来构建复杂的depsipeptide核心.
- 为了使抗微生物药物发现的新类型的合成.
主要方法:
- 融合合成策略涉及三个关键子单位.
- 不对称的合成L-threo-beta-hydroxyasparagine. 这是一个非常好的方法.
- 优化了化条件,以防止种族化.
- 战略性合和宏循环化,以实现高效的环闭.
主要成果:
- 成功制备和合三个关键和depsipeptide子单元.
- 拉莫普拉诺斯亚格利康的49个成员的depsipeptide核心的构建.
- 对于阻碍酒精化而言,近乎无种族化条件的证明.
- 识别受益于β叶预组织和D-氨基终端的宏环化位点.
结论:
- 开发的合成途径对构建拉莫普拉诺酸甘有效.
- 晚期引入性和侧链有助于模拟合成.
- 合成的亚格利康及其类似物对开发新的抗菌剂具有前景.
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