总合成 (+/-) - 平素和 (-) - 平素
K C Nicolaou1, G Scott Tria, David J Edmonds
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. kcn@scripps.edu
Journal of the American Chemical Society
|October 15, 2009
概括
研究人员合成了来自Streptomyces platensis的新型抗生素平素,对MRSA等耐药细菌表现出强大的活性. 合成利用了先进的不对称的迪尔斯-阿尔德反应,以有效制备.
科学领域:
- 自然产品化学 自然产品化学
- 合成有机化学 合成有机化学
- 微生物学 微生物学
背景情况:
- 平胺和平素是来自Streptomyces platensis的新型二次代谢产物.
- 这些天然产品表现出强大的抗菌活性,对抗格拉姆阳性病原体.
- 柏素的向是脂质延长酶FabF和FabH,与柏素的机制不同.
研究的目的:
- 为了实现平坦素的总合成.
- 开发racemic和非对称的合成路径.
- 展示特定合成方法的实用性.
主要方法:
- 催化不对称的迪尔斯-阿尔德反应用于立体化学控制.
- 双循环子的单降低性重组,使其成为双循环烯酸.
- 整体合成平素,包括种族和enantioselective方法.
主要成果:
- 顺利合成了白血在racemic和不对称的形式.
- 已证明对抗抗生素耐药菌株如MRSA,VISA和VRE的有效性.
- 对复杂天然产品制备的合成策略的验证.
结论:
- 完成了平素的总合成,验证了关键的合成转化.
- 青素和青素是新抗菌剂的有希望的来源.
- 合成途径为这些有价值的化合物提供了进一步研究的途径.
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