综合和立体化学确定A和B复合素 (神经保护蛋白A和B)
Steven P Breazzano1, Dale L Boger
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Journal of the American Chemical Society
|October 14, 2011
概括
研究人员通过二氧化II (complestatin) 的新型氧化合成了二氧化A和B (神经保护素). 这项工作建立了立体化学赋值,并为这些复杂的自然产品提供了高效的合成路线.
科学领域:
- 有机化学 有机化学
- 自然产品的合成自然产品的合成
- 药用化学 医学化学
背景情况:
- 烯是一种具有潜在治疗应用的天然产品.
- 之前的工作确定了罗白丁II (complestatin) 的总合成.
- 叶绿素A (神经保护蛋白A) 和叶绿素B (神经保护蛋白B) 的立体化学和合成仍然具有挑战性.
研究的目的:
- 为罗白丁A和罗白丁B开发合成途径.
- 确定罗白A和罗白B的立体化学分配.
- 探索二烯II的新型氧化策略.
主要方法:
- 开发了两种独特的单阶段醇氧化方法 (HCl-DMSO和NBS,THF-H2O) 用于烯A合成.
- 使用两步,单氧化 (NCS,THF-H2O;Cs2CO3,DMF-H2O) 进行甲B合成.
- 对二烯二的合成DEF环系统进行了广泛的研究,以赋予立体化学.
主要成果:
- 实现了第一个合成烯A (神经保护素A) 的优异产量 (93%和82%).
- 通过一种新的两步,单氧化方法,成功合成了烯B (神经保护蛋白B).
- 毫不含糊地分配了这两种天然产品的立体化学.
结论:
- 开发的氧化方法可以有效地获得甲甲和乙.
- 这项研究阐明了这些重要的自然产品的立体化学.
- 合成策略提供了宝贵的见解,对二的反应性.
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