Synthetic strategies based on epoxide-coupling reactions

项目摘要 该建议的统一主题是通过环氧化物开环级联进行聚醚合成 在水性环境中进行。这些方法构成了一种新的战略， “梯形”结构类别的聚醚的合成（类似于短杆菌毒素和其它 “赤潮”毒素），并模仿Nakanishi提出的环氧化物级联生物发生 在二十多年前。这些有效的环氧化物打开级联的效用是 在梯形聚醚天然产物和衍生物的合成中证明了 生物医学相关性。这些方法是在考虑到一般性的情况下开发的， 合成物是为灵活性而设计的。因此，这项建议的一个重要组成部分是 制备适合测试的特定化合物。针对的疾病 包括囊性纤维化（短静脉和结构变异），以及必要的 已经为这些活动建立了协作关系。

Project Summary The unifying theme this proposal is polyether synthesis via epoxide-opening cascades conducted in aqueous environments. The methods constitute a new strategy for the synthesis of polyethers of the "ladder" structural class (similar to brevetoxin and other "Red Tide" toxins) and emulate the epoxide cascade biogenesis proposed by Nakanishi more than two decades ago. The utility of these efficient epoxide-opening cascades is demonstrated in the syntheses of ladder polyether natural products and derivatives of biomedical relevance. The methods are developed with generality in mind and the syntheses are designed for flexibility. Thus, an important component of this proposal is the preparation of specific compounds suitable for testing. The diseases targeted include cystic fibrosis (brevenal and structural variants), and the necessary collaborations for these activities have already been established.