Synthetic strategies based on epoxide-coupling reactions

项目摘要 这项提议的统一主题是通过环氧化物开级联合成聚醚 在水环境中进行。这些方法构成了一种新的战略 “梯形”结构的聚醚的合成(类似于短杆菌毒素等 赤潮毒素)，仿照中西提出的环氧化物级联生物发生 二十多年前。这些高效的环氧化合物开启级联的效用是 在梯形聚醚天然产物及其衍生物的合成中得到证实 生物医学相关性。这些方法是在考虑一般性的情况下开发的， 合成是为灵活性而设计的。因此，这项提案的一个重要组成部分是 制备适合测试的特定化合物。有针对性的疾病 包括囊性纤维化(短型和结构性变异型)，以及必要的 已经为这些活动建立了协作。

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.