Synthetic Strategies based on expoxide 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。 这些方法构成了合成“梯形”聚醚的新策略 结构类(类似于短杆菌毒素和其他“赤潮”毒素)并模拟 Nakanishi和Nicolaou提出的环氧化物级联生物发生。这些工具的效用 在梯形聚醚的合成中展示了高效的环氧级联 与生物医学相关的天然产品和衍生产品。发展了这些方法。 考虑到一般性，合成是为灵活性而设计的。因此，一个 这一建议的重要组成部分是制备适合的特定化合物 以供测试。目标疾病包括囊性纤维化(短暂性和结构性)。 变体)，并且这些活动所需的合作已经 已经成立了。新的合成方法的发展和对苯二酚的研究 这些过程中涉及的反应机制对于实现 这些目标因此正在接受严密的调查。

Project Summary The unifying theme this proposal is polyether synthesis via epoxide-opening cascades. 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 and Nicolaou. 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. The development of new methods of synthesis and the study of the reaction mechanisms involved in these processes are critical for the achievement of these goals and thus are under intense investigation.