Synthetic Strategies based on expoxide coupling reactions

描述(申请人提供)：本提案的统一主题是通过开环氧基级联合成聚醚。这些方法构成了一种合成“阶梯”结构类聚醚(类似于短杆菌毒素和其他“赤潮”毒素)的新策略，并模仿了Nakanishi和Nicolaou提出的环氧化物级联生物发生。这些高效的环氧化物级联在合成梯形聚醚天然产物和具有生物医学意义的衍生物中得到了应用。这些方法是在考虑一般性的情况下开发的，而合成是为了灵活性而设计的。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(短囊性和结构性变异型)，已经为这些活动建立了必要的合作。开发新的合成方法和研究这些过程中涉及的反应机理对于实现这些目标至关重要，因此正在进行深入的研究。

DESCRIPTION (provided by applicant): 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.