Synthetic Strategies based on expoxide coupling reactions

描述（由申请人提供）：该提案的统一主题是通过环氧化物开环级联进行聚醚合成。该方法构成了一种新的策略，用于合成聚醚的“阶梯”结构类（类似于短尾藻毒素和其他“赤潮”毒素），并模仿Nakanishi和Nicolaou提出的环氧化物级联生物发生。这些有效的环氧化物开放级联的效用证明在梯形聚醚天然产物和生物医学相关的衍生物的合成。开发的方法具有一般性，合成的灵活性。因此，该提案的一个重要组成部分是制备适合测试的特定化合物。所针对的疾病包括囊性纤维化（短静脉和结构变异），并且已经建立了这些活动的必要合作。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.