Synthetic Strategies based on expoxide coupling reactions

描述（由申请人提供）：本提案的统一主题是通过环氧化合物开孔级联合成聚醚。这些方法构成了合成“阶梯”结构类聚醚（类似于brevetoxin和其他“赤潮”毒素）的新策略，并模拟了Nakanishi和Nicolaou提出的环氧化物级联生物发生。在梯形聚醚天然产物和生物医学相关衍生物的合成中证明了这些有效的环氧化合物打开级联的效用。这些方法的发展具有通用性，综合设计具有灵活性。因此，该建议的一个重要组成部分是制备适合于测试的特定化合物。针对的疾病包括囊性纤维化（短暂性和结构性变异），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制对于实现这些目标至关重要，因此正在加紧研究。

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.