Synthetic strategies based on epoxide-coupling reactions

描述（由申请人提供）：该提案的统一主题是通过在水性环境中进行的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二十多年前提出的环氧化物级联生物合成。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。 公共卫生相关性：该提案的统一主题是通过在水性环境中进行的环氧化物开放级联进行聚醚合成。该方法构成了合成“梯形”结构类别的聚醚（类似于短尾藻毒素和其他“赤潮”毒素）的新策略，并将用于制备具有生物医学相关性（包括甘比洛尔和裸藻素B）或具有治疗潜力（包括短尾藻醛）的这种类型的化合物。目标疾病包括囊性纤维化。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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 will be used to prepare compounds of this type that are of biomedical relevance (including gambierol and gymnocin B) or have therapeutic potential (including brevenal). The diseases targeted include cystic fibrosis.