Synthetic strategies based on epoxide-coupling reactions

描述(由申请人提供)：本提案的统一主题是通过在水环境中进行的环氧级联反应合成聚醚。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，并模仿了中西二十多年前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。 与公共健康相关：该提案的统一主题是通过在水环境中进行的环氧化物开级联反应合成聚醚。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)的新战略，并将用于制备具有生物医学意义的这类化合物(包括冈比亚红素和裸子菌素B)或具有治疗潜力的化合物(包括短链藻毒素)。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.