Synthetic strategies based on epoxide-coupling reactions

基于环氧化物偶联反应的合成策略

• 批准号: 7579688
• 负责人: Timothy F Jamison
• 金额: $ 31.69万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-17 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7579688
• 关键词: Acids; Affect; Biogenesis; Biological Factors; Brevenal; Classification; Collaborations; Cystic Fibrosis; Development; Disease; Environment; Epoxy Compounds; Goals; Gymnodinium breve toxin; Heating; Knowledge; Methanol; Methods; Mind; Pattern; Preparation; Reaction; Structure; System; Testing; Therapeutic; Variant; Water; aqueous; base; brevetoxin; design; flexibility; functional group; gambierol; improved; method development; methyl group; novel; public health relevance; research study

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.

描述（由申请人提供）：统一主题该提案是通过在水性环境中进行的环氧式级联反应的聚醚合成。该方法构成了一种新的策略，用于合成“梯子”结构类别（类似于Brevetoxin和其他“红潮”毒素），并效仿二十多年前Nakanishi提出的环氧氧化级联生物发生。这些有效的环氧开放级联反应的效用在梯子多醚天然产物和生物医学相关性的衍生物的合成中得到了证明。这些方法的开发为一般性，并为灵活性而设计。因此，该提案的重要组成部分是制备适合测试的特定化合物。针对性的疾病包括囊性纤维化（头脑和结构变体），并且已经建立了这些活动的必要协作。 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的级联反应的聚醚合成。该方法构成了一种合成“梯子”结构类别（类似于Brevetoxin和其他“红潮”毒素）的新策略，并将用于制备这种类型的化合物，这些化合物具有生物医学相关性（包括Gambierol和Gymnocin b）或裸露的潜在潜力（包括Brevenal）。靶向的疾病包括囊性纤维化。