Synthesis of Abyssomicin C and Novel Analogs

描述(由申请人提供)： 本研究的目的是开发一种高效、不对称合成新近分离的抗菌剂abysSomicin C的方法，该化合物是在筛选对氨基苯甲酸(PABA)生物合成途径的抑制剂时被鉴定出来的。推测abysSomicin C作为模拟分支酸的底物，不可逆地与氨基脱氧分叶酸合成酶结合。这种独特的作用方式表明，海索米星C可能是一种高度选择性的抗菌或抗原虫药物。建议的合成具有关键的不对称反电子需求Diels-Alder反应来建立天然产物的核心，以及分子内的硝酮环加成来完成大环环。这一策略也将被用于制备阿司索米星C类似物，以进一步探索该化合物的独特作用模式，并描绘具有生物活性的药效团。

DESCRIPTION (provided by applicant): The purpose of this research is the development of an efficient, asymmetric synthesis of the recently isolated antimicrobial agent abyssomicin C which was identified while screening for inhibitors of the paraaminobenzoate (pABA) biosynthetic pathway. It is postulated that abyssomicin C acts as a substrate mimic of chorismate and binds irreversibly to the enzyme aminodeoxychorismate synthase. This unique mode of action suggests that abyssomicin C may act as a highly selective antibacterial or antiprotozoic agent. The proposed synthesis features a key asymmetric inverse electron demand Diels-Alder reaction to establish the core of the natural product and an intramolecular nitrone cycloaddition to complete the macrocyclic ring. This strategy will also be employed for the preparation of abyssomicin C analogs in order to further explore the unique mode of action of this compound and delineate the biologically active pharmacophore.