Synthesis of Abyssomicin C and Novel Analogs

Abyssomicin C 和新型类似物的合成

• 批准号: 7068616
• 负责人: JAMES R FUCHS
• 金额: $ 4.6万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-21 至 2007-04-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7068616
• 关键词: Diels Alder reaction; antibiotics; biological products; chemical addition; drug design /synthesis /production; nitrone; p aminobenzoate; postdoctoral investigator

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.

描述（由申请人提供）： 本研究的目的是开发最近分离的抗菌剂 abyssomicin C 的高效、不对称合成方法，该药物是在筛选对氨基苯甲酸酯 (pABA) 生物合成途径抑制剂时发现的。据推测，abyssomicin C 充当分支酸的底物模拟物，并不可逆地与氨基脱氧分支酸合酶结合。这种独特的作用方式表明 abyssomicin C 可能作为一种高度选择性的抗菌剂或抗原生动物剂。所提出的合成以关键的不对称逆电子需求狄尔斯-阿尔德反应为特征，以建立天然产物的核心，并通过分子内硝酮环加成来完成大环。该策略也将用于阿比索米星C类似物的制备，以进一步探索该化合物的独特作用模式并描绘生物活性药效团。