Synthesis of Abyssomicin C and Novel Analogs

Abyssomicin C 和新型类似物的合成

• 批准号: 6936278
• 负责人: JAMES R FUCHS
• 金额: $ 4.21万
• 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/6936278
• 关键词: Diels Alder reaction; antibiotics; biological products; chemical addition; drug design /synthesis /production; nitrone; p aminobenzoate; postdoctoral investigator; 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）： 这项研究的目的是开发最近分离的抗微生物剂深渊C的有效，不对称的合成，该抗菌剂核酸蛋白C在筛选旁氨基苯甲酸酯（PABA）生物合成途径时被鉴定出来。据推测，深渊C充当模仿绒毛层的底物，并与氨基氧化酶合成酶的酶无可逆地结合。这种独特的作用方式表明，深渊C可以充当高度选择性的抗菌或抗植物剂。该提出的合成具有关键的不对称逆电子需求DIELS-ALDER反应，以建立天然产物的核心和分子内硝基环载量以完成大环环。该策略还将用于制备深渊C类似物，以进一步探索该化合物的独特作用方式并描述生物活性的药效团。