The Total Synthesis of Spiroxin A

螺环素A的全合成

• 批准号: 6630430
• 负责人: STEPHEN M LYNCH
• 金额: $ 4.11万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6630430
• 关键词: antineoplastic antibiotics; biological products; carbopolycyclic compound; chemical addition; cyclization; drug design /synthesis /production; iodine; ketal; postdoctoral investigator; stereochemistry

DESCRIPTION (provided by applicant): This proposal describes a total synthesis of the marine fungal metabolite spiroxin A. In spite of a wide array of promising biological activity, which includes antibiotic and antitumor properties, no syntheses of spiroxins, either partial or total, have been reported. The construction of spiroxin A relies upon two key hypervalent iodine mediated ring closures to form the hexacyclic core structure. Iodine (III) will be used to induce both an oxidative spiroketalization and an intramolecular phenolic oxidative biaryl coupling. The possibility of achieving diasteroselectivity in the latter process and relaying that to an asymmetric synthesis of spiroxin a will also be explored. In addition, methodology for the synthesis of functionalized 1,4,5,8-tetrahydroxynaphthalenes via a sterically controlled, regioselective benzyne-furan cycloaddition will be developed to access intermediates necessary for the key coupling reaction. The proposed route to spiroxin A is concise and should allow for further biological screening and the elucidation of the SAR of this intriguing natural product.

描述（由申请人提供）：该提案描述了海洋真菌代谢物螺旋素 A 的全合成。尽管螺旋素具有广泛的有前景的生物活性，包括抗生素和抗肿瘤特性，但螺旋素的合成，无论是部分还是全部，都没有得到证实。被举报。螺环素 A 的构建依赖于两个关键的高价碘介导的闭环来形成六环核心结构。 碘 (III) 将用于诱导氧化螺缩酮化和分子内酚氧化联芳基偶联。还将探讨在后一个过程中实现非对映选择性并将其转变成螺环素a的不对称合成的可能性。此外，还将开发通过空间控制的区域选择性苯甲醇-呋喃环加成合成官能化1,4,5,8-四羟基萘的方法，以获得关键偶联反应所需的中间体。拟定的螺环素 A 路线非常简洁，应该能够进行进一步的生物筛选并阐明这种有趣的天然产物的 SAR。