School of Chemistry, University of Glasgow, Joseph Black Building, University Avenue, Glasgow G12 8QQ, U.K.
J Org Chem. 2022 Jun 17;87(12):8126-8141. doi: 10.1021/acs.joc.2c00850. Epub 2022 Jun 8.
The complete carbon framework of the macrocyclic marine natural product amphidinolide F has been prepared by a convergent synthetic route in which three fragments of similar size and complexity have been coupled. Key features of the syntheses of the fragments include the stereoselective construction of the tetrahydrofuran in the C1-C9 fragment by oxonium ylide (free or metal-bound) formation and rearrangement triggered by the direct generation of a rhodium carbenoid from 1-sulfonyl-1,2,3-triazole, the highly diastereoselective aldol reaction between a boron enolate and an aldehyde with 1,4-control to prepare the C10-C17 fragment, and the formation of the tetrahydrofuran in the C18-C29 fragment by intramolecular nucleophilic ring opening of an epoxide with a hydroxyl group under acidic conditions.
大环海洋天然产物 Amphidinolide F 的完整碳骨架已通过一种收敛性合成途径来制备，其中三个相似大小和复杂性的片段已被连接。片段合成的关键特征包括通过氧鎓叶立德（游离或金属结合）形成和直接从 1-磺酰基-1,2,3-三唑生成铑卡宾引发的 C1-C9 片段中环戊烷的立体选择性构建，硼烯醇盐和醛之间的高度非对映选择性羟醛反应，具有 1,4-控制以制备 C10-C17 片段，以及在酸性条件下通过具有羟基的环氧化物的分子内亲核开环形成 C18-C29 片段中环戊烷。
