Betkekar Vipul V, Suzuki Keisuke, Ohmori Ken
Department of Chemistry, Tokyo Institute of Technology, 2-12-1, O-okayama, Meguro-ku, Tokyo, 152-8551, Japan.
Angew Chem Int Ed Engl. 2022 Jul 11;61(28):e202205106. doi: 10.1002/anie.202205106. Epub 2022 May 20.
The first total synthesis of parameritannin A2 (1), a branched epicatechin (EC) tetramer is reported. The "phloroglucinol trick" was used to circumvent two synthetic issues encountered when assembling four EC units, namely, the steric constraint and the formation of the C4-C6 interflavan linkage. As a substructure of the middle EC unit, phloroglucinol enabled the single-step assembly of two EC units (top and side) through A-type linkages. The middle EC unit was constructed by conducting a newly developed three-carbon flavan annulation via a Pummerer/Friedel-Crafts cascade reaction to furnish a trimeric intermediate bearing a thio-leaving group at C4 position, which allowed the final installation of the bottom EC unit.
据报道，首次全合成了支链表儿茶素（EC）四聚体parameritannin A2（1）。“间苯三酚技巧”被用于规避组装四个EC单元时遇到的两个合成问题，即空间限制和C4-C6 黄酮间键的形成。作为中间EC单元的一个子结构，间苯三酚能够通过A型键一步组装两个EC单元（顶部和侧面）。通过普默勒尔/傅克串联反应进行新开发的三碳黄酮环化反应，构建中间EC单元，以提供在C4位置带有硫离去基团的三聚体中间体，这使得底部EC单元能够最终安装。
