Mizukami Daichi, Iio Kei, Oda Mami, Onodera Yu, Fuwa Haruhiko
Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo, 112-8551, Japan.
Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, 981-8577, Japan.
Angew Chem Int Ed Engl. 2022 May 23;61(22):e202202549. doi: 10.1002/anie.202202549. Epub 2022 Mar 16.
Tetrahydropyran-containing macrolactones were synthesized by integrating Meyer-Schuster rearrangement, macrocyclic ring-closing metathesis, and transannular oxa-Michael addition under gold and ruthenium catalysis. Single-step access to a variety of 14- to 20-membered macrolactones containing a tetrahydropyran ring was possible from readily available linear precursors in good yields and with moderate to excellent diastereoselectivity. A 13-step synthesis of (-)-exiguolide, an anticancer marine macrolide, showcased the feasibility of our tandem reaction sequence for macrolactone synthesis and also demonstrated the power of transannular reactions for rapid assembly of the tetrahydropyran rings of the target natural product.
通过在金和钌催化下整合迈耶-舒斯特重排、大环闭环复分解反应和跨环氧杂迈克尔加成反应，合成了含四氢吡喃的大环内酯。从容易获得的线性前体出发，能够以良好的产率和中等至优异的非对映选择性一步合成多种含四氢吡喃环的14至20元大环内酯。抗癌海洋大环内酯（-）-exiguolide的13步合成展示了我们用于大环内酯合成的串联反应序列的可行性，也证明了跨环反应在快速组装目标天然产物的四氢吡喃环方面的作用。
