Lu Heyuan, Handore Kishor L, Wood Tabitha E, Shimokura Grace K, Schimmer Aaron D, Batey Robert A
Davenport Research Laboratories, Dept. of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON M5S 3H6, Canada.
Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, ON M5G 1L7, Canada.
Org Lett. 2023 Oct 20;25(41):7502-7506. doi: 10.1021/acs.orglett.3c02761. Epub 2023 Oct 6.
The first total synthesis of the E1 ubiquitin-activating enzyme inhibitor, himeic acid A, is reported. A McCombie reaction was used to form the core γ-pyrone via a 6π-electrocyclization. A dioxenone ring-opening/acyl ketene trapping reaction with a primary amide provided the unusual unsymmetrical imide functionality. Other key steps include the use of an Evans auxiliary alkylation (d.r. ≥ 95:5) to install the ()-2-methyl succinic acid fragment and a cross-metathesis to install the unsaturated side-chain.
报道了E1泛素激活酶抑制剂姬松茸酸A的首次全合成。采用McCombie反应通过6π电环化形成核心γ-吡喃酮。与伯酰胺的二氧杂环戊烯开环/酰基烯酮捕获反应提供了不寻常的不对称酰亚胺官能团。其他关键步骤包括使用Evans辅助烷基化（非对映体比例≥95:5）引入()-2-甲基琥珀酸片段以及交叉复分解反应引入不饱和侧链。
