Divergent Synthetic Approach to Grayanane Diterpenoids
An Zhu, Yumeng Lyu, Qi‐Dong Xia, Yufei Wu, Dongmin Tang, Chi He, Guijuan Zheng, Yuanyuan Feng, Yong Wang, Guangmin Yao, Hanfeng Ding
Abstract
The total syntheses of nine grayanane diterpenoids, namely, GTX-II ( 1 ), GTX-III ( 2 ), rhodojaponin III ( 3 ), GTX-XV ( 4 ), principinol D ( 5 ), iso-GTX-II ( 6 ), 1,5-seco-GTX-Δ 1,10 -ene (7), and leucothols B ( 8 ) and D ( 9 ), that belong to five distinct subtypes, were disclosed in a divergent manner. Among them, six members were accomplished for the first time. The concise synthetic approach features three key transformations: (1) an oxidative dearomatization-induced [5 + 2] cycloaddition/pinacol rearrangement cascade to assemble the bicyclo[3.2.1]octane carbon framework (CD rings); (2) a photosantonin rearrangement to build up the 5/7 bicycle (AB rings) of 1- epi -grayanoids; and (3) a Grob fragmentation/carbonyl–ene process to access four additional subtypes of grayanane skeletons. Density functional theory calculations were performed to elucidate the mechanistic origins of the crucial divergent transformation, which combined with late-stage synthetic findings provided insights into the biosynthetic relationships between these diverse skeletons.