posted on 2022-12-20, 21:31authored byXian-He Zhao, Le-Le Meng, Xiao-Tao Liu, Peng-Fei Shu, Cheng Yuan, Xian-Tao An, Tian-Xi Jia, Qi-Qiong Yang, Xiang Zhen, Chun-An Fan
A unified
strategy toward asymmetric divergent syntheses of nine
C8-ethano-bridged diterpenoids A1–A9 (candol A,
powerol, sicanadiol, epi-candol A, atisirene, ent-atisan-16α-ol, 4-decarboxy-4-methyl-GA12, trachinol, and ent-beyerane) has been developed
based on late-stage transformations of common synthons having ent-kaurane and ent-trachylobane cores.
The expeditious assembly of crucial advanced ent-kaurane-
and ent-trachylobane-type building blocks is strategically
explored through a regioselective and diastereoselective Fe-mediated
hydrogen atom transfer (HAT) 6-exo-trig cyclization
of the alkene/enone and 3-exo-trig cyclization of
the alkene/ketone, showing the multi-reactivity of densely functionalized
polycyclic substrates with πCC and πCO systems in HAT-initiated reactions. Following the
rapid construction of five major structural skeletons (ent-kaurane-, ent-atisane-, ent-beyerane-, ent-trachylobane-, and ent-gibberellane-type),
nine C8-ethano-bridged diterpenoids A1–A9 could
be accessed in the longest linear 8 to 11 steps starting from readily
available chiral γ-cyclogeraniol 1 and known chiral
γ-substituted cyclohexenone 2, in which enantioselective
total syntheses of candol A (A1, 8 steps), powerol (A2, 9 steps), sicanadiol (A3, 10 steps), epi-candol A (A4, 8 steps), ent-atisan-16α-ol (A6, 11 steps), and trachinol (A8, 10 steps) are achieved for the first time.