Asymmetric Divergent Synthesis of ent-Kaurane‑, ent-Atisane‑, ent-Beyerane‑, ent-Trachylobane‑, and ent-Gibberellane-type Diterpenoids

• Published in: Journal of the American Chemical Society Vol. 145; no. 1; pp. 311 - 321
• Main Authors: Zhao, Xian-He, Meng, Le-Le, Liu, Xiao-Tao, Shu, Peng-Fei, Yuan, Cheng, An, Xian-Tao, Jia, Tian-Xi, Yang, Qi-Qiong, Zhen, Xiang, Fan, Chun-An
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 11.01.2023
• Subjects: Diterpenes; Diterpenes, Kaurane
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.2c09985

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 πCC and πCO 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.