Total Synthesis of (−)-Ceforalide B and (−)-Cephanolides B–D

Abstract

Metrics & More Article Recommendations * sı Supporting Information ABSTRACT: (−)-Ceforalide B (1) and (−)-cephanolides B−D (2−4) are benzenoid cephanolide diterpenoids possessing the same pentacyclic skeleton, which contains three C 13 −C 15 substituent patterns and different benzylic oxidation states. An olefination/6π-electrocyclization/oxidative aromatization cascade has been verified as divergent access to three C 13 −C 15 patterns. The benzylic aerobic oxidations enabled by the Co(OAc) 2 •4H 2 O/ bromide salt/O 2 /PPh 3 /N-hydroxyphthalimide system have been developed to deliver expected site-selectivity and different oxidation states. Through the divergent strategy, total synthesis of (−)-ceforalide B and (−)-cephanolides B−D is accomplished.

Cephalotane diterpenoids: structural diversity, biological activity, biosynthetic proposal, and chemical synthesis

“…In 2022, Hu and co-workers reported the asymmetric synthesis of (−)-ceforalide B ( 87 ) and (−)-cephanolides B–D ( 90 , 89 , and 85 , respectively) (Scheme 24). 56 The synthesis of (−)-cephanolide B ( 90 ) commenced by subjecting a known compound (−)- 163 (10 steps from 158 , Scheme 13) 55 to nucleophilic addition with alkynyl lithium reagent in situ generated from the Colvin rearrangement of TMSCHN 2 and ( E )-3-ethoxy-2-methylacrolein. IBX oxidation of the resulting propargyl alcohol afforded ketone 277 , which underwent Pauson–Khand reaction to give tetracycle 278 with good stereoselectivity.…”

“…27,28 In addition, due to the complex cage-like framework and remarkable bioactivities of cephalotane diterpenoids, they are regarded as excellent targets for total synthesis. The past 30 years have witnessed a multitude of synthetic efforts toward this diterpenoid class, 29–49 leading to a battery of elegant completed total syntheses by the groups of Mander, 50 Tang, 51 Zhai, 52–54 Hu, 55–57 Gao, 58–60 Zhao, 61 Cai, 62 Zhang/Yang, 63 and Sarpong. 64,65…”