Total Synthesis of (+)-Elisapterosin F

Keywords

(+)-elisapterosin F - elisapterane diterpenoid - oxidative dearomatization-induced (5+2) cycloaddition - pinacol coupling - Grob fragmentation - Ley–Griffith oxidation - Mukaiyama aldol addition - Mukaiyama hydration

Significance

Xia, Ding and co-workers report rapid access to elisapterane and related diterpenoids through a divergent total synthesis approach. ( + )-Elisapterosin F features a highly oxygenated pentacyclic scaffold bearing a hemiketal endoperoxide. The authors accessed the natural product in 17 steps and revised the initial structural assignment. ( + )-Elisapterosin F has been isolated from the gorgonian octocoral Pseudopterogorgia elisabethae and shows minor activity against the malaria parasite plasmodium falciparum W2.

Comment

Alcohol B undergoes oxidative dearomatization, followed by intramolecular (5 + 2) cycloaddition, 1,2-acyl migration and subsequent epoxidation to form diketone C. From there, the authors perform a SmI₂-mediated pinacol coupling and subsequent Grob fragmentation to furnish diol D. Conjugate addition to enone E, α-acylation and methylation of the established 1,3-diketone motif affords triketone F. Afterwards, intramolecular Mukaiyama aldol addition followed by Mukaiyama hydration and alcohol elimination yields tetracycle G. Enone dihydroxylation, alcohol elimination and hydroperoxidation completes the total synthesis of ( + )-elisapterosin F.