Recent total syntheses of fusicoccanes

Abstract

Fusicoccane diterpenoids, originating from fungi, plants, and bacteria, constitute a diverse natural product family featuring a 5-8-5 tricyclic framework. They were restricted to plant physiology in the past. However, fusicoccanes are presently at the forefront of biomedicine and are indispensable for probing 14-3-3 protein-protein interactions (PPIs). The need for material supply and scaffold diversification encouraged their study by the synthetic community. This review highlights the total synthetic works on fusicoccane diterpenoids published in the last 5 years. Key transformations including ring-closing metathesis, metal-catalyzed cross-coupling, and carbocyclization markedly enhanced synthetic efficiency and versatility. Recently identified biosynthetic transformations inspired innovative chemoenzymatic strategies. Investigation into the functional aspects of fusicoccanes should be the future direction to realize their therapeutic potential as general 14-3-3 PPI modulators.