Concise total synthesis of the cage-like sesquiterpenoid (+)-daphnepapytone A

Abstract

We report a non-biomimetic total synthesis of (+)-daphnepapytone A, an unprecedented member of the guaiane-derived sesquiterpenoids that displays moderate inhibitory activity against α-glycosidase (IC₅₀ = 159 ± 2.1 μM) and possesses a highly strained bridging cyclobutane motif. Our de novo approach provided expedient access to the tetracyclic core of (+)-daphnepapytone A through an intramolecular allenyl thermal [2 + 2] cycloaddition and a Pauson–Khand reaction with a labile cyclobutane. Finally, a late-stage oxidation/reduction sequence delivered (+)-daphnepapytone A with striking chemoselectivity and excellent diastereoselectivity.