Total synthesis of spiro Ganoderma meroterpenoids spiroapplanatumines B, D, F, and H†

Abstract

The first total synthesis of spiroapplanatumines B (2), D (4), F (6), and H (8) as well as the possibly undiscovered natural product spiroapplanatumine R (10) has been realized in a linear sequence of 15–20 steps. The unusual [6–5–7] tricyclic core including a [5–7] spirocyclic system, found in the title molecules and some other naturally occurring spiro Ganoderma meroterpenoids, was efficiently synthesized through a Claisen rearrangement followed by an RCM reaction. The Pd-catalyzed methoxycarbonylation/regioselective epoxide opening cascade reaction efficiently installed the desired ester moiety at C3′ and produced an allylic hydroxy group at C7′. Further functional group transformations enabled the divergent synthesis of the final products.