Asymmetric Synthesis of the Antiviral Diterpene Wickerol A

Wickerol A (1) is an
unusual diterpene with remarkable
activity against the H1N1 influenza virus. Its tetracyclic skeleton
contains three quaternary carbons and is marked by several syn-pentane interactions which force a six-membered ring
into a twist-boat conformation. We present an asymmetric synthesis
of wickerol A (1) that is based on a Jung Diels–Alder
reaction, an intramolecular alkylation to complete the 6–5–6–6
ring system, and a conjugate addition, all of which overcome considerable
steric strain. During the synthesis, we isolated an unexpected cyclopropane
that presumably stems from a carbonium ion intermediate.