Enantioselective Total Synthesis of Terreumols A and C from the Mushroom Tricholoma terreum.

The cytotoxic meroterpenoids terreumol A and C from the grey knight mushroom Tricholoma terreum were synthesized for the first time. The key step of the enantioselective total synthesis of terreumol C is a ring-closing metathesis to form a trisubstituted Z double bond embedded in the 10-membered ring of the [8.4.0] bicycle. Interestingly, the presence of a free hydroxy group in the metathesis precursor prevents cyclization and favors cross metathesis. (-)-Terreumol C was converted into (-)-terreumol A by diastereoselective epoxidation. Starting from 2-bromo-3,5-dimethoxybenzaldehyde, 14 steps with an overall yield of 23 % are needed for the synthesis of (-)-terreumol A. X-ray analysis of the benzoquinone analogue of terreumol A provides independent proof of the absolute configuration.