Synthesis of (±)-6-O-methyl and 7-demethylannulatomarin

Abstract

Synthesis of 6-O-methyl and 7-demethyl derivatives of annulatomarin (1) (6,8-dihydroxy-7-methoxy-3-phenyl-3,4-dihydroisocoumarin) isolated from the aerial parts of Hypericum annulatum is described. The key step involves an efficient, microwave-accelerated solvent and catalyst-free condensation of methyl benzoate with 3,4,5-trimethoxyhomophthalic acid (2) to afford 6,7,8-trimethoxy-3-phenylisocoumarin (3). Saponification of the latter to keto acid (4) followed reduction to furnish 6,7,8-trimethoxy-3-phenyl-3,4-dihydroisocoumarin (5), which was either regioselectively demethylated to ( ± )-6-O-methylannulatomarin (6) or completely demethylated to ( ± )-7-demethylannulatomarin (7).

Keywords:

• annulatomarin
• microwave-accelerated
• dihydroisocoumarin
• synthesis