Synthesis, Characterization, and Bioactivity of the Lichen Pigments Pulvinamide, Rhizocarpic Acid, and Epanorin and Congeners.

ABSTRACT

The lichen natural products pulvinamide, rhizocarpic acid, and epanorin have been synthesized and characterized spectroscopically and by X-ray crystallography. The syntheses, by ring-opening of pulvinic acid dilactone (PAD), may well be biomimetic, given the well-known occurrence of PAD in lichen. The enantiomers, ent-rhizocarpic acid and ent-epanorin, and corresponding carboxylic acids, norrhizocarpic acid and norepanorin, were similarly prepared. All compounds were assessed for growth inhibitory activity against selected bacteria, fungi, a protist, a mammalian tumor cell line, and normal cells. Rhizocarpic acid is weakly antibacterial (Bacillus subtilis MIC = 50 µg/mL) and possesses modest but selective antitumor activity (NS-1 murine myeloma MIC = 3.1 µg/mL) with >10-fold potency relative to its enantiomer (MIC = 50 µg/mL).