Perlatolic acid

Perlatolic acid is a lichen product with the molecular formula C₂₅H₃₂O₇ (relative molecular mass 444.51). It forms needle-like crystals from methanol–water mixtures and melts at about 107–108 °C. In simple microchemical tests, ethanolic solutions of the acid give a violet colour with ferric chloride, indicating phenolic hydroxyl groups.^[9] In alcoholic solution, perlatolic acid undergoes alcoholysis to give 2,4-dihydroxy-6-n-pentylbenzoic acid together with a series of alkyl 2-hydroxy-4-methoxy-6-n-pentylbenzoates and the phenolic fragment 1,3-dihydroxy-5-n-pentylbenzene (olivetol).^[3] In a study of Cladina macaronesica, the authors cautioned that some simpler phenolics may be artefacts formed by degradation of perlatolic acid during processing, and they experimentally converted perlatolic acid into mono-aryl products by refluxing it with silica gel in benzene, consistent with its "great lability".^[5] Perlatolic acid has a very low first dissociation constant (pKa1 = 2.7; measured in methanol), and its occurrence in several lichen species has been linked to growth on strongly acidic substrata and tolerance of acidic air pollution.^[10]

Its ultraviolet spectrum in methanol shows absorption maxima in the near-ultraviolet region, and infrared spectra display bands consistent with aromatic rings, hydroxyl groups and carboxylic or ester carbonyl functions. Proton and carbon-13 NMR data obtained in deuterated dimethyl sulphoxide and acetone reveal signals from a methoxy group, several aliphatic methylene units and an aromatic system bearing oxygenated substituents. The mass spectrum shows multiple fragment peaks; the base peak is at m/z 164. Perlatolic acid can be converted into the dimethyl ether methyl di-O-methylperlatolate by treatment with methyl iodide and potassium carbonate; this derivative crystallises from methanol as needles melting at about 57 °C and is convenient for further analytical work.^[9]

Under dry heating conditions perlatolic acid decomposes above its melting point. In a comparative study of lichen depsides, heating solid perlatolic acid at about 160 °C for 1 h gave a mixture of olivetol, the bis-olivetol derivative anziol, and the ether 2'-O-methylperlatolol as identifiable products of the pyrolysate. In the same work, measurements of carbon dioxide evolution showed that perlatolic acid decarboxylates more slowly than lecanoric, evernic, planaic and sekikaic acids under comparable conditions, indicating relatively low thermal lability among this series of depsides.^[11]

Perlatolic acid and several simple esters derived from it have been tested for phytotoxic and potential herbicidal effects. In germination and seedling assays using lettuce (Lactuca sativa) and onion (Allium cepa), perlatolic acid itself showed only low inhibition of germination, whereas some of its alkyl 2-hydroxy-4-methoxy-6-n-pentylbenzoate derivatives caused marked reductions in root and shoot growth. In particular, the iso-propyl and sec-butyl esters reduced root and hypocotyl elongation and dry mass in lettuce seedlings, while the n-butyl, n-pentyl and n-hexyl esters delayed germination and inhibited root and coleoptile growth in onion to an extent comparable with commercial herbicides used as positive controls in the same bioassays. The authors proposed these esters as model molecules for the development of natural herbicides targeting dicotyledonous and monocotyledonous weeds.^[3]

In cell-culture screening against human coronaviruses, perlatolic acid showed antiviral activity against HCoV-229E, with micromolar inhibitory concentrations and no detectable toxicity at active doses; time-of-addition experiments indicated that inhibition occurred after virus entry, consistent with an effect on a post-inoculation (replication-associated) step. It was also active against SARS-CoV-2 in vitro, producing a dose-dependent reduction in infection without obvious toxicity.^[12]