Amorfrutin-type phytocannabinoids from Helichrysum umbraculigerum

Helichrysum umbraculigerum Less. has been reported to be a prolific producer of phytocannabinoids from the alkyl-, aralkyl-, normal-, and abnormal types. Investigation of an acetone extract from the aerial parts of the plant afforded two novel amorfrutin-type phytocannabinoids (3b, 4) and the new geranylated phloroglucinol 5a. The presence of cannabigerol (CBG, 1a) and its acidic precursor (pre-CBG, CBGA, 1b), previously reported from this plant, could not be confirmed, but the phenethyl analogue of CBG (Heli-CBG, 2a) and the methyl ester of its carboxylated version (2b) were isolated. Heli-CBG (2a) was assayed against a series of metabotropic (CBI and CB2)- and ionotropic (thermo-TRPs) targets of phytocannabinoids, comparing its profile with the one of cannabigerol (CBG). A decreased affinity for cannabinoid receptor was observed, along with substantial retention of the thermo-TRP profile. The biogenetic relationships between the isoprenylated phenolics from H. urnbraculigerum are discussed, highlighting the relevance of this species for biogenetic investigations on phytocannabinoids