Hyperhelianthemones A-D: Polycyclic polyprenylated benzoylphloroglucinols from Hypericum helianthemoides

Phytochemical investigation of the n-hexane-soluble fraction of the aqueous ethanol extract of the aerial parts of Hypericum helianthemoides (Spach) Boiss. (Hypericaceae), furnished four undescribed polycylic polyprenylated benzoylphloroglucinols (PPBPs) 1-4, together with phytyl formate (5) and thirteen previously reported prenylated phloroglucinol derivatives, including yezo'otogirin C (6), hyperibrins A (7) and F (8), hyperibones G (9), J (10), La (11a)/Lb (11b), 7-epi-clusianone a (12a)/7-epi-clusianone b (12b), and hypermongones A (13), C (14), E (15), G (16), H (17), and sampsonione L (18). The structures of 1-4 were established by extensive 1D and 2D NMR spectral analysis as well as HREI-MS. The absolute configurations of the stereogenic carbons in 1 were established by X-ray crystallographic analysis, while the stereochemistry of 2 was assigned by quantum chemical calculation of its ¹H and ¹³C NMR chemical shift values using DP4⁺ probability analysis. The isolated compounds were assayed for antileishmanial activity on Leishmania tropica and L. major parasites. Compounds 9 and 16 displayed activities against L. tropica, with IC₅₀ values of 17.7 and 31.5 μM, respectively. Moreover, 9 was only active against L. major, with IC₅₀ value of 34.2 μM.