Hyperhelianthemones A-D: Polycyclic polyprenylated benzoylphloroglucinols from Hypericum helianthemoides

Abstract

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.