Przewalcyrones A–F, epoxychromene-containing polycyclic polyprenylated acylphloroglucinols with immunosuppressive activity from <i>Hypericum przewalskii</i> Maxim.

Abstract

Chemical investigation of the extracts of the aerial parts of Hypericum przewalskii Maxim. resulted in the isolation and identification of six new epoxychromene-containing polycyclic polyprenylated acylphloroglucinols (PPAPs), named przewalcyrones A-F (1-6), and one known analogue (7). All of the structures were determined based on extensive spectroscopic analyses, X-ray crystallographic analysis, modified Mosher's method, [Rh₂(OCOCF₃)₄]-induced ECD, and electronic circular dichroism (ECD) comparison. Structurally, przewalcyrones A-F represent the first examples of PPAPs containing an unexpected 8,8-dimethyl-3,9-epoxychromene moiety. All these compounds were evaluated for the immunosuppressive activity in anti-CD3/anti-CD28 monoclonal antibody (mAb)-stimulated human T cells. Among them, przewalcyrones C and D exhibited potential in vitro immunosuppressive activity, with IC₅₀ values of (5.01 ± 0.52) μM and (5.26 ± 0.56) μM, respectively, highlighting those compounds as a promising starting point for the development of new immunosuppressive agents.