Xanthrysols A–D, novel meroterpenoids with antiviral activities from Xanthostemon chrysanthus†

Abstract

(+)/(−)-Xanthrysol A (1), an enantiomeric pair of novel macrocyclic meroterpenoids, along with three enantiomeric pairs of biogenetically related meroterpenoids (+)/(−)-xanthrysols B–D (2–4), were isolated and identified from the leaves of Xanthostemon chrysanthus. Structurally, compounds 1–4 are unique phenylpropanoyl–phloroglucinol-based meroterpenoids with three kinds of new carbon skeletons. Notably, xanthrysol A (1) features an unprecedented 6/6/16 fused ring system, incorporating a 2,4,16-trioxatricyclo[12.6.2.0^17,21]docosane core. Their structures with absolute configurations were established by comprehensive spectroscopic analyses, single-crystal X-ray diffraction, and quantum chemical calculations. A plausible biogenetic pathway for 1–4 was proposed. Moreover, xanthrysol A demonstrated potent antiviral activity against respiratory syncytial virus (RSV) and acyclovir-resistant strains of herpes simplex virus type 1 (HSV-1/106, HSV-1/blue and HSV-1/153) with IC₅₀ values ranging from 4.68 to 8.10 μM. Time-of-addition assays showed that compound 1 specifically acts on the early stages of the virus replication process in both RSV and HSV-1.