Phloroglucinol Derivatives with Unusual Skeletons from Cleistocalyx operculatus and Their in Vitro Antiviral Activity

Four novel phloroglucinol derivatives (1–4) featuring a 2,4-dimethyl-cinnamyl-phloroglucinol moiety, along with their putative biosynthetic precursors 5 and 6, were isolated from the leaves of Cleistocalyx operculatus. Compounds 1 and 2 are two pairs of new enantiomeric phloroglucinol dimers possessing an unprecedented polycyclic skeleton with a highly functionalized dihydropyrano[3,2-d]xanthene tetracyclic core. Compounds 3 and 4 are two new phloroglucinol-terpene adducts (PTAs) with a novel carbon skeleton. The structures of 1–4 including their absolute configurations were unambiguously accomplished by combination of extensive spectroscopic analyses, X-ray crystallography, and quantum chemical ECD calculations. A hypothetical biosynthetic pathway for 1–4 was also proposed. Compound 1 exhibited a promising in vitro antiherpes simplex virus type-1 (HSV-1) effect.