Haliclomeroterpenes A–D: Four Meroterpenes with Unprecedented Skeletons from the Marine Sponge <i>Haliclona</i> sp

Four novel meroterpenes, haliclomeroterpenes A-D (<b>1-</b><b>4</b>), were isolated from the marine sponge <i>Haliclona</i> sp. Their structures with absolute configurations were elucidated by spectroscopic methods, quantum chemical calculations, and X-ray diffraction. Compounds <b>1</b> and <b>2</b> are meroterpenes bearing a bicyclo[4.4.0]-1-decene coupled tetrahydrofuro[3,4-<i>b</i>]furanone with a C-4-spiro-fused 6/6/5/5 tetracyclic skeleton. Compound <b>3</b> is a meroterpene possessing a bicyclo[4.4.0]-1-decene coupled furanone with a C-4-spiro-fused 6/6/5 tricyclic skeleton. Compound <b>4</b> represents the unusual skeleton of furanone[3,2-<i>b</i>]bicyclo[4.4.0]-1-decene. The plausible biogenetic pathways of <b>1-4</b> were also proposed. The formation of all four of these compounds was proposed to arise from the condensation of cadinene sesquiterpene and 2,4-dimethyl-3-oxopentanoic acid or propionic acid, respectively. Notably, compounds <b>1</b> and <b>2</b> showed moderate inhibitory activities against the K562 cell line with IC₅₀ values of 17.23 and 27.91 μM, respectively. In addition, compound <b>2</b> showed weak anti-NO activities with IC₅₀ values of 40.22 μM.