Discovery of new polycyclic polyprenylated acylphloroglucinols with diverse architectures as potent cyclooxygenase-2 inhibitors

Cyclooxygenase-2 (COX-2) is a significant therapeutic target of chronic inflammatory diseases. Soniiglucinols A-D (1-4), four new polycyclic polyprenylated acylphloroglucinols (PPAPs) with diverse architectures, were isolated from Hypericum wilsonii. Structurally, 1 and 2 represent the first examples of PPAPs that are uniquely defined by the presence of a fascinating tricyclo-[7.3.1.0(3,7)]tridecane core bearing an unusual 5/7/6 carbon skeleton. Compounds 3 and 4 were the first PPAPs sharing intriguing tricyclo-[7.3.1.0(2,7)]tridecane and tricyclo-[6.3.1.0(2,6)]dodecane moieties, respectively. More significantly, 1 and 2 were the first reported PPAPs functioning as potent cyclooxygenase-2 (COX-2) inhibitors with efficient anti-inflammatory activities, which provided a basis to design novel COX-2 inhibitors based on the new tricyclo-[7.3.1.0(3,7)]tridecane fragment.