Hawanoids A‒E, unprecedented diterpenoids with PAF-induced platelet aggregation inhibitory activities from the deep-sea-derived fungus Paraconiothyrium hawaiiense

Hawanoids A‒E (1‒5), five highly cyclized diterpenoids were isolated from the deep-sea-derived fungus Paraconiothyrium hawaiiense FS482. Compounds 1 and 2 possessed an unprecedented tetracyclo[6.6.2.02,7.011,15]cetane carbon skeleton while 3 and 4 possessed an unusual 11,14-macrocyclic ether moiety in phomactin family. Their structures including the stereo-chemistry were determined through spectroscopic analysis, X-ray diffractions and computational calculations. The plausible biosynthetic pathway was proposed based on the predicted biosynthetic gene cluster. All of the isolated compounds exhibited inhibitory activities against PAF-induced platelet aggregation. The molecular docking study was carried out understand the interaction between the PAF receptor and hawanoids with different skeletons.