Novel Potent Antimalarial Diterpene Isocyanates, Isothiocyanates, and Isonitriles from the Tropical Marine Sponge Cymbastela hooperi

The isolation and structural elucidation of 15 diterpenes (1−15) which contain isocyanate, isothiocyanate, and isonitrile functionalities are reported from the tropical marine sponge Cymbastela hooperi. Of the 15, 12 (1, 3−9, 11, and 13−15) are new natural products, two of which (4 and 5) contain the rare isocyanate functionality. With the exception of compounds 1 and 15, all of the compounds are based on amphilectane, cycloamphilectane, or modified cycloamphilectane (isocycloamphilectane) ground structures. Compound 1 is an “extended” sesquiterpene, with 15 representing the first of a new class of tricyclic marine-derived diterpenes. All structures were established by spectroscopic methods, particularly 1H−1H and 1H−13C shift correlated 2D NMR spectroscopy and accurate mass measurement (HREIMS). All isolates with the exception of 1 demonstrated significant and selective in vitro antimalarial activity.