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

Abstract

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 1 H− 1 H and 1 H− 13 C 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.