Structures, semisyntheses, and absolute configurations of the antiplasmodial ?-substituted ?-lactam monamphilectines B and C from the sponge Svenzea flava.

ABSTRACT: Bioassay-guided fractionation of the Caribbean sponge Svenzea flava collected near Mona Island, off the west coast of Puerto Rico, led to the isolation of two isocyanide amphilectane-type diterpenes named monamphilectines B and C (2 and 3). Attached to the backbone of each of these compounds is the first ?-substituted monocyclic ?-lactam ring to be isolated from a marine organism. The molecular structures of 2 and 3 were established by spectroscopic methods and then confirmed unequivocally by chemical correlation and comparison of physical and chemical data with the natural products. The new ?-lactams were successfully synthesized in one step, starting from the known diisocyanide 4, via parallel Ugi four-center three-component reactions (U-4C-3CR) that also established their absolute stereostructures. Interestingly, compounds 2 and 3 exhibited activities in the low nanomolar range against the human malaria parasite Plasmodium falciparum.

SUBMITTER: Aviles E 

PROVIDER: S-EPMC4610402 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature