Structures, semisyntheses, and absolute configurations of the antiplasmodial α-substituted β-lactam monamphilectines B and C from the spongeSvenzea flava.
Bioassay-guided fractionation of the Caribbean spongeSvenzea flavacollected 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 (2and3). Attached to the backbone of each of these compounds is the first α-substituted monocyclic β-lactam ring to be isolated from a marine organism. The molecular structures of2and3were established by spectroscopic methods and then confirmed unequivocally by chemical correlation and comparison of physical and chemical data with the natural products. The new β-lactams were successfully synthesized in one step, starting from the known diisocyanide4, via parallel Ugi four-center three-component reactions (U-4C-3CR) that also established their absolute stereostructures. Interestingly, compounds2and3exhibited activities in the low nanomolar range against the human malaria parasitePlasmodium falciparum.
Department of Chemistry, University of Puerto Rico, P.O. Box 23346, U.P.R. Station, San Juan, Puerto Rico 00931-3346.
Edward
E
Avilés
Department of Cell Biology and Neuroscience, University of California at Riverside, California 92521.
Jacques
J
Prudhomme
Department of Cell Biology and Neuroscience, University of California at Riverside, California 92521.
Karine G
KG
Le Roch
Department of Chemistry, University of Puerto Rico, P.O. Box 23346, U.P.R. Station, San Juan, Puerto Rico 00931-3346.
Abimael D
AD
Rodríguez
Drug discovery, Isocyanide; Malaria; Monamphilectines; Svenzea flava; Ugi multicomponent reaction; β-lactams