Luquilloamides, Cytotoxic Lipopeptides from a Puerto Rican Collection of the Filamentous Marine Cyanobacterium sp.

Luquilloamides A-G (-) were isolated from a small environmental collection of a marine cyanobacterium found growing on eelgrass ( sp.) near Luquillo, Puerto Rico. Structure elucidation of the luquilloamides was accomplished via detailed NMR and MS analyses, and absolute configurations were determined using a combination of advanced Mosher's method, -based configuration analysis, semisynthetic fragment analysis derived from ozonolysis, methylation, Baeyer-Villiger oxidation, Mosher's esterification, specific rotations, and ECD data. Except for , the luquilloamides share a characteristic -butyl-containing polyketide fragment, β-alanine, and a proposed highly modified polyketide extension. While compound is a linear lipopeptide with two α-methyl branches and a vinyl chloride functionality in the polyketide portion, compounds , , and possess a cyclohexanone structure with methylation on the α- or β-positions of the polyketide as well as an acetyl group. Interestingly, the absolute configuration at C-5 and C-6 on the cyclohexanone unit in is opposite to that of -. Compound was revealed to have a -butyl-containing polyketide, β-alanine, and a PKS/NRPS-derived γ-isopropyl pyrrolinone. Compound may be a hydrolysis product of . Of the seven new compounds, showed the most potent cytotoxicity to human H-460 lung cancer cells.