Isolation and structure elucidation of five new cytotoxic chlorinated lipopetides from Moorea bouillonii

Marine cyanobacteria have been widely studied and proven to be prolific sources of structurally intriguing natural products possessing interesting pharmacological activities. A subset of these natural products are highly halogenated, such as the crossbyanols, lyngbyabellins, dysidenins, jamaicamide A and taveuniamide, and represent both structural diversity and a broad range of biological activity. A recent investigation into two collections of Moorea bouillonii from Palmyra Atoll yielded five new lipopetides, all exhibiting isotopic patterns consistent with the presence of mono- or di- chlorination, similar to the lyngbyabellin family of compounds. The planar structures and absolute configurations were elucidated by the combination of various techniques in spectroscopy, chromatography and semi-synthesis. These new metabolites possess not only the characteristic structural features of known lyngbyabellins such as two thiazole rings and a 2-methylocatanoate residue with halogenations and acylations, but they also possess unique structural features such as mono-chlorination on the 3-acyloxy-2-methyloctanoate residue and a terminal N,N-dimethylvaline residue, that have never been observed in this structure class before. Lyngbyabellin N, possessing N,N-dimehthylvaline and leucine statine, showed moderate anti-cancer activity against H460 human lung cancer cells with the IC₅₀ of 3.3µM.