Lyngbyabellins K-N from Two Palmyra Atoll Collections of the Marine Cyanobacterium Moorea bouillonii

Abstract

Five lipopeptides of the lyngbyabellin structure class, four cyclic (1-3, and 5) and one linear (4), were isolated from the extracts of two collections of filamentous marine cyanobacteria obtained from Palmyra Atoll in the Central Pacific Ocean. Their planar structures and absolute configurations were elucidated by combined spectroscopic and chromatographic analyses as well as chemical synthesis of fragments. In addition to structural features typical of the lyngbyabellins, such as two thiazole rings and a chlorinated 2-methyloctanoate residue, these new compounds possess several unique aspects. Of note, metabolites 2 and 3 possessed rare mono-chlorination on the 3-acyloxy-2-methyloctanoate residue while lyngbyabellin N (5) had an unusual N,N-dimethylvaline terminus. Lyngbyabellin N also possessed a leucine statine residue, and showed strong cytotoxic activity against HCT116 colon cancer cell line (IC₅₀ = 40.9 ± 3.3 nM).

Keywords: Biological Activity; Natural Products; Peptides; Structure Elucidation.

Figure 1

Structures of lyngbyabellin K-N (1-5) and lyngbabellin H (6).

Figure 2

Approaches to determination of relative configuration of the C-7 stereocenter in the DCAMO residue of lyngbyabellin L (2) and 7-epi-lyngbyabellin L (3): a) homonuclear coupling constant and nOe-based determination of relative configuration b) J-based configuration analysis on lyngbyabellin L (2), and c) deshielding effects to non-equivalent protons from the chlorine atom at C-7 and oxygen atom at C-3 of lyngbyabellin L (2) and 7-epi-lyngbyabellin L (3). [a] The coupling constant is not observed due to overlap. [b] The coupling constant is not detected due to weak signal.

Figure 3

Δδ_S-R values of the di-Mosher esters of lyngbyabellin M (4).