A new polyether ladder compound produced by the dinoflagellate Karenia brevis

Abstract

A new ladder-frame polyether compound containing five fused ether rings was isolated from laboratory cultures of the marine dinoflagellate Karenia brevis. This compound, named brevenal, and its dimethyl acetal derivative both competitively displace brevetoxin from its binding site in rat brain synaptosomes. Significantly, these compounds are also nontoxic to fish and antagonize the toxic effects of brevetoxins in fish. The structure and biological activity of brevenal, as well as the dimethyl acetal derivative, are described in this paper.

Figure 1

Structure of the nine known brevetoxins.

Figure 2

Hemibrevetoxin-B.

Figure 3

Structure of (a) brevenal and (b) brevenal acetal.

Figure 4

Structure of brevenal determined from NMR data in d₆-benzene: (a) ¹H–¹H-COSY (bold lines) and HMBC (arrows) correlations, (b) ¹H–¹H-NOESY correlations, (c) detailed view of ring E and side chain from part b.

Figure 5

Displacement of tritium-labeled PbTx-3 ([³H]-PbTx-3) from rat brain synaptosomes. All values are the mean of at least three experiments, with duplicate determinations at each concentration of competitor in each experiment. Radioactivity associated with the pellet (bound) and the supernatant (free) was determined. A displacement curve for PbTx-2 is provided for reference. Linear regression analysis of each double reciprocal plot yielded r² values > 0.98 (data not shown). Convergence of the plots near the ordinate indicates that the interaction between the ligands and [³H]-PbTx-3 is competitive.