Biogenesis of 3-alkylpyridine alakloids in the marine mollusc Haminoea Orbignyana

In comparison with our knowledge of terrestrial plant and microbial systems, little is known about the biogenesis of secondary metabolites in marine organisms, such as sponges, tunicates, algae and molluscs. Although most of these compounds show more than one analogy with terrestrial metabolites, there are a few categories of products that seem to be structurally specific of marine species. One such group of compounds is formed by 3-alkylpyridine alkaloids (also named 3-alkylpiperidine alkaloids), a family of natural products that encompasses a very heterogeneous collection of molecules sharing an hypothetical common origin from a putative 3-alkylpyridine precursor (or a biochemical analogous). Herein, we describe the biosynthesis of haminol-2 (1) in the Mediterranean mollusc Haminoea orbignyana, the first in vivo evidence on the biogenesis of 3-alkylpyridines in marine organisms. The experiments prove the origin of the pyridine ring and C-12 from nicotinic acid, as well as the contribution of acetate to the formation of the alkyl chain.