Polyaxibetaines A-C, three unique amino acids derivatives isolated from the marine sponge Axinella polypoides.

Betaines and similar zwitterionic compounds are widely distributed in terrestrial plants and algae, as well as in marine invertebrates. In biological systems, these highly soluble dipolar molecules serve as organic osmolytes (osmoprotectants), namely substances synthesized or taken up from the environment by cells for protection against osmotic stress. Osmoprotectants can stabilize proteins and membranes when salt levels or temperatures are unfavourable; therefore, they could play important roles in the adaption of cells of marine invertebrates to various adverse environmental conditions. Examples of betaines isolated from marine invertebrates are homarine,1 trigonelline,2 taurines, baikiain betaine,3 β-stachydrine, 4 nor- and aminozooanemonin, 5 pyridinebetaines A and B.5 Most of these compounds are amphoteric low-molecular weight quaternary ammonium compounds deriving from proteinogenic or non- proteinogenic amino acids in which the nitrogen atom if fully methylated. Within a recent investigation of alkaloids from Axinella sponges, we have examined specimens of Axinella polypoides collected along Sardinian coasts and we have isolated three novel unique compounds, polyaxibetaines A-C (1-3), whose structure elucidations are the subject of this paper.Polyaxibetaines A-C extend the structural variety of the so far known betaines; in compounds 1 and 2, indeed, the nitrogen atom of the -amino group of phenylalanine and tyrosine, respectively, is comprised in a piperidine ring and further methylated, while compound 3 is a pyridine derivative sharing the nitrogen atom with the alfa-amino group of a tyrosine residue.