Aminosterols from the dogfish shark Squalus-acanthias

Seven new aminosterols related to squalamine (8) were isolated from the liv er of the dogfish shark Squalus acanthias. Their structures (1-7) were dete rmined using spectroscopic methods, including 2D NMR and HRFABMS. These ami nosterols possess a relatively invariant cholestane skeleton with a trans A B ring junction, a spermidine or spermine attached equatorially at C3, and a steroidal side-chain that may be sulfated. The structure of the lone sper mine conjugate, 7 (MSI-1436), was confirmed by its synthesis from (5 alpha, 7 alpha, 24R)-7-hydroxy-3-ketocholestan-24-yl sulfate. Some members of thi s family of aminosterols exhibit a broad spectrum of antimicrobial activity comparable to squalamine.