Pseudotheonamides, serine protease inhibitors from the marine sponge Theonella swinhoei

Six new peptides with serine protease inhibitory activity have been isolated from the marine sponge Theonella swinhoei. Their structures including absolute stereochemistry were unambiguously established by interpretation of spectral data and chemical degradation. Pseudotheonamides A₁ (1), A₂ (2), and B₂ (3) are linear pentapeptides embracing the rare piperazinone and piperidinoiminoimidazolone ring systems. Pseudotheonamide C (4) contains v-Tyr (vinylogous tyrosine) instead of a piperazinone ring. Pseudotheonamide D (5) is a tetrapeptide which lacks a C-terminal k-Arg (α- ketohomoarginine) unit. Dihydrocyclotheonamide A (6) is a reduction product of the known cyclotheonamide A (7).