Tetradehydrohalicyclamine B, a new proteasome inhibitor from the marine sponge Acanthostrongylophora ingens.

A new halicyclamine derivative, tetradehydrohalicyclamine B (1), was isolated from the marine sponge Acanthostrongylophora ingens, along with halicyclamine B (2) as proteasome inhibitors. Compound 1 is the second example found to have a pyridinium ring in the halicyclamine family. Although the relative configuration of 2 was previously determined by X-ray crystallographic analysis, here we determined the absolute configuration of 2 by ECD experiment. Compounds 1 and 2 inhibited the constitutive proteasome as well as the immunoproteasome. The inhibitory activities of 2 were 4- to 10-fold more potent than those of 1.