Synthesis of crambescin B carboxylic acid, a potent inhibitor of voltage-gated sodium channels

Abstract

The stereocontrolled synthesis of a racemic carboxylic acid of crambescin B, a marine alkaloid, is described. The synthesis features two highly stereoselective reactions: (i) palladium-catalyzed hydroxymethylation of an alkynyl aziridine having an N-guanidino group and (ii) cascade bromocyclization providing a spiro-hemiaminal structure. The cell-based colorimetric assay showed that the synthesized carboxylic acid exhibited a potent inhibitory activity on voltage-gated sodium channels.