Synthesis of Phidianidine B, a highly cytotoxic 1,2,4-oxadiazole marine metabolite

Phidianidine B (1), a natural 1,2,4-oxadiazole linking both an indole system and an aminoalkyl guanidine group that has been recently reported from a marine mollusk, has been synthesized in seven steps (14% total yield). The synthetic procedure, which is based on the coupling of 3-indolacetic acid methyl ester and the amino-alkyl hydroxy guanidine intermediate 2, opportunely prepared, is of general application and allows the synthesis of analogues with either different alkyl chain length or substitution on the indole ring.