SYNTHESIS OF POLYCARPINE, A CYTOTOXIC SULFUR-CONTAINING ALKALOID FROMTHE ASCIDIAN POLYCARPA-AURATA, AND RELATED-COMPOUNDS

Polycarpine 1, a highly cytotoxic marine natural product, has been syn thesized in three steps from p-methoxyphenacyl bromide 4 in 57% overal l yield. The key reaction for construction of tile symmetrically subst ituted disulfide linkage of polycarpine is the treatment of 2-amino-4- (4-methoxyphenyl)-1-methylimidazole 17 with S2Cl2 in acetic acid. In a similar way ten related compounds, including three thiazole analogues , have been prepared. Most of them exhibit high cytotoxic activities a gainst an array of human cancer cell lines. (C) 1997 Elsevier Science Ltd.