Jozipeltine A, a Novel, Unnatural Dimer of the Highly Hydroxylated Naphthylisoquinoline Alkaloid Dioncopeltine A

The synthesis of jozipeltine A (5), the 6′-coupled constitutionally symmetric dimer of the highly antimalarial naphthylisoquinoline alkaloid dioncopeltine A (4), is described. After selective protection of two of the four OH- and NH-functionalities of 4, the coupling succeeds oxidatively, with Ag2O as the reagent. Deprotection gives the target molecule 5, in only three steps from 4. Jozipeltine A is the first naphthylisoquinoline dimer with oxygen functions in the side chain of the naphthalene part. Investigations on its antiplasmodial and antiviral activities provide valuable insight into structure–activity relationships within this promising class of bioactive quateraryls.