Jozipeltine A, a novel, unnatural dimer of the highly hydroxylated naphthylisoquinoline alkaloid dioncopeltine A

The synthesis of jozipeltine A (5), the 6'-coupled constitutionally symmetr ic dimer of the highly antimalarial naphthylisoquinoline alkaloid dioncopel tine 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 ste ps from 4. Jozipeltine A is the first naphthylisoquinoline dimer with oxyge n functions in the side chain of the naphthalene part. Investigations on it s antiplasmodial and antiviral activities provide valuable insight into str ucture-activity relationships within this promising class of bioactive quat eraryls. (C) 2000 Elsevier Science Ltd. All rights reserved.