Acetogenic isoquinoline alkaloids. Part 123. Octadehydromichellamine, a structural analog of the anti-HIV michellamines without centrochirality

The synthesis of octadehydromichellamine (4), as the fully dehydrogenated structural analog of the naturally occurring michellamines (1), is described. This derivative is the first michellamine-type quateraryl without centrochirality and thus constitutes a distinctly simplified structural michellamine analog. Key step of the total synthesis is the twofold coupling of a bis-O-triflate activated central binaphthalene building block 9 with 2 eq. of the isoquinoline boronic acid 8, to give the quateraryl 11, whose deprotection delivers the target molecule 4, in an apparently stereochemically pure form. Octadehydromichellamine (4) shows a good order of anti-HIV activity and, compared with natural michellamines, enhanced antimalarial activity against Plasmodium falciparum. (C) 1999 Elsevier Science Ltd. All rights reserved.