Octadehydromichellamine, a structural analog of the anti-HIV michellamines without centrochirality☆

Abstract 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 .