The synthesis and biological activity of two analogs of the anti‐HIV alkaloid michellamine B

Two simplified analogs of the dimeric naphthalenyltetrahydroisoquinoline alkaloid michellamine B [4′,4″‐didesmethoxy‐2′,2″‐didesmethylmichellamine B and 6,8‐dihydroxy‐5‐(1′,1″‐dihydroxy‐2′,2″‐binaphthalen‐4′‐yl)‐1R,3R‐dimethyl‐1,2,3,4‐tetrahydroisoquinoline] were synthesized using Suzuki palladiumcatalyzed biaryl cross‐coupling of 4‐(2‐benzyl‐6,8‐dibenzyloxy‐1R,3R‐dimethyl‐1,2,3,4‐tetrahydroisoquinolin‐5‐yl)‐1‐benzyloxy‐2‐bromonaphthalene to its corresponding atropisomeric 2‐naphthaleneboronic acid and 1‐benzyloxy‐2‐naphthaleneboronic acid, respectively. These analogs inhibited recombinant HIV reverse transcriptase with IC5() values of 62 μM and 1000 μM, respectively, whereas the IC5() value for michellamine B was 33 μM. Both michellamine B and the analogs inhibited the phosphorylation of histories by rat brain protein kinase C. The analogs were more active (IC50 values of 36 μM and 30 μM, respectively) than michellamine B (IC50 = 130 μM).