THE SYNTHESIS AND BIOLOGICAL-ACTIVITY OF 2 ANALOGS OF THE ANTI-HIV ALKALOID MICHELLAMINE-B

Two simplified analogs of the dimeric naphthalenyltetrahydroisoquinoli ne alkaloid michellamine B [4',4 ''-didesmethoxy-2',2 ''-didesmethylmi chellamine B and 6,8-dihydroxy-5-(1',1 ''-dihydroxy-2',2 ''-binaphthal en-4'-yl)-1R, 3R-dimethyl-1,2,3,4-tetrahydroisoquinoline] were synthes ized using Suzuki palladium-catalyzed biaryl cross-coupling of roisoqu inolin-5-yl)-1-benzyloxy-2-bromonaphthalene to its corresponding atrop isomeric 2-naphthaleneboronic acid and 1-benzyloxy-2-naphthaleneboroni c acid, respectively. These analogs inhibited recombinant HIV reverse transcriptase with IC50 values of 62 mu M and 1000 mu M, respectively, whereas the IC50 value for michellamine B was 33 mu M. Both michellam ine B and the analogs inhibited the phosphorylation of histones by rat brain protein kinase C. The analogs were more active (IC50 values of 36 mu M and 30 mu M, respectively) than michellamine B (IC50 = 130 mu M).