Synthesis of 5-Aryl-3-Methyl-1,2,3,4-Tetrahydroisoquinoline derivatives

Abstract

Ancistrocladine and other naphthylisoquinoline alkaloids have been reported to possess various interesting biological activities including an antimalarial activity. The present investigation was to synthesize new series of 5-ary1-3-methy1-1,2,3,4-tetrahydroisoquinoline derivatives. These synthetic derivatives were designed using the 5- naphthy1-1,2,3,4-tetrahydroisoquinoline alkaloid as lead compound. The synthetic procedure was started with the reaction of 1,2,3,4-tetrahydro¬isoquinoline derivatives (THIQ), prepared through O,N-acetal intermediates from the phenylethylamine derivative and consequently reacted with iodine to afford the corresponding 5-iodo-3-methyl-1,2,3,4-tetrahydroisoquinoline derivatives. Various aryl groups were introduced in to the position-5 of the THIQ via an efficient Suzuki coupling reaction in the presence of tetrakis (triphenylphosphine) palladium and a suitable base in toluene to give the corresponding 5-aryl-1,2,3,4-tetrahydroisoquinoline derivatives in good yields. The structures of synthetic products were identified by the spectroscopic techniques (IR, ¹H-NMR, ¹³C-NMR and 2-D NMR) and elemental analysis.