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Abstract

A straightforward approach for the synthesis of several new, aryl-substituted derivatives of the conformationally constrained phenylalanine analogue 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) is described. Tic, nitrosubstituted at the 6 or 7 position, was prepared by base-catalyzed cyclization of diethyl acetamidomalonate with α,α-dibromo-4-nitro-o-xylene followed by decarboxylation and deacylation under refluxing conditions in aqueous HCl. Catalytic hydrogenation of nitro-Tic in the presence of 10% Pd/C afforded amino-Tic, which was then converted to iodo-Tic by a modified Sandmeyer reaction. Both amino-Tic and iodo-Tic can easily be transformed to other substituents.