Thyroxine analogues: synthesis of 3,3′,5,5′-tetramethyl-L-thyronine

Abstract

The optically active thyroxine analogue, 3,3′,5,5′-tetramethyl-L-thyronine (VI), in which the iodine atoms of thryoxine have been replaced by methyl groups, is of considerable biological interest. Its synthesis via the catalytic hydrogenation of N-acetyl-3,5-dicyano-(4-methoxy-3,5-dimethylphenoxy)-L-phenylalanine ethyl ester (II) in p-cymene under reflux is described. 3,5-Dimethyl-L-thyronine (VII) was also prepared by reduction of N-acetyl-3,5-dicyano-4-(4-methoxyphenoxy)-L-phenylalanine ethyl ester (IV).