Synthesis of (9R, 12S)- and (S, 12S)-cycloisodityrosine and their N-methyl derivatives

The characteristics of intramolecular nucleophilic aromatic substitution reactions were analyzed during the synthesis of (9R, 12S)- and (9S, 12S)-cycloisodityrosine and their N-methyl derivatives. The benzylic bromination of 2-fluoro-4-methylnitrobenzene by 1,3-dibromo-5,5,-dimethylhydantoin led to the synthesis of (S)- and (R)-3-fluoro-4-nitrophenylalanine methyl ester. Furthermore, 14-membered ring macrocyclization reactions led to formation of a biaryl ether by smooth 14-membered ring closure.