Unnatural Amino Acid Derivatives through Click Chemistry: Synthesis of Triazolylalanine Analogues.

A novel -butyl 2-(1-oxoisolndolin-2-yl)acetate derivative is selectively alkylated with propargyl bromide in the presence of lithium hexamethyldisilazide. After removal of the -butyl protecting group, the resulting -isoindolinyl (ethynylalanine) derivative is reacted with a series of azides under 'click conditions'. The click reactions afford an array of -isoindolinyl-1,2,3-triazolylalanine derivatives as the free carboxylic adds. Following esterification, the -isoindolinone protecting group is then transformed into the more easily removable phthaloyl group by selective oxidation at the benzylic position.