PREPARATION OF CARBOALKOXYALKYLPHENYLALANINE DERIVATIVES FROM TYROSINE

In order to provide the means for the synthesis of peptides incorporating stable and relatively nonpolar mimics of tyrosine phosphates and sulfates, procedures for the conversion of tyrosine derivatives to the corresponding carboalkoxyalkylphenylalanines have been developed. For the synthesis of carboalkoxyethylphenylalanines, a benzyl or benzhydryl ester of N-(Boc)tyrosine triflate (2) is coupled with an acrylate ester or preferably a 3-(trialkylstannyl)acrylate in the presence of bis(triphenylphosphine)palladium dichloride to give a carboalkoxyethenylphenylalanine derivative. Hydrogenation affords the corresponding N-(Boc)carboalkoxyethylphenylalanine. For the preparation of carboalkoxymethylphenylalanines, an ester of 2 is coupled with allyltributyl tin in the presence of bis(triphenylphosphine)palladium dichloride and lithium chloride to give an ester of 4- allylphenylalanine. A two-stage oxidation using ruthenium tetroxide/sodium periodate followed by sodium chlorite in phosphate buffer gives a carboxymethylphenylalanine. Appropriate esterification of the newly formed carboxylic acid and selective deesterification of the α-carboxylate then completes the synthesis of AT-(Boc)-carboalkoxymethylphenylalanine. © 1990, American Chemical Society. All rights reserved.