A CONVENIENT SYNTHESIS OF PEPTIDYL PERFLUOROALKYL KETONES

A convenient method is described for the preparation of alpha-amino pe rfluoroalkyl ketones via direct nucleophilic perfluoroalkylation of th e corresponding peptide eater, This method was used to prepare dehydro valine pentafluoroethyl ketone 2 from the corresponding N-Boc-protecte d dehydrovaline methyl ester 3. Similar alpha-amino esters, N-Boc-vali ne methyl ester 4, Boc-Valyl-prolyl-dehydrovaline methyl ester 8a and Boc-valyl-prolyl-valine methyl ester 8b were also converted directly t o the corresponding pentafluoroethyl ketones 6, 9a and 9b. The method was also applied to the synthesis of heptafluoropropyl- and nonafluoro butyl peptidyl ketones 11a and 11b from their corresponding esters, al beit in lower yield, These amino ketones are useful as intermediates i n the preparation of peptidyl perfluoroalkyl ketones which have been s hown to be potent inhibitors of human neutrophil elastase. (C) 1998 El sevier Science S.A.