SILICA GEL-CATALYZED KNOEVENAGEL CONDENSATION OF PEPTIDYL CYANOMETHYL KETONES WITH AROMATIC-ALDEHYDES AND KETONES - A NOVEL MICHAEL ACCEPTOR FUNCTIONALITY FOR C-MODIFIED PEPTIDES - THE BENZYLIDENE AND ALKYLIDENE CYANOMETHYL KETONE FUNCTION

Simple preparation of cyanomethyl ketone derivatives 5a-5b of N-acetylphenylalanine and N-acetylleucylphenylalanine is accomplished by condensation of the corresponding activated carboxylic acids 3a-3b and the carbanion of tert-butyl cyanoacetate to give enols 4a-4b, which are then hydrolyzed and decarboxylated. These cyanomethyl ketone compounds 5a-5b are allowed to react with aromatic aldehydes and ketones in the presence of silica gel to give the Knoevenagel condensation adducts 7-18. Malononitrile, benzoylacetonitrile, and nitroacetonitrile are also reactive. These transformations can be brought about without significant epimerization.