γ-Lactam-containing peptidomimetics

Abstract

Protected diaminoalcohols obtained through allyl addition to α-amino acid-derived imines and subsequent hydroboration were used for the preparation of pyrrolidinones and pyrrolidines. Pyrrolidinones were synthesized with moderate yields by oxidation of the hydroxy function with tetrapropylammonium perruthenate/ N-methylmorpholine- N-oxide and concomitant cyclization while pyrrolidines were synthesized in good yields by tosylation of the hydroxy group and subsequent intramolecular nucleophilic substitution. Thus accessible substrates were transferred into peptidomimetics by attachment of amino acid moieties at both termini using conventional peptide coupling strategies. Molecular mechanics optimizations suggest that these substrates preferentially adopt a turn conformation.