A beta-lactam-based stereoselective access to beta,gamma-dihydroxy alpha-amino acid-derived peptides with either alpha,beta-like or unlike configurations

A concise access to alpha,beta -dihydroxy alpha -amino acid-derived N-carbo xy anhydrides (NCAs) with either like or unlike relative configuration is d escribed. The key steps of the synthetic route are the preparation of the n onracemic Li-alkenyl beta -lactams, through either Horner-type olefination of a common 4-formyl beta -lactam or the Corey-Winter alkene synthesis appl ied to 4-dihydroxyalkyl beta -lactams, followed by the Sharpless AD reactio n, and a subsequent ring expansion of the corresponding 4-substituted 3-hyd roxy beta -lactams promoted by TEMPO. The opening of thus-prepared NCAs upo n treatment with different O- and N-nucleophiles, including alpha -amino es ters which lead to peptides, has also been studied under various reaction c onditions.