Synthesis of cbz-protected ketomethylene dipeptide isosteres

Ketomethylene peptide isosteres have been the focus of a variety of synthetic studies because of their potential as therapeutic agents in the treatment of medical conditions mediated by proteases (1-3). The dipeptide core units 1 are chemically characterized by a 1,4-disposition of the carbonyl groups (ketone and carboxylate) and have an alkyl group at C-2 that is a chiral center. Protecting groups at amino nitrogen (typically carbamate such as Cbz or Boc) and the carboxyl group (typically ester) are usually present to make processing easier but must be readily and independently removable to permit extension in either the N-terminal or C-terminal directions (Fig. 1). Figure 1.