Use Of A Removable Backbone Modification Strategy To Prevent Aspartimide Formation In The Synthesis Of Asp Lactam Cyclic Peptides(Dagger)

Main observation and conclusion The synthesis of an Asp lactam derivative of A-183, a selective inhibitor of Factor 7a with good anticoagulant and antithrombotic activity, is described. Our synthesis depends on the use of a removable backbone modification (RBM) strategy to prevent aspartimide formation, which thwarted all attempts to synthesize this target using direct solid-phase peptide synthesis. Validation of the RBM strategy in the synthesis of a second Asp lactam derivative was also accomplished. The RBM strategy is therefore proposed as a general method for the synthesis of Asp lactam cyclic peptides.