Use of a Removable Backbone Modification Strategy to Prevent Aspartimide Formation in the Synthesis of Asp Lactam Cyclic Peptides

摘要

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 ac-tivity,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 gen-eral method for the synthesis of Asp lactam cyclic peptides.