Use of a Removable Backbone Modification Strategy to Prevent Aspartimide Formation in the Synthesis of Asp Lactam Cyclic Peptides<sup>†</sup>
Tingting Cui, Junyou Chen, Rui Zhao, Yanyan Guo, Jiahui Tang, Yulei Li, Yulei Li, Yi‐Ming Li, Yi‐Ming Li, Donald Bierer, Lei Liu
Abstract
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.
Topics & Concepts
ChemistryLactamAntithromboticCyclic peptideCombinatorial chemistryDerivative (finance)StereochemistryPeptidePeptide synthesisBiochemistryMedicineCardiologyFinancial economicsEconomicsChemical Synthesis and AnalysisSynthesis and Catalytic ReactionsPeptidase Inhibition and Analysis