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 modificat...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.展开更多
基金supported by the National Key R&D Program of China(No.2017YFA0505200)the National Natural Science Foundation of China(Nos.91753205,21877024,21621003,81621002)the Fundamental Research Funds for the Central Universities(No.JZ2019HGPB0105).
文摘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.
