Synthesis and biological investigation of new 4″-malonyl tethered derivatives of erythromycin and clarithromycin

A new approach to 4″-substituted derivatives of erythromycin and clarithromycin was developed by converting them into corresponding 4″-malonic monoesters. Subsequent carbodiimide coupling with alcohols and amines provided new macrolide derivatives that are capable of binding to 50S ribosomal subunits and inhibiting protein synthesis in cell-free system.