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.