Synthesis of 8-Fluorinated Erythromycin Cyclic 2′,3′-Carbamates

Abstract

Methodology is described for the preparation of a 2′,3′-carbamate-11,12-carbonate analog of flurithromycin and its 3-O-descladinosylflurithromycin analog from (9E)-erythromycin A 9-oxime. Phosgene was used for the carbonylation reactions. Selectfluor^TM was an effective fluorinating agent of the intermediate 8,9-anhydro-N-demethylerythromycin A 2′,3′-carbamate-11,12-carbonate-6,9-hemiketal under mild aqueous conditions.

Keywords:

• Antibacterial activity
• carbonylation
• fluorination
• phosgene reactions

ACKNOWLEDGMENTS

We thank the Norwegian Research Council and Alpharma AS for financial support and a research fellowship (A. H.).