Synthesis and biological activity of photoactive derivatives of erythromycin

Abstract

Five photoactive derivatives of erythromycin have been synthesized by linking to 9(S)-aminoerythromycin either an aryl azide or a p-nitrophenyl ether. One derivative is an amide formed by reaction with (5-azido-2-formyl-phenoxy)acetic acid. Three derivatives are also amides, synthesized with 4-(p-nitroguaiacoxy)butanoic acid as a photoreactive group either directly or by interposing an amino acid (glycine or tyrosine). The last derivative is the product of the aldehyde condensation of aminoerythromycin with 10-(p-nitroguaiacoxy)decanal. Two of these derivatives can easily be made radioactive for affinity labeling studies either by reduction with [3H]borohydride (aryl azide derivative) or by 125I iodination (4-(p-nitroguaiacoxy)tyrosyl derivative). Although affected to different extents, the five erythromycin derivatives are biologically active and bind to the erythromycin-specific site on the bacterial ribosomes. In addition, the introduction of these groups changes the erythromycin inhibition pattern of peptide bond model reactions.