Synthesis of 6-O-methyl-azithromycin and its ketolide analogue via Beckmann rearrangement of 9(E)-6-O-methyl-erythromycin oxime.
The synthesis of 6-O-methyl-azithromycin and its aza-ketolide analogue have been achieved by carrying out the Beckmann rearrangement of the readily available 9(E)-6-O-methyl-erythromycin oxime 1. In contrast to the C14 ketolides like HMR 3647, the aza-ketolide turns out to be inactive, thus demonstrating that the addition of a 3 keto function and ring expansion, from 14 to 15 membered ring, could be deleterious for the antibacterial activity.
Denis
A
A
Dpt., Hoechst Marion Roussel, Romainville Research Center, France. alexis.denis@hmrag.com
Agouridas
C
C
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D017963:Azithromycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D006193:Haemophilus influenzae / Q000187:drug effects; D048628:Ketolides; D018942:Macrolides; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D013211:Staphylococcus aureus / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; D004917:Erythromycin; D017963:Azithromycin; C106791:telithromycin