Synthesis and antibacterial activity of O-methyl derivatives of azalide antibiotics: I. 4", 11 and 12-OMe derivatives via direct methylation.
A series of O-Me derivatives of 9-deoxo-8a-aza-8a-homoerythromycin has been prepared and evaluated for antibacterial activity. The relative rates of methylation of the four available hydroxyls (4", 6, 11 and 12) in 2',3'-bis-Cbz protected 9-deoxo-8a-aza-8a-homoerythromycin were compared to those given in a published report for the similarly protected 9a-azalide. An incongruity in the results prompted reinvestigation of the O-methylation of the 9a-azalide, and an error in structure assignment in the published report was discovered: the compound reported as the 6-OMe-9a-azalide has been determined to be the 12-OMe derivative.
Waddell
S T
ST
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
Santorelli
G M
GM
Blizzard
T A
TA
Graham
A
A
Occi
J
J
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure
D000900:Anti-Bacterial Agents; D004917:Erythromycin; C057301:9-deoxy-9a-aza-9a-methyl-9a-homoerythromycin A