Chemical modification of erythromycins. II. Synthesis and antibacterial activity of O-alkyl derivatives of erythromycin A.
A series of O-alkyl erythromycin A derivatives have been synthesized and their antibacterial activities compared with those of erythromycin A (1) and 6-O-methylerythromycin A (3). Methylation of the hydroxyl groups of erythromycin A analogue proceeded stepwise by the two main pathways beginning at the C-6 and C-11 positions, individually. O-Alkylation, other than methylation, took place at the C-11 hydroxyl group exclusively. Among O-alkyl derivatives, 6,12-di-O-methylerythromycin A (5) showed comparable in vitro antibacterial activity to those of 1 and 3. 11-O-Methylerythromycin A (8) was slightly less active than 1. O-Methylation at the C-4" position resulted in a decrease of antibacterial activity.
Morimoto
S
S
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Misawa
Y
Y
Adachi
T
T
Nagate
T
T
Watanabe
Y
Y
Omura
S
S
D000818:Animals; D001419:Bacteria / Q000187:drug effects*; D004355:Drug Stability; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D013203:Staphylococcal Infections / Q000188:drug therapy; D014018:Tissue Distribution
D004917:Erythromycin