RESUMEN
Some novel josamycin derivatives bearing an arylalkyl-type side chain were designed and synthesized. By HWE or Wittig reaction, 16-aldehyde group of josamycin analogs were converted into unsaturated carbonyl compounds. They were evaluated for their in vitro antibacterial activities against a panel of respiratory pathogens. 8b and 8e exhibited comparable activities against a panel of respiratory pathogens, especially to resistant ones in the series of desmycarosyl josamycin analogs. Among of all the target molecules, 21 showed the best antibacterial activities.
Asunto(s)
Antibacterianos , Josamicina , Cetonas , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Josamicina/análogos & derivados , Josamicina/síntesis química , Josamicina/química , Josamicina/farmacología , Cetonas/síntesis química , Cetonas/química , Cetonas/farmacología , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Staphylococcus aureus/efectos de los fármacosRESUMEN
A series of novel 9-O-acetyl-4'-substituted 16-membered macrolides derived from josamycin has been designed and synthesized by cleavage of the mycarose of josamycin and subsequent modification of the 4'-hydroxyl group. These derivatives were evaluated for their in vitro antibacterial activities against a panel of Staphylococcus aureus and Staphylococcus epidermidis. 15 (4'-O-(3-Phenylpropanoyl)-9-O-acetyl-desmycarosyl josamycin) and 16 (4'-O-butanoyl-9-O-acetyl-desmycarosyl josamycin) exhibited comparable activities to josamycin against S. aureus (MSSA) and S. epidermidis (MSSE).