ABSTRACT
Fifteen-membered 8a-aza-8a-homoerythromycins derived from either erythromycin or clarithromycin have been acylated to form 4''-O-propenoyl derivative. These functionalized analogues underwent Michael reaction with primary or secondary amines to afford novel 8a-aza-8a-homoerythromycin-4''-(3-substituted-amino)propionates. This preparative sequence was adapted so that analogues could be made by parallel synthesis. Among them, 4-quinolone derivatives show particularly good antibacterial potency against macrolide resistant bacteria, comparable or better than azithromycin and telithromycin.
Subject(s)
Anti-Bacterial Agents/pharmacology , Erythromycin/analogs & derivatives , Anti-Bacterial Agents/chemistry , Bacteria/classification , Bacteria/drug effects , Erythromycin/pharmacology , Microbial Sensitivity TestsABSTRACT
New amidino-benzimidazolyl derivatives of antibiotics tylosin and desmycosin are prepared in the reaction of corresponding amidino-substituted o-phenylendiamine with tylosin respectively desmyicosin on the 20-C aldehyde group. The reaction was carried out in absolute ethanol in the presence ofp-benzoquinone. On this way are prepared: 20-[5-(N-isopropylamidino)-2-benzimidazolyl]tylosin hydrochloride 9, 20-[5-(2-imidazolinyl)-2-benzimidazolyl]tylosin hydrochloride 10, 20-[5-(N-morpholinylamidino)-2-benzimidazolyl]tylosin hydrochloride 11, 20-[5-(N-isopropylamidino)-2-benzimidazolyl]desmycosin hydrochloride 12, 20-[5-(2-imidazolinyl)-2-benzimidazolyl]desmycosin hydrochloride 13, 20-[5-(N-morpholinylamidino)-2-benzimidazolyl]desmycosin hydrochloride 14. Their antimicrobial activity was tested on a series of microorganisms.
