Novel 9a-carbamoyl- and 9a-thiocarbamoyl-3-decladinosyl-6-hydroxy and 6-methoxy derivatives of 15-membered macrolides

• Published in: Bioorganic & medicinal chemistry Vol. 15; no. 13; pp. 4498 - 4510
• Main Authors: Ištuk, Zorica Marušić, Mutak, Stjepan, Kujundžić, Nedjeljko, Kragol, Goran
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-07-2007; Elsevier Science
• Subjects: 3-Decladinosyl; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Antibacterial activity; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Azalide; Bacteria - drug effects; Biological and medical sciences; Indicators and Reagents; Macrolide; Macrolides - chemical synthesis; Macrolides - pharmacology; Magnetic Resonance Spectroscopy; Mass Spectrometry; Medical sciences; Microbial Sensitivity Tests; Pharmacology. Drug treatments; Spectrophotometry, Infrared; Spectroscopy, Fourier Transform Infrared; Thiourea - analogs & derivatives; Thiourea - chemical synthesis; Thiourea - pharmacology; Urea - analogs & derivatives; Urea - chemical synthesis; Urea - pharmacology; Antibacterial activity; Azalide; 3-Decladinosyl; Macrolide; Metabolite; Hemiacetal; Thioureas; In vitro; Biological activity; Ureas; Antibacterial agent; Chemical reactivity; Chemical synthesis; Ketolide; Oxygen nitrogen heterocycle
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2007.04.021

An efficient method for the synthesis of diverse 9a-carbamoyl- and 9a-thiocarbamoyl-3-decladinosyl-6-hydroxy and 3-decladinosyl-6-methoxy derivatives of 15-membered azalides has been developed. These derivatives bear various alkyl and aryl groups attached to macrolide scaffold through urea or thiourea moieties at 9a position. Chemical transformations of hydroxy group at position C-3 afforded range of ketolides, anhydrolides, hemiketals, cyclic ethers, and acylides. It has been shown that 6-hydroxy and 6-methoxy derivatives undergo different chemical transformations under otherwise identical reaction conditions. Antimicrobial properties of prepared compounds were evaluated.