Assessment of the biological value of the 11-hydroxy group of the azalides.

Bioorganic & Medicinal Chemistry Letters
1993.0

Abstract

Two deoxy azalides, 11-deoxy L-701,677 (18) and 11-deoxy -10-epi L-701,677 (15), were prepared and retained much of the in vitro antimicrobial potency of the parent azalide. The azalides are a new class of macrolide antibiotic. The first of these, azithromycin (1), recently made its market debut (as Zithromax®) with indications for skin and respiratory tract infections and uncomplicated genital chlamydial infections. Work from these laboratories has been reported recently describing the preparation of two new azalide types; L-701,677 (2) and a 14-membered azalide, L-731,352 (3). It is clearly desirable to evaluate the biological significance of various features of these molecules given the important changes in antimicrobial character that the azalides display (relative to erythromycin A). During work with a precursor to L-701,677 we observed a facile dehydration process. The subsequent follow up study revealed unexpected leniency in the substitution pattern of the C10-C11 region and it is this we now wish to report.

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