Macrolides, literature review

In this chapter, the latest applications published in the literature from 1994 to 1998 are reviewed. The following groups of antimicrobial agents are discussed tetracyclines, penicillins, poiyethers, aminoglycosides, macrolides, amphenicols, nitrofurans, sulphonamides, quinolones and other antimicrobials. 

Modifications other than esterifications have been less extensively reported, although many derivatives have been described in the older literature that were prepared during structure elucidation and basic chemical studies of new macrolides. Some of this work has been compiled in reviews [1, 3, 6, 49], None of these older compounds has been commercially developed. Results from these early studies indicated that antibacterial activity was only minimally affected by epimerization of the C-9 substituent, alkylation of the 9-hydroxyl group, saturation of the C-10,11,12,13-diene, or epoxidation of the C-12,13 double bond [26, 49-52]. The aglycone of niddamycin (11a) Figure 5.4) was recently transformed into a series of 9-a-and 9-j8-A, iV-dialkylamino-9-deoxo-10,11,12,13-tetrahydro derivatives the 9-a-N,iV-dimethylamino analogue (A-65352) (11c) exhibited activity comparable to josamycin in vitro and in vivo [53]. The 9-a-N,N-dimethylamino derivative of niddamycin itself (A-75835) (lib) was subsequently reported to be more active than josamycin [54]. 

This review will summarize structural modifications of the classical macrolide antibiotics which have been reported in the scientific literature during the past several years and will highlight those compounds which have exhibited potential utility in clinical or veterinary medicine. 

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