Spiramycin chemical modification

The 16-membered macrolide antibiotics are generally classified into two large groups, namely, the leucomycin-related family and the tylosin-related family, on the basis of the substitution patterns of their aglycons (Fig. 28) [187]. Interestingly, the leucomycin series, such as leucomycin, josamycin, midecamycin, and spiramycin, have been used clinically for humans, while the tylosin series has been utilized in veterinary medicine. In this section, we describe recent studies on the chemical modification of 16-membered macrolides and their structure-activity relationships. 

O-acetylspiramycin I (acetylspiramycin) exhibited greater in vivo activity than that of spiramycin and received clinical evaluation [195]. Chemical modification of the 4"-hydroxyl group to sulfonyl and alkyl groups retained the antibacterial activity [196]. Acylation of the 3"-hydroxyl group of spiramycin analogues showed better antibacterial activity. 

Chemical modification of the saccharide substituents in spiramycin has been the subject of several publications. A series of 3-0- and 4 -0-tetrahydrofuranyl and tetrahydropyranyl derivatives of neospiramycin I have been prepared, with one of the former demonstrating activity comparable to that of spiramycin I [158]. The 4 -deoxy derivative of neospiramycin I was obtained by Bu3SnH reduction of the 4 -chloro intermediate isomerization of the 12,13-double bond occurred simultaneously, yielding a mixture of the natural (E) and unnatural (Z) isomers [159]. Finally, selective N-demethylation of either dimethylamino group has been accomplished AT-bromosuccinimide (NBS) in aqueous dimeth-... 

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