Chemical modification tylosin

This chapter deals with recent progress in the chemical modification and structure-activity relationships of 14- and 15-membered macrolides (mainly erythromycin derivatives), 16-membered macrolides (mainly the leucomycin and tylosin families), and the avermectin family of macrolides, showing nematocidal, insecticidal, and arachnidicidal activities. Previous reviews of these macrolides were given by Sakakibara and Omura in the first edition of this book in 1984 [1]. 

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. 

Various modifications of tylosin have been reported [204]. The following chemical modifications have been made 4"-Substitution, removal of the neutral sugars, and alteration of the 9-ketone and 20-aldehyde. 4"-0-Acylation of tylosin has been described, and all the derivatives obtained showed improved antimycoplasmal... 

A variety of chemical modifications at the C-20 aldehyde group in tylosin and related macrolides have been reported [206]. The C-20 aldehyde can be radically modified or removed entirely without reducing the antibiotic activity. Reductive amination of C-20 aldehyde of tylosin and related macrolides has yielded a large group of derivatives with useful antibiotic properties. Omura et al. reported that 20-deoxy-20-aminotylosin and 20,20 -dideoxo-iminotylosin had lower antibacterial... 

Matsubara, H., Inokoshi, J., Nakagawa, A., Tanaka, H., and Omura, S. (1983). Chemical modification of tylosin Synthesis of amino derivatives at C-20 position of tylosin and demycarosyl tylosin. J. Antibiot. 36,1713-1721. 

Chemical modifications of 16-membered macrolides have also been extensively explored in order to improve either antimicrobial or pharmacokinetic properties. Much of the early research was directed toward acylation of hydroxyl groups on the lactone ring and neutral sugar (mycarose), since such modifications often improved antimicrobial activity against resistant organisms or increased oral bioavailability [82]. Acylation of mycarose in tylosin by bio-... 

Epoxidation of the dienone system in tylosin-related macrolides has been shown to yield the 12,13-P-epoxyenone system [103]. Methods for conversion of the epoxyenone system to the dienone system have long been known [82]. In addition, tylosin-related macrolides containing the epoxyenone system are being reported from fermentations, providing additional substrates for chemical modifications [150, 151]. 

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