Tylosin chemical structure

The first of these compounds to be used in animal medicines, Tylosin, was isolated from Streptomyces fradiae. Its chemical structure which is typical of this group of compounds, is based on a lactone ring to which carbohydrate... 

Figure 1 Structural and bioconverting relationships among tylosin, AIV, and its related acyltylosins. (A) Chemical structures of tylosin, AIV, and its related acyltylosins. (B) Biotransformation of tylosin to AIV by two types of macrolide acyltransferases in S. ther-motolerans 3-O-acyltransferase and 4"-0-acyltransferase catalyze acetylation at the 3-hydroxyl group of tylonolide and isovalerylation at the 4"-hydroxyl group of mycarose, respectively.

Complementary to the bioconversion studies on tylosin, chemical methods for selective esterification of its 4"-hydroxyl group were developed in order to synthesize additional esters for structure-activity studies which were not available from bioconversion methods [100,101]. Although deacylation of the 4"-0-acyl group has generally been encountered in vivo, increased resistance to such hydrolysis by mouse liver esterase has been recently reported for two 4"-esters of tylosin [101, 102]. 

Figure 11.17 (a) Chemical structures of macrolide antibiotics (note that erythromycin, ETM, was analyzed as its anhydro form shown, (ETM-H2O)), but tylosin (TLS) was analyzed as the intact protonated molecule. Spiromycin (SPM) was used as the internal standard, (b) Multiple reaction monitoring (MRM) chromatograms of macrolides, each spiked at a concentration of 300ng.L before extraction from 100 mL of influent wastewater from a water reclamation plant. The MRM transitions used for quantitation are shown in each case (the precursor ion for Spiromycin I was the (M+2H) + ion, the others were (M+H)+ ions), and the total ion current (TIC) chromatogram is simply the sum of the three MRM traces. Reproduced from Yang, Anal. Bioanal Chem. 385, 623 (2006), with permission from Springer Science and Business Media. 

Other macrolides have been prepared which represent hybrids of structures within the 14-membered family, within the 16-membered family, or between the two families. These hybrids have been made by chemical, bioconversion, or genetic manipulations. The 9-0-[(2-methoxyethoxy)methyl]oxime of tylosin (Table 7) was synthesized, using the oxime found in roxithromycin (33) (369). 3-O-Qadinosyl derivatives of 16-membered macrolides were synthesized in which the neutral sugar of erythromycin (Table 3) was attached to tylosin derivatives at their 3-hydroxyl group, analogous to its position in erythromycin... 

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. 

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