Chemical modification of tylosin. Thioether derivatives of tylosin and demycarosyltylosin.

Chemical modification of tylosin. Thioether derivatives of tylosin and demycarosyltylosin.

Thioether derivatives of tylosin and demycarosyltylosin were synthesized by Michael-type addition of thiol to C-11 of the enone moiety on the aglycone. Some of tylosin derivatives were effective to macrolide resistant Staphylococcus aureus, and their in vivo activities were same or superior than that of tylosin.

Chemical modification of tylosin: synthesis of amino derivatives at C-20 position of tylosin and demycarosyltylosin.

Reductive aminations of the aldehyde group at C-20 position of tylosin and demycarosyltylosin (desmycosin) were carried out using primary and secondary amines in the presence of sodium cyanoborohydride. Some of these derivatives brought about higher antimicrobial and ribosome-binding activities, and the structure-activity relationship is discussed.

Chemical modification of tylosin.

20-Homo tylosin, 20-nor tylosin, 20-deoxy-19,20-didehydro tylosin (6-vinyl tylosin) and 2",3"-didehydro-3"-deoxy tylosin were prepared by multi-step procedures. 20-Homo tylosin was about twice less active than tylosin while the other compounds exhibited very weak antibacterial activity.

Syntheses and antimicrobial activities of 9-O-acyl derivatives of tylosin and demycarosyltylosin.

Biological properties of new acyl derivatives of tylosin.

The antibacterial activity of acyl derivatives of tylosin were examined in vitro and in vivo. The 4"-acyl group in the acylated tylosins enhanced the antibacterial activity and antimycoplasmal activity against some macrolide-resistant strains. The orally administered 3-acetyl-4" -isovaleryltylosin produced a higher blood level in mice and rabbits than tylosin and a good therapeutic effect on th...