Modifications and Biological Activity of Natural and Semisynthetic 16-Membered Macrolide Antibiotics

Piotr      Przybylski

doi:10.2174/138527211794072588

Abstract

Macrolides are produced by various Streptomyces strains and make up a large group of compounds among antibiotics used against various infectious diseases. There are many criteria of classification of compounds of this type but natural macrolides usually consist of 14- or 16- membered macrocyclic lactone rings and differ from each other by the type and number of sugar moieties attached as well as by their various modes of binding to the aglycone part. Recently, renewed interest in synthesis of 16-membered macrolide derivatives has been evoked by their interesting biological properties, relatively good gastric tolerance and low tendency for producing allergy and inducing resistance. Many reviews have been devoted to the biological properties of various macrolides but only a few of them have been focused on a very important natural and semi-synthetic 16-membered macrolides and the fast growing group of their derivatives. I have, therefore, attempted to review the past and recent advances in the modifications and biological investigation of selected 16- membered leucomycin type macrolides group, including natural leucomycins (kitasamycins), spiramycins, midecamycins, semi-synthetic rokitamycin and miocamycin as well as 16-membered macrolides not belonging to the leucomycin group – tylosins and desmycosins, important from the biological application point of view. This review is dedicated to organic chemists who wish to stay abreast with the modification and properties of 16-membered macrolides and their derivatives. Despite enormous number of studies of diverse derivatives of leucomycin-type macrolides as well as tylosins and desmycosins, the 16-membered macrolides, due to their high biological potential and many possibilities for further modifications, have not yet revealed all their secrets.

Keywords: 16-membered macrolides, leucomycin, tylosin, desmycosin, antibiotics, synthesis of macrolides derivatives, biological activity, macrolide applications, Poecillastrin D, Misakinolide, Erythromycins, Oleandomycin, Sporeamicin, Spiramycins, Midecamycins, Roxithromycin, Azithromycin, Rokitamycin, Dirithromycin, Miocamycin, Flurithromycin, Clarithromycin, Davericin, Decarestrictine M, Octalactin A, Botcinolide, Amphidinolide W, Formosalide A, Tedanolide C, Amphidinolide T, Amphidinolide U, Dolabelide B, Bryostatin 10, Amphotericin B, Misakinolide A, Streptomyces kitasatoensis, Streptococcus pneumoniae, leucomycin A7, Enterococcus faecalis, Mycobacterium vaccae, Haloarcula marismortui, Staphylococcus albus, Escherichia coli, Streptomyces coelicolor, bitespiramycins, Tylosins, Streptomyces fradiae, 20-deoxo-20-morpholinotylosin, Pasteurella multocida, Pasteurella haemolytica, Haemophilus influenzae, TBDPSCl, Mitsunobu reaction, PSCB-0543, Wallach reaction