Peptide Derivatives of Tylosin-Related Macrolides

G. A. Korshunova1 #, N. V. Sumbatyan1, N. V. Fedorova1, I. V. Kuznetsova1, A. V. Shishkina1 and A. A. Bogdanov1

#Phone: (495) 939-55-20; fax: (495) 939-31-81; e-mail:

1Belozersky Research Institute of Physicochemical Biology, Faculty of Chemistry, Moscow State University, Vorob’evy Gory, Moscow, 119992, Russia

Received: September 26, 2005; in final form: September 6, 2006

Abstract.  Approaches to the synthesis of model compounds based on the tylosin-related macrolides desmycosin and O=mycaminosyltylonolide were developed to study the conformation and topography of the nascent peptide chain in the ribosome tunnel using specially designed peptide derivatives of macrolide antibiotics. A method for selective bromoacetylation of desmycosin at the hydroxyl group of mycinose was developed, which involves preliminary acetylation of mycaminose. The reaction of the 4″-bromoacetyl derivative of the antibiotic with cesium salts of the dipeptide Boc-Ala-Ala-OH and the hexapeptide MeOTr-Gly-Pro-Gly-Pro-Gly-Pro-OH led to the corresponding peptide derivatives of desmycosin. The protected peptides Boc-Ala-Ala-OH, Boc-Ala-Ala-Phe-OH, and Boc-Gly-Pro-Gly-Pro-Gly-Pro-OH were condensed with the C23-hydroxyl group of O-mycaminosyltylonolide.

Key words:  tylosindesmycosin, O-mycaminosyltylonolide, peptide derivatives of macrolides

Russian Journal of Bioorganic Chemistry 2007, 33 (2): 218-226