Synthesis and antimicrobial activities of 9(S)-N,N-dimethyl-amino-9-deoxo-10, 11,12,13-tetrahydroniddamycin

• Published in: Journal of antibiotics 1991-04, Vol.44 (4), p.448-450
• Main Authors: Maring, C J, Freiberg, L A, Lartey, P A, Grampovnik, D J, Edwards, C M, Hardy, D J, Swanson, R, Fernandes, P B
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Bacteria - drug effects; Chemical Phenomena; Chemistry; Macrolides; Mice; Molecular Structure; Staphylococcal Infections - drug therapy; Streptococcal Infections - drug therapy
• ISSN: 0021-8820
• DOI: 10.7164/antibiotics.44.448

Introduction of basic amino groups at the C-9 position of the macrolide ring of 14-membered macrolide antibiotics has been an important strategy to improve the potency and spectrum of activity of these antibiotics. For example, reductive amination of the 9-ketone of erythromycin or ring expansion at C-9 with a basic amine has resulted in a number of compounds with improved efficacy. Yet, the C-9 position of 16-membered macrolides has gone unexplored with regard to the introduction of basic amino groups. The objective of the present work is to explore the effect of basic amine substitution at the C-9 position of a 16-membered macrolide on antibacterial efficacy. Based on the established precedents that there is essentially no difference in activity between the C-9 epimers of the leucomycins and that reduction of the diene system of the leucomycins has minimal effect on activity, the 9-N, N-dimethylamino-9-deoxo-10,11,12,13-tetrahydroniddamycin derivatives (5 and 6) were targeted for synthesis.