Muraymycins, novel peptidoglycan biosynthesis inhibitors: Semisynthesis and SAR of their derivatives

Sixteen muraymycin derivatives 2-17 were synthesized based on selective reactions of the primary and secondary amino groups of muraymycin Cl (1) with isocyanates and aldehydes. Disubstituted derivatives 3-9 demonstrated no activity against either MraY or MurG at less than or equal to 100 mug/mL whereas mono substituted derivatives 11-17 demonstrated good inhibitory activity, well correlated with the lipophilicity of the substituent introduced. In particular, the activity of derivatives 13 and 14 was comparable to that of muraymycin C1 in this assay. (C) 2002 Elsevier Science Ltd. All rights reserved.