1234357-55-1

Upstream product

• 629-80-1 n-hexadecylaldehyde 
• 1211774-29-6 C₁₈H₃₀Cl₃N₅O₈S 
• 1146698-92-1 tert-butyl 5-O-[5-tert-butoxycarbonylamino-5-deoxy-2,3-O-(3-pentylidene)-β-D-ribo-pentofuranosyl]-6-deoxy-6-(3-isocyanopropyl)amino-2,3-O-isopropylidene-1-(uracil-1-yl)-β-D-glycelo-L-talo-heptofuranuronate 
• 20781-20-8 2,4-Dimethoxybenzylamine 

Relevant academic research and scientific papers

Synthesis and biological evaluation of muraymycin analogues active against anti-drug-resistant bacteria

Muraymycin analogues with a lipophilic substituent were synthesized using an Ugi four-component assemblage. This approach provides ready access to a range of analogues simply by altering the aldehyde component. The impact of the lipophilic substituent on the antibacterial activity was very large, and analogues 7b-e and 8b-e exhibited good activity against a range of Gram-positive bacterial pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. This study also showed that the accessory urea-dipeptide motif contributes to MraY inhibitory and antibacterial activity. The knowledge obtained from our structure-activity relationship study of muraymycins provides further direction toward the design of potent MraY inhibitors. This study has set the stage for the generation of novel antibacterial lead compounds based on muraymycins.

Mechanistic analysis of muraymycin analogues: A guide to the design of MraY inhibitors

The systematic structure-activity relationship (SAR) of the muraymycins (MRYs) using an Ugi four-component reaction (U4CR) was investigated. The impact of the lipophilic substituent on antibacterial activity was significant, and the analogues 8 and 9 having a lipophilic side chain exhibited good activity against a range of Gram-positive bacterial pathogens, including MRSA and VRE. Further investigation of compounds 8 and 9 revealed these analogues to be selective inhibitors of the MraY transferase and nontoxic to HepG2 cells. The SAR of the accessory urea-peptide moiety indicated that it could be simplified. Our SAR study of the MRYs suggests a probable mechanism for inhibition of the MraY, where the inner moiety of the urea-dipeptide motif interacts with the carbohydrate recognition domain in the cytoplasmic loop 5. The predicted binding model would provide further direction toward the design of potent MraY inhibitors. This study has set the stage for the generation of novel antibacterial "lead" compounds based on MRYs. (Figure presented)