1452578-75-4

Upstream product

• 1452578-74-3 (3aR,4S,6S,6aR)-methyl 6-(4-ethynylphenyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylate 
• 932-87-6 1-Bromo-2-phenylacetylene 
• 1452578-73-2 (3aR,4S,6S,6aR)-methyl 2,2-dimethyl-6-(4-((trimethylsilyl)ethynyl)phenyl)tetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylate 

Downstream Products

• 1452578-76-5 (2S,3R,4S,5S)-methyl 3,4-dihydroxy-5-(4-(phenylbuta-1,3-diyn-1-yl)phenyl)tetrahydrofuran-2-carboxylate 

Relevant academic research and scientific papers

Synthesis and biological evaluation of flexible and conformationally constrained LpxC inhibitors

Inhibitors of the UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC) represent promising candidates for the development of antibiotics possessing a so far unexploited mechanism of action. In a chiral pool synthesis, starting from the d-mannose derived mannonolactone 4, conformationally constrained C-glycosidic as well as open chained hydroxamic acids with a defined stereochemistry were prepared. Diversity was introduced by performing C-C coupling reactions like the Sonogashira and Suzuki cross-coupling reactions. The biological evaluation of the synthesized compounds revealed that in the case of the C-glycosides a long, linear and rigid hydrophobic side chain is required for antibiotic activity against E. coli. The open chain derivatives show higher biological activity than the conformationally constrained C-glycosides. The morpholinomethyl substituted open chain derivative 43, being the most potent compound presented in this paper, inhibits LpxC with a K i value of 0.35 μM and represents a promising lead structure. The Royal Society of Chemistry.