1395409-50-3

Upstream product

• 1093191-20-8 4-[4-(2-(trimethylsilyl)ethynyl)benzyl]morpholine 
• 132833-51-3 4-[(4-bromophenyl)methyl]morpholine 
• 589-15-1 1-bromomethyl-4-bromobenzene 
• 1395409-46-7 methyl (3aR,4S,6S,6aR)-6-(4-iodophenyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylate 
• 933986-59-5 4-(morpholinomethyl)phenylacetylene 
• 1395409-48-9 methyl (2S,3R,4S,5S)-3,4-dihydroxy-5-(4-iodophenyl)-2,3,4,5-tetrahydrofuran-2-carboxylate 
• 1395409-44-5 (R)-1-[(3aS,4R,6S,6aR)-6-(4-iodophenyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]ethane-1,2-diol 

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.

Design and stereoselective synthesis of a C-aryl furanoside as a conformationally constrained CHIR-090 analogue

The UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC) is a promising target for the development of novel antibiotic substances against multidrug-resistant Gram-negative bacteria. The C-aryl glycoside 3 was designed as conformationally constrained analogue of the potent LpxC-inhibitor CHIR-090. The chiral pool synthesis of 3 started with d-mannose. The C-aryl glycoside 8 was synthesized stereoselectively by nucleophilic attack of 4-iodine-substituted phenyllithium and subsequent reduction with Et 3SiH. The ester 10 was obtained in a one-pot diol cleavage, CrO 3 oxidation, and esterification. A Sonogashira reaction of the aryl iodide 11 led to the alkyne 17 which was transformed with H2NOH into the hydroxamic acid 3.