130222-84-3Relevant articles and documents
Chiral Pool Synthesis, Biological Evaluation and Molecular Docking Studies of C-Furanosidic LpxC Inhibitors
Dreger, Alexander,Kharwb, Omar,Agoglitta, Oriana,Bülbül, Emre F.,Melesina, Jelena,Sippl, Wolfgang,Holl, Ralph
, (2019)
Inhibitors of the bacterial deacetylase LpxC are a promising class of novel antibiotics, being selectively active against Gram-negative bacteria. To improve the biological activity of reported C-furanosidic LpxC inhibitors, the stereochemistry at positions 3 and 4 of the tetrahydrofuran ring was varied. In chiral pool syntheses starting from d-gulono-γ-lactone and d-ribose, a series of (3S,4R)-configured dihydroxytetrahydrofuran derivatives was obtained, of which the (2S,5S)-configured hydroxamic acid 15 ((2S,3S,4R,5S)-N,3,4-trihydroxy-5-(4-{[4-(morpholinomethyl)phenyl]ethynyl}phenyl)tetrahydrofuran-2-carboxamide) was found to be the most potent LpxC inhibitor (Ki=0.4 μm), exhibiting the highest antibacterial activity against E. coli BL21 (DE3) and the D22 strain. Additionally, molecular docking studies were performed to rationalize the obtained structure–activity relationships.
Synthesis, biological evaluation, and molecular docking studies of deoxygenated C-glycosides as LpxC inhibitors
Dreger, Alexander,Hoff, Katharina,Agoglitta, Oriana,Bülbül, Emre F.,Melesina, Jelena,Sippl, Wolfgang,Holl, Ralph
, (2021/11/11)
The bacterial deacetylase LpxC is a promising target for the development of novel antibiotics being selectively active against Gram-negative bacteria. In chiral pool syntheses starting from D- and L-ribose, a series regio- and stereoisomeric monohydroxyte
Sequential Norrish type II photoelimination and intramolecular aldol cyclization of α-diketones: Synthesis of polyhydroxylated cyclopentitols by ring contraction of hexopyranose carbohydrate derivatives
Alvarez-Dorta, Dimitri,Leon, Elisa I.,Kennedy, Alan R.,Martin, Angeles,Perez-Martin, Ines,Riesco-Fagundo, Concepcion,Suarez, Ernesto
, p. 10312 - 10333 (2013/09/02)
The excitation of the innermost carbonyl of nono-2,3-diulose derivatives by irradiation with visible-light initiates a sequential Norrish type II photoelimination and aldol cyclization process that finally gives polyfunctionalized cyclopentitols. The rearrangement has been confirmed by the isolation of stable acyclic photoenol intermediates that can be independently cyclized by a thermal 5-(enolexo)-exo-trig uncatalyzed aldol reaction with high diastereoselectivity. In this last step, the large deuterium kinetic isotope effect found for the 1,5-hydrogen atom transfer seems to indicate that the aldol reaction runs through a concerted pericyclic mechanism. Owing to the ready availability of pyranose sugars of various configurations, this protocol has been used to study the influence of pyranose ring-substituents on the diastereoselectivity of the aldol cyclization reaction. In contrast with other pyranose ring contraction methodologies no transition-metal reagents are needed and the sequential rearrangement occurs simply by using visible light and moderate heating (0 to 60 °C). Copyright
