2912-98-3Relevant articles and documents
Analogues of the Herbicide, N-Hydroxy- N-isopropyloxamate, Inhibit Mycobacterium tuberculosis Ketol-Acid Reductoisomerase and Their Prodrugs Are Promising Anti-TB Drug Leads
Kandale, Ajit,Patel, Khushboo,Hussein, Waleed M.,Wun, Shun Jie,Zheng, Shan,Tan, Lendl,West, Nicholas P.,Schenk, Gerhard,Guddat, Luke W.,McGeary, Ross P.
, p. 1670 - 1684 (2021/02/27)
New drugs to treat tuberculosis (TB) are urgently needed to combat the increase in resistance observed among the current first-line and second-line treatments. Here, we propose ketol-acid reductoisomerase (KARI) as a target for anti-TB drug discovery. Twenty-two analogues of IpOHA, an inhibitor of plant KARI, were evaluated as antimycobacterial agents. The strongest inhibitor of Mycobacterium tuberculosis (Mt) KARI has a Ki value of 19.7 nM, fivefold more potent than IpOHA (Ki = 97.7 nM). This and four other potent analogues are slow- and tight-binding inhibitors of MtKARI. Three compounds were cocrystallized with Staphylococcus aureus KARI and yielded crystals that diffracted to 1.6-2.0 ? resolution. Prodrugs of these compounds possess antimycobacterial activity against H37Rv, a virulent strain of human TB, with the most active compound having an MIC90 of 2.32 ± 0.04 μM. This compound demonstrates a very favorable selectivity window and represents a highly promising lead as an anti-TB agent.
Chiral N-hydroxybenzamides as potential catalysts for aerobic asymmetric oxidations
Capraro, Maria Grazia,Franchi, Paola,Lanzalunga, Osvaldo,Lapi, Andrea,Lucarini, Marco
, p. 6435 - 6443 (2014/08/05)
Chiral N-hydroxybenzamides (1H-3H) have been synthesized as precursors of chiral short-lived N-oxyl radicals 1?-3?. The latter species have been generated by oxidation of 1H-3H with Pb(OAc)4 or hydrogen abstraction from 1H-3H by the tert-butoxyl radical and characterized by UV-vis spectrophotometry and EPR spectroscopy. Through a kinetic study of the hydrogen atom transfer processes promoted by 1?-3? from three chiral benzylic substrates (1-phenylethylamine, 1-phenylethanol, and α-vinylbenzyl alcohol), a moderate chiral discrimination has been found, with selectivity factors 0.5 ≥ kH(S)/kH(R) ≥ 2.
A simple protocol for NMR analysis of the enantiomeric purity of chiral hydroxylamines
Tickell, David A.,Mahon, Mary F.,Bull, Steven D.,James, Tony D.
, p. 860 - 863 (2013/03/29)
A practically simple three-component chiral derivatization protocol for determining the enantiopurity of chiral hydroxylamines by 1H NMR spectroscopic analysis is described, involving their treatment with 2-formylphenylboronic acid and enantiopure BINOL to afford a mixture of diastereomeric nitrono-boronate esters whose ratio is an accurate reflection of the enantiopurity of the parent hydroxylamine.