2234-14-2Relevant academic research and scientific papers
Steric Demand and Rate-determining Step for Photoenolization of Di-ortho-substituted Acetophenone Derivatives
Das, Anushree,Thomas, Suma S.,Garofoli, August A.,Chavez, Kevin A.,Krause, Jeanette A.,Bohne, Cornelia,Gudmundsdottir, Anna D.
, p. 154 - 162 (2019)
Laser flash photolysis of ketone 1 in argon-saturated methanol yields triplet biradical 1BR (τ = 63 ns) that intersystem crosses to form photoenols Z-1P (λmax = 350 nm, τ ~ 10 μs) and E-1P (λmax = 350 nm, τ > 6 ms). The activation barrier for Z-1P re-forming ketone 1 through a 1,5-H shift was determined as 7.7 ± 0.3 kcal mol?1. In contrast, for ketone 2, which has a less sterically hindered carbonyl moiety, laser flash photolysis in argon-saturated methanol revealed the formation of biradical 2BR (λmax = 330 nm, τ ~ 303 ns) that intersystem crosses to form photoenol E-2P (λmax = 350 nm, τ > 42 μs), but photoenol Z-2P was not detected. However, in more viscous basic H-bond acceptor (BHA) solvent, such as hexamethylphosphoramide, triplet 2BR intersystem crosses to form both Z-2P (λmax = 370 nm, τ ~ 1.5 μs) and E-2P. Thus, laser flash photolysis of ketone 2 in methanol reveals that intersystem crossing from 2BR to form Z-2P is slower than the 1,5-H shift of Z-2P, whereas in viscous BHA solvents, the 1,5-H shift becomes slower than the intersystem crossing from 2BR to Z-2P. Density functional theory and coupled cluster calculations were performed to support the reaction mechanisms for photoenolization of ketones 1 and 2.
Design, synthesis and biological evaluation of novel aryldiketo acids with enhanced antibacterial activity against multidrug resistant bacterial strains
Cvijeti?, Ilija N.,Verbi?, Tatjana ?.,Ernesto de Resende, Pedro,Stapleton, Paul,Gibbons, Simon,Jurani?, Ivan O.,Drakuli?, Branko J.,Zloh, Mire
, p. 1474 - 1488 (2017/11/17)
Antimicrobial resistance (AMR) is a major health problem worldwide, because of ability of bacteria, fungi and viruses to evade known therapeutic agents used in treatment of infections. Aryldiketo acids (ADK) have shown antimicrobial activity against several resistant strains including Gram-positive Staphylococcus aureus bacteria. Our previous studies revealed that ADK analogues having bulky alkyl group in ortho position on a phenyl ring have up to ten times better activity than norfloxacin against the same strains. Rational modifications of analogues by introduction of hydrophobic substituents on the aromatic ring has led to more than tenfold increase in antibacterial activity against multidrug resistant Gram positive strains. To elucidate a potential mechanism of action for this potentially novel class of antimicrobials, several bacterial enzymes were identified as putative targets according to literature data and pharmacophoric similarity searches for potent ADK analogues. Among the seven bacterial targets chosen, the strongest favorable binding interactions were observed between most active analogue and S. aureus dehydrosqualene synthase and DNA gyrase. Furthermore, the docking results in combination with literature data suggest that these novel molecules could also target several other bacterial enzymes, including prenyl-transferases and methionine aminopeptidase. These results and our statistically significant 3D QSAR model could be used to guide the further design of more potent derivatives as well as in virtual screening for novel antibacterial agents.
Bispentiptycenyl-N-Heterocyclic Carbene (NHC) Gold Complexes: Highly Active Catalysts for the Room Temperature Hydration of Alkynes
Bergmann, Marvin,Heidrich, Maximillian,Müller-Borges, Dorian,Plenio, Herbert
, p. 3572 - 3578 (2018/09/22)
The virtually quantitative, room temperature hydration of various terminal and internal alkynes in methanol/water requires between 0.01–0.05 molpercent of [AuCl(NHC)] activated with 1.5 equiv. of silver triflate and 45 equiv. of triflic acid (both relative to gold complex) with ton of up to 300.000. Iptycenyl-substituted NHC ligands play the key role and the most efficient NHC ligand is characterized by a hemispherical shape formed by two N-pentiptycenyl substituents. (Figure presented.).
5-Aryl-1H-pyrazole-3-carboxylic acids as selective inhibitors of human carbonic anhydrases IX and XII
Cvijeti?, Ilija N.,Tan?, Muhammet,Jurani?, Ivan O.,Verbi?, Tatjana ?.,Supuran, Claudiu T.,Drakuli?, Branko J.
, p. 4649 - 4659 (2015/08/03)
Inhibitory activity of a congeneric set of 23 phenyl-substituted 5-phenyl-pyrazole-3-carboxylic acids toward human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I, II, IX and XII was evaluated by a stopped-flow CO2 hydrase assay. These compounds exerted a clear, selective inhibition of hCA IX and XII over hCAI and II, with Ki in two to one digit micromolar concentrations (4-50 μM). Derivatives bearing bulkier substituents in para-position of the phenyl ring inhibited hCA XII at one-digit micromolar concentrations, while derivatives having alkyl substituents in both ortho- and meta-positions inhibited hCA IX with Kis ranging between 5 and 25 μM. Results of docking experiments offered a rational explanation on the selectivity of these compounds toward CA IX and XII, as well as on the substitution patterns leading to best CA IX or CA XII inhibitors. By examining the active sites of these four isoforms with GRID generated molecular-interaction fields, striking differences between hCA XII and the other three isoforms were observed. The field of hydrophobic probe (DRY) appeared significantly different in CA XII active site, comparing to other three isoforms studied. To the best of our knowledge such an observation was not reported in literature so far. Considering the selectivity of these carboxylates towards membrane-associated over cytosolic CA isoforms, the title compounds could be useful for the development of isoform-specific non-sulfonamide CA inhibitors.
Observation of 1,3-diketones formation in the reaction of bulky acyl chlorides with methyllithium
Zhang, Jian,Yang, Nianfa,Yang, Liwen
, p. 6415 - 6423 (2012/09/08)
The formation of 1,3-diketones was observed in the reactions of bulky acyl chlorides with methyllithium. The reaction products depend on the steric hindrance around the carbonyl group of the acyl chloride and the electronic effect of the group(s) linked to the carbonyl. When the steric hindrance around the carbonyl group of the acyl chloride is big enough, the 1,3-diketone is the only product. In the case of the moderate hindrance around the carbonyl group of the acyl chloride, a moderate yield of 1,3-diketone is obtained and some tertiary alcohol is generated. When there is no steric hindrance around the carbonyl group of the acyl chloride, the tertiary alcohol is the only product. When the steric hindrance around the carbonyl group is moderate and an electron-donating group is connected to the carbonyl of the acyl chloride, all three products-ketone, 1,3-diketone and tertiary alcohol-can be isolated from the reaction mixture after long reaction times.
Efficient, large-scale preparation of (R)- and (S)-1-(2,4,6-triisopropylphenyl)ethanol, versatile chiral auxiliary for cyclopentenone, γ-butyrolactone, and γ-butyrolactam synthesis
Delair, Philippe,Kanazawa, Alice M.,De Azevedo, Mariangela B.M.,Greene, Andrew E.
, p. 2707 - 2710 (2007/10/03)
A particularly efficacious, low-cost preparation of both (R)- and (S)-triisopropylphenyl)-ethanol, useful chiral controllers in the dichloroketene-enol ether cycloaddition reaction, has been developed.
