774-55-0Relevant academic research and scientific papers
Nickel- and zinc-promoted [2 + 2 + 2] cycloaddition of diynes and α, β-enones
Ikeda, Shin-Ichi,Watanabe, Hitomi,Sato, Yoshiro
, p. 7026 - 7029 (1998)
The [2 + 2 + 2] cycloaddition of diynes and enones occurred in the presence of both nickel and zinc together. This binary metal-mediated reaction had two interesting features: (1) a terminally unsubstituted diyne reacted with an enone to give an aromatic compound with the concomitant incorporation of two hydrogen atoms abstracted from an expected 1, 3-diene product into another molecule of the starting enone and (2) a trimethylsilyl-substituted diyne reacted with an equimolar amount of enone to regioselectively afford a 1, 3-diene, in which the trimethylsilyl group is adjacent to the carbonyl group.
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.
Hydrogen bond donor solvents enabled metal and halogen-free Friedel–Crafts acylations with virtually no waste stream
Liu, Guangchang,Xu, Bo
supporting information, p. 869 - 872 (2018/02/09)
We have developed a metal and halogen-free Friedel–Crafts acylation protocol with virtually no waste stream generation. We propose a hydrogen bonding donor solvent will form a hydrogen bonding network and may provide significant rate enhancement for Friedel–Crafts reactions. Trifluoroacetic acid is one of the strongest H-bond donor solvents, which is also volatile and can be easily recovered by distillation without need for reaction workup. Our protocol is a ‘green’ Friedel–Crafts acylation process: 1) the catalyst can be recovered and reused; 2) using halogen free starting material (carboxylic acids anhydride or carboxylic acids); 3) no need for aqueous reaction work-up; 4) minimum or no waste steam generation.
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.
Selective catalytic hydrogenation of polycyclic aromatic hydrocarbons promoted by ruthenium nanoparticles
Bresó-Femenia, Emma,Chaudret, Bruno,Castillón, Sergio
, p. 2741 - 2751 (2015/05/27)
Ru nanoparticles stabilised by PPh3 are efficient catalysts for hydrogenation of polycyclic aromatic hydrocarbons (PAHs) containing 2-4 rings under mild reaction conditions. These compounds were partially hydrogenated with good to excellent selectivities just by optimizing the reaction conditions. The influence of the nature of substituents present in different positions of naphthalene on the selectivity of hydrogenation was also studied. Hydrogenation of products containing substituents at position 1 is slower than that of products containing substituents at position 2. In all cases, hydrogenation takes place mainly on the less substituted ring.
Exploring naphthyl-carbohydrazides as inhibitors of influenza A viruses
Barman, Sanmitra,You, Lei,Chen, Ran,Codrea, Vlad,Kago, Grace,Edupuganti, Ramakrishna,Robertus, Jon,Krug, Robert M.,Anslyn, Eric V.
, p. 81 - 90 (2014/01/06)
A library of hydrazide derivatives was synthesized to target non-structural protein 1 of influenza A virus (NS1) as a means to develop anti-influenza drug leads. The lead compound 3-hydroxy-N-[(Z)-1-(5,6,7,8-tetrahydronaphthalen-2-yl) ethylideneamino]naphthalene-2-carboxamide, which we denoted as "HENC", was identified by its ability to increase the melting temperature of the effector domain (ED) of the NS1 protein, as assayed using differential scanning fluorimetry. A library of HENC analogs was tested for inhibitory effect against influenza A virus replication in MDCK cells. A systematic diversification of HENC revealed the identity of the R group attached to the imine carbon atom significantly influenced the antiviral activity. A phenyl or cyclohexyl at this position yielded the most potent antiviral activity. The phenyl containing compound had antiviral activity similar to that of the active form of oseltamivir (Tamiflu), and had no detectable effect on cell viability.
Aromatic alkenylation using electrophilic organogallium reagent generated from allenylsilane and GaCl3
Kido, Yoshiyuki,Yonehara, Fumi,Yamaguchi, Masahiko
, p. 827 - 833 (2007/10/03)
Aromatic hydrocarbons are alkenylated with silylallene in the presence of GaCl3 at -90°C. Organometallic electrophiles generated from the allene and GaCl3 are the active species in this reaction. A modest level of ortho-selectivity is observed. While the silylallene reacts exclusively at the 2-position, 1,2-alkadiene reacts at the 1-position predominantly.
Ketone precursors for organoleptic compounds
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, (2008/06/13)
The invention discloses ketones of formula I: wherein, Y is an optionally substituted alkyl, cycloalkyl, or cycloalkylalkyl, wherein each alkyl group is straight or branched and each alkyl and cycloalkyl group is saturated or unsaturated; R1is hydrogen or a C1-6alkyl group that is substituted, saturated or unsaturated, straight or branched; A is a chromophoric substituted aromatic ring or ring system; n is an integer; and with the proviso that formula I is not 2-ethoxy-1-phenyl-ethanone. These compositions are useful for the delivery of organoleptic compounds, especially of flavors, fragrances, masking agents and antimicrobial compounds.
Highly regio- and stereoselective cocyclotrimerization and linear cotrimerization of α,β-unsaturated carbonyl compounds with alkynes catalyzed by nickel complexes
Sambaiah,Li,Huang,Lin,Rayabarapu,Cheng
, p. 3663 - 3670 (2007/10/03)
Cyclic enones 2-cyclohexen-1-one (1a), 4,4-dimethyl-2-cyclohexen-1-one (1b), 2-cyclopenten-1-one (1c), and 2-cyclohepten-1-one (1d) react with octa- 1,7-diyne (2) in THF in the presence of Ni(PPh3)2I2, ZnI2, and Zn powder at 62 °C to give [2 + 2 + 2] cycloaddition-dehydrogenation products 3a-d in 32-80% yields, α,β-Unsaturated lactone 5a (5,6-dihydro-2H-pyran-2-one) undergoes [2 + 2 + 2] cycloaddition with 2 to give both the corresponding cyclohexadiene product 6 (29%) and dehydrogenation product 7 (39%). Under similar reaction conditions, 3-buten-2-one reacts with 2 and various substituted hepta-1,6-diynes 9a-c to give [2 + 2 + 2] cycloaddition- dehydrogenation products 11a-d in 68-80% yields. Diphenylacetylene also reacts with 1a-d, 5a, and 2(5H)-furanone (5b) to afford the corresponding [2 + 2 + 2] cocyclotrimerization products 13a-d and 14a-b. No dehydrogenation of products 13 and 14 was observed under the reaction and workup conditions. The reactions of acrylates with alkynes catalyzed by nickel complexes give products that depend greatly on the reaction conditions. Treating ethyl acrylate (15a) with 1-phenyl-1-propyne (16) in the presence of Ni(PPh3)2Cl2 and Zn at 90 °C in toluene affords cocyclotrimerization product 19a as the major product (54% yield). However, treatment of CH2CHCOOR (R = Et and t-Bu) with mono alkynes 16 and 12 in the presence of Ni(PPh3)2X2 (X = Cl and I) and Zn powder in toluene at 60 °C affords the corresponding conjugated trienes 17a-c in 82-92% yields. The MS data of 17 firmly support an adduct of two molecules of alkyne and a molecule of acrylate. Similarly, the reaction of 15a with octa-1,7-diyne in the presence of Ni(PPh3)2I2, ZnI2, and zinc gives triene derivative 21 in 68% yield. NOE and X-ray results indicate that in these trienes the substituents from each alkyne and alkene moiety are cis to each other. The unique stereoselectivity can be attributed to the exclusive formation of seven- membered nickelacycloheptadiene intermediate 25 during the catalytic reaction.
Evaluation of retinoid lactones as topical therapeutic agents in dermatology
Lewin,Black,Bos,Goehring,Nair,Whiting,Bouquin,Tetrault,Carroll
, p. 983 - 992 (2007/10/03)
Purpose. Optimization of the therapeutic ratio of analogs of the topically active 11-cis,13-cis-12-hydroxymethylretinoic acid, δ-lactone (I) relative to antihyperproliferation and antihyperkeratinization vs. toxicity. Methods. Nine analogs of 1, in which variations were made in the lipophilic cyclohexenyl moiety or in the lactone ring, were evaluated for topical activity against hyperkeratinization, inhibition of TPA-induced DNA synthesis and for skin irritation. Results. Although more potent lactones than the parent lactone 1 were identified, none possessed the favorable therapeutic ratio associated with 1. Conclusions. The δ-lactone 1 possesses unique molecular features responsible for its desirable therapeutic ratio as an anti-hyperproliferative and antihyperkeratotic agent. In view of its very low systemic retinoid toxicity and the absence of any systemic toxicity, this lactone may be a good candidate for use in the topical treatment of acne.
