313963-79-0Relevant academic research and scientific papers
Bianthryl-based organocatalysts for the asymmetric Henry reaction of fluoroketones
Otevrel, Jan,Svestka, David,Bobal, Pavel
supporting information, p. 5244 - 5248 (2019/06/07)
We have developed a catalytic system based on bianthrylbis(thiourea) for the asymmetric Henry reaction of fluoroketones and nitroalkanes that resulted from the screening of a library containing 31 chiral non-racemic organocatalysts. The corresponding adducts were isolated in up to 6 times shorter reaction time in comparison with the previously published organocatalysts. High levels of stereocontrol have been generally observed, with measured product enantiomeric excesses up to 97% and diastereomeric ratio 3:2 (anti/syn). The above-mentioned catalysts have been successfully applied to the total asymmetric synthesis of CF3-tethered (S)-halostachines, which has proved that this method constitutes an easy entry to similar enantiopure compounds.
8-Hydroxyquinoline-based inhibitors of the Rce1 protease disrupt Ras membrane localization in human cells
Mohammed, Idrees,Hampton, Shahienaz E.,Ashall, Louise,Hildebrandt, Emily R.,Kutlik, Robert A.,Manandhar, Surya P.,Floyd, Brandon J.,Smith, Haley E.,Dozier, Jonathan K.,Distefano, Mark D.,Schmidt, Walter K.,Dore, Timothy M.
, p. 160 - 178 (2015/12/31)
Ras converting enzyme 1 (Rce1) is an endoprotease that catalyzes processing of the C-terminus of Ras protein by removing -aaX from the CaaX motif. The activity of Rce1 is crucial for proper localization of Ras to the plasma membrane where it functions. Ras is responsible for transmitting signals related to cell proliferation, cell cycle progression, and apoptosis. The disregulation of these pathways due to constitutively active oncogenic Ras can ultimately lead to cancer. Ras, its effectors and regulators, and the enzymes that are involved in its maturation process are all targets for anti-cancer therapeutics. Key enzymes required for Ras maturation and localization are the farnesyltransferase (FTase), Rce1, and isoprenylcysteine carboxyl methyltransferase (ICMT). Among these proteins, the physiological role of Rce1 in regulating Ras and other CaaX proteins has not been fully explored. Small-molecule inhibitors of Rce1 could be useful as chemical biology tools to understand further the downstream impact of Rce1 on Ras function and serve as potential leads for cancer therapeutics. Structure-activity relationship (SAR) analysis of a previously reported Rce1 inhibitor, NSC1011, has been performed to generate a new library of Rce1 inhibitors. The new inhibitors caused a reduction in Rce1 in vitro activity, exhibited low cell toxicity, and induced mislocalization of EGFP-Ras from the plasma membrane in human colon carcinoma cells giving rise to a phenotype similar to that observed with siRNA knockdowns of Rce1 expression. Several of the new inhibitors were more effective at mislocalizing K-Ras compared to a potent farnesyltransferase inhibitor (FTI), which is significant because of the preponderance of K-Ras mutations in cancer.
Synthesis of P-Stereogenic Phosphoramidite and Phosphorodiamidite Ligands and Their Application in Asymmetric Catalysis
Schmitz, Christian,Leitner, Walter,Franciò, Giancarlo
, p. 6205 - 6230 (2015/10/06)
A series of P-stereogenic monodentate phosphoramidite (PNO2) and phosphorodiamidite (PN2O) ligands based on chiral Betti bases has been prepared by modular synthetic procedures. The chirality at the phosphorus can be controlled to a large extent by the synthetic route, leading to stereoselective access to single P-epimers. The absolute configuration of the P-atom was assigned by X-ray diffraction analysis. The new ligands were evaluated in asymmetric catalysis and the influence of the exocyclic amine or alcohol moiety as well as the interplay between the P-chirality and the stereocenters in the backbone were investigated. Enantioselectivities of up to 85 and 83 % ee were obtained in the Rh-catalyzed hydrogenation of dimethyl itaconate and in the Pd-catalyzed allylic amination of (rac)-(E)-1,3-diphenylallyl acetate with benzylamine, respectively. In the Ni-catalyzed hydrovinylation of styrene, ee values of up to 68 %, excellent chemoselectivities, and high activities (TOFav up to 3000 h-1) were achieved. A series of phosphoramidite (R = OR) and phosphorodiamidite (R = NR2) ligands containing a stereogenic phosphorus atom has been synthesized from chiral Betti bases as amino alcohol building blocks. The new ligands have been applied in three different asymmetric metal-catalyzed reactions, and the interplay between P-stereochemistry, structural features of R, and chirality at the backbone evaluated.
Development of chiral heteroleptic magnesium amides; Asymmetric deprotonations mediated by six-membered metallocyclic amidomagnesium naphtholates
Carswell, Emma L.,Kerr, William J.,McArthur, Duncan,Pa?icky, Marek,Watson, Allan J.B.
, p. 7344 - 7349 (2016/01/25)
A series of enantioenriched six-membered metallocyclic amidomagnesium naphtholates were prepared and used to probe the structure-reactivity/selectivity relationships of heteroleptic magnesium base complexes within asymmetric deprotonation reactions. An ef
Borane-mediated asymmetric reduction of acetophenone by enantiopure aminonaphthols and aminoalcohols as catalytic source
Cimarelli, Cristina,Fratoni, Davide,Palmieri, Gianni
scheme or table, p. 655 - 661 (2010/08/22)
Practical, cheap, and stereoselective synthetic methods were applied to the preparation of novel 1-(aminoalkyl)naphthol and γ-aminoalcohol tridentate ligands. The ligands obtained were conveniently applied with good results as catalytic sources in the bor
Simple and convenient methods for synthesis, resolution and application of aminonaphthols
Periasamy, Mariappan,Anwar, Shaik,Reddy, Meda Narsi
experimental part, p. 1261 - 1273 (2010/02/28)
Racemic aminonaphthols are obtained in 70-95% yield by simple and straightforward condensation of benzaldehyde, 2naphlhol and 1° or 2° amines in ethanol solvent under refluxing conditions. The racemic aminonaphthols 1-(αaminobcnzyl)-2-naphthol and 1-(α-pyrrolidinylbenzyl)-2-naphthol have been resolved using L -(+)-tartaric acid. The racemic l-(a-/V- butylaminobenzyl)-2-naphthol and l-(a-piperidylbenzyl)-2-naphthol have been resolved using fl-(+)-BINOL and boric acid. The racemic (2-methoxynaphth-1-yl) benzylamine is resolved using dibenzoyl-L-(-)-tartaric acid. The readiliy accessible chiral aminonaphthols are useful for resolution of important moieties like racemic BINOL, ibuprofen and mandclic acid.
Highly diastereoselective aminoalkylation of naphthols with chiral amines mediated by lithium perchlorate solution in diethyl ether
Saidi, Mohammad R.,Azizi, Najmoddin
, p. 389 - 392 (2007/10/03)
One-pot, three-component, Mannich reaction of naphthols with in situ prepared imines in 5 M ethereal lithium perchlorate at room temperature affords the corresponding aminoalkylated products in high yields with high diastereoselectivities. The process is exemplified by the reaction of 2-naphthol with (R)-1-phenylethylamine and an aromatic aldehyde in concentrated ethereal lithium perchlorate solution, which affords a highly diastereoselective access to the requisite 2-aminoalkylated product.
Ready N-alkylation of enantiopure aminophenols: Synthesis of tertiary aminophenols
Cimarelli, Cristina,Palmieri, Gianni,Volpini, Emanuela
, p. 6089 - 6096 (2007/10/03)
A regioselective indirect alkylation of aminophenols to enantiopure tertiary aminophenols, which are useful chiral ligands for metal-catalysed asymmetric reactions, is reported. This very simple synthetic methodology, through reduction or alkylation of an intermediate benzoxazine, was performed in mild conditions, suitable for the conservation of the configuration of the stereogenic centres. Some crystalline aminophenols show the phenomenon of 'crystallization-induced asymmetric transformation'.
Solvent-free asymmetric aminoalkylation of electron-rich aromatic compounds: Stereoselective synthesis of aminoalkylnaphthols by crystallization-induced asymmetric transformation
Cimarelli,Mazzanti,Palmieri,Volpini
, p. 4759 - 4765 (2007/10/03)
Electron-rich aromatic compounds such as 2-naphthol give a faster and asymmetric 1-aminoalkylation with high yields when treated with (R)-1-phenylethylamine and aromatic aldehydes in solvent-free conditions. An asymmetric transformation of a second kind, probably induced by the preferential crystallization of one diastereomer, affords the straightforward and stereoselective synthesis of aminoalkylnaphthols. Mechanisms predictable for this asymmetric reaction are reported. The absolute configurations and the conformations of the unknown aminonaphthols are widely ascertained.
A practical o-hydroxybenzylamines promoted enantioselective addition of dialkylzincs to aldehydes with asymmetric amplification
Palmieri, Gianni
, p. 3361 - 3373 (2007/10/03)
The addition of dialkylzincs to aldehydes is accelerated considerably by the presence of a catalytic amount of o-hydroxybenzylamine (R,R)-2e to give, after hydrolysis, the corresponding alcohol (S)-9 in good enantiomeric purity. The origins of the enantioselection have been elucidated. A strong positive nonlinear relationship was observed for the reaction enantioselctivity with the use of o-hydroxybenzylamine 2e, which is very accessible through a short stereoselective synthetic route. The enantiomeric purity of the product 9 is much higher than the d.e. of the chiral source 2e, and the rate of the enantioselective catalysis increases considerably with the increase of the d.e. of (R,R)-2e. Copyright (C) 2000 Elsevier Science Ltd.
