845674-61-5Relevant 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.
Construction of an all-substituted pyrrolidine derivative with multiple stereogenic centers and Betti-base-derived γ-amino alcohols by [1,2]-Wittig rearrangement
Wang, Cai-Yun,Dong, Cheng,Zheng, Zhan-Jiang,Xu, Zheng,Yang, Ke-Fang,Xu, Li-Wen
, p. 55819 - 55824 (2015/07/15)
A new class of substituted γ-amino alcohols and downstream pyrrolidine derivatives have been synthesized successfully from simple 1-phenyl-ethylamine, in which a representative all-substituted pyrrolidine derivative with multiple stereogenic centers was obtained by highly diastereoselective [1,2]-Wittig rearrangement and intramolecular cyclization with perfect chirality transfer (up to >99.9% de) and good yields.
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.
Application of optically active aminonaphthols as NMR solvating agents for chiral discrimination of mandelic acid
Chaudhary, Anju R.,Yadav, Priyanka,Bedekar, Ashutosh V.
, p. 767 - 774 (2014/06/09)
A series of optically active aminonaphthol derivatives were prepared and screened as chiral solvating agents to discriminate the CαH of racemic mandelic acid by 1H NMR analysis. An effort was made to establish a correlation of the structure of aminonaphthol derivatives and the selectivity in this non-covalent interaction. A linear relationship between the experimental and calculated enantiomeric purity was established by indicating the potential use of the system to determine the ee for the samples of mandelic acid of unknown enantiomeric purity.
Bioactivity of a family of chiral nonracemic aminobenzylnaphthols towards candida albicans
Capozzi, Maria Annunziata M.,Cardellicchio, Cosimo,Magaletti, Angela,Bevilacqua, Antonio,Perricone, Marianne,Corbo, Maria Rosaria
, p. 5219 - 5230 (2014/05/20)
Chiral nonracemic aminobenzylnaphthols were obtained by a Betti multicomponent reaction between 2-naphthol, aryl aldehydes and enantiopure arylethylamine. Moreover, some new aminobenzylnaphthols were synthesized by a similar reaction between 2-naphthol, aryl aldehydes and prolinol. These aminobenzylnaphthols, synthesized from different components and thus having different structural features, were tested as anti-yeast agents inhibiting Candida albicans. The effect towards the test strain was studied with a microdilution approach and three different concentrations (150, 300 and 450 μg/mL) were tested. The best results were found for the aminobenzylnaphthols obtained from 1-naphthylethylamine and from natural prolinol. The use of the two-way ANOVA highlighted the better performances of the prolinol derivative among the differently structured aminobenzylnaphthols that were screened. The activity towards C. albicans of this prolinol derivative resulted to be interesting and could represent a promising alternative to overcome the problem of the strains resistant to the traditional antifungals.
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
Investigation on the weak interactions assembling the crystal structures of Betti bases
Cardellicchio, Cosimo,Capozzi, Maria Annunziata M.,Alvarez-Larena, Angel,Piniella, Joan F.,Capitelli, Francesco
experimental part, p. 3972 - 3981 (2012/07/28)
The crystal structures of (S, S)-aminobenzylnaphthols, easily produced by a chromatography-free highly stereoselective Betti reaction, were investigated by means of single crystal X-ray diffraction analysis, and the main intra- and intermolecular interactions were described. The presence of a strong intramolecular hydrogen bond was confirmed, whereas the whole crystal building was found to be due mainly to other bondings, such as CH...O and CH...π interactions. As far as the last interactions were concerned, we observed many short distances from one hydrogen atom to an aryl plane, together with the appropriate geometric requirements for the assemblies. The observations suggest that these interactions can play a relevant role in the crystal building. The absence of similar short distance CH...π interactions in the crystal of a diastereomeric (R, S)-aminobenzylnaphthol could be a suggestion of the preferential crystallisation of the (S, S)-stereoisomer and, consequently, its prevalence as a product of the Betti reaction.
Application of 1-(α-aminobenzyl)-2-naphthols as air-stable ligands for pd-catalyzed Mizoroki-Heck coupling reaction
Chaudhary, Anju R.,Bedekar, Ashutosh V.
experimental part, p. 1778 - 1785 (2012/04/10)
Air-stable, easily accessible Mannich bases, 1-(α-aminobenzyl)-2- naphthols, are used as ligands in palladium-catalyzed Mizoroki-Heck reaction on a variety of substrates. High turnover numbers are observed for both the reactions with aryl bromides and iodides, while aryl chlorides are inert. Copyright Taylor & Francis Group, LLC.
Structural influence of chiral tertiary aminonaphthol ligands on the asymmetric phenyl transfer to aromatic aldehydes
Wei, Hui,Yin, Lu,Luo, Haibin,Li, Xingshu,Chan, Albert S. C.
experimental part, p. 222 - 227 (2012/03/27)
A series of chiral tertiary aminonaphthol ligands were prepared from 2-naphthol, (S)-1-phenylethylamine, and aldehydes with diverse substituted groups. The results of asymmetric phenyl transfer to aromatic aldehydes catalyzed by these chiral ligands indicated that enantioselectivities were greatly influenced by the electronic and steric effects of the ligands. Copyright
