Towards an asymmetric organocatalytic α-cyanation of β-ketoesters

AbstractThis communication describes the first proof of concept for an asymmetric α-cyanation of β-ketoesters using a hypervalent iodine-based electrophilic cyanide-transfer reagent. A series of different organocatalysts has been investigated and it was found that the use of naturally occurring Cinchona alkaloids allows obtaining the target products in good yields and with moderate enantioselectivities up to er=76:24 under operationally simple conditions

Susceptibility testing of Atopobium vaginae for dequalinium chloride

<p>Abstract</p> <p>Background</p> <p><it>Atopobium vaginae </it>and <it>Gardnerella vaginalis </it>are major markers for bacterial vaginosis. We aimed to determine the MIC and MBC range of the broad-spectrum anti-infective and antiseptic dequalinium chloride for 28 strains, belonging to 4 species of the genus <it>Atopobium, i.e. A. vaginae, A. minutum, A. rimae </it>and <it>A. parvulum</it>.</p> <p>Methods</p> <p>The MIC was determined with a broth microdilution assay.</p> <p>Results</p> <p>The MIC and MBC for <it>Atopobium </it>spp. for dequalinium chloride ranged between < 0.0625 and 2 μg/ml.</p> <p>Conclusions</p> <p>This study demonstrated that dequalinium chloride inhibits and kills clinical isolates of <it>A. vaginae </it>at concentrations similar to those of clindamycin and lower than those of metronidazole.</p

Isothiourea-catalyzed enantioselective functionalisation of glycine Schiff base aryl esters via 1,6- and 1,4-additions

The St Andrews team thanks the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT, grant code EP/L016419/1) (RC) for funding. The Linz team gratefully acknowledges generous financial support by the Austrian Science Funds (FWF) through project No. P31784.The enantioselective α-functionalisation of glycine Schiff base aryl esters through isothiourea catalysis is successfully demonstrated for 1,6-additions to para-quinone methides (21 examples, up to 95 : 5 dr and 96 : 4 er) and 1,4- additions to methylene substituted dicarbonyl or disulfonyl Michael acceptors (17 examples, up to 98 : 2 er). This nucleophilic organocatalysis approach gives access to a range of α-functionalised α-amino acid derivatives and further transformations of the activated aryl ester group provide a straightforward entry to advanced amino acid-based esters, amides or thioesters.Publisher PDFPeer reviewe

Bifunctional Phase Transfer Catalysis in the Asymmetric Synthesis of Biologically Active Isoindolinones

New bifunctional chiral ammonium salts were investigated in an asymmetric cascade synthesis of a key building block for a variety of biologically relevant isoindolinones. With this chiral compound in hand, the development of further transformations allowed for the synthesis of diverse derivatives of high pharmaceutical value, such as the Belliotti (S)-PD172938 and arylated analogues with hypnotic sedative activity, obtained in good overall total yield (50%) and high enantiomeric purity (95% ee). The synthetic routes developed herein are particularly convenient in comparison with the current methods available in literature and are particularly promising for large scale applications

Unveiling the impact of a CF2 motif in the isothiourea catalyst skeleton : evaluating C(3)-F2-HBTM and its catalytic activity

The St Andrews Team (A. D. S., K. K., M. T. W.) thanks the EaSI-CAT centre for Doctoral Training (MTW) and the EPSRC (EP/T023643/1; KK). The Linz team (L. S., A. E., M. W.) gratefully acknowledges generous financial support by the Austrian Science Funds (FWF) through project No. P31784, the Erasmus+ program and the JKU Linz/Upper Austria scheme. The Madrid team (J. A. F.-S., J. A., R. d. R-R.) gratefully acknowledges the Spanish Government (RTI2018-095038-B-100), “Communidad de Madrid” for European Structural Funds (S2018/NMT-4367) and proyectos sinergicos I + D (Y2020/NMT-6469) for funding. J. A. F.-S. thanks the Spanish government for a Ramón y Cajal contract.The incorporation of the CF2 motif within organic structures is known to affect the susceptibility of functional groups to oxidation, as well as altering conformation and reactivity. In this manuscript, the incorporation of the CF2 functional group within an isothiourea catalyst skeleton to give C(3)-F2-HBTM is reported. Effective gram-scale routes to both racemic and enantiopure heterocyclic Lewis bases are developed, with preliminary catalytic and kinetic activity evaluated.Peer reviewe

Asthma in changing environments - chances and challenges of international research collaborations between South America and Europe - study protocol and description of the data acquisition of a case-control-study

<p>Abstract</p> <p>Background</p> <p>Asthma in children is an emerging public health problem in South America. So far, research in this part of the world is limited. This paper presents the methodology and description of the data acquisition of an asthma case-control study conducted in the Central South of Chile.</p> <p>Methods/Design</p> <p>A hospital-based case-control study about asthma (188 cases, 294 controls) in children (6-15 years) was carried out in Valdivia, Chile between November 2008 and December 2009. Data on asthma risk factors were collected by computer-assisted personal interview using validated questions from e.g. ISAAC phase II. Data on household dust exposure (endotoxin, allergen analyses), skin prick tests to most common allergens, stool examinations for parasitic infection, and blood samples (total IgE, genetics) were collected. Additionally, 492 randomly chosen blood donors were recruited in order to assess allele frequencies in the population of Valdivia.</p> <p>Discussion</p> <p>Overall 1,173 participants were contacted. Response was 82% among cases and 65% among controls. Atopic sensitization was high (78% among cases, 47% among controls). Cases had a statistically significantly (p < .0001) increased self-reported 12-month prevalence of symptoms of rhinitis (82% vs. 51%) and wheeze (68% vs. 16%). The study is well placed to address current hypotheses about asthma and its correlates in the South American context. Results of this study might help develop novel, innovative and individualized prevention strategies in countries in transition with respect to the South American context.</p

Ammonium salt-catalyzed ring-opening of aryl-aziridines with β-keto esters

We herein report an ammonium salt-catalyzed protocol for the regioselective ring opening of aryl-aziridines with beta-keto esters. The reaction gives access to a variety of highly functionalized target molecules with two consecutive stereogenic centers and can be rendered enantioselective (up to e.r. = 91:9) by using bifunctional chiral ammonium salt catalysts

Benzylic Ammonium Ylide Mediated Epoxidations

A high yielding synthesis of stilbene oxides using ammonium ylides has been developed. It turned out that the amine leaving group plays a crucial role as trimethylamine gives higher yields than DABCO or quinuclidine. The amine group also influences the diastereoselectivity, and detailed DFT calculations to understand the key parameters of these reactions have been carried out

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

Chiral phase-transfer catalysis is one of the major catalytic principles in asymmetric catalysis. A broad variety of different catalysts and their use for challenging applications have been reported over the last decades. Besides asymmetric C–C bond forming reactions the use of chiral phase-transfer catalysts for enantioselective α-heterofunctionalization reactions of prochiral nucleophiles became one of the most important field of application of this catalytic principle. Based on several highly spectacular recent reports, we thus wish to discuss some of the most important achievements in this field within the context of this review