Phosphine-Catalyzed Doubly Stereoconvergent γ-Additions of Racemic Heterocycles to Racemic Allenoates: The Catalytic Enantioselective Synthesis of Protected α,α-Disubstituted α-Amino Acid Derivatives

Methods have recently been developed for the phosphine-catalyzed asymmetric γ-addition of nucleophiles to readily available allenoates and alkynoates to generate useful α,β-unsaturated carbonyl compounds that bear a stereogenic center in either the γ or the δ position (but not both) with high stereoselectivity. The utility of this approach would be enhanced considerably if the stereochemistry at both termini of the new bond could be controlled effectively. In this report, we describe the achievement of this objective, specifically, that a chiral phosphepine can catalyze the stereoconvergent γ-addition of a racemic nucleophile to a racemic electrophile; through the choice of an appropriate heterocycle as the nucleophilic partner, this new method enables the synthesis of protected α,α-disubstituted α-amino acid derivatives in good yield, diastereoselectivity, and enantioselectivity

Poliisina politiikassa, vai poliitikkona poliisissa?

Opinnäytetyön tavoitteena on selvittää kunnallispolitiikassa toimivien poliisien ajatus- ja arvomaailmaa ja heidän ammatillisen kaksoisroolinsa yhdistämisen mukanaan tuomia mahdollisia ristiriitoja ja haasteita. Työssä pyritään myös vastaamaan siihen, miten poliisi pystyy politiikassa toimiessaan edistämään sekä kansalaisten, että poliisin asioita ja miten poliisin arvomaailma, ammatti-identiteetti ja eettiset periaatteet näkyvät poliittisessa toimintaympäristössä. Tutkimuksessa pohditaan myös miten puolueettomuus virkamiehenä ja poliittinen asioiden ajaminen kohtaavat politiikassa. Työn teoreettinen viitekehys tarkastelee Suomen julkisen vallan historiaa ja nykytilaa, selventää politiikan käsitteitä ja avaa kunnallisen päätöksenteon keskeisiä elementtejä. Työssä arvioidaan poliisin etiikkaa, arvomaailmaa ja ammatti-identiteettiä. Tietoperustana on hyödynnetty poliisin etiikkaa ja arvoja käsitteleviä ohjeita ja kommentaareja, Suomen valtiosäännöstä ja hallintotavasta kertovia teoksia sekä kunnallispolitiikasta kertovaa kirjallisuutta. Opinnäytetyö toteutettiin kvalitatiivisena tutkimuksena teemahaastatteluiden muodossa. Haastateltaviksi valikoitui kolme useita vuosia poliisissa toiminutta ja kunnallispolitiikassa vaikuttanutta henkilöä eri puolilta Suomea. Haastattelut tallennettiin ja litteroitiin, ennen kuin ne purettiin ja jaoteltiin analysoitaviksi teemoiksi. Tutkimuksessa selvisi, että poliisien ammatti-identiteetti näkyy ja kuuluu kunnallispolitiikassakin. Tutkimuksen mukaan poliisius on positiivinen arvo myös politiikassa ja poliisin eettisiä periaatteita halutaan noudattaa niin työssä, kuin vapaa-ajallakin. Poliisin monipuolisesta ammattitaidosta ja ihmistuntemuksesta on hyötyä politiikassa, mutta yhtä lailla politiikka hyödyntää poliisia laajemman yhteiskunnallisen tuntemuksen ja avarakatseisuuden merkeissä

Caution in the Use of Nonlinear Effects as a Mechanistic Tool for Catalytic Enantioconvergent Reactions: Intrinsic Negative Nonlinear Effects in the Absence of Higher-Order Species

Investigation of the dependence of product enantiometric excess (ee) on catalyst ee is a widely used tool to probe the mechanism of an enantioselective reaction; in particular, the observation of a nonlinear relationship is usually interpreted as an indication of the presence of one or more species that contain at least two units of the chiral entity. In this report, we demonstrate that catalytic enantioconvergent reactions can display an intrinsic negative nonlinear effect that originates purely from the kinetic characteristics of certain enantioconvergent processes and is independent of possible aggregation of the chiral entity. Specifically, this intrinsic negative nonlinear effect can arise when there is a kinetic resolution of the racemic starting material, and its magnitude is correlated with the selectivity factor and the conversion; the dependence on conversion provides a ready means to distinguish it from a more conventional nonlinear effect. We support our analysis with experimental data for two distinct enantioconvergent processes, one catalyzed by a chiral phosphine and the other by a chiral Pd/phosphine complex

Phosphine-Catalyzed Enantioselective Intramolecular [3+2] Annulations To Generate Fused Ring Systems

Substantial progress has been described in the development of asymmetric variants of the phosphine-catalyzed intermolecular [3+2] annulation of allenes with alkenes; however, there have not been corresponding advances for the intramolecular process, which can generate a higher level of complexity (an additional ring and stereocenter(s)). In this study, we describe the application of chiral phosphepine catalysts to address this challenge, thereby providing access to useful scaffolds that are found in bioactive compounds, including diquinane and quinolin-2-one derivatives, with very good stereoselectivity. The products of the [3+2] annulation can be readily transformed into structures that are even more stereochemically rich. Mechanistic studies are consistent with β addition of the phosphepine to the allene being the turnover-limiting step of the catalytic cycle, followed by a concerted [3+2] cycloaddition to the pendant olefin

Mg2+-Dependent Methyl Transfer by a Knotted Protein: A Molecular Dynamics Simulation and Quantum Mechanics Study

Mg2+ is required for the catalytic activity of TrmD, a bacteria-specific methyltransferase that is made up of a protein topological knot-fold, to synthesize methylated m1G37-tRNA to support life. However, neither the location of Mg2+ in the structure of TrmD nor its role in the catalytic mechanism is known. Using molecular dynamics (MD) simulations, we identify a plausible Mg2+ binding pocket within the active site of the enzyme, wherein the ion is coordinated by two aspartates and a glutamate. In this position, Mg2+ additionally interacts with the carboxylate of a methyl donor cofactor S-adenosylmethionine (SAM). The computational results are validated by experimental mutation studies, which demonstrate the importance of the Mg2+-binding residues for the catalytic activity. The presence of Mg2+ in the binding pocket induces SAM to adopt a unique bent shape required for the methyl transfer activity and causes a structural reorganization of the active site. Quantum mechanical calculations show that the methyl transfer is energetically feasible only when Mg2+ is bound in the position revealed by the MD simulations, demonstrating that its function is to align the active site residues within the topological knot-fold in a geometry optimal for catalysis. The obtained insights provide the opportunity for developing a strategy of antibacterial drug discovery based on targeting of Mg2+-binding to TrmD

Cleavage of pyrene-stabilized RNA bulge loops by trans-(±)-cyclohexane-1,2-diamine

Chemical agents that cleave HIV genome can be potentially used for anti-HIV therapy. In this report, the cleavage of the upper stem-loop region of HIV-1 TAR RNA was studied in a variety of buffers containing organic catalysts. trans-(±)-Cyclohexane-1,2-diamine was found to cleave the RNA with the highest activity (31%, 37°C, 18 h). Cleavage of the RNA in trans-(±)-cyclohexane-1,2-diamine buffer was also studied when the RNA was hybridized with complementary DNAs. A pyrene-modified C3 spacer was incorporated to the DNA strand to facilitate the formation of a RNA bulge loop in the RNA/DNA duplex. In contrast, unmodified DNAs cannot efficiently generate RNA bulge loops, regardless of the DNA sequences. The results showed that the pyrene-stablized RNA bulge loops were efficiently and site-specifically cleaved by trans-(±)-cyclohexane-1,2-diamine

Chirality transfer in metal-­‐catalysed intermolecular addition reactions involving allenes

Allene chemistry in the presence of transition metal complexes is nowadays a very important topic that underpins many challenges and advances in organic synthesis. The amount of research articles covering new transformations of allenes is vast and the development of enantioselective reactions involving allenes has flourished in the last 10-15 years. In this review we cover three important topics in allene chemistry that we feel are timely appropriate for this special issue celebrating the work of Prof Trost: the metal-catalysed reactions involving chirality transfer from chiral allenes to products; the analysis of the possible racemization processes that have been observed in the interaction of some metals with allenes; and the chirality transfer using racemic allenes in reactions catalysed by metal complexes bearing chiral ligands to produce enantioriched products. We have focussed the review on intermolecular addition reactions as they are still much less explored than the intramolecular version