András Kotschy

The first total synthesis of cicerfuran utilizing a one-pot synthesis of hydroxylated benzofurans

Abstract A simple one-pot procedure was elaborated for the preparation of hydroxylated benzofurans from halogenated phenols and was successfully applied to the first total synthesis of Cicerfuran, a natural defence agent of wild chickpea.

Efficient Copper-Catalyzed Trifluoromethylation of Aromatic and Heteroaromatic Iodides: The Beneficial Anchoring Effect of Borates

Efficient copper-catalyzed trifluoromethylation of aromatic iodides was achieved with TMSCF3 in the presence of trimethylborate. The Lewis acid was used to anchor the in situ generated trifluoromethyl anion and suppress its rapid decomposition. Broad applicability of the new trifluoromethylating reaction was demonstrated in the functionalization of different aromatic and heteroaromatic iodides.

A novel double ‘inverse electron-demand’ Diels-Alder reaction of azolyldienamines and tetrazines

Abstract Appropriately substituted azolyldienamines were found to undergo double ‘inverse electron-demand’ Diels-Alder reactions with tetrazine derivatives, yielding azolypyridazines and dihydropyridazines as products.

Selective ring opening of linearly and angularly fused triazolium salts

Abstract Angularly and linearly fused 1.2-. and 1.3-disubstituted [1,2,4]triazolium salts were synthesised and reacted with nucleophiles. The sites of attack were found to depend both on the type of annelation and substitution pattern: the linearly fused derivative reacted at the pyridine moiety, whereas the angularly condensed salts were attacked at one of the carbon atoms of the triazole ring, and subsequent ring openings occurred in both cases. For the experienced ambident reactivity a general mechanistic scheme was proposed and the annelation-dependent regioselectivity was rationalised on the basis of an MO approach.

Computational Prediction and Rationalization, and Experimental Validation of Handedness Induction in Helical Aromatic Oligoamide Foldamers

Metadynamics simulations were used to describe the conformational energy landscapes of several helically folded aromatic quinoline carboxamide oligomers bearing a single chiral group at either the C or N terminus. The calculations allowed the prediction of whether a helix handedness bias occurs under the influence of the chiral group and gave insight into the interactions (sterics, electrostatics, hydrogen bonds) responsible for a particular helix sense preference. In the case of camphanyl-based and morpholine-based chiral groups, experimental data confirming the validity of the calculations were already available. New chiral groups with a proline residue were also investigated and were predicted to induce handedness. This prediction was verified experimentally through the synthesis of proline-containing monomers, their incorporation into an oligoamide sequence by solid phase synthesis and the investigation of handedness induction by NMR spectroscopy and circular dichroism.

Synthesis and transformations of tetrazolylacroleins

1-Methoxy-4-aryltetrazolyldienes have been subjected to oxidative degradation to yield tetrazolyl acroleins. These compounds when reacted with 1,1-dimethylhydrazine gave 1-dimethylamino-4-aryltetrazolyl-1-azadienes. Both the acroleins and the new 1-azadienes underwent ring transformation in reaction with fumaronitrile to afford pyrazolyl derivatives.

Structure–Activity Relationship of Azaindole-Based Glucokinase Activators

7-Azaindole has been identified as a novel bidentate anchor point for allosteric glucokinase activators. A systematic investigation around three principal parts of the new small molecule glucokinase activators led to a robust SAR in agreement with structural data that also helped to assess the conformational flexibility of the allosteric activation site. The increase in glucose uptake resulting from glucokinase activation in hepatocytes in vitro translated into the efficient lowering of glucose levels in vivo with the best compounds.

Computational study on the reactivity of tetrazines toward organometallic reagents.

The possible reaction pathways between methyllithium and disubstituted 1,2,4,5-tetrazines (bearing methyl, methylthio, phenyl, and 3,5-dimethylpyrazolyl groups) were investigated by means of the density functional theory B3LYP/6-31G* method. Solvation was modeled using the supermolecule approach, adding one tetrahydrofuran molecule to the complexes. Comparison of the calculated energies and structures for the alternate azaphilic and nucleophilic addition pathways showed that the azaphilic addition is kinetically favored over nucleophilic addition, while thermodynamically the nucleophilic addition is usually preferred. The coordination of the tetrazine molecule with methyllithium was found to play a crucial role in the process. These findings provide the first rationale for the experimentally observed unique reactivity of tetrazines toward polar organometallic reagents, suggesting the presence of a kinetically controlled process.

The influence of aryl substitution on the photophysics of 1-aryl-fluorenones

Abstract 1-aryl-fluorenone derivatives were prepared from fluorenone via 9-fluorenone-1-boronic acid by coupling with the corresponding aryl-halides. The photophysical properties of these derivatives were found to be strongly influenced by a new CT transition, resulting in some cases in dual luminescence.

Reactivity of some condensed heterocyclic cations towards ortho-positronium atoms in acetonitrile solution

Abstract The effect of changes in chemical structure and charge distribution of molecules on their reactivity towards an ortho-positronium ( o -Ps) atom was investigated by positron annihilation lifetime spectroscopy. Molecules with very similar structural frameworks were selected as model systems. Bridgehead nitrogen-containing condensed heterocyclic pyridoazinium salts with 1–3 nitrogen atoms and their methyl-substituted analogues were studied in acetonitrile solutions. In both groups the reactivity towards o -Ps atoms increased drastically with the increasing number of N atoms, while only a slight decrease of reactivity was observed due to methyl substitution. The strong electron-withdrawing effect of the N atoms and the weak electron-donating character of the methyl group accounted for these observations. In contrast to the reaction with o -Ps atom, methyl substitution affected drastically the chemical reactivity of these molecules in ring opening reactions with secondary amines, where the methylated compounds did not react even under forcing conditions. In the light of the o -Ps lifetime measurements a possible explanation for this fact is that the methyl group sterically hinders the attack of the secondary amines.