Investigation Of Enantioselectivity Research Articles

Investigation of Enantioselectivity Using TADDOL Derivatives as Chiral Ligands in Asymmetric Cyanation Reactions.

This study investigates the enantioselectivity challenges of asymmetric cyanation reactions using TADDOL derivatives as chiral ligands, specifically focusing on the cyanosilylation of aldehydes and the cyanation of imines. Despite extensive optimization efforts, the highest achieved ee was only modest, peaking at 71% for the cyanosilylation reaction, while the cyanation of imines consistently resulted in racemic mixtures. Our comprehensive analysis, supported by experimental data and computational modeling, reveals significant barriers to enhancing the enantioselectivity. The results highlight a complex interplay between ligand structure and reaction conditions, demonstrating that even promising ligands such as TADDOL derivatives face substantial challenges in these reaction types. This study underscores the importance of understanding the mechanistic details through computational insights to guide future improvements in asymmetric catalysis.

New chiral derivatives of xanthones: Synthesis and investigation of enantioselectivity as inhibitors of growth of human tumor cell lines

A highly efficient and practical methodology for synthesis of new chiral derivatives of xanthones (CDXs) in enantiomerically pure form has been developed. According to this approach, thirty CDXs (3–32) were synthesized by coupling a carboxyxanthone (1) and a carboxymethoxyxanthone (2) with both enantiomers of commercially available chiral building blocks, namely six amino alcohols, one amine and one amino ester. The activation of the carboxylic acid group of the xanthonic scaffold was carried out with the coupling reagent O-(benzotriazol-1-yl)-N-N-N′-N′-tetramethyluronium tetrafluoroborate (TBTU), in the presence of a catalytic amount of TEA in anhydrous THF. The coupling reactions with the chiral blocks were performed at room temperature with short reactions times, excellent yields (ranging from 94% to 99%), and very high enantiomeric excess. The synthesized CDXs were evaluated for their effect on the in vitro growth of three human tumor cell lines, namely A375-C5 (melanoma), MCF-7 (breast adenocarcinoma), and NCI-H460 (non-small cell lung cancer). The most active compound was CDX 15 being active in all human tumor cell lines with values of GI50 of 32.15±2.03μM for A375-C5, 22.55±1.99μM for MCF-7, and 14.05±1.82μM for NCI-H460. Nevertheless, some CDXs showed cell-type selectivity. Furthermore, the growth inhibitory effects, in some cases, demonstrated to be depending on the stereochemistry of the CDXs. An interesting example was observed with the enantiomers 3 and 4, which demonstrated high enantioselectivity for MCF-7 and NCI-H460 cell lines. It can be inferred that the effects on the growth of the human tumor cell lines can be ascribed not only to the nature and positions of substituents on the xanthonic scaffold but also to the stereochemistry of the CDXs. Some considerations regarding structure–activity relationship within this class of compounds will be highlighted.

An Investigation of Adsorption Enantioselectivity of Faceted Polycrystalline Platinum and Gold Electrodes

The present work presents an investigation of the enantioselectivity of (111) and (100) faceted polycrystalline platinum and gold electrodes. Electrochemical faceting of these polycrystalline electrodes was carried out by application of a suitable square wave that induces preferential dissolution of some crystallographic planes. The chirality of the produced surfaces was investigated by testing the ability of the prepared surfaces to discriminate voltammetrically between some amino acids and sugar enantiomers upon adsorption at the above-mentioned surfaces. The results indicate that all the polycrystalline electrodes were achiral. Faceted platinum and gold electrodes, however, possess some chirality depending on the surface orientation. Pt(111) faceted electrodes were able to discriminate between enantiomers of the investigated phenylalanine and serine. Pt(100) faceted electrodes also were able to discriminate between the investigated enantiomers, but to a lower extent. Faceted gold electrodes showed a similar ability of discrimination between the investigated phenylalanine and serine enantiomers.

Investigation of enantioselectivity and enantiomeric elution order of propranolol and its ester derivatives on an ovomucoid-bonded column

The enantioselectivity and enantiomeric elution order of racemic propranolol (PP) and its ester derivatives (O-acetyl, -propionyl, -butyryl and -valeryl) on an ovomucoid (OVM)-bonded silica column were investigated with respect to eluent pH (from 3 to 7) and organic modifier (2-propanol, ethanol, methanol and acetonitrile). The enantioselectivity was dependent on the eluent pH and organic modifier used. Reversal of the enantiomeric elution order of racemic PP and its ester derivatives occurred around eluent pH 5–7 and/or by variation of the organic modifier used. The results reveal that chiral recognition or binding properties may be altered by a change in eluent pH and/or addition of orgnaic solvents. Reversal of the enantiomeric elution order suggests that there may be more than one binding site on the OVM-bonded column, and/or that at least two chiral recognition mechanisms may operate on the OVM-bonded column with regard to PP and its ester derivatives. Also, a conformational change of the OVM bonded structure might be caused by a change in eluent pH and/or addition of organic modifier.

ChemInform Abstract: A Theoretical Investigation of Enantioselectivity: Michael Reaction of Secondary Enamines with Enones

A theoretical study of the enantioselective Michael-type addition of chiral secondary enamines to enones has been achieved. In a first step, the structures of various free enamines have been investigated at the ab initio and MNDO levels. The results clearly show that upon substitution of the prototype vinylamine, the N-center is pyramidalized. The study of enamines with chiral N-substituents such as (S)-Ph(Me)CH or (S)-cyclohexyl(Me)CH reveals a very complex pattern, where up to 8 local energy minimums are characterized whose examination shows that no prediction can be. done regarding the final enantioselectivity of their reaction with enones. These sets of conformers can be regarded as nearly energetically degenerate, at least for the three or four ones of lowest energy. The study of the compact complexes formed between the latter optimal conformers and acrylaldehyde shows that: (i)syn complexation with respect to the N lone pair is the only one which remains possible for steric reason, (ii) small geometrical rearrangements take place as the complexation proceeds, (iii) no clear-cut correspondence exists between the relative sequence of the low-energy conformers of the free enamines and the sequence of the low-energy complexes, (iv) the examination of the relative gradients of the complexation energies provides an index for predicting the relative facilities of the enantiometric pathways, in good agreement with the experimental facts. Our study emphasizes the great complexity of systems of realistic size and brings about critical conclusions regarding classical ad hoc models.