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Four common cinchona alkaloids, i.e. quinine, quinidine, cinchonine and cinchonidine, were studied by Raman spectroscopy to show differences between corresponding pairs of pseudoenantiomers. Single spectra of the alkaloids measured with excitation at 532 and 1064 nm exhibit similar pattern and cannot be used for fast and reliable differentiation between the compounds. However, Raman Optical Activity (ROA) method applied to study aqueous solution of the alkaloids showed distinct differences between the compounds related to the absolute configuration at chiral atoms. It allowed unequivocal identification of the pseudoenantiomers on the basis of the sign of characteristic bands from a single measurement. The most important bands in Raman and ROA spectra were assigned according to literature. The work presented here shows for the first time ROA analysis of cinchona alkaloids and its powerfulness for investigation of chiral compounds that show similar Raman spectra. [ABSTRACT FROM AUTHOR]

Highlights: [•] Heterogeneous enantioselective hydrogenation of β-dehydroamino acids was achieved. [•] The enantioselectivity approached 46% for alky substituted β-dehydroamino acids. [•] The β-dehydroamino acids interacted efficiently with the chiral modifier. [•] This result offered a new approach to synthesize optical β-amino acids. [ABSTRACT FROM AUTHOR]

ABSTRACT In order to define an (NMR) method for the antiasthmatic drug montelukast, a series of nine easily available products were evaluated as NMR chiral solvating agents (CSAs): D-dibenzoyltartaric acid, D-ditoluoyltartaric acid, (+)-camphorsulfonic acid, ( S)-BINOL, ( S)-3,3'-diphenyl-2,2'-binaphthyl-1,1'-diol, ( R)-3,3'′-di-9-anthracenyl-1,1'′-bi-2-naphthol, ( R)-3,3'′-di-9-phenanthrenyl-1,1'′-bi-2-naphthol, Pirkle's alcohol, and (−)-cinchonidine. It was proved that most of the studied agents constitute diastereomeric complexes with both drug enantiomers in CD2Cl2 or CDCl3 solutions, thus permitting the direct 1H NMR detection of the unwanted S-enantiomer, even at levels of 0.75%. (−)-Cinchonidine was found to be the more convenient CSA in terms of NMR enantiodiscrimination power and ease of experimental requirements. The final method was validated and applied to the fast monitoring of the optical purity of montelukast 'in-process' samples, circumventing the need for tedious and slower analytical procedures like chromatography or . In addition, a method for the enantiopurity control of the commercial drug (montelukast sodium salt) was also established using ( S)-BINOL as NMR CSA. Chirality 25: 780-786, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Solvent effects in the enantioselective hydrogenation of ethyl benzoylformate (EBF) to ( R)-ethyl mandelate over (−)-cinchonidine (CD)-modified Pt/AlO catalyst were studied in a semi-batch reactor. Solvents of different nature were used: protic (2-propanol, 1-propanol, 1-octanol and ethanol), aprotic polar (methyl acetate, acetone, ethyl acetate and tetrahydrofuran) and apolar solvents (methyl cyclohexane and toluene). The effects of pure solvents and binary solvent mixtures on hydrogenation rates and enantioselectivity were investigated. The highest enantiomeric excess ( ee) of 72 % was obtained in ethyl acetate, decreasing nonlinearly with increasing dielectric constant (ε) being close to 20 % in ethanol. The highest value of the initial hydrogenation rate was obtained in the apolar solvents (21 mmol dm ming) while the lowest one was observed in tetrahydrofuran (2 mmol dm min g). A kinetic model was proposed for the enantioselectivity dependence on dielectric constant based on Kirkwood treatment. The non-linear dependence of ee on (ε) was included in the model to describe quantitatively the variation of ee in different solvents. The results showed a good fit for ee as a function of ε. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: The feasibility of the enantioselective electroreduction of pro-chiral acetophenone was investigated at the silver cathode in an undivided cell for the first time. Electroreduction of acetophenone in the presence of cinchonidine (CD) yielded two main products: the optically active alcohol, and the dimer product pinacol with no optical rotation. The influence of water in the co-solvent (MeCN/H2O), supporting electrolyte, electrode material, current density, and the alkaloid type on the enantiomeric excesses (ee) and yield was investigated. Under the optimized conditions, the alcohol was obtained with a 21.6% ee and a 3.6% yield, whereas, an 83.2% yield and a 5.5dl/meso ratio were obtained for pinacol. The electrochemical behavior of the samples was also studied through cyclic voltammetry (CV). Finally, we proposed a possible induction mechanism based on the results of the electrolysis and CV. [Copyright &y& Elsevier]

Highlights: [•] Cinchonidine was anchored over γ-Al2O3 using trimethoxysilane as coupling agent. [•] Pt catalysts, with different wt% cinchonidine, were prepared using H2 high-pressure synthesis. [•] Catalyst systems were tested in enantioselective hydrogenation of 1-phenyl-1,2-propanodione. [•] The catalysts displayed dependence between wt% of cinchonidine, and activity-ee (%). [•] Consecutive cycles showed leaching and hydrogenation of cinchonidine on the surface. [ABSTRACT FROM AUTHOR]

The enantioselective hydrogenation of α-methylcinnamic acid (MCA) over cinchonidine modified 5 wt% Pd/AlO was studied in a liquid batch reactor. Both the reaction activity and enantioselectivity towards the (R) product are strongly solvent dependent. The reaction is zero order in hydrogen pressure and first order in MCA. The presence of cinchonidine does not affect the reaction order with respect to either acid or H pressure, but has a significant inhibiting effect on the reaction rate. The catalyst exhibits stable activity during the reaction with no sign of deactivation. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: A series of 16 hybrids of Cinchona alkaloids and bile acids (4a–h, 5a–h) was prepared by means of a Barton–Zard decarboxylation reaction. Quinine, quinidine, cinchonine and cinchonidine were functionalized at position C-2 of the quinoline nucleus by radical attack of a norcholane substituent. The newly synthesized hybrids were evaluated in vitro for their antitrypanosomal, antileishmanial and antiplasmodial activities, along with their cytotoxicity against WI38, a normal human fibroblast cell line. Seven compounds (4d, 4f, 4h, 5b, 5d, 5f, 5h) showed promising trypanocidal activity with IC50 values in the same range as the commercial drug suramine. Moreover all the 16 hybrids showed antiplasmodial activity (IC50 ≤ 6 μg/ml), particularly those containing a nor-chenodeoxycholane moiety (4b, 4d, 4f, 4h, 5b, 5d, 5f, 5h) with IC50 values comparable to those of the natural alkaloids, and selectivity indices in the range of 5.6–15.7. [Copyright &y& Elsevier]

Highlights: [•] The fluorescence of native and denatured BSA was quenched by cinchonidine at pH 7.4. [•] Fluorescence spectrum indicated urea-induced unfolding of native BSA. [•] The pH 7.40 is the optimal acidity in the binding reaction. [•] Cinchonidine was harder to bind to the denatured BSA. [ABSTRACT FROM AUTHOR]

A successful optical resolution of the racemic modification of citronellic acid was carried out by using (-)-cinchonidine, one of the cinchona alkaloids. The resultant crystals contain the protonated cinchonidinium cation and the ( S)-(-)-citronellate anion in 1:1 ratio. Graphical Abstract: A successful optical resolution of the racemic modification of citronellic acid was carried out by using (-)-cinchonidine, one of the cinchona alkaloids. The resultant crystals contain the protonated cinchonidinium cation and the ( S)-(-)-citronellate anion in 1:1 ratio. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: An efficient and practical asymmetric synthesis of the 2,3-dihydrobenzo[b]furan neolignan acuminatin was achieved by using trans-isoeugenol as the starting material. The key step is an intramolecular C–H insertion through a non-stabilized carbenoid, prepared by decomposition of a tosylhydrazone in the presence of an anthracenyl-derived cinchonidine quaternary ammonium salt as a chiral phase-transfer catalyst. [Copyright &y& Elsevier]

Abstract: Main-chain chiral quaternary ammonium polymers have been synthesized using cinchonidine or 10,11-dihydrocinchonidine as a chiral source. Since the quinuclidine moiety of cinchonidine is easily quaternized with halide to form cinchonidinium salt, the quaternized reaction (Menshutkin reaction) was applied to the dimeric compound of cinchonidine and dihalide. The quaternization polymerization between cinchonidine dimer and dihalide smoothly occurred to afford the chiral polymers containing cinchonidinium salt structure in its main-chain. This atom economical addition polymerization was also applied to dimer of 10,11-dihydrocinchonidine. The corresponding chiral quaternary ammonium polymers were found to perform as polymeric organocatalysts for enantioselective benzylation of N-diphenylmethylene glycine tert-butyl ester to afford the desired (S)-phenylalanine derivative in high yields and high enantioselectivities (up to 95% ee). [Copyright &y& Elsevier]

Three bridged bis(β-cyclodextrin)s 3–5 possessing 1,2,3-triazole moieties and polyether chains of different lengths have been synthesized by click reactions in high yields. Their binding affinities towards four cinchona alkaloids, namely, cinchonine, cinchonidine, quinine, and quinidine, have been quantitatively investigated by means of spectrophotometric titrations and 2D NMR spectroscopy. Spectroscopic analyses demonstrated that, compared with native β- and γ-cyclodextrins, bridged bis(β-cyclodextrin)s with a rigid spacer give enhanced molecular binding abilities towards the selected substrates. Moreover, the factors resulting in the significant differences in photophysical behaviors of bridged bis(β-cyclodextrin)s towards cinchona alkaloids are discussed from the viewpoint of the binding geometry of host–guest complexes, revealing that the aromatic ring containing the nitrogen atom of quinine is accommodated in the cavity of 3, whereas the rings of cinchonine, cinchonidine, and quinidine are located out of the cavity of the cyclodextrin and are exposed to aqueous media. [ABSTRACT FROM AUTHOR]

Abstract: The enantioselective hydrogenation of ketopantolactone (KPL) on Pt–alumina catalyst modified by β-isocinchonine (β-ICN) and O-phenylcinchonidine (PhOCD) in toluene, acetic acid and their mixtures under otherwise identical experimental conditions was studied. Reversal of the enantioselection was obtained dependent on the concentration of acetic acid (eemax =17% (S) on Pt–PhOCD and 50% (R) on Pt–β-ICN, respectively). The possible role in enantioselection of adducts forming in the reaction mixture and the stability of PhOCD under the conditions of the hydrogenation was investigated by ESI-MS. The results of the nonlinear phenomenon measurements on β-ICN+PhOCD mixtures suggest that the intermediate surface complexes β-ICN–KPL and PhOCD–KPL responsible for the opposite enantioselection include different types of interactions and the enantioselection is directed by the competition between these interactions. [Copyright &y& Elsevier]

Abstract: Enantioselective hydrogenation of α-phenylcinnamic acid was investigated on Pd/C catalysts prepared in our laboratory to compare activity and selectivity with those on commercial Pd/C and Pd/TiO2 catalysts. The Pd/C catalysts after the 353 K-H2-pretreatment exhibited satisfactory and comparable performances obtained with commercially available best ever Pd/C by optimizing catalyst preparation. In contrast to Pd/TiO2, a high loading of Pd is not necessary with Pd/C, but only 5% loading on a certain activated carbon was found to result in high e.e. It is suggested that the optimum size or size-distribution of Pd metal particle are different between the two supports, suggesting a support effect of this catalyst system. [Copyright &y& Elsevier]

The catalytic performance of cinchonidine in the promotion of thiol additions to conjugated ketones was used as a probe to assess the tethering of molecular functionality onto solid surfaces using well-known "click" chemistry involving easy-to-react linkers. It has been assumed in many applications that the tethered molecules retain their chemical properties and dominate the chemistry of the resulting solid systems, but it is shown here that this is not always the case. Indeed, a loss of enantioselectivity was observed upon tethering, which could be accounted for by a combination of at least three effects: (1) the nonselective catalytic activity of the surface of the solid itself, (2) the activity of the OH species generated by hydrolysis of some of the Si-alkoxy groups in the trialkoxy moieties used to bind many linkers to oxide surfaces; and (3) the bonding of the molecule to be tethered directly to the surface. Several ideas were also tested to minimize these problems, including the silylation of the active OH groups within the surface of the oxide support, the selection of solvents to optimize silane polymerization and minimize their breaking up via hydrolysis or alcoholysis reactions, and the linking at defined positions in the molecule to be tethered in order to minimize its ability to interact with the surface. [ABSTRACT FROM AUTHOR]

Pt nanoparticles supported on CMK-8 ordered mesoporous carbons (OMCs) with Ia3d symmetry after chirally modified with cinchonidine (CD) proved to be highly efficient for asymmetric hydrogenation of α-ketoesters. Up to 34,819 h TOF with 75 % ee was furnished for the enantioselective hydrogenation of ethyl 2-oxo-4-phenylbutyrate with CD-modified Pt/CMK-8 catalyst. To the best of our knowledge, these results obtained with chirally modified Pt/CMK-8 catalyst are the best ones among those with Pt catalysts supported on carbon materials. It is suggested that both the physical structure features of CMK-8 OMCs and the chemical nature of Pt catalyst are beneficial for the asymmetric hydrogenation. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The enantioselective hydrogenation of 2-methyl-2-pentenoic acid (MPeA) over cinchonidine-modified 5 wt % Pd/γ-AlO catalyst has been studied. The reaction exhibited a strong solvent-dependent behavior in terms of activity. The presence of cinchonidine does not affect the reaction order with respect to either acid or H pressure, but has a significant inhibiting effect on the reaction rate. [ABSTRACT FROM AUTHOR]

An asymmetric synthesis of chiral N-substituted 3-methylisoindolin-1-ones was performed using the Pd-catalyzed diastereoselective hydrogenation of their 3-methylene-substituted precursors, that has not been investigated earlier. The highest diastereoselectivity (67% de) was achieved when the hydrogenation was carried out in methanol mediated by a palladium catalyst (Pd/C) modified with cinchonidine. [ABSTRACT FROM AUTHOR]

Abstract: The influence of the configuration at the C8 and C9 positions of cinchona alkaloids was investigated by comparing the efficiency of cinchonidine, cinchonine, and 9-epi-cinchonidine as chiral modifiers. In the hydrogenation of ketones (methyl benzoylformate, ketopantolactone, methylglyoxal dimethylacetal, 2,2,2-trifluoroacetophenone) on Pt, a change in the configuration at C9 did not affect the absolute configuration of the main products; however, the ees and rates dropped significantly. In the hydrogenation of α-functionalized olefins (E-2-methyl-2-hexenoic acid, 2-phenylcinnamic acid, and 4-methoxy-6-methyl-2H-pyran-2-one) on Pd, replacement of cinchonidine or cinchonine by epi-cinchonidine diminished the rates and almost eliminated the enantioselection, indicating that a subtle combination of C8 and C9 configurations is required on Pd. DFT calculations of the adsorption of the modifiers and the nonlinear behavior of modifier mixtures revealed that the lower reaction rates observed for 9-epi-cinchonidine-modified surfaces cannot be related to different adsorption strength of this modifier. Additionally, substrate–modifier docking interactions are presented. [Copyright &y& Elsevier]

The enantioselective hydrogenation of ( E)-2,3-diphenylpropenoic acids substituted by hydroxyl group has been studied over Pd/AlO catalyst modified by cinchonidine. The effect of the acidic hydroxyl substituents was compared with that of the methoxy group in the same position. The para-hydroxyl substituent on the 3-phenyl ring had similar effect on the enantioselectivity as the methoxy group, whereas the meta positioned decreased the optical purity of the saturated acid. This was explained by different origin of the increase in the enantioselectivity obtained in the presence of electron releasing substituents in these positions. Although, the para-hydroxyl group on the 2-phenyl ring had beneficial influence on the enantioselectivity of the hydrogenation of the mono-substituted acid, in the presence of fluorine or hydroxyl group on the 3-phenyl ring the effect of the two substituents was not additive. This study demonstrated that the cinchonidine-modified Pd catalyst is appropriate for the preparation of several hydroxy-substituted 2,3-diphenylpropionic acids in good optical purities, extending the scope of this catalytic system to new types of versatile chiral building blocks. Graphical Abstract: Heterogeneous Enantioselective Hydrogenation of Hydroxy-substituted ( E)-2,3-diphenylpropenoic Acids over Pd/AlO Modified by Cinchonidine.[Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: The effect of the achiral amine additive structure was studied on the enantioselective hydrogenation of (E)-2-methyl-2-butenoic acid and (E)-2-methyl-2-hexenoic acid over Pd/Al2O3 catalyst modified by cinchonidine. It was found that secondary amines are similarly or even more efficient in increasing the enantioselectivity as primary amines. The right basicity of the amine, which may vary in a rather wide range, should be coupled with appropriate steric properties to be effective in increasing the enantioselectivity. The best performing amines was the earlier widely used benzylamine and N-methylbenzylamine. The influence of these amines on the effect of the catalyst amount, H2 pressure and reaction temperature was studied. The effect of the amine amount on the hydrogenation of the two acids was also investigated. Based on the results the involvement of the amine additive in the formation of surface intermediates responsible for enantioselection is proposed. Decrease of the reaction temperature to 273K increased the enantiomeric excess in the presence of amines, resulting in the hydrogenation of (E)-2-methyl-2-hexenoic acid in up to 71% enantioselectivity in favour of the S product enantiomer, the highest value obtained until now in the enantioselective hydrogenation of aliphatic unsaturated carboxylic acids over chirally modified heterogeneous catalyst. [Copyright &y& Elsevier]

The reaction pathway in the heterogeneous enantioselective hydrogenation of nitro-substituted (E)-2,3-diphenylpropenoic acids over Pd catalyst modified by cinchonidine is determined by the position of the substituent. The reaction route was indicated by the H2 consumption curve and enantioselectivity of the final amino acid or 3-phenyl-1,2,3,4-tetrahydro-2-quinolone formed by intramolecular amidation. The obtained enantioselectivities were low with the exception of acids bearing nitro substituent in para position on the 3-phenyl moiety, the latter resulting in good, up to 80 % optical purity. The present study is the first to report the enantioselective heterogeneous catalytic preparation of 1,2,3,4-tetrahydro-2-quinolones and presents an attractive method for obtaining optically enriched 3-(4-aminophenyl)-2-phenylpropionic acids. [ABSTRACT FROM AUTHOR]

Cinchonidine, a naturally occurring cinchona alkaloid, was tethered to a high-surface-area silica substrate in order to create a new solid chiral catalyst. Two synthetic routes were explored for this grafting, relying on the use of an intermediate linker and so-called 'click' chemistry. Both routes proved viable, but the procedure where cinchonidine is first derivatized with 3-isocyanatopropyltriethoxysilane (ICPTEOS) at the alcohol position and the resulting product then anchored to the silica surface was deemed the most efficient. Bonding to the surface occurs via the formation of Si-O-Si bonds, on average two out of the three possible per cinchonidine, and takes place preferentially at silica surface sites with two geminal hydroxyl groups on the same silicon atom. Approximately 10% of the available OH surface groups are derivatized in this procedure. The resulting catalyst was successfully tested for the addition of aromatic thiols to unsaturated ketones, a reaction promoted by amines (the tertiary quinuclidine nitrogen atom in the case of cinchonidine). The activity of the supported cinchonidine proved comparable to that of the free molecule, but tethering does lead to a significant loss in enantioselectivity. [ABSTRACT FROM AUTHOR]

Under the experimental conditions of the Orito reaction the competitive hydrogenations of four binary mixtures of ethyl pyruvate (EP), methyl benzoylformate (MBF), pyruvic aldehyde dimethyl acetal (PA) and 2,2-diethoxyacetophenone (DAP) on unmodified Pt/AlO (racemic hydrogenation) and catalyst modified by cinchonidine (chiral hydrogenation) were studied using continuous-flow fixed-bed reactor system (CFBR). Conversions of chiral and racemic hydrogenations were determined under 4 MPa H pressure, at 293 K using toluene/acetic acid 9/1 as solvent. In the competitive chiral hydrogenation of MBF + EP and DAP + PA binary mixtures (S1 + S2) a new phenomenon was observed: namely the EP and PA are hydrogenated faster than MBF and DAP, whereas in racemic one the MBF and DAP are hydrogenated faster than the former ketones. The phenomenon verified for the first time in CFBR is dependent on the adsorption mode of the surface complexes of various compositions (S1-Pt, S2-Pt, S1-CD-Pt, S2-CD-Pt, CD = cinchonidine). In the chiral hydrogenation of DAP a rate decrease, i.e., 'ligand deceleration' was observed instead of rate enhancement. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: Competitive hydrogenations of eight binary mixtures of ethyl pyruvate (EP), methyl benzoylformate (MBF), ketopantolactone (KPL), pyruvic aldehyde dimethyl acetal (PA) and trifluoroacetophenone (TFAP) on platinum/alumina catalysts unmodified (racemic hydrogenation) and modified by cinchonidine (chiral hydrogenation) were studied under the experimental conditions of the Orito reaction. Reaction rates of chiral and racemic hydrogenations were determined and relative adsorption coefficients were calculated. In the competitive chiral hydrogenation of EP+MBF, EP+TFAP and KPL+MBF binary mixtures a new phenomenon was observed: namely the EP and KPL are hydrogenated faster than MBF and TFAP, whereas in racemic one the MBF and TFAP are hydrogenated faster than EP or KPL. Effects of the activated ketones structure on their reactivity and the stability of the surface complexes are discussed. It was found that differences in rate enhancement are caused by the differences both in the adsorptivity and in the reactivity of adsorbed substrates and adsorbed intermediate complexes. [Copyright &y& Elsevier]

Abstract: The surface modifier cinchonidine and its diastereomer cinchonine have been investigated and their vibrational spectra assigned, below 1000cm−1. Scaled DFT ab initio calculations with PED assignments were in good agreement with neutron and optical vibrational spectroscopy. 4-Quinolinol, and quinuclidine hydrochloride were used as model compounds and their eigenvectors were compared with those of the parent molecules to aid in the assignments. This is the first low frequency assignment attempted on these systems and extends our understanding of the vibrations of the enantioselective promoters into regions not normally exploited by conventional spectroscopy. [Copyright &y& Elsevier]

Abstract: Chirally modified SiO2 containing different amounts of cinchonidine was prepared by the chemical modification of cinchonidine (CD) with trimethoxysilane over SiO2 that had been chemically activated with 1,4-dioxane/HCl. This solid was used to support Pt catalysts containing 1wt%Pt obtained by the chemical reduction of hexachloroplatinic acid with H2 at 298K and 40bar. The materials were characterised by elemental analyses of C, H, and N, as well as thermal gravimetry (TG), DRIFT, 13C NMR, 29Si solid state NMR, N2 adsorption–desorption at 77K, X-ray diffraction (XDR), XPS, and HR-TEM. Catalytic activity for the hydrogenation of 1-phenyl-propane-1,2-dione was evaluated in a batch reactor at 298K and 40bar, and recycling of the catalysts yielding the largest enantiomeric excess in the products were also studied. All catalysts were found to be active in the reaction, with enantiomeric excesses of the target product (1-R-phenyl-1-hydroxy-2-propanone) ranging from 35 to 50%. The best catalyst studied was SiO2-supported, with a nominal content of 7.5mmolCD/L g. The recycling tests showed a loss of activity that was attributed to the surface modification of the catalyst. [Copyright &y& Elsevier]

Abstract: In the present paper we report spectral and photophysical properties of two probes viz. cinchonidine and quinidine in two different polymers viz. polyvinyl alcohol (PVA) and polymethylmethacrylate (PMMA). The emission spectra exhibit edge excitation red shift (EERS) for both the probes and multiexponential decays are observed. Presence of various conformers and geometries is suggested to explain the observed results. The photophysical properties and excited state behavior of Cd++ are more sensitive towards the microenvironment of the polymer. [Copyright &y& Elsevier]

The paper presents an application of the asymmetry approach to spirooxindoles via Brevicolline, Cinchonidine or Cinchonine catalyzed one-pot multicomponent synthesis. Brevicolline, in comparison with Cinchonidine or Cinchonine, catalyzes the reaction of isatins, acetylacetone/ethyl 3-oxobutanoate and malononitrile, with the formation of spiro[oxindole-3,4′-4′H-pirane] derivatives in an optically active form in very good to excellent yields. [ABSTRACT FROM AUTHOR]

Abstract: A single unit catalyst system (Pt/silica–chiral modifier) is developed for the enantioselective hydrogenation of ethyl pyruvate. Cinchonidine was tethered directly without prior modification over carboxylate functionalized SBA-15 by the reaction of vinyl group in cinchonidine with –COOH group in functionalized SBA-15 through ester linkage. Then Pt nanoparticles were deposited over cinchonidine tethered SBA-15. The mesostructures were characterized by small-angle XRD, N2 sorption and TEM, while the surface functionalization was confirmed by FTIR, TG/DTA and solid state 13C NMR. Enantioselectivity of the catalyst system for hydrogenation of ethyl pyruvate was determined by GC/FID. The highest enantiomeric excess was achieved as 70.8% and the catalyst recyclability was authenticated even after 3rd reuse without significant loss in enantiomeric excess. [Copyright &y& Elsevier]

Abstract: The influence of acidic and basic supports on the enantioselective hydrogenation of acetophenone and its aryl-substituted derivates was studied. The Pt/Al2O3, Pt/Al2O3–SiO2, and Pt/Al2O3–Cs2O catalysts were prepared by single-step flame spray pyrolysis, and cinchonidine (CD) was used as chiral modifier. For all five aromatic ketones, the acidic support improved the ee, while the basic support diminished it. Opposite tendencies were observed for the reaction rate: acidic support lowered and basic support enhanced the rate of ketone conversion. In situ investigation of the hydrogenation of the quinoline ring of CD revealed for the first time that degradation of the modifier leads to remarkable variation in the substrate/modifier ratio. This effect and a possible catalyst deactivation due to aldol condensation of the ketones may be the origin of the decrease in ee with conversion. Following the diastereoselectivity during hydrogenation of the heteroaromatic ring of the quinoline unit of CD proved dominantly pro(S) adsorption mode on Pt/Al2O3 and Pt/Al2O3–SiO2, and pro(R) on Pt/Al2O3–Cs2O catalysts. Changes in the adsorption mode were minor during hydrogenation of aromatic ketones. This, together with the small effect of ketones on the hydrogenation rate of CD, is interpreted as an indication to weak substrate–modifier interactions, in contrast to the situation during the hydrogenation of α-ketoesters (methyl benzoylformate). [Copyright &y& Elsevier]

Abstract: Scaffold varied quaternized quinine and cinchonidine alkaloid derivatives were evaluated for their selective butyrylcholinesterase (BChE) inhibitory potential. K i values were between 0.4–260.5 μM (non-competitive inhibition) while corresponding K ivalues to acetylcholinesterase (AChE) ranged from 7.0–400 μM exhibiting a 250-fold selectivity for BChE. Docking arrangements (GOLD, PLANT) revealed that the extended aromatic moieties and the quaternized nitrogen of the inhibitors were responsible for specific π–π stacking and π–cation interactions with the choline binding site and the peripheral anionic site of BChE’s active site. [Copyright &y& Elsevier]

A molecular assembly with a two-fold screw axis, a so-called 21helical assembly, is one of the most fundamental and important motifs of organic noncentrosymmetric crystals. 21Helical assemblies are observed frequently in the crystals of Cinchona alkaloids, crucial compounds for asymmetric organic syntheses. Despite of importance of their superstructures, there are no reports about the handedness of 21helical assemblies. In this study, we revealed crystal structures of BH3complexes with a series of Cinchona alkaloids: cinchonidine, quinine, hydroquinine, cinchonine, quinidine, and hydroquinidine (Cnd·BH3, Qn·BH3, HyQn·BH3, Cnn·BH3, Qd·BH3, and HyQd·BH3, respectively), and we first defined the handedness of 21helical assemblies of Cinchona alkaloids on the basis of a supramolecular-tilt-chirality method we have proposed. Interestingly, in crystalline states, Qn·BH3and HyQn·BH3form 32helical motifs, while Cnd·BH3forms a left-handed 21motif and Cnn·BH3, Qd·BH3, and HyQd·BH3form right-handed 21helices despite their similar O−H···N intermolecular hydrogen bonds. Therefore, this set of these structures, which is the first example of crystal structures obtained for a series of Cinchona alkaloids or their derivatives chemically modified in the same way, enables us to elucidate a chiral relationship between molecular structures and supramolecular assembly manners. [ABSTRACT FROM AUTHOR]

Abstract: The effect of the chlorine position on the C–Cl bond hydrogenolysis and the enantioselective hydrogenation of Cl substituted (E)-2,3-diphenylpropenoic acid derivatives has been studied over cinchonidine-modified Pd/Al2O3. In contrast to the fast hydrodechlorination of the β-phenyl-para-Cl substituted acids the Cl on the α-phenyl ring was barely hydrogenolized. These observations were interpreted by the different arrangements of the two phenyl rings on the surface, with the α- and β-phenyl rings adsorbed tilted and parallel, respectively. The results confirmed the beneficial effect of the α-phenyl-ortho-substituents on the chiral discrimination, thus the 2,3-diphenylpropionic acids substituted by Cl on the α-phenyl ring could be prepared in good yields and optical purities. The conclusions were used for the rational design of an acid, i.e. (E)-2-(2-methoxyphenyl)-3-(3,4-difluorophenyl)propenoic acid, which afforded the best optical purity (ee up to 95% at 295K) described until now in this heterogeneous system. [ABSTRACT FROM AUTHOR]

Abstract: The role of metal–support interaction in the hydrogenation of cinchonidine (CD) was studied on acid- and base-doped flame-made Pt/alumina. Analysis of the product distribution revealed that on Pt/alumina and Pt/alumina–silica CD adsorbs on Pt in pro(S) geometry, but doping the support with only 0.25wt.% Cs2O is sufficient to invert the major adsorption mode to pro(R). The origin of differences between the effect of an acidic additive and support acidity is discussed. [Copyright &y& Elsevier]