169,742 research outputs found
Stereochemistry of 2-(6-fluorophenanthren-1-yl)propionic acid unveiled by enantioselective HPLC, ECD spectroscopy, and TD-DFT calculations
No full text1. Introduction
Owing to its peculiarities, fluorine has drawn an increasing attention in the design of new drugs. Among them, fluorinated profens have received particular consideration in reference to the biological activity as successful non-steroidal anti-inflammatory drugs (NSAIDs). In the present communication we report the development of an enantioselective HPLC method for the resolution of racemic 2-(6-fluorophenanthren-1-yl)propionic acid (1),1 and the determination of the absolute configuration (AC) of its enantiomers through electronic circular dichroism (ECD) and time-dependent density functional theory (TD-DFT) computations.
2. Results and Discussion
The column (S,S)-Whelk-O®1 was efficient for the enantioresolution of profen 1. The single enantiomeric fractions were collected and analyzed for determining their enantiomeric excess and ECD spectra. The AC of the enantiomers of 1 was determined by means of ECD theoretical calculations on (S)-1.2 Molecular mechanics conformational analysis and DFT geometry optimization at the B3LYP/TZ2P level isolated the 4 most populated conformers (a, 53.04%; b, 25.70%; c, 19.81%; d, 1.45%). TD-DFT calculations were performed at the B3LYP/TZ2P level and the theoretical ECD spectrum was determined. The ECD spectrum of the second-eluted enantiomer was found to be in excellent agreement with theoretical calculations on (S)-1; therefore, the AC of the first- and second-eluted enantiomers were assessed as (2R)-1 and (2S)-1, respectively.
3. References
[1] Ricci, G., and Ruzziconi, R., J. Org. Chem. 2005, 70, 611-623.
[2] Autschbach, J., Chirality 2009, 21, E116-E152
Synthesis and Far-UV Circular Dichroism Spectra Analysed by Coupled Oscillator Calculations of Some New 4-Substituted [2.2]Paracyclophanes
No full textUn Facile Accesso a Benzofurani Regioselettivamente Sostituiti Basato sull’Addizione Ossidativa di 1-Trimetilsililossicicloeseni e 2-thrimetilsililossi-1,3-cicloesadieni all’Etil Vinil Etere Promossa dal Cerio Ammonio Nitrato
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Un facile accesso a benzofurani regioselettivamente sostituiti basato sull’addizione ossidativa di 1-trimetilsililossicicloeseni e 2-trimetilsililossi-1,3-cicloesadieni a vinil etil eteri promossa dal Cerio (IV) Ammonio Nitrato
No full textCF3: An overlooked chromophore in VCD spectra. A review of recent applications in structural determination
No full textThe VCD spectra of several chiral compounds containing the CF3 group are reviewed and analyzed. The list of compounds contains pharmaceutically relevant molecules as well as simple model molecules, having the value of case studies. In particular we point out the importance of the sign of the VCD band relative to some stretching normal mode of CF3 in the region 1110–1150 cm−1, as diagnostic of the configuration of stereogenic carbons C* to which the CF3 group is bound: the correspondence (−) ↔ (R) and (+) ↔ (S) holds for 100% of 1-aryl-2,2,2-trifluoroethanols. DFT calculations confirm these conclusions, but for the rule established here they serve just as a check. This rule is tested on two new compounds, namely N-tert-butanesulfinyl-1-(quinoline-4-yl)-2,2,2-trifluoroethylamine, 8, and 4-[2-(2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile, 10, both containing two stereogenic elements, one of them being an asymmetric carbon C* of unknown configuration binding a CF3 group. Discussion of the general validity of the rule is provided and some further tests are run on compounds in well-established drugs
The Torsional Barriers of 2-Hydroxy- and 2-Fluorobiphenyl: Small but Measurable
No full textBy making use of a novel diastereotopicity probe, namely C(CF3)(2)OH, it has been possible to measure by very low temperature F-19 NMR spectroscopy the elusive aryl aryl rotation barriers of biphenyls bearing an OH or F group in one rill position. The experimental values (5.4 and 4.4 kcal mol(-1), respectively) are matched by those from ab initio calculations (5.3 and 4.3 kcal mol(-1), respectively).S
B-Values as a Sensitive Measure of Steric Effects
No full textAccurate torsional barriers of 15 ortho-substituted biphenyls have been determined computationally using the B3LYP density functional and experimentally by variable-temperature ("dynamic") nuclear magnetic resonance. Taking advantage of the
3'-isopropyldimethylsilyl group as a novel and superior diastereotopicity probe and tracking coalescence temperatures down to –173 °C (100 K), activation energies of aryl-aryl rotation as small as 5 kcal/mol can be assessed. The 2-X/2'-H repulsion increments thus derived are powerful parameters for rationalizing and predicting the conformational behavior of aromatic compounds carrying ortho-substituent
Are carboxylic esters really refractory to DAST? On the fluorination of α-hydroxyesters with DAST
No full textDiethyl 2-alkyl-2-hydroxymalonates react with DAST almost exclusively at the ester carbonyl giving a mixture of ethyl 2-(ethoxydifluoromethyl)-2-hydroxyalkanoates, 1,1-bis(ethoxydifluoromethyl)alkan-1-ols when administered at room temperature in dichloromethane. The reaction was exploited in the synthesis of nucleus- and side-chain polyfluorinated indoles. The fluorination of substituted diethyl 2-[(1-tert-butoxycarbonylindol-3-yl)methyl]-2-hydroxymalonates with DAST gave a mixture of ethyl 2-(ethoxydifluoromethyl)-2-hydroxy-3-(1-tert-butoxycarbonylindol-3-yl)propionate, diastereomeric 1'-tert-butoxycarbonyl-2'-hydroxy-2,2-diethoxycarbonylspiro(cyclopropane-1,3'-indoline) and only traces of 1,1-bis(ethoxydifluoromethyl)-2-(1-tert-butoxycarbonylindol-3-yl)ethanol. The composition of these mixtures changes depending on the reaction conditions. Regioselectively substituted ethyl 2-hydroxy-2[(1-tert-butoxycarbonylindol-3-yl)methyl]-3,3,3-trifluoropropionate reacts with DAST at 0 degrees C in dichloromethane giving satisfactory yields of the corresponding 1-ethoxy-2-[(1-tert-butoxycarbonylindol-3-yl)methyl]-1,1,3,3,3-pentafluoropropan-2-ols as the exclusive reaction products. In the same reaction conditions, ethyl 3-(1-tert-butoxycarbonylindol-3-yl)-2-hydroxypropionate mainly provides 1'-tert-butoxycarbonyl-2'-hydroxy-2,2-diethoxycarbonylspiro(cyclopropane-1,3'-indoline) together with the "normal" fluorination product ethyl 3-(1-tert-butoxycarbonylindol-3-yl)-2-fluoropropionate. A plausible mechanism of this process is proposed in the following. (C) 2014 Elsevier B.V. All rights reserved
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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