Synthesis and chromatographic resolution of conformationally constrained analogues of homotaurine

Fulco, Maria Carmela; Marinozzi, Maura; Ergün, Burcu Çaliskan; Sardella, Roccaldo; Natalini, Benedetto; Pellicciari, Roberto

doi:10.1016/j.tet.2009.08.018

Cited by 6 publications

(2 citation statements)

References 21 publications

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“…The masking action of the underivatized silanols as well as of other out-of-the-stereoselective binding site functionalities usually contributes to the reduction of band broadening and peak asymmetry rather than to overall retention (Ye and Stringham, 2001a;Fulco et al, 2009).…”

Section: Basic Additivesmentioning

confidence: 99%

The effect of mobile phase composition in the enantioseparation of pharmaceutically relevant compounds with polysaccharide‐based stationary phases

Sardella

Ianni

Lisanti

et al. 2013

Biomedical Chromatography

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Mobile phase variables have a deep influence on the chromatographic behavior with polysaccharide-based chiral stationary phases. Basic additives are generally used to minimize peak broadening arising from unwanted interactions between polar solutes and underivatized silanols. However, basic additives can improve enantioselectivity through disruption of hydrogen bonds and modification of the polymer morphology. Acidic additives are incorporated into the mobile phase during the analysis of acidic compounds as efficiency enhancers. Acidic additives can also improve enantioselectivity by minimizing within the chiral recognition site nonenantioselective retention. Peak shape without acidic additive in the eluent could be severely distorted during the analysis of salified compounds. Concentration and type of alcohol modifier can have an effect on the morphology of the polymer. The different winding of the chiral selector, caused by alcohol modifiers of different size/shape, ultimately results in different stereo environment of the chiral cavities in the polymer chain. Trace amounts of water in normal-phase eluents can affect retention time, tailing, and resolution. Deliberate addition of water to the eluent can improve peak resolution and save analysis time and solvent needs. Immobilized-type polysaccharide-derived chiral stationary phases offer new selectivity profiles and often improved enantioselectivity.

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Section: Basic Additivesmentioning

confidence: 99%

The effect of mobile phase composition in the enantioseparation of pharmaceutically relevant compounds with polysaccharide‐based stationary phases

Sardella

Ianni

Lisanti

et al. 2013

Biomedical Chromatography

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“…15 Recently, cis-and trans-2aminomethylcyclopropane-1-sulfonic acids were synthesized as conformationally restricted GABA analogues as pharmacological tools to study GABA receptor subtypes. 16 However, there is no general reported method for the synthesis of 1-substituted homotaurines. Recently, we prepared substituted taurines through Michael addition of thioacetic acid and sodium O-ethyl xanthate to nitroolefins and subsequent oxidation and reduction.…”

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Synthesis of Homotaurine and 1-Substituted Homotaurines from α,β-Unsaturated Nitriles

2012

Synthesis

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Homotaurine and a series of 1-substituted homotaurines were readily synthesized in satisfactory to good yields via the Michael addition of thioacetic acid to aliphatic and aromatic α,β-unsaturated nitriles followed by lithium aluminum hydride mediated reduction and performic acid oxidation. The synthesis of 1,1-disubstituted homotaurines was attempted with β,β-disubstituted acrylonitriles as starting materials but failed due to steric hindrance. The current process is an efficient method for the synthesis of 1-substituted homotaurines.Homotaurine (3-aminopropanesulfonic acid) and taurine (2-aminoethanesulfonic acid) are two powerful inhibitory amino acids with anticonvulsant properties against various experimental models of focal epilepsy. 1 Homotaurine, as a sulfur-containing amino acid, has attracted much attention in recent years as a drug candidate for the treatment of Alzheimer's disease and haemorrhagic stroke. 2 Recent studies indicate that it binds to soluble amyloid β-peptide (Aβ) and decreases Aβ42-induced cell death in neuronal cell culture. 3 It is believed that the reduction or inhibition of amyloid deposition in the brain and cerebral vasculature is responsible for the beneficial effects observed in vivo studies. 2 Moreover, calcium 3-acetylaminopropanesulfonate (acamprosate) is one of the few medications currently approved for the prevention of alcohol relapse in detoxified alcohol dependent patients both in Europe and USA. 4 Both homotaurine and substituted homotaurine derivatives are considered as bioisosteres of γ-aminobutyric acid (GABA). 5 Homotaurine was synthesized from 3-aminopropanol via bromination with hydrogen bromide and subsequent displacement with sodium bisulfite or sulfite, 6,7 and via addition of acrylonitrile with sodium bisulfite and subsequent reduction. 8 2-Substituted homotaurines were prepared as competitive antagonists of the GABA receptor through addition of isobutenal with sodium bisulfite and subsequent reductive amination, 9 via addition of 1-arylacrylonitriles with sodium bisulfate and subsequent reduction, 10 via the oxygen-catalyzed radical addition of bisulfite to 2-arylallylamines or their N-phthalyl derivatives, 11 and via ring-opening reactions of 2-alkylpropane-1,3-sultones with ammonia or with sodium azide followed by reduction. 12 3-Substituted homotaurines were synthesized through oxidation of homocysteine, 13 via reduction of amino esters to amino aldehydes, which underwent the Horner-Wadsworth-Emmons reaction with ethyl (diethoxyphosphoryl)methanesulfonate in the presence of butyllithium and subsequent hydrogenation and deprotection. 14 3-Nitroalkanesulfonic acids are precursors of 1,3-disubstituted homotaurines and were obtained through addition of arylmethanesulfonates to nitroolefins in the presence of n-butyllithium. 15 Recently, cis-and trans-2-aminomethylcyclopropane-1-sulfonic acids were synthesized as conformationally restricted GABA analogues as pharmacological tools to study GABA receptor subtypes. 16 However, there is no general reported metho...

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Evaporative‐Based Detectors as Global Response Instruments

Sillero¹,

Aranzana²

2012

Encyclopedia of Analytical Chemistry

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Evaporative‐based detectors are a new generation of instruments, which provide a universal response for a wide variety of compounds or their families whose determination by other conventional detection systems is limited by different reasons. Both evaporative light scattering detector (ELSD) and corona‐charged aerosol detector (C‐CAD) have been recognized as global response detectors in liquid and supercritical chromatographies. Their advantage over optical or electrochemical detectors is that they do not require from the analytes to present special physicochemical properties. The evaporative‐based detectors nebulized the mobile‐phase/liquid stream effluent, producing analyte particles that are optically detected through the scattered light in the case of ELSD or by charge transfer in the case of the C‐CAD. The foundation of the detection and the main applications of these detectors will be deeply commented in this article. Moreover, a comparison with conventional detectors (ultraviolet/visible (UV/VIS), refractive index (RI), and mass spectrometers (MSs)) is included. In the light of the bibliography available on this topic, future applications of and perspectives on the use of these detectors can also be anticipated.

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Synthesis and chromatographic resolution of conformationally constrained analogues of homotaurine

Cited by 6 publications

References 21 publications

The effect of mobile phase composition in the enantioseparation of pharmaceutically relevant compounds with polysaccharide‐based stationary phases

The effect of mobile phase composition in the enantioseparation of pharmaceutically relevant compounds with polysaccharide‐based stationary phases

Synthesis of Homotaurine and 1-Substituted Homotaurines from α,β-Unsaturated Nitriles

Evaporative‐Based Detectors as Global Response Instruments

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