Spectroscopic Analysis: NMR and Shift Reagents

Barretta, Gloria Uccello; Wenzel, Thomas J.; Balzano, Federica

doi:10.1016/b978-0-32-390644-9.00012-3

Cited by 3 publications

(3 citation statements)

References 324 publications

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“…Their absolute configurations were not determined at this stage (vide infra), but the recovered substrate (+)- 12 was chemically acetylated to give (+)- 13 exhibiting almost the same value (though obviously of the opposite sign) of optical rotation as (−)- 13 , which could be taken as proof of the efficiency of the kinetic resolution ( Scheme 5 ). The enantiomeric excess of the recovered amine (+)- 12 was determined by 31 P NMR using optically pure (+)-( R )- t -butylphenylphosphinothioic acid as a chiral solvating agent [ 22 , 23 ]. In turn, the enantiomeric excess of the acetylation product, acetamide 13 , was determined on the basis of its optical rotation and via a chemical correlation shown in Scheme 5 .…”

Section: Resultsmentioning

confidence: 99%

Towards Chemoenzymatic Syntheses of Both Enantiomers of Phosphoemeriamine

Kiełbasiński,

Kwiatkowska,

Łyżwa

et al. 2024

Molecules

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An enzyme-promoted addition of nitromethane to the appropriate phosphorylated imine (aza-Henry reaction) intended to be used in the synthesis of the title phosphoemeriamine, a phospha-analog of emeriamine (aminocarnitine), failed due to the tautomerization of the imine to the corresponding enamine. Nevertheless, both enantiomers of phosphoemeriamine were synthesized in high yield and enantiomeric purity using another chemoenzymatic approach, starting with a crucial step involving a CAL-B-mediated acetylation of the appropriate racemic precursor—diethyl 2-amino-3-dimethylaminopropylphosphonate—under kinetic resolution conditions. The enzymatic reaction was very efficient and provided each enantiomeric product in acceptable yield and with enantiomeric excess of 91 and 92%. The following appropriate chemical transformations led to the desired enantiomers of phosphoemeriamine in the form of phosphoemeriamine sesquichloride with enantiomeric excess up to 90%.

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Section: Resultsmentioning

confidence: 99%

Towards Chemoenzymatic Syntheses of Both Enantiomers of Phosphoemeriamine

Kiełbasiński,

Kwiatkowska,

Łyżwa

et al. 2024

Molecules

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Section: Introductionmentioning

confidence: 99%

“…Nuclear magnetic resonance (NMR) spectroscopy has often been favored in chiral analysis due to its effectiveness, reliability, and versatility [10][11][12][13][14][15][16]. Specifically, chiral derivatizing agents (CDAs) have played a crucial role in NMR-based configurational assignments [12][13][14][15][16]. CDAs are enantiomerically pure chiral reagents that are employed to derivatize enantiomeric substrates to form their diastereomeric derivatives distinguishable in solution.…”

Section: Introductionmentioning

confidence: 99%

A Thiourea Derivative of 2-[(1R)-1-Aminoethyl]phenol as a Chiral Sensor for the Determination of the Absolute Configuration of N-3,5-Dinitrobenzoyl Derivatives of Amino Acids

Aiello,

Recchimurzo,

Balzano

et al. 2024

Molecules

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In the exploration of chiral solvating agents (CSAs) for nuclear magnetic resonance (NMR) spectroscopy designed for the chiral analysis of amino acid derivatives, notable advancements have been made with thiourea–CSAs. 1-TU, derived from 2-[(1R)-1-aminoethyl]phenol and benzoyl isothiocyanate, is effective in the enantiodifferentiation of N-3,5-dinitrobenzoyl (N-DNB) amino acids. In order to broaden the application of 1-TU for configurational assignment, enantiomerically enriched N-DNB amino acids were analyzed via NMR. A robust correlation was established between the relative position of specific 1H and 13C NMR resonances of the enantiomers in the presence of 1-TU. 1,4-Diazabicyclo[2.2.2]octane (DABCO) was selected for the complete solubilization of amino acid substrates. Notably, the para and ortho protons of the N-DNB moiety displayed higher frequency shifts for the (R)-enantiomers as opposed to the (S)-enantiomers. This trend was consistently observed in the 13C NMR spectra for quaternary carbons bonded to NO2 groups. Conversely, an inverse correlation was noted for quaternary carbon resonances of the carboxyl moiety, amide carbonyl, and methine carbon at the chiral center. This observed trend aligns with the interaction mechanism previously reported for the same chiral auxiliary. The configurational correlation can be effectively exploited under conditions of high dilution or, significantly, under sub-stoichiometric conditions.

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Unraveling the Source of Self‐Induced Diastereomeric Anisochronism in Chiral Dipeptides

Spiaggia,

Aiello,

Sementa

et al. 2024

Chemistry A European J

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Mastering of analytical methods for accurate quantitative determinations of enantiomeric excess is a crucial aspect in asymmetric catalysis, chiral synthesis, and pharmaceutical applications. In this context, the phenomenon of Self‐Induced Diastereomeric Anisochronism (SIDA) can be exploited in NMR spectroscopy for accurate determinations of enantiomeric composition, without using a chiral auxiliary that could interfere with the spectroscopic investigation. This phenomenon can be particularly useful for improving the quantitative analysis of mixtures with low enantiomeric excesses, where direct integration of signals can be tricky. Here, we describe a novel analysis protocol to correctly determine the enantiomeric composition of scalemic mixtures and investigate the thermodynamic and stereochemical features at the basis of SIDA. Dipeptide derivatives were chosen as substrates for this study, given their central role in drug design. By integrating the experiments with a conformational stochastic search that includes entropic contributions, we provide valuable information on the dimerization thermodynamics, the nature of non‐covalent interactions leading to self‐association, and the differences in the chemical environment responsible for the anisochrony, highlighting the importance of different stereochemical arrangement and tight association for the distinction between homochiral and heterochiral adducts. An important role played by the counterion was pointed out by computational studies.

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Spectroscopic Analysis: NMR and Shift Reagents

Cited by 3 publications

References 324 publications

Towards Chemoenzymatic Syntheses of Both Enantiomers of Phosphoemeriamine

Towards Chemoenzymatic Syntheses of Both Enantiomers of Phosphoemeriamine

A Thiourea Derivative of 2-[(1R)-1-Aminoethyl]phenol as a Chiral Sensor for the Determination of the Absolute Configuration of N-3,5-Dinitrobenzoyl Derivatives of Amino Acids

Unraveling the Source of Self‐Induced Diastereomeric Anisochronism in Chiral Dipeptides

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