The Renaissance of H/D Exchange

Atzrodt, Jens; Derdau, Volker; Fey, Thorsten; Zimmermann, Jochen

doi:10.1002/chin.200751243

Cited by 45 publications

(84 citation statements)

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“…Research into deuterium ( 2 H or D) and tritium ( 3 H or T) labelling is more substantial than for other isotopes, and has been developed on a number of fronts over the past 60 years [1][2][3][4][5][6][7][8][9][10]. Further to this, key developments in synthetic strategies and analytical techniques for tritium labelling over the past three decades now makes this the preferred technique for many ADMET studies [5].…”

Section: Introductionmentioning

confidence: 99%

Iridium-Catalysed ortho-Directed Deuterium Labelling of Aromatic Esters—An Experimental and Theoretical Study on Directing Group Chemoselectivity

et al. 2015

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Herein we report a combined experimental and theoretical study on the deuterium labelling of benzoate ester derivatives, utilizing our developed iridium N-heterocyclic carbene/phosphine catalysts. A range of benzoate esters were screened, including derivatives with electron-donating and -withdrawing groups in the para-position. The substrate scope, in terms of the alkoxy group, was studied and the nature of the catalyst counter-ion was shown to have a profound effect on the efficiency of isotope exchange. Finally, the observed chemoselectivity was rationalized by rate studies and theoretical calculations, and this insight was applied to the selective labelling of benzoate esters bearing a second directing group.

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Section: Introductionmentioning

confidence: 99%

Iridium-Catalysed ortho-Directed Deuterium Labelling of Aromatic Esters—An Experimental and Theoretical Study on Directing Group Chemoselectivity

et al. 2015

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“…Many attempts for deuterium introduction in the aromatic portions of compounds have been reported. Hydrogen/deuterium exchange (H/D exchange) [3][4][5] at a specific position and universal H/D exchange in acidic condition 6) and/or metal catalysis 7) on aromatics have been reported in the literature. Although aromatic α-amino acids were considered to be the substrate for H/D exchange, the α-amino acid skeleton sometimes inhibited to apply previous H/D exchange methods due to their solubility in many organic solvent.…”

Section: Introductionmentioning

confidence: 99%

Hydrogen/deuterium exchange of cross-linkable α-amino acid derivatives in deuterated triflic acid

Wang

Murai

Yoshida

et al. 2014

Bioscience, Biotechnology, and Biochemistry

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In this paper we report here a hydrogen/deuterium exchange (H/D exchange) of cross-linkable α-amino acid derivatives with deuterated trifluoromethanesulfonic acid (TfOD). H/D exchange with TfOD was easily applied to o-catechol containing phenylalanine (DOPA) within an hour. A partial H/D exchange was observed for trifluoromethyldiazirinyl (TFMD) phenylalanine derivatives. N-Acetylprotected natural aromatic α-amino acids (Tyr and Trp) were more effective in H/D exchange than unprotected ones. The N-acetylated TFMD phenylalanine derivative afforded slightly higher H/D exchange than unprotected derivatives. An effective post-deuteration method for cross-linkable α-amino acid derivatives will be useful for the analysis of biological functions of bioactive peptides and proteins by mass spectrometry.

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“…The base‐catalyzed, hydrogen‐deuterium exchange (HDX) reactions also provide a simple method for the exchange of acidic hydrogen atoms for deuterium by means of keto–enol equilibria . The acidic hydrogen atoms bound to carbon in carbonyl compounds such as N ‐substituted acetamides and diketopiperazines are exchanged with high yield .…”

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confidence: 99%

The unusual hydrogen-deuterium exchange ofα-carbon protons inN-substituted glycine-containing peptides

et al. 2014

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Hydrogens connected to α-carbon (α-C) of amino acid residues are usually resistant to hydrogen-deuterium exchange (HDX) unless reaction conditions promote racemization. Although N-methylglycine (sarcosine) residue has been found in biologically active peptide such as cyclosporine, to the best of our knowledge, the HDX of α-C protons of this residue was not explored yet. Here, we presented a new and efficient methodology of α-C deuteration in sarcosine residues under basic aqueous conditions. The deuterons, introduced at α-C atom, do not undergo back-exchange in acidic aqueous solution. The electrospray ionization-MS and MS/MS experiments on proposed model peptides confirmed the HDX at α-C and revealed the unexpected hydrogen scrambling in sarcosine-containing peptides. Although the observed HDX of α-C protons is only successful in N-acylglycine when the amide possesses a certain degree of alkylation, it offers a new approach to the analysis of sarcosine-containing peptides such as cyclosporine.

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The Renaissance of H/D Exchange

Abstract: Organic chemistry Z 0200The Renaissance of H/D Exchange -[282 refs.]. -(ATZRODT, J.; DERDAU, V.; FEY, T.; ZIMMERMANN, J.; Angew. Chem., Int. Ed. 46 (2007) 41, 7744-7765; Isotope Chem. Metab. Synth., Sanofi-Aventis Dtschl. GmbH, D-65926 Frankfurt/M., Germany; Eng.) -Bartels 51-243

Cited by 45 publications

References 1 publication

Iridium-Catalysed ortho-Directed Deuterium Labelling of Aromatic Esters—An Experimental and Theoretical Study on Directing Group Chemoselectivity

Iridium-Catalysed ortho-Directed Deuterium Labelling of Aromatic Esters—An Experimental and Theoretical Study on Directing Group Chemoselectivity

Hydrogen/deuterium exchange of cross-linkable α-amino acid derivatives in deuterated triflic acid

The unusual hydrogen-deuterium exchange ofα-carbon protons inN-substituted glycine-containing peptides

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