Efficient Access to Deuterated and Tritiated Nucleobase Pharmaceuticals and Oligonucleotides using Hydrogen-Isotope Exchange

Alberto Palazzolo (1) , Sophie Feuillastre (1) , Viktor Pfeifer (1) , Sébastien Garcia-Argote (1) , Donia Bouzouita (2) , Simon Tricard (2) , Celine Chollet (1) , Elodie Marcon (1) , David-Alexandre Buisson (1) , Sophie Cholet (3) , François A Fenaille (3) , Guy Lippens (4) , Bruno Chaudret (2) , Grégory Pieters (1)

1 SCBM - Service de Chimie Bio-Organique et de Marquage
2 LPCNO - Laboratoire de physique et chimie des nano-objets
3 LEMM - Laboratoire d'Etude du Métabolisme des Médicaments
4 LISBP - Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés

A general approach for the efficient hydrogen-isotope exchange of nucleobase derivatives is described. Catalyzed by ruthenium nanoparticles, using mild reaction conditions, and involving either D2 or T2 as isotopic sources, this reaction possesses a wide substrate scope and a high solvent tolerability. This novel method facilitates the access to essential diagnostic tools in drug discovery and development: tritiated pharmaceuticals with high specific activities and deuterated oligonucleotides suitable for use as internal standards during LC-MS quantification.

Keywords: C−H activation; isotopes; isotopic labelling; nucleotides; nanoparticles

Domains: Chemical Sciences

Alberto Palazzolo, Sophie Feuillastre, Viktor Pfeifer, Sébastien Garcia-Argote, Donia Bouzouita, et al.. Efficient Access to Deuterated and Tritiated Nucleobase Pharmaceuticals and Oligonucleotides using Hydrogen-Isotope Exchange. Angewandte Chemie International Edition, 2019, 58 (15), pp.4891-4895. ⟨10.1002/anie.201813946⟩. ⟨cea-02075752⟩