Pd0-Catalyzed Methyl Transfer on Nucleosides and Oligonucleotides, Envisaged as a PET Tracer

Damien James,Jean-Marc Escudier,Magali Szlosek-Pinaud,Eric Fouquet

doi:10.3390/molecules181113654

Abstract

The methyl transfer reaction from activated monomethyltin, via a modified Stille coupling reaction, was studied under “ligandless” conditions on fully deprotected 5'-modified nucleosides and one dinucleotide. The reaction was optimized to proceed in a few minutes and quantitative yield, even under dilute conditions, thus affording a rapid and efficient new method for oligonucleotide labelling with carbon-11.

Highlights

Coupling reactions mediated by transition metal catalysis are powerful methods for the creation of carbon-carbon bonds
Starting from thymidine aldehyde, we have synthesized 5'C-substituted thymidine derivatives either with alkyne or azide groups and engaged them into a conjugation reaction with iodoaryl moieties by “click chemistry’’ leading to compounds 1a–c (Figure 1) [16]. They were used as substrates for the methyl transfer study
The monomethyltin reagent was prepared from iodomethane and Lappert’s stannylene [17,18] (Sn[N(TMS)2]2) and activated in situ with TBAF giving the corresponding methylstannate, according to the previously described procedure [12]

Summary

Introduction

Coupling reactions mediated by transition metal catalysis are powerful methods for the creation of carbon-carbon bonds. Simple and rapid synthetic processes including organic transformations and purifications are required Such a strategy becomes even more challenging when the biomolecule used as substrate is available in very low quantity, as the coupling reaction has to meet four mandatory constraints: (i) the selectivity of the reaction which is imposed by the presence of several functionalities and the absence of protecting groups, (ii) the mildness of the conditions required by the fragility of most of the substrates, (iii) the rapidity of the reaction which is directly related to the short half-live of the isotopes, especially for carbon-11, and (iv) the efficiency of the reaction which may have to occur under extremely dilute conditions either of the radiotracer and/or the biomolecule to be labeled

Methods

Results

Conclusion