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

Abstract

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.

Modular, Step-Efficient Palladium-Catalyzed Cross-Coupling Strategy To Access C6-Heteroaryl 2-Aminopurine Ribonucleosides

“…To circumvent this problem, current strategies that have been developed for the preparation of 6-heteroaryl guanosines require the use of the expensive 6-iodo-2-aminoguanosine ( 2 ) substrate, ,, prepared from 1 via Finkelstein reaction . Cross-coupling strategies such as Stille, − Negishi, − and other bespoke variants , of these have been explored using both 1 and 2 . However, the toxicity associated with organotin reagents and the presence of a number of Lewis basic sites and electrophilic O-protecting groups have limited their broader utility.…”

Convertible and Constrained Nucleotides: The 2’-Deoxyribose 5’-C-Functionalization Approach, a French Touch

“…As the reaction requires high temperatures detrimental to the stability of ONs, microwave activation was used without the presence of copper as a first proof of concept on a dinucleotide. The palladium-catalyzed reaction went to completion within 5 min with no detected formation of the hydrogenated by-product [ 77 ].…”

Last-Step Pd-Mediated [11C]CO Labeling of a Moxestrol-Conjugated o-Iodobenzyl Alcohol: From Model Experiments to in Vivo Positron Emission Tomography Studies

“…Thus, last-step radiolabeling of biomolecule-based structures has emerged as a powerful strategy, 5,6 and various prosthetic groups have been designed aiming 18 F 7,8 or 11 C labeling. 9,10 In this last case, [ 11 C]CH 3 I, which is obtained in two steps from the cyclotron-produced [ 11 C]CO 2 , has been probably the most investigated 11 Csynthon. 11 Simple alkylations on heteroatoms or moreadvanced strategies based on cross-coupling reactions have been used, but chemo-and regioselectivity issues can occur when dealing with more-complex substrates.…”

“…Starting from a known ligand for a defined biological target, the replacement of a 12 C by its carbon-11 isotope allows identical biodistribution, and fluorine-18 can generally be introduced onto the original structure without significant change in the activity. − However, these approaches are lacking in modularity and often remain poorly compatible with highly functionalized biomolecules (i.e., peptides, oligonucleotides, etc.). Thus, last-step radiolabeling of biomolecule-based structures has emerged as a powerful strategy, , and various prosthetic groups have been designed aiming 18 F , or 11 C labeling. , In this last case, [ 11 C]­CH 3 I, which is obtained in two steps from the cyclotron-produced [ 11 C]­CO 2 , has been probably the most investigated 11 C-synthon . Simple alkylations on heteroatoms or more-advanced strategies based on cross-coupling reactions have been used, but chemo- and regioselectivity issues can occur when dealing with more-complex substrates.…”