Gérald Enderlin

Palladium-catalyzed Suzuki reaction in aqueous solvents applied to unprotected nucleosides and nucleotides

Nucleoside analogues have attracted much attention due to their potential biological activities. Amongst all synthetic nucleosides, C5-modified pyrimidines and C2- or C8-modified purines have been particularly studied. A large variety of palladium cross-coupling reactions, with a majority of them based on the Suzuki–Miyaura reaction, have been developed for preparing the desired nucleoside derivatives. Our objective is to focus this review on the Suzuki–Miyaura cross-coupling of nucleosides using methodologies compatible with green chemistry and sustainable development for one part and bioorthogonality for the other part, which means using aqueous medium and no protection/deprotection steps.

Improved microwave-assisted ligand-free Suzuki–Miyaura cross-coupling of 5-iodo-2′-deoxyuridine in pure water

A facile and efficient methodology for direct synthesis of 5-aryl-2′-deoxyuridines was developed through ligand-free Suzuki–Miyaura cross-coupling reactions starting from totally deprotected 5-iodo-2′-deoxyuridine and various boronic acids. Reactions were performed, in pure water, in the presence of very low loading of palladium either by classical thermal heating or with the assistance of microwave irradiation yielding 5-arylated uridine derivatives in moderate to good yields within short reaction times.

An efficient route to acyclic C-nucleosides and fused-ring analogues of uridine from exo-glycals.

Beta-amino esters prepared from activated exo-glycals are transformed into acyclic C-nucleoside with a C-4-substituted uracil derivative that can be cyclized under Mitsunobu conditions to provide a new family of fused-ring analogues of uridine nucleoside in which the N-1 nitrogen atom is embedded in an imino sugar ring. An analogue of uridine of D-ribo configuration is prepared.

Original access to 5-aryluracils from 5-iodo-2′-deoxyuridine via a microwave assisted Suzuki-Miyaura cross-coupling/deglycosylation sequence in pure water

A facile and efficient methodology to obtain various 5-aryluracil derivatives was developed through a two steps sequence: a ligand-free Suzuki-Miyaura cross-coupling reaction starting from totally deprotected 5-iodo-(2′-deoxy)uridine followed by a very simple deglycosylation procedure in pure water with assistance of microwave irradiation.

Synthesis of C-arylnucleoside analogues.

Modified nucleoside analogues are of great biological importance as antiviral and antitumoral agents. There is special interest in the preparation of C-aryl nucleosides with an aromatic ring in different positions of the glycone for their biological activity. Different chemical synthesis strategies for these targets are described in this review.