Christophe Len

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.

Synthesis of Bicyclonucleosides Having a C−C Bridge†

Université de Nantes, CNRS, Laboratoire CEISAM-UMR-CNRS 6230, Faculté des Sciences et des Techniques, 2 rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France, Université Paul Sabatier Laboratoire de Synthèse et Physicochimie des Molécules d’Intérêt Biologique UMR-CNRS 5068, 31062 Toulouse Cedex, France, and Université de Technologie de Compiègne, Ecole Supérieure de Chimie Organique Minérale, EA 4297, Transformations Intégrées de la Matière Renouvelable, 1 allée du Réseau Jean-Marie Buckmaster, F-60200 Compiègne, France

Continuous flow transformations of glycerol to valuable products: an overview

Glycerol conversion to valuable products has been a research avenue that attracted a significant interest in recent years due to its large available volumes (as by-product of biodiesel production) and the different possibilities for chemical and biological conversion into high added value chemicals profiting from the unique presence of three hydroxyl groups in its structure. The utilization of continuous flow processes in combination with transformation of platform chemicals (e.g. glycerol) can offer several advantages to batch processes in view of their potential implementation in industry. This minireview has been aimed to highlight most recent key continuous flow systems for glycerol valorization to valuable products using different types of catalysts and processes.

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.

Nucleoside Analogues with a Novel Glycone Based on the Benzo[C]Furan Core

Abstract Routes to novel nucleoside analogues based on 1, 3-dihydrobenzo[c]furan have been investigated. Thus l-(1, 3-dihydro-3-hydroxymethylbenzo[c]furan-1-yl)-thymine, an analogue of d4T, was obtained as two diastereoisomers. The cis compound (quasi β-D/α-L stereochemistry) was obtained pure but the trans compound was only 90% pure. A purine analogue with a four atom spacer group between base and glycone was also prepared. The conformation of these constrained nucleosides was studied by molecular modelling.

Solventless Oxidative Coupling of Amines to Imines by Using Transition-Metal-Free Metal-Organic Frameworks

A highly efficient, simple, and versatile transition-metal-free metal-organic framework catalytic system is proposed for the oxidative coupling of amines to imines. The catalytic protocol features high activities and selectivities to target products; compatibility with a variety of substrates, including aliphatic amines and secondary amines; and the possibility to efficiently and selectively promote amine cross-coupling reactions. A high stability and recyclability of the catalyst is also observed under the investigated conditions. Insights into the reaction mechanism indicate the formation of a superoxide species able to efficiently promote oxidative couplings.

Diol Appended Quenchers for Fluorescein Boronic Acid

Fluorescein isothiocyanate is treated with 3-aminophenylboronic acid to provide a fluorescently tagged boronic acid derivative which is used to assess Förster resonance energy transfer (FRET) quenching upon boronate ester formation with a series of bespoke diol appended quenchers. Fluorescence spectroscopy comparison of quenching efficiency between treatment of fluorescein and its boronic acid appended congener with quencher appended diol reveals boronate ester formation (covalently linked) to be the more efficient regime and from the panel of quenchers which also included nucleosides.

Facile separation of chiral 1,3-dihydrobenzo[c]furan derivatives using a d-xylose moiety as a protecting group

Abstract 1,2-O-Isopropylidene-α- d -xylofuranose has been used to protect one aldehyde group of o-phthalaldehyde. This chiral protecting group acts as a resolving agent and this leads to separable diastereoisomers when a new stereogenic centre is created by the conversion of the second aldehyde group to a benzyloxyhydroxyethyl chain. These separated diastereoisomers were cyclised to 1,3-dihydrobenzo[c]furans with retention of chiral integrity at the C3 site thus allowing further elaboration to enantiomerically pure nucleoside analogues.

Micellar Catalysis Using a Photochromic Surfactant: Application to the Pd-Catalyzed Tsuji–Trost Reaction in Water

The first example of a Pd-catalyzed Tsuji-Trost reaction, applied in a photochromic micellar media under conventional heating and microwave irradiation, is reported. The surfactant activity and recycling ability were investigated and compared with those of a few commercially available surfactants. The synthetic photochromic surfactant proved to be efficient, recyclable, and versatile for Pd-catalyzed coupling reactions.

Quinoline and phenanthroline preparation starting from glycerol via improved microwave-assisted modified Skraup reaction

An efficient “green” modified Skraup reaction in neat water was developed using inexpensive, abundant and environmentally-friendly glycerol under microwave irradiation conditions. Starting from aniline derivatives, various quinolines were obtained in 10–66% yields. The use of nitroaniline led to the corresponding phenanthrolines in 15–52% yields, respectively.