Developments in the chemistry and biology of 1,2,3-triazolyl-C-nucleosides.

In the last 50 years, nucleoside analogs have been introduced to drug therapy as antivirals for different types of cancer due to their interference in cellular proliferation. Among the first line of nucleoside treatment drugs, ribavirin (RBV) is a synthetic N-nucleoside with a 1,2,4-triazole moiety that acts as a broad-spectrum antiviral. It is on the World Health Organization (WHO) list of essential medicines.

Studies on the synthesis of 1'-CN-triazolyl--ribosides.

The search for broad-spectrum antiviral compounds is a continuous mandatory effort. The recent approval of the first -nucleoside carrying a nitrile as a substituent at the C1' position of the ribose ring has raised interest in this underexplored substitution pattern. We have previously reported the development of different 1,2,3-triazolyl--ribonucleosides with anticancer and antiviral activities.

Anti-HCV and Zika activities of ribavirin C-nucleosides analogues.

Ribavirin is an unnatural nucleoside exhibiting broad spectrum of antiviral and antitumor activities, still very widely studied particularly in a repositioning approach. C-triazolyl nucleoside analogues of ribavirin have been synthesized, as well as prodrugs and glycosylated or peptide conjugates to allow a better activity by vectorization into the liver or by facilitating uptake into the cells. The antiviral properties of all synthesized compounds have been evaluated in vitro against two important human viral pathogens belonging to the Flaviviridae family: hepatitis C virus (HCV) and Zika virus (ZIKV).

Synthesis, antiviral and antitumor activities investigations of a series of Ribavirin C-nucleoside analogue prodrugs.

Phosphoramidates obtained according to the ProTide strategy are known for their ability to increase the biological activity of various nucleosides. A series of such prodrugs of SRO-91, a non-natural ribofuranosyl-1,2,3-triazole C-nucleoside obtained by a synthetic sequence involving an indium mediated alkynylation and a Huisgen cycloaddition, was prepared and the antitumor activity on 3 strains of tumor cells was investigated. Two compounds 9a and 9c exhibited interesting cell proliferative inhibitions (IC = 2.

Organocatalysis applied to carbohydrates: from roots to current developments.

Organocatalysis emerged in the last decade as a powerful tool for the synthesis of complex molecules. In the field of carbohydrates, it found widespread use in the synthesis of rare and non-natural carbohydrate derivatives. Additionally, it has also found important application in the stereoselective functionalization of the anomeric carbon in glycosylation reactions.

Direct Synthesis of Mesoporous Organosilica and Proof-of-Concept Applications in Lysozyme Adsorption and Supported Catalysis.

Mesoporous materials represent a useful alternative for exploiting the effects of confinement on molecular trapping and catalysis. Their efficiency often depends on the interactions between the surface and the targeted molecules. One way to enhance these interactions is to adjust the hydrophobic/hydrophilic balance of the surface.

Synthesis and antitumor activities investigation of a C-nucleoside analogue of ribavirin.

SRO-91 is a non-natural ribofuranosyl-1,2,3-triazole C-nucleoside obtained by a synthetic sequence involving a C-alkynyl glycosylation mediated by metallic indium and a Huisgen cycloaddition for the construction of the triazole. Its structure is close to the one of ribavirin, a drug presenting a broad-spectrum against viral infections. SRO-91 antitumor activities were investigated on 9 strains of tumor cells and IC of the order of 1 μM were obtained on A431 epidermoid carcinoma cells and B16F10 skin melanoma cells.

Studies of membranotropic and fusogenic activity of two putative HCV fusion peptides.

Over the past decades, membranotropic peptides such as positively charged cell-penetrating peptides (CPPs) or amphipathic antimicrobial peptides (AMPs) have received increasing interest in order to improve therapeutic agent cellular uptake. As far as we are concerned, we were interested in studying HCV fusion peptides as putative anchors. Two peptides, HCV6 and HCV7, were identified and conjugated to a fluorescent tag NBD and tested for their interaction with liposomes as model membranes.

Enantioselective Access to Robinson Annulation Products and Michael Adducts as Precursors.

The Robinson annulation is a reaction that has been useful for numerous syntheses since its discovery in 1935, especially in the field of steroid synthesis. The products are usually obtained after three consecutive steps: the formation of an enolate (or derivative), a conjugate addition, and an aldol reaction. Over the years, several methodological improvements have been made for each individual step or alternative routes have been devised to access the Robinson annulation products.

Hetero-Diels-Alder reactions of cyclic ketone derived enamide. A new and efficient concept for the asymmetric Robinson annulation.

Chiral enamides, easily prepared in one step from a cyclic ketone and an oxazolidinone, are successfully employed in high-yielding, endo, and facially selective Hetero-Diels-Alder reactions involving activated oxadienes and Siever's reagent as catalyst. From the resulting bicyclic heteroadducts, a novel and efficient asymmetric modification for the Robinson annulation of cyclic monoketones is described.

Glycosidations of 2-deoxy glycosyl dithiophosphates using a tagged iodine(III)-promoter for simple purification.

The preparation of the 4-i-butylsulfonate derivative of the Zefirov reagent (5) and its use in a novel purification strategy for iodine(III)-promoted glycosidations of 2-deoxy diethyldithiophosphate glycosides is described.

Tagged hypervalent iodine reagents: a new purification concept based on ion exchange through SN2 substitution.

The preparation of phenylsulfonate-tagged iodine(III) reagents as well as their use in a novel purification strategy for iodine(III)-promoted reactions is described. The concept is based on ion exchange and is initiated by an azide-promoted SN2-reaction at the alkyl sulfonate followed by trapping of the resulting aryl sulfonate anion with an ion-exchange resin. The concept is successfully proven for Ru-catalyzed oxidations of alcohols, the activation and glycosidation of thioglycosides, and the SuArez reaction of pyranoses.