From 5-HMF to Novel Cyclopentenone-Based Aza Spirocycles: An Intramolecular Aza-Piancatelli Reaction in Action.

With a double objective to upgrade biobased 5-HMF and to access to original spirocycles an intramolecular aza-Piancatelli reaction, a multistep sequence was designed toward appropriate furylcarbinols. The impacts of both the nucleophiles, arylamines compared to alkoxyamines, and the length of the intramolecular tether were studied. After an in-depth evaluation of the different parameters, an extension of the scope provided a library of original azaspiro[4.

Borrowing hydrogen -alkylation with secondary saturated heterocyclic alcohols.

The borrowing hydrogen methodology (BH) has emerged as a powerful tool for the rapid construction of C-C bonds, offering a greener alternative to traditional multi-step syntheses. This methodology involves the activation of inactivated alcohols followed by condensation or aldolization, ultimately leading to the regeneration of the saturated product. Herein, we report the -alkylation of a hindered ketone with challenging secondary saturated heterocyclic alcohols.

The Use of 5-Hydroxymethylfurfural (5-HMF) in Multi-Component Hantzsch Dihydropyridine Synthesis.

The renewable 5-hydroxymethylfurfural (5-HMF) has gained a wide interest from the chemistry community as a valuable biobased platform opening the way to many applications. Despite an impressive number of publications reporting either its preparation or its functionalization, its direct use in fine chemistry, and especially in multi-component reaction (MCR), is less reported. Here, we report a complete study of the use of 5-HMF in the Hantzsch dihydropyridines synthesis.

Design of a structure-activity relationship model of vitamin K epoxide reductase (VKORC1) inhibitors combining chemical synthesis of new compounds, enzymatic assays and molecular modelling.

Vitamin K antagonists (VKAs) anticoagulants have been used since the 1950s as medicines and rodenticides. These molecules are mainly 4-hydroxycoumarin derivatives and act by inhibiting the vitamin K epoxide reductase (VKORC1), an endoplasmic reticulum membrane resident enzyme. However, many VKORC1 mutations have been reported over the last decade, inducing VKAs resistances and thus treatments failures.

Membrane plasticity induced by -inositol derived archaeal lipids: chemical synthesis and biophysical characterization.

Archaeal membrane lipids have specific structures that allow Archaea to withstand extreme conditions of temperature and pressure. In order to understand the molecular parameters that govern such resistance, the synthesis of 1,2-di--phytanyl--3-phosphoinositol (DoPhPI), an archaeal lipid derived from -inositol, is reported. Benzyl protected -inositol was first prepared and then transformed to phosphodiester derivatives using a phosphoramidite based-coupling reaction with archaeol.

Ir-Catalyzed Synthesis of Functionalized Pyrrolidines and Piperidines Using the Borrowing Hydrogen Methodology.

The Ir(III)-catalyzed synthesis of 3-pyrrolidinols and 4-piperidinols combining 1,2,4-butanetriol or 1,3,5-pentanetriol with primary amines was carried out. This borrowing hydrogen methodology was further extended to the sequential diamination of triols leading to amino-pyrrolidines and amino-piperidines.

1,4-d-Sorbitan: A Promising Biobased-Platform for the Synthesis of Chiral Amines.

The regio- and diastereoselective synthesis of chiral amines derived from 1,4-d-sorbitan has been developed the borrowing hydrogen reaction using a cooperative catalysis between an achiral iridium catalyst and diphenylphosphoric acid. The different reactivities of the four hydroxyl groups on the 1,4-d-sorbitan scaffold have also been highlighted.

Splice variants of protein disulfide isomerase - identification, distribution and functional characterization in the rat.

Background: Protein Disulfide Isomerase (PDI) enzyme is an emerging therapeutic target in oncology and hematology. Although PDI reductase activity has been studied with isolated fragments of the protein, natural structural variations affecting reductase activity have not been addressed.

Methods: In this study, we discovered four coding splice variants of the Pdi pre-mRNA in rats.

What is a supercoiling-sensitive gene? Insights from topoisomerase I inhibition in the Gram-negative bacterium Dickeya dadantii.

DNA supercoiling is an essential mechanism of bacterial chromosome compaction, whose level is mainly regulated by topoisomerase I and DNA gyrase. Inhibiting either of these enzymes with antibiotics leads to global supercoiling modifications and subsequent changes in global gene expression. In previous studies, genes responding to DNA relaxation induced by DNA gyrase inhibition were categorised as 'supercoiling-sensitive'.

Synthesis of Phospholipids Under Plausible Prebiotic Conditions and Analogies with Phospholipid Biochemistry for Origin of Life Studies.

Phospholipids are essential components of biological membranes and are involved in cell signalization, in several enzymatic reactions, and in energy metabolism. In addition, phospholipids represent an evolutionary and non-negligible step in life emergence. Progress in the past decades has led to a deeper understanding of these unique hydrophobic molecules and their most pertinent functions in cell biology.

Natural-product-inspired design and synthesis of two series of compounds active against Trypanosoma cruzi: Insights into structure-activity relationship, toxicity, and mechanism of action.

Chemical scaffolds of natural products have historically been sources of inspiration for the development of novel molecules of biological relevance, including hit and lead compounds. To identify new compounds active against Trypanosoma cruzi, we designed and synthesized 46 synthetic derivatives based on the structure of two classes of natural products: tetrahydrofuran lignans (Series 1) and oxazole alkaloids (Series 2). Compounds were screened in vitro using a cellular model of T.

Straightforward Synthesis of Chiral Terpenoid Building Blocks by Ru-Catalyzed Enantioselective Hydrogenation.

Starting from commercially available ()- and ()-β-citronellol, two strategies were designed to synthesize all four stereoisomers of 2,6-dimethyloctane monoterpene chirons in four or five steps in 32-47% overall yield. The desired fragments were obtained by a key Ru-catalyzed asymmetric olefin hydrogenation step under moderate temperature (50 °C), pressure (4 bar), and low catalyst loadings (0.5 mol %) under optimized conditions.

5-Hydroxymethylfurfural (HMF) in Organic Synthesis: A Review of its Recent Applications Towards Fine Chemicals.

Background: 5-Hydroxymethylfurfural (5-HMF) is a biomass-derived platform chemical, which can be produced from carbohydrates. In the past decades, 5- HMF has received tremendous attention because of its wide applications in the production of various value-added chemicals, materials and biofuels. The manufacture and the catalytic conversion of 5-HMF to simple industrially-important bulk chemicals have been well reviewed.

The synthesis of HMF-based α-amino phosphonates one-pot Kabachnik-Fields reaction.

The first use of biomass-derived HMF in the one-pot Kabachnik-Fields reaction is reported here. A wide range of furan-based α-amino phosphonates were prepared in moderate to excellent yields under mild, effective and environmentally-benign conditions: iodine as a non-metal catalyst, biobased 2-MeTHF as the solvent and room or moderate temperature. The hydroxymethyl group of HMF persists in the Kabachnik-Fields products, widening the scope of further modification and derivatization compared to those arising from furfural.

A Continuous and Sensitive Spectrophotometric Assay for Lipase and Phospholipase A Activities Using α-Eleostearic Acid-Containing Substrates.

To date, several sensitive methods, based on radiolabeled elements or sterically hindered fluorochrome groups, are usually employed to screen lipase and phospholipase A (PLA) activities. Here, a new ultraviolet spectrophotometric assay for lipase or PLA was developed using natural triglycerides or synthetic glycerophosphatidylcholines containing α-eleostearic acid (9Z, 11E, 13E-octadecatrienoic acid) purified from Aleurites fordii seed oil. The conjugated triene present in α-eleostearic acid constitutes an intrinsic chromophore and consequently confers strong UV absorption properties of this free fatty acid as well as of lipid substrates harboring it.

Diastereoselective Iridium-Catalyzed Amination of Biosourced Isohexides Through Borrowing Hydrogen Methodology.

A novel direct and diastereoselective amination of biosourced monobenzylated isohexides has been developed through borrowing hydrogen methodology using a cooperative catalysis between an iridium complex and a phosphoric acid. We also report herein the first regio- and diastereoselective direct amination of isosorbide.

The Piancatelli reaction and its variants: recent applications to high added-value chemicals and biomass valorization.

The Piancatelli reaction, also called the Piancatelli rearrangement, consists in the direct conversion of furfuryl alcohols to cyclopentenone derivatives through a furan ring opening-electrocyclization process. Discovered in the late 70's, this reaction has been scarcely used for more than 40 years but recently has been the focus of particular interest from the scientific community and an increasing number of publications on the topic have emerged in the last few years. The first part of this review provides an overview of the recent achievements in classical Piancatelli reactions, discussing reaction conditions and catalytic systems, whereas the second part focuses on the variants recently developed, including the use of new nucleophiles in the process.

Superacidic Cyclization of Activated Anthranilonitriles into 2-Unsubstituted-4-aminoquinolines.

4-Aminoquinolines were prepared in a three-step synthesis starting from substituted anthranilonitriles. The condensation on 1,1,1-trichloro-4-ethoxybut-3-enone proceeded efficiently either neat or in refluxing EtOH. Cyclization in superacidic trifluoromethanesulfonic acid provided unstable intermediate, which upon treatment with NaOEt in ethanol, afforded the expected esters.

Synthesis and biological evaluation of C-3 aliphatic coumarins as vitamin K antagonists.

Since the discovery of Warfarin in the 1940s, the design of new warfarin-derived anticoagulants for rodent management has been challenging, with mainly structural modifications performed on the C3 position of the coumarin skeleton. In order to better understand the pharmacomodulation of such derivatives, we have synthesized a family of C3 (linear and branched) alkyl-4-hydroxycoumarins, which led to the identification of compounds 5e and 5f as potential short-term active anticoagulants.

Development of an Ecofriendly Anticoagulant Rodenticide Based on the Stereochemistry of Difenacoum.

Difenacoum, an antivitamin K anticoagulant, has been widely used as rodenticide to manage populations of rodents. Difenacoum belongs to the second generation of anticoagulant, and, as all the molecules belonging to the second generation of anticoagulant, difenacoum is often involved in primary poisonings of domestic animals and secondary poisonings of wildlife by feeding contaminated rodents. To develop a new and ecofriendly difenacoum, we explored in this study the differences in properties between diastereomers of difenacoum.

A continuous spectrophotometric assay that distinguishes between phospholipase A1 and A2 activities.

A new spectrophotometric assay was developed to measure, continuously and specifically, phospholipase A1 (PLA1) or phospholipase A2 (PLA2) activities using synthetic glycerophosphatidylcholines (PCs) containing α-eleostearic acid, either at the sn-1 position [1-α-eleostearoyl-2-octadecyl-rac-glycero-3-phosphocholine (EOPC)] or at the sn-2 position [1-octadecyl-2-α-eleostearoyl-rac-glycero-3-phosphocholine (OEPC)]. The substrates were coated onto the wells of microtiter plates. A nonhydrolyzable ether bond, with a non-UV-absorbing alkyl chain, was introduced at the other sn position to prevent acyl chain migration during lipolysis.

Nitrogen-functionalized Isohexides in Asymmetric Induction.

Biosourced isohexides have attracted the considerable attention of both the academic and industrial chemistry communities over the last 50 years. This highlight focuses on the synthesis of nitrogen-containing isohexides and their applications in asymmetric catalysis.

Synthesis of benzofuran derivatives as selective inhibitors of tissue-nonspecific alkaline phosphatase: effects on cell toxicity and osteoblast-induced mineralization.

Tissue-nonspecific alkaline phosphatase (TNAP) by hydrolyzing pyrophosphate, an inhibitor of apatite formation, promotes extracellular matrix calcification during bone formation and growth, as well as during ectopic calcification under pathological conditions. TNAP is a target for the treatment of soft tissue pathological ossification. We synthesized a series of benzofuran derivatives.

C2 Arylated Benzo[b]thiophene Derivatives as Staphylococcus aureus NorA Efflux Pump Inhibitors.

An innovative and straightforward synthesis of second-generation 2-arylbenzo[b]thiophenes as structural analogues of INF55 and the first generation of our laboratory-made molecules was developed. The synthesis of C2-arylated benzo[b]thiophene derivatives was achieved through a method involving direct arylation, followed by simple structural modifications. Among the 34 compounds tested, two of them were potent NorA pump inhibitors, which led to a 16-fold decrease in the ciprofloxacin minimum inhibitory concentration (MIC) against the SA-1199B strain at concentrations of 0.

Comparative inhibitory effect of prenylated coumarins, ferulenol and ferprenin, contained in the 'poisonous chemotype' of Ferula communis on mammal liver microsomal VKORC1 activity.

Two distinguishable chemotypes of Ferula communis have been described: the 'nonpoisonous' chemotype, containing as main constituents the daucane esters; and the 'poisonous' chemotype containing prenylated coumarins, such as ferulenol and ferprenin. Ferulenol and ferprenin are 4-oxygenated molecules such as dicoumarol and warfarin, the first developed antivitamin K molecules. Antivitamin K molecules specifically inhibit VKORC1, an enzyme essential for recycling vitamin K.