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 via 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[4.5]non-8-en-7-ones and azaspiro[4.6]dec-3-en-2-ones whose skeletons have so far never been listed. The application of the aza-Piancatelli reaction associated with the use of biobased HMF in fine chemistry gives credit to the development of novative structures, as raised by the green chemistry community. Combining efforts in synthetic methodology with integration of biosourced platforms could open the way to new molecules exhibiting different properties from the ones raised from petrochemical sources.

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. Finally, the third part of this review deals with the recent application of this transformation to the production of commodity chemicals from renewable carbon feedstocks based on sugar-derived furanic platforms.

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.

Synthesis of new dicinnamoyl 4-deoxy quinic acid and methyl ester derivatives and evaluation of the toxicity against the pea aphid Acyrthosiphon pisum.

New dicinnamoyl (caffeoyl, feruloyl, ortho and para-coumaroyl) 4-deoxyquinic acid and esters were synthesized by using a new 4-deoxy quinic acid triol intermediate. The optimisation of both coupling and deprotection steps allowed the preparation in good yields of the target products either as the carboxylic acid or the methyl ester form. Eight new compounds were evaluated for their ability to influence the feeding behaviour of the pea aphid Acyrthosiphon pisum. Artificial diet bioassays showed that two compounds are toxic (mortality and growth inhibition) at lower concentrations than the reference 3,5-dicaffeoyl quinic acid.

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.

Identifying Potent Nonsense-Mediated mRNA Decay Inhibitors with a Novel Screening System.

Nonsense-mediated mRNA decay (NMD) is a quality control mechanism that degrades mRNAs carrying a premature termination codon. Its inhibition, alone or in combination with other approaches, could be exploited to develop therapies for genetic diseases caused by a nonsense mutation. This, however, requires molecules capable of inhibiting NMD effectively without inducing toxicity. We have built a new screening system and used it to identify and validate two new molecules that can inhibit NMD at least as effectively as cycloheximide, a reference NMD inhibitor molecule. These new NMD inhibitors show no cellular toxicity at tested concentrations and have a working concentration between 6.2 and 12.5 µM. We have further validated this NMD-inhibiting property in a physiopathological model of lung cancer in which the TP53 gene carries a nonsense mutation. These new molecules may potentially be of interest in the development of therapies for genetic diseases caused by a nonsense mutation.

Tracking reactive intermediates in phosphine-promoted reactions with ambiphilic phosphino-boranes.

The ambiphilic phosphino-borane i-Pr2P(o-C6H4)BMes2 affords stable versions of key zwitterionic intermediates by reactions with diethyl azodicarboxylate or PhNCO.

Hydrogen fluoride adduct of an ambiphilic phosphine-borane: NMR characterization and theoretical analysis of the bonding situation.

The HF adduct of the ambiphilic phosphine-borane [o-iPr(2)P(C(6)H(4))BMes(2)] has been spectroscopically characterized and the nature of the interaction between the ensuing hydrogenophosphonium and fluoroborate moieties has been analyzed computationally.