Stereocontrolled synthesis of new iminosugar lipophilic derivatives and evaluation of biological activities.

Iminosugars' similarity to carbohydrates determines the exceptional potential for this class of polyhydroxylated alkaloids to serve as potential drug candidates for a wide variety of diseases such as diabetes, lysosomal storage diseases, cancer, bacterial and viral infections. The presence of lipophilic substituents has a significant impact on their biological activities. This work reports the synthesis of three new pyrrolidine lipophilic derivatives O-alkylated in C-6 position. The biological activities of our iminosugars' collection were tested in two cancer cell lines and, due to the pharmaceutical potential, in the model yeast system Saccharomyces cerevisiae to assess their toxicity.

Metal-free photosensitized radical relay 1,4-carboimination across two distinct olefins.

Intermolecular carboamination of olefins offers a powerful platform for the rapid construction of structurally complex amines from abundant feedstocks. However, these reactions often require transition-metal catalysis, and are mainly limited to 1,2-carboamination. Herein, we report a novel radical relay 1,4-carboimination across two distinct olefins with alkyl carboxylic acid-derived bifunctional oxime esters via energy transfer catalysis. The reaction is highly chemo- and regioselective, and multiple C-C and C-N bonds were formed in a single orchestrated operation. This mild and metal-free method features a remarkably broad substrate scope with excellent tolerance of sensitive functional groups, therefore providing easy access to structurally diverse 1,4-carboiminated products. Moreover, the obtained imines could be easily converted into valuable biologically relevant free γ-amino acids.

Electrosynthesis of Stabilized Diazo Compounds from Hydrazones.

An electrochemical synthesis of diazo compounds from hydrazones in yields as high as 99% was performed. This method was elaborated as a useful synthetic method and demonstrated on various diazo compounds (24 examples). Apart from exhibiting an efficiency that matched that of commonly used harsh and toxic chemical oxidants, this reaction is practically simple to set up, requires mild conditions, and is highly electron efficient (3 F/mol).

Anodic Oxidation of Aminotetrazoles: A Mild and Safe Route to Isocyanides.

A new electrochemical method for the preparation of isocyanides from easily accessible aminotetrazole derivatives has been developed, which tolerates an unprecedented range of functional groups. The use of chemical, rather than electrochemical, oxidation to afford isocyanides was also demonstrated, which provides access to these compounds for those without electrosynthesis equipment. The practicality of scale-up using flow electrochemistry has been demonstrated, in addition to the possibility of using electrochemically generated isocyanides in further reactions.

Anodic Oxidation of Dithiane Carboxylic Acids: A Rapid and Mild Way to Access Functionalized Orthoesters.

A new electrochemical methodology has been developed for the preparation of a wide variety of functionalized orthoesters under mild and green conditions from easily accessible dithiane derivatives. The new methodology also offers an unprecedented way to access tri(fluorinated) orthoesters, a class of compound that has never been studied before. This provides the community with a rapid and general method to prepare libraries of functionalized orthoesters from simple and readily available starting materials.

Economical, Green, and Safe Route Towards Substituted Lactones by Anodic Generation of Oxycarbonyl Radicals.

A new electrochemical methodology has been developed for the generation of oxycarbonyl radicals under mild and green conditions from readily available hemioxalate salts. Mono- and multi-functionalised γ-butyrolactones were synthesised through exo-cyclisation of these oxycarbonyl radicals with an alkene, followed by the sp3 -sp3 capture of the newly formed carbon-centred radical. The synthesis of functionalised valerolactone derivatives was also achieved, demonstrating the versatility of the newly developed methodology. This represents a viable synthetic route towards pharmaceutically important fragments and further demonstrates the practicality of electrosynthesis as a green and economical method to activate small organic molecules.