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Photoinduced hydrothiolation and hydrophosphonylation of alkenes and alkynes

Staderini, Samuele (2014) Photoinduced hydrothiolation and hydrophosphonylation of alkenes and alkynes. PhD Thesis , Università degli Studi di Ferrara.

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    Hydrofunctionalization of terminal double or triple bonds have become classical ligation tools for facile assembly of building blocks into larger molecules especially because comply Sharpless’ prerequisite to be considered “click-chemistry” reactions. In particular the free-metal photoinduced radical thiol-ene (TEC) and thiol-yne (TYC) couplings are well-known to be atom economy, high-efficient, catalyzed only by light and completely regioselective. If both TEC and TYC have already been studied on simple substrates as linear terminal alkenes or alkynes, only few researches have been carried out about particular molecules as protein, peptides and endo-glycals. Hydrothiolation of protein, peptides and aminoacids has been studied to obtain a double different substitution of the peptidic scaffold with one carbohydrate and one marker (fluoresceine or biotine) using TYC. A new technique to synthesize S-disaccharides has been developed starting from different glycals and thio-glucose, demonstrating the efficiency of TEC on internal internal double bonds. The successful work about hydrothiolation of different substrates has pushed us to study both hydrophosphonylation of alkenes and alkynes starting from the same conditions of TEC and TYC reactions. The different reactivity of the functionalization agent (thiol or H-phosphonate) has resulted in different conditions for the addition to double bonds, but not in a loss of efficiency o regioselectivity. On the other hand the addition on a triple bond has resulted to be ineffective and to stop at the internal double bond intermediate. A thiol-ene coupling on this intermediate, formally a vinyl phosphonate, gives equilibration to E form of the alkene without traces of hydrothiolation adducts. It is well known that multivalent effect is a key factor in supramolecular chemistry and it governs many biological interactions, in particular in the relationship between pathogenic microorganisms and their host that involves protein–glycan recognition. The affinity of a multivalent cluster is highly dependent on the combination of the carbohydrate head with the cluster core and the spacer between them; several families of multivalent bioactive molecules have been developed by a large numbers of groups all around the world using disparate synthetic techniques. Thiol-Ene (TEC) and Thiol-Yne (TYC) couplings have been chosen as ligation tool for the synthesis of a variety of multivalent biomolecules containing carbohydrates or peptidic termini supported on different bio-inactive clusters as dendrimers and the rigid silica cube known as POSS (polyhedral oligomeric silsesquioxane). Both TEC and TYC are highly efficient, regioselective and atom economy reactions that, moreover, permit us to avoid purification problems due to metal catalysis or to use large excess of reagents to have a complete substitution on the central core. In fact all the reactions have been carried out with success, high yield and without by-products of any kind. Affinity toward specific target of this large library of compounds has been tested by Enzyme-Linked Lectin Assay (ELLA) and results from good to excellent have been found in all classes of compounds.

    Item Type:Thesis (PhD Thesis)
    Date:28 March 2014
    Tutor:Marra, Alberto
    Coordinator:Bignozzi, Carlo Alberto
    Institution:Università degli Studi di Ferrara
    Divisions:Dipartimento > Scienze chimiche e farmaceutiche
    Subjects:Area 03 - Scienze chimiche > CHIM/06 Chimica organica
    Uncontrolled Keywords:Thiol-ene, thiol-yne,radicals, metal-free, photo-induction, multivalency, phosphonates,
    Deposited on:06 Jul 2015 10:30


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