Exhaustive glycosylation, pegylation, and glutathionylation of a [G4]‐ene_(48) dendrimer via photoinduced thiol‐ene coupling

The use of free‐radical thiol‐ene coupling (TEC) for the introduction of carbohydrate, poly(ethylene glycol), and peptide fragments at the periphery of an alkene functional dendrimer has been reported in this article. Four different sugar thiols including glucose, mannose, lactose, and sialic acid, two PEGylated thiols, and the natural tripeptide glutathione were reacted with a fourth generation alkene functional dendrimer [G4]‐ene48 on irradiation at λmax 365 nm. In all cases, the 1H NMR spectra of the crude reaction mixture revealed the complete disappearance of alkene proton signals indicating the quantitative conversion of all 48 alkene groups of the dendrimer. With one exception only, all dendrimer conjugates were isolated in high yields (70–94%), validating the high efficiency of multiple TEC reactions on a single substrate. All isolated and purified compounds were analyzed by matrix assisted laser desorption ionization‐time of flight (MALDI‐TOF) spectrometry and gave spectra consistent with the assigned structure

Picomolar inhibition of cholera toxin by a pentavalent ganglioside GM1os-calix[5]arene

Cholera toxin (CT), the causative agent of cholera, displays a pentavalent binding domain that targets the oligosaccharide of ganglioside GM1 (GM1os) on the periphery of human abdominal epithelial cells. Here, we report the first GM1os-based CT inhibitor that matches the valency of the CT binding domain (CTB). This pentavalent inhibitor contains five GM1os moieties linked to a calix[5]arene scaffold. When evaluated by an inhibition assay, it achieved a picomolar inhibition potency (IC50 = 450 pM) for CTB. This represents a significant multivalency effect, with a relative inhibitory potency of 100000 compared to a monovalent GM1os derivative, making GM1os-calix[5]arene one of the most potent known CTB inhibitors

The Emergence of Thiol-Ene Coupling as a Click Process for Materials and Bioorganic Chemistry

The Emergence of Thiol-Ene Coupling as a Click Process for Materials and Bioorganic Chemistry is described

Synthesis of Heterocycle-Linked C-Glycosyl alpha-Amino Acids and C-Glycopeptides

Non-natural C-glycosyl alpha-amino acids are building-blocks for the co-translational modification of natural glycopeptides. These are key components of the complex machinery that operates in vital processes of all living organisms, ranging from eubacteria to eukaryotes. While a wide range of C-glycosyl amino acids have been synthesized, we have designed and prepared a small collection of a new class of these amino acids whose structure features a heterocycle ring holding the carbohydrate and the amino acid fragments. Isoxazole, triazole, tetrazole, and pyridine moieties were used as suitable linkers in this project owing to their easy construction via Huisgen cycloaddition and Hantzsch multicomponent reaction. Details on the synthesis of each family of these glycolconjugates are given below, some emphasis being given to the efficiency and generality of each method employed. The potential of these glycosyl amino acids in non-natural glycopeptide synthesis is exemplified by the coupling of a pyridine-linked derivative with two natural amino acids to give a non-natural glycotripeptide

Advances In The Use Of Synthons In organic Chemestry

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Design and Synthesis of New Classes of Heterocycle Glycoconjugates and Amino Acid by Asymmetric Multicomponent Reactions (AMCRs)

none2noneMassi A.; Dondoni A.Massi, Alessandro; Dondoni, Alessandr

General Synthesis of C-Glycosyl Amino Acids via Proline-Catalyzed Direct Electrophilic alpha-Amination of C-Glycosylalkyl Aldehydes

Non-natural axially and equatorially linked C-glycosyl alpha-amino acids (glycines, alanines, and CH2-serine isosteres) with either S or R alpha-configuration were prepared by D- and L-proline-catalyzed (de >95%) alpha-amination of C-glycosylalkyl aldehydes using dibenzyl azodicarboxylate as the electrophilic reagent

Synthesis of L-gulose, L-idose and the disaccharide subunit of Bleomycin A2

none3noneMassi A.; Dondoni A.; Marra A.Massi, Alessandro; Dondoni, Alessandro; Marra, A

Metal-Catalyzed and Metal-Free Alkyne Hydrothiolation: Synthetic Aspects and Application Trends

International audienceAlkyne hydrothiolation – that is, the addition of the SH bond of a thiol across the carbon-carbon triple bond of an unactivated alkyne – belongs to the ample class of hydrofunctionalization reactions whose main feature is their occurrence with total atom economy. Hence this reaction is emerging as a valuable tool for the preparation of sulfur-containing compounds such as vinyl thioethers, which are of interest for their own biological properties and for their use as intermediates in total synthesis. Thus, the first part of this review deals with the various efforts directed towards the preparation of vinyl thioethers in a regio- and diastereoselective manner by metal-catalyzed approaches in recent years. The number of methods employed, with use of a variety of catalysts and reaction conditions, allow the synthesis of vinyl thioethers to be carried out with high efficiency and selectivity. The second part of the article is based on the use of the photoinduced free-radical approach to hydrothiolation, which allows the introduction of two thiol fragments across the carbon-carbon triple bond, thereby leading to the formation of dithioethers. This approach turned out to be especially useful as a ligation tool for the installation of densely functionalized arrays on various scaffolds and complex biomolecular systems. Concluding remarks emphasize the role of the photoinduced free-radical strategy as a complementary tool to copper-catalyzed azide-alkyne cycloaddition