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Stable glyco-fused 1,4-oxathiine derivatives, prepared by inverse electron-demand Diels−Alder reactions between suitable 1-glycals and 3-thioxopentane-2,4-dione, have been transformed into unusual glycosyl donors which, after “remote activation”, react efficiently with glycosyl acceptors to afford 2-thio-β-O-glycosides with total stereoselectivity. Several O-nucleophiles were successfully glycosylated. Reductive removal of sulfur transformed the 2-thio-β-O-glycosides into the corresponding 2-deoxy-β-O-glycosides without affecting the stereochemistry of the anomeric carbon atom.

Sulfenylation of 6,6‘-dimethoxy-2,2‘-dihydroxybiphenyl, used as a racemic mixture and single enantiomers, by phthalimidesulfenyl chloride afforded the corresponding 3,3‘-N,N‘-dithiophthalimide with complete regioselectivity. Simple manipulations of the latter compound allowed access to the corresponding bis-thiol or o-thioquinone as useful intermediates for the synthesis of new sulfur-containing open-chain and macrocyclic C2 enantiopure ligands. The application of this methodology to the preparation of a biphenyl bearing two cysteine units as potential HIV-1 protease inhibitor is also described.

Immunotherapy of tumors and of melanoma in particular has a long history, and recently this therapeutic approach found a reliable scientific rationale. This biological therapy aims to teach the patients immune system to recognize the antigens expressed on tumor cells and destroy them, leaving normal cells intact. The success of this therapy highly depends on the selection of target antigens that are essential for tumors growth and progression. The overexpression of GM3 ganglioside 1 and especially the expression of its metabolite GM3 lactone 2 characterize murine and human melanomas, playing an important role in tumor progression and making such self-antigens potential targets for the immunotherapy of these neoplasms. Although more immunogenic than its precursor, GM3 lactone 2 is unsuitable to be used in immunotherapy as a melanoma-associated antigen (MAA) because it is unstable under physiological conditions. We designed and synthesized the hydrolytically stable mimetic 3, which is remarkably simpler than the native lactone 2; after conjugation of 3 to the protein carrier keyhole-limpet hemocyanin (KLH), the obtained glycoprotein 5 was used as the immunogen in vivo to successfully elicit specific antimelanoma antibodies. In fact, no appreciable binding to GM1 was observed. Capitalizing on the stability and on the reduced structural complexity of mimetic 3, the immunostimulant 5 we report represents a new promising synthetic glycoconjugate for the immunotherapy of melanoma. © 2010 American Chemical Society.

β-Ketothio derivatives 4, prepared by reaction of phthalimidosulphenyl chloride with enolizable carbonyl compounds, afford, in presence of pyridine, unstable functionalized thiones which can be trapped with 1,3-dienes to give the corresponding cycloaddition products 8 and 9.

[reaction: see text] Glycals are effective starting materials for the synthesis of enantiopure beta-ketone-delta-lactones. They are easily transformed, through a two-step, one-pot reaction, into the corresponding alpha,alpha'-dioxothiones which in turn can be quantitatively trapped with dienophiles in inverse electron-demand [4 + 2] cycloadditions. The reaction of dioxothione 8b with endo and exo glucals allowed the elaboration of a new protocol to prepare 2-thio- or 2-deoxydisaccharides stereoselectively.

The design and synthesis of biotin chain-terminated inhibitors (BTI) showing high affinity for matrix metalloproteinases (MMPs) on one side and high affinity for avidin through the biotinylated tag on the other are reported. The affinity of the designed BTI toward five different MMPs has been evaluated and the simultaneous formation of a highly stable ternary system Avidin-BTI-MMP clearly assessed. This system will permit the development of new approaches to detect, quantify, or collect MMPs in biological samples, with potential applications in vivo.

Improved synthesis of 1,3-disaccharides, obtained diastereomerically pure by [4+2] hetero cycloadditions between glycals and -thiono- -keto- -lactones, has been reported. The choice of appropriate protecting groups for -keto- -lactones, stable under cycloaddition conditions employed, sensibly shortened the synthesis of heterodienic precursors. The first example of a -oxy-imino- -lactone synthesized from -keto- -lactones was also reported. Molecular modeling and conformational evaluations about the cycloaddition features allowed tentatively rationalizing the experimental results. © 2009 Taylor & Francis Group.

The hetero Diels-Alder reactions between α,α’-dioxothiones, α-imino-α’-oxothiones or ortho -thioquinones and glycals represent an effective way to prepare α- or β-, O- or N -glycosides with impressivechemo-, regio- and diastereoselectivity. The glycoderivatives so obtained are bicyclic, sulfur-containing, rigidstructures, which, due to their differentiable functional groups, allow easy manipulations of the moleculararchitecture and can be used as veritable glycosyl scaffolds. INTRODUCTION The advantage of the “molecular scaffolding” concept isthat starting from a single molecular skeleton a variety ofdifferently armed molecules can be synthesized. Theadvantages are even more evident if the scaffold is acarbohydrate-containing scaffold.Monosaccharides represent, indeed, an appealingplatform to tailor molecular “diversity” by introducingdifferent substituents at desired positions around the sugartemplate, thus giving plenty of opportunities to designcustom-tailored molecules to pharmacophore model.In 1992, Hirschmann, Nicolaou

Summary The human pathogenic bacterium Pseudomonas aeruginosa produces a fucose-specific lectin, LecB, implicated in tissue attachment and the formation of biofilms. To investigate if LecB inhibition disrupts these processes, high-affinity ligands were obtained by screening two 15,536-member combinatorial libraries of multivalent fucosyl-peptide dendrimers. The most potent LecB-ligands identified were dendrimers FD2 (C-Fuc-LysProLeu) 4 ( Lys PheLysIle) 2 Lys HisIleNH 2 (IC 50 = 0.14 μM by ELLA) and PA8 (OFuc-LysAlaAsp) 4 ( Lys SerGlyAla) 2 Lys HisIleNH 2 (IC 50 = 0.11 μM by ELLA). Dendrimer FD2 led to complete inhibition of P. aeruginosa biofilm formation (IC 50 ∼ 10 μM) and induced complete dispersion of established biofilms in the wild-type strain and in several clinical P. aeruginosa isolates. These experiments suggest that LecB inhibition by high-affinity multivalent ligands could represent a therapeutic approach against P. aeruginosa infections by inhibition of biofilm formation and dispersion of established biofilms.