The glycosylation of five-coordinate Pt(ii) compounds through a Pt–C linkage can be a very effective strategy for attacking cancer cells, while preserving the survival of the healthy ones.

Chondroitin sulfate (CS) is a glycosaminoglycan playing several biological functions, which seem to be encoded through its sulfation pattern. This "sulfation code" is still to be deciphered. One of the barriers to this goal is the difficulty in achieving structurally well-defined CS polysaccharides since extraction from natural sources often leads to complex heterogeneous structures. Instead, an approach relying on chemical modification of a microbially sourced unsulfated chondroitin can allow access to semisynthetic CS polysaccharides with a well-defined sulfation pattern. We report herein some new, suitably developed chemical strategies affording CSs with unprecedented sulfation patterns, carrying a single sulfate group regioselectively placed at either C-2 or C-3 position of the glucuronic acid residues or at both sites. In this way, all the possible variants of CS sulfation patterns can be now accessed. This will allow more detailed and complete structure−activity relationship investigations of CS biological functions and applications.

tert-Butyldimethylsilyl (TBDMS) and tert-butyldiphenylsilyl (TBDPS) are alcohol protecting groups widely employed in organic synthesis in view of their compatibility with a wide range of conditions. Their regioselective installation on polyols generally requires lengthy reactions and the use of high boiling solvents. In the first part of this paper we demonstrate that regioselective silylation of sugar polyols can be conducted in short times with the requisite silyl chloride and a very limited excess of pyridine (2–3 equivalents). Under these conditions, that can be regarded as solvent-free conditions in view of the insolubility of the polyol substrates, the reactions are faster than in most examples reported in the literature, and can even be further accelerated with a catalytic amount of tetrabutylammonium bromide (TBAB). The strategy proved also useful for either the selective TBDMS protection of secondary alcohols or the fast per-O-trimethylsilylation of saccharide polyols. In the second part of the paper the scope of the silylation approach was significantly extended with the development of unprecedented “one-pot” and “solvent-free” sequences allowing the regioselective silylation/alkylation (or the reverse sequence) of saccharide polyols in short times. The developed methodologies represent a very useful and experimentally simple tool for the straightforward access to saccharide building-blocks useful in organic synthesis.

Fucosylated chondroitin sulfate (fCS) is a glycosaminoglycan found up to now exclusively in the body wall of sea cucumbers. It shows several interesting activities, with the anticoagulant and antithrombotic as the most attractive ones. Its different mechanism of action on the blood coagulation cascade with respect to heparin and the retention of its activity by oral administration make fCS a very promising anticoagulant drug candidate for heparin replacement. Nonetheless, its typically heterogeneous structure, the detection of some adverse effects and the preference for new drugs not sourced from animal tissues, explain how mandatory is to open an access to safer and less heterogeneous non-natural fCS species. Here we contribute to this aim by investigating a suitable chemical strategy to obtain a regioisomer of the natural fCS polysaccharide, with sulfated l-fucosyl branches placed at position O-6 of N-acetyl-d-galactosamine (GalNAc) units instead of O-3 of d-glucuronic acid (GlcA) ones, as in natural fCSs. This strategy is based on the structural modification of a microbial sourced chondroitin polysaccharide by regioselective insertion of fucosyl branches and sulfate groups on its polymeric structure. A preliminary in vitro evaluation of the anticoagulant activity of three of such semi-synthetic fCS analogues is also reported.been the most intensely studied in the last two decades. It attracted a constantly increasing interest for its activity in biological events related to inflammation, hyperglycemia, atherosclerosis, cellular growth, cancer metastasis, angiogenesis, and, above all, coagulation and thrombosis [2]. The anticoagulant and antithrombotic activity is observed also on antithrombin (AT) and heparin cofactor II (HC-II)-free plasmas, for which the most widespread and long-term used anticoagulant drug-unfractionated heparin-is inactive, due to some differences in the mechanism of action of fCS on the blood coagulation cascade [3,4]. Furthermore, oral administration of fCS retains its activity, because it is digested neither during its adsorption in the gastrointestinal tract nor by intestinal bacterial enzymes [5]. These features make fCS a very promising anticoagulant drug candidate for heparin replacement [6].From a structural point of view, fCS shares the same linear core backbone as chondroitin sulfate (CS) polysaccharide, with alternating N-acetyl-d-galactosamine (GalNAc) and d-glucuronic acid (GlcA) residues linked together through alternating β-1→3 and β-1→4 glycosidic bonds and sulfated to a different extent on their hydroxyls. The unique structural peculiarity of fCSs is the additional presence of variously sulfated fucose (Fuc) branches [7,8], which are essential for the observed biological activities [9][10][11]. Very often the branches are constituted of a single Fuc unit α-glycosidically linked at O-3 site of GlcA residues. Nonetheless, fCSs from some sea cucumbers species with slightly different structural features have also been found [12]. Indeed, Ludwigothurea grisea [13], Eupentacta f...

Symmetrical diglycosyl-selenides or diselenides can be readily prepared with high chemoselectivity by direct use of elemen-tary selenium as a cheap selenating agent (reduced in situ by sodium borohydride), and glycosyl...

Galectins are soluble β-D-galactoside-binding proteins whose implication in cancer progression and disease outcome makes them prominent targets for therapeutic intervention. In this frame, the development of small inhibitors that block selectively the activity of galectins represents an important strategy for cancer therapy which is, however, still relatively underdeveloped. To this end, we designed here a rationally and efficiently novel diglycosylated compound, characterized by a selenoglycoside bond and the presence of a lipophilic benzyl group at both saccharide residues. The relatively high binding affinity of the new compound to the carbohydrate recognition domain of two galectins, galectin 3 and galectin 9, its good antiproliferative and anti-migration activity towards melanoma cells, as well as its anti-angiogenesis properties, pave the way for its further development as an anticancer agent.

Three alternative protocols were developed to carry out the selective installation of acetal groups on carbohydrates and polyols under mildly acidic, solvent-free conditions. One protocol is based on a diol/aldehyde condensation at room temperature, with an acetolysis process serving for the activation of the carbonyl component. A second approach is based on an orthoester-mediated activation of the carbonyl component at high temperature. The third protocol is instead entailing a transacetalation mechanism. Combination of these methods allows a wide set of acetal-protected building blocks to be accessed in short times under very simple experimental conditions working under air. The scope of the latter two approaches was also extended to unusual one-pot synthetic sequences leading to concomitant Fischer glycosidation/acetal protection of reducing sugars

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