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The huge importance of carbohydrates and their derivatives in biomedical and industrial applications call for the development of streamlined and sustainable procedures for their synthetic elaboration. Here reported a novel glycosylation method based on direct activation of readily available per-O-acylated (acetylated or benzoylated) donors, promoted under air by methanesulfonic acid as a cheap and green catalyst in the absence of any solvent. Besides the beneficial avoidance of toxic and polluting organic solvents, these conditions were found critical for activating such poorly reactive donors with a very small catalyst loading (only 5 mol %), instead of stoichiometric Lewis acid promoters typically employed. Desired glycosides were quickly obtained, in most cases with high 1,2-trans stereoselectivity. Other main advantages over reported glycosylations with similar donors are the limited stoichiometric excess of the acceptor (or the donor), the easy applicability and low cost of the procedure and the wide target scope, also covering the synthesis of disaccharides and other non-trivial glycosides with applicable potential.

The oxidative addition of α-glucosyl and α-galactosyl halides to the platinum(0) complex [Pt(2,9-dimethyl-1,10-phenanthroline)(ethene)] has been investigated. In all cases the main reaction product is the five-coordinate Pt(II) complex containing in axial position an α-glycosyl fragment in the unusual 1C4 conformation. In the case of glucose, a minor product could be identified as the β isomer, which retains the typical 4C1 chair. The single crystal structures of two diastereomers are compared. The outcome of the reaction does not depend on the nature of the halide and is only slightly affected by the solvent. The addition mechanism is discussed, also in the light of literature data. Experimental data, along with DFT calculations, point towards a radical chain mechanism.

Symmetrical diglycosyl-selenides or diselenides can be readily prepared with high chemoselectivity by direct use of elementary selenium as a cheap selenating agent (reduced in situ by sodium borohydride), and glycosyl iodides (or other halides) as reactive glycosyl donors. The chemoselectivity of the synthesis is critically affected by both the presence or not of triethyl phosphite, and the sodium borohydride to selenium stoichiometric ratio. Taking advantage of indications from mechanistic studies, the scope of the strategy was further extended to the synthesis of unsymmetrical diglycosyl selenides. Preliminary biological experiments evidenced an interesting antiproliferative effect of galactosyl diselenide against some tumor cell lines, otherwise negligible with the corresponding selenide.

The several interesting activities detected for fucosylated chondroitin sulfate (fCS) have fueled in the last years several efforts toward the obtainment of fCS oligosaccharides and low molecular weight (LMW) polysaccharides with a well-defined structure, in order to avoid the problems associated with the potential employment of native, sea cucumber sourced fCSs as a drug. Total synthesis and controlled depolymerization of the natural fCS polysaccharides are the main approaches to this aim; nonetheless, they present some limitations. These could be circumvented by semisynthesis, a strategy relying upon the regioselective fucosylation and sulfation of a microbial sourced polysaccharide sharing the same chondroitin backbone of fCS but devoid of any fucose (Fuc) and sulfate decoration on it. This approach is highly versatile, as it could open access also to fCS isomers carrying Fuc and sulfate groups at non-natural sites. Here we prepare for the first time some structurally homogeneous fCS isomers through a multistep procedure with a glycosylation reaction between a LMW polysaccharide acceptor and three different Fuc donors as key step. The obtained products were subjected to a detailed structural characterization by 2D-NMR. The conformational behavior was also investigated by NMR and molecular dynamics simulation methods and compared with data reported for natural fCS.

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.