RESUMO
The preparation of anomeric tetrabutylammonium sulphates of glucose and galactose derivatives is reported and their role as donors in glycosylation reactions is studied. Metal triflates showed good performance in activating sulphate as a leaving group. Among them, ytterbium triflate in stoichiometric amounts gave the best results. Basic conditions using barium oxide in combination with trimethylsilyl trifluoromethanesulfonate (TMSOTf) were also shown to give good results. Benzylated sulphates were much more reactive than benzoylated donors when activated either by ytterbium triflate or by BaO and TMSOTf. Different acceptors were tested, such as isopropanol, cholesterol, and other common sugar derivatives. High reaction rates and excellent glycosylation yields were obtained under mild reaction conditions. The α/ß anomeric ratio suggests a predominant SN2-like reaction mechanism.
RESUMO
The synthesis of a carba-analogue corresponding to the trisaccharide repeating unit of Streptococcus pneumoniae type 19F capsular polysaccharide, where a residue of carba-L-rhamnose has been inserted into the natural trisaccharide in place of L-rhamnose, is described. The conformational properties of the analogue were investigated with the aid of molecular dynamics simulations and were strictly analogous to those of the natural compound. The biological activity of the carba-analogue was comparable to that of the corresponding natural repeating unit, thus suggesting that this compound, more stable to hydrolysis, is a good mimic of the natural structure.
Assuntos
Cápsulas Bacterianas/química , Simulação de Dinâmica Molecular , Streptococcus pneumoniae , Trissacarídeos/química , Trissacarídeos/farmacologia , Animais , Anticorpos/imunologia , Reações Antígeno-Anticorpo/efeitos dos fármacos , Cápsulas Bacterianas/imunologia , Configuração de Carboidratos , Sequência de Carboidratos , Bovinos , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Humanos , Ramnose/química , Trissacarídeos/síntese químicaRESUMO
Two new HA derivatives bearing carborane rings were synthesized by click chemistry. The optimal conditions were assessed for the preparation of biocompatible boron carriers, potentially suitable for application in BNCT and capable of targeting the CD44 antigen. The new polymeric samples were characterized by means of NMR-spectroscopy techniques that gave degrees of 17 and 8% for HAAACB and HapACB, respectively. Both HAAACB and HApACB turned out to be nontoxic for colorectal, ovarian and bladder tumor cell lines, to disclose a specific interaction with the CD44 antigen as the native hyaluronan moiety, and to deliver boron-atom concentrations largely sufficient for BNCT therapy when accumulated in cancer cells.