Under solvent-free conditions the reaction of epoxides 1a–i with trimethylsilylazide (2) catalyzed by poly- stiryl-supported fluoride (PS-DABCOF2) has led to the efficient preparation of the corresponding O-TMS protected 1,2-azido alcohols 3a–i that, by treatment with Dowex-H, gave the related 1,2-azido alcohols 4a–i in excellent yields (83–99% and 82–96%, respectively). The use of a flow procedure has allowed us to significantly minimize waste in the preparation of representative 1,2-azido alcohols 4a, 4c and 4i that have been obtained with E-factors of 1.6, 2.1, and 1.9, respectively. The 1,2-amino alcohols 5a, 5c and 5f have been also prepared, in quantitative yields, by reduction of the corresponding O-TMS protected 1,2-azido alcohols 3a, 3c, and 3f by Pd on the Al3O3/HCOOH system

Inhibitors of human lactate dehydrogenase A (LDH-A) are promising therapeutic agents against cancer. The development of LDH-A inhibitors that possess cellular activities has so far proved to be particularly challenging, since the enzyme’s active site is narrow and highly polar. In the recent past, we were able to develop a glucose-conjugated N-hydroxyindole-based LDH-A inhibitor designed to exploit the sugar avidity expressed by cancer cells (the Warburg effect). Herein we describe a structural modulation of the sugar moiety of this class of inhibitors, with the insertion of α-D-mannose, β-D-gulose, or β-N-acetyl-D-glucosamine portions in their structures. Their stereospecific chemical synthesis, which involves a substrate-dependent stereospecific glycosylation step, and their biological activity in reducing lactate production and proliferation in cancer cells are reported. Interestingly, the α-D-mannose conjugate displayed the best properties in the cellular assays, demonstrating an efficient antiglycolytic and antiproliferative activity in cancer cells.

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A convenient method for the stereoselective synthesis of diasteroisomeric vinyl epoxides (-)-2α and (-)-2β, the carba analogs of D-galactal and D-allal-derived vinyl epoxides 1α and 1β, has been elaborated starting from tri-O-acetyl-D-glucal. The key step of this synthesis is an application of the known Claisen thermal rearrangement of a glucal derivative, the vinyl allyl ether (+)-3b, which allows to switch the glycal structure into the corresponding carba analog scaffold. Epoxides (-)-2α and (-)-2β derive from the same synthetic intermediate, the trans diol (+)-5.

Antagonists of the C-type lectin DC-SIGN are promising therapeutic agents against viruses and bacteria. The development of glycomimetic ligands for DC-SIGN has so far proved to be challenging, since this membrane-protein presents four carbohydrate-binding domains (CRD) that specifically recognize mannose and fucose. In the recent past, we were able to develop inhibitors mimicking the minimal natural epitope Manα(1,2)Man using a mannoside with conformationally restricted dimethyl cycloexandicarboxylate-based aglycons designed to exploit the high enzymatic stability and to generate multivalent or solid supported systems as potent lectin ligands. Herein we describe the innovative synthesis of a different class of pseudodisaccharides, mimics of the natural Manα(1,2)Man moiety, characterized by the presence of a real d-carbamannose unit instead of a simpler mimic structure. Their chemical synthesis and biological activity using an SPR inhibition assay are reported. These pseudodisaccharides display inhibition values similar to those of the natural disaccharide Manα(1,2)Man, with a good affinity for DC-SIGN and can be considered as possible candidates for further structural modifications towards improved inhibitors