Jinq-Chyi Lee

Regioselective one-pot protection of carbohydrates

Carbohydrates are involved in a wide range of biological processes. These structurally diverse compounds are more complex than other biological polymers, and are often present as heterogeneous mixtures in nature. The chemical synthesis of carbohydrates is one way to obtain pure oligosaccharides, but it is hampered by difficulties associated with the regioselective protection of polyhydroxyls and challenges related to the stereoselective assembly of glycosidic linkages. Here we describe a combinatorial, and highly-regioselective, method that can be used to protect individual hydroxy groups of a monosaccharide. This approach can be used to install an orthogonal protecting group pattern in a single reaction vessel (a ‘one-pot’ reaction), which removes the need to carry out the time-consuming isolation and purification of intermediates. Hundreds of building blocks have been efficiently prepared starting from d-glucose, and the iterative coupling of these building blocks enabled us to assemble β-1,6-glucans and a library of oligosaccharides based on the influenza-virus-binding trisaccharide.

Regioselective one-pot protection of glucose

Detailed protocols for the regioselective protection of individual hydroxyls in monosaccharide units are described here. This expedient methodology incorporates up to seven reaction sequences, obviating the necessity to carry out intermittent tedious work-ups and time-consuming purifications. Using this TMSOTf-catalyzed one-pot protocol, the 2,3,4,6-tetra-O-trimethylsilylated hexopyranosides bearing an anomeric group could be transformed into a whole set of differentially protected 2-alcohols, 3-alcohols, 4-alcohols, 6-alcohols and fully protected monosaccharides in high yields. These tailor-made glycosyl donors and acceptors can then be used for stereoselective one-pot glycosylation for oligosaccharide synthesis. The total time for the preparation of a purified protected sugar unit ranges between 1 and 2 d. This process would otherwise take 1–2 weeks.

Sc(OTf)3-catalyzed acetolysis of 1,6-anhydro-β-hexopyranoses and solvent-free per-acetylation of hexoses

Acetolysis of 1,6-anhydro-β-hexopyranoses and solvent-free per-acetylation of hexoses with acetic anhydride at room temperature in excellent yields employing 0.5 mol% scandium(III) trifluoromethanesulfonate as an extremely efficient catalyst are, respectively, described here.

Development of sodium-dependent glucose co-transporter 2 inhibitors as potential anti-diabetic therapeutics.

The kidney plays an important role in the regulation of plasma glucose. It is estimated that greater than 99% of the renal glucose filtered by kidney glomerulus is resorbed by sodium-dependent glucose co-transporters (SGLTs), and that SGLT2 located in the proximal renal tubule achieves the most of this assignment. Studies of SGLT2 inhibitors indicate that raising renal glucose excretion by inhibiting SGLT2 helps effectively normalize the plasma glucose levels in individuals with type 2 diabetes mellitus (T2DM). This review discusses the discovery of SGLT2 inhibitors and the related structure-activity relationship (SAR) studies. The clinical trial data of dapagliflozin is also involved.