Stereochemical Control in Organic-Synthesis Using Silicon-Containing Compounds

The C-aryl glucoside 6 (dapagliflozin) was identified as a potent and selective hSGLT2 inhibitor which reduced blood glucose levels in a dose-dependent manner by as much as 55% in hyperglycemic streptozotocin (STZ) rats. These findings, combined with a favorable ADME profile, have prompted clinical evaluation of dapagliflozin for the treatment of type 2 diabetes.

Discovery of Dapagliflozin: A Potent, Selective Renal Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes

Synthetic routes to 2,5-disubstituted tetrahydrofurans

A novel asymmetric radical trifluoromethyl-arylation of alkenes has been developed, which provides an efficient approach to access chiral CF3-containing 1,1-diarylmethane derivatives with good to excellent enantioselectivity. Various vinyl arenes and aryl boronic acids are compatible with these conditions. The utility of the method is demonstrated by accessing modified bioactive molecules.

Asymmetric Cu-Catalyzed Intermolecular Trifluoromethylarylation of Styrenes: Enantioselective Arylation of Benzylic Radicals

The factors controlling the highly α-selective C-glycosylation of ribose derivatives were determined by examining the stereoselective reactions of 18 ribose analogues differing in substitution at C-2, C-3, and C-4. The lowest energy conformers of the intermediate oxocarbenium ions display the C-3 alkoxy group in a pseudoaxial orientation to maximize electrostatic effects. To a lesser extent, the C-2 substituent prefers a pseudoequatorial position, and the alkyl group at C-4 has little influence on conformational preferences. In all cases, the product was formed by stereoelectronically preferred inside attack on the lowest energy conformer.

G. Ville

Papers

C-Glycosides. 7. Stereospecific C-glycosylation of aromatic and heterocyclic rings