Synthesis of SGLT2 Inhibitors by Means of Fukuyama Coupling Reaction.

Disclosed herein is a novel and efficient synthesis of dapagliflozin and canagliflozin, the most advanced sodium glucose cotransporter 2 inhibitors (SGLT2 inhibitors), for the treatment of type 2 diabetes mellitus (T2DM). Per Ac-protected thioester was prepared by the treatment of per Ac d-gluconolactone with 1-dodecanethiol and PrMgCl without affecting labile Ac-protecting groups. Aryl bromide (ArBr) was synthesized through reduction of diaryl ketone to diaryl methane by the TiCl/NaBH/DME-MeOH reduction system.

New Synthesis of Diarylmethanes, Key Building Blocks for SGLT2 Inhibitors.

Synthesis of diarylmethanes, a key building block for SGLT2 inhibitors, has been developed through ketone synthesis by Friedel-Crafts acylation with TiCl, followed by reduction with TiCl/NaBH. The new protocol proceeded more cleanly than the previous methods employing AlCl and BF·OEt/EtSiH to provide the diarylmethanes corresponding to canagliflozin, empagliflozin, and luseogliflozin in a highly expedient and affordable manner. In the case of a diarylmethane for the synthesis of dapagliflozin, the reduction step took place by an alternative method using InCl/Al/BF·OEt.

General Homologation Strategy for Synthesis of L-glycero- and D-glycero-Heptopyranoses.

A general and stereospecific homologation strategy for the synthesis of heptopyranosides is reported. The strategy employs the Wittig olefination and proline-catalyzed α-aminoxylation to achieve one carbon elongation and stereoselective hydroxylation at the C6 position, respectively. The L-glycero- and D-glycero-heptopyranosides can be obtained with nearly perfect stereoselectivity.

A general synthetic strategy and the anti-proliferation properties on prostate cancer cell lines for natural phenylethanoid glycosides.

A general strategy for the synthesis of phenylethanoid glycosides (PhG) including echinacoside 1, acteoside 2, calceolarioside-A 3 and calceolarioside-B 4 is reported. The strategy features the application of low substrate concentration glycosylation and N-formyl morpholine modulated glycosylation methods for the construction of 1,2-trans β- and α-glycosidic bonds. The reported strategy does not invoke the use of the participatory acyl protecting function, which is incompatible with the ester function present in target PhG compounds.

Modulating glycosylation with exogenous nucleophiles: an overview.

The major challenge in carbohydrate synthesis is stereochemical control of glycosidic bond formation. Different glycosylation methods have been developed that are based on the modulation effect of external nucleophiles. This review highlights the development, synthetic application, challenges and outlook of the modulated glycosylation methods.