Construction of C-glucoside in SGLT2 Inhibitors

Sodium-dependent glucose transporter 2 (SGLT2) inhibitors suppress reabsorption of filtered glucose in renal proximal tubule. Therefore, the inhibitors can control blood glucose by excreting the excess glucose in the urine. Six SGLT2 inhibitors have already been approved in Japan for type 2 diabetes treatments. The structural feature is that sugar is directly connected to benzene. Starting with dapagliflozin, pioneering C-glucoside, a modification of the aglycon and the sugar moiety has been made and the various preparation methods are developed. This review focuses on the sophisticated organic chemistry of C-glucoside construction.