Syntheses of isotope-labeled SGLT2 inhibitor canagliflozin (JNJ-28431754).

Canagliflozin (Invokana, JNJ-28431754) is an orally bioavailable and selective SGLT2 (subtype 2 sodium-glucose transport protein) inhibitor approved for the treatment of type 2 diabetes. Herein, we report the synthesis of C and C-labeled canagliflozin. Stable isotope-labeled [ C ]canagliflozin was synthesized in 4 steps starting from [ C ]-labeled glucose. The [ C]-Labeled canagliflozin was synthesized by incorporation of [ C] into the benzylic position between the thiophene and benzene rings of the compound. Detailed synthesis of the isotope-labeled compounds is reported.