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

Abstract

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 ¹³ C and ¹⁴ C-labeled canagliflozin. Stable isotope-labeled [¹³ C₆ ]canagliflozin was synthesized in 4 steps starting from [¹³ C₆ ]-labeled glucose. The [¹⁴ C]-Labeled canagliflozin was synthesized by incorporation of [¹⁴ C] into the benzylic position between the thiophene and benzene rings of the compound. Detailed synthesis of the isotope-labeled compounds is reported.

Keywords: SGLT2 inhibitor; canagliflozin; isotope label; synthesis.