Investigation into methods for N-trifluoromethylation of a key intermediate in the synthesis of an SGLT1 inhibitor and potential starting point for anti-diabetes drugs

Abstract: Sodium-glucose transporters (SGLTs) are a group of membrane proteins involved in regulating blood-glucose levels. Compounds which inhibit SGLTs are therefore of interest in the development of new treatments for diabetes. The SGLT class is divided into SGLT1 and SGLT2, the primary difference between the two being where in the body they are expressed. Several SGLT2 inhibitors have been approved and are being used to treat diabetes in current clinical practice. No SGLT1 inhibitors have been approved as of yet but there are several under development at various pharmaceutical companies. In this work, methods to N-trifluoromethylate a key intermediate in the synthesis of an SGLT1 inhibitor and potential anti-diabetes drug were investigated. A previously reported procedure as well as potential alternatives were examined. Multiple methods were capable of producing the N-CF3 intermediate (confirmed by NMR and GC-MS analysis) but all inefficiently and in poor yields. Further research in this area is needed to improve the overall efficiency of the synthesis of the SGLT1 inhibitor.