Synthesis of metabolites of dapagliflozin: an SGLT2 inhibitor

Dapagliflozin is one of the gliflozin class drugs, useful for the treatment of type-2 diabetes. Dapagliflozin undergoes extensive metabolism and transforms to metabolites in humans. The contribution of pharmacologically active metabolites in drug discovery and development is significant. A streamlined synthetic approach is devised to access three metabolites of dapagliflozin namely, benzylic hydroxy dapagliflozin, oxo dapagliflozin and desethyl dapagliflozin. Two synthetic protocols have been proposed for the synthesis of benzylic hydroxy dapagliflozin and oxo dapagliflozin. An enantioselective deethylation of dapagliflozin is also reported.

Graphic abstract

Synthesis of three metabolites of Dapagliflozin namely benzylic hydroxy dapagliflozin, oxo dapagliflozin and desethyl dapagliflozin is reported from commercially accessible raw materials.