The synthesis of the molecular chaperone 2,5-dideoxy-2,5-imino-d-altritol via diastereoselective reductive amination and carbamate annulation

Abstract

The iminosugar 2,5-dideoxy-2,5-imino-d-altritol (DIA, 2) is a powerful competitive inhibitor of α-galactosidase A and has shown much promise as a pharmacological chaperone for the treatment for Fabry disease. Notwithstanding, syntheses of DIA are in want of optimisation. Accordingly, we report on the total synthesis of DIA in 7 steps and in 22% overall yield from readily available d-tagatose. This is the shortest and most efficient synthesis of DIA to date, with key steps in our synthetic strategy including a diastereoselective reductive amination and an I2-mediated carbamate annulation.