Chiral 1,4-morpholine-2,5-dione derivatives as alpha-glucosidase inhibitors

Some 1,4-morpholin-2,5-dione derivatives have been synthesized in good yields by a procedure already employed by us starting from (S)- phenylethylamine, ethylbromoacetate and 2 chloropropionyl chloride. Both (6S)- and (6R)-6-methy-1,4-morpholin-2,5 diones were alkylated with allylbromide, then converted into epoxiderivatives and finally hydrolised to the vicinal diols. The absolute configuration of the C-2’ stereocenter in the epoxides, and then in the diols, was established by the conversion of the diols into the respective gamma-lactones. Except the allylderivatives which show a weak biological activity (Ki=1300 and 3300 micromolar), both epoxides and diols are non competitive inhibitors towards the alpha-glucosidase from bakers yeast (Ki values between 47-470 micromolar). No significant inhibitory effect towards both beta-glucosidase (from almonds) and alpha-mannosidase (from jack beans) was observed.