We report the total syntheses of a series of pyrrolizidine analogs of casuarine (1) together with their 6-O-α-glucoside derivatives. The synthetic strategy is based on a totally regio- and stereoselective 1,3 dipolar cycloaddition of suitable substituted alkenes with a carbohydrate-based nitrone. We also report the evaluation of biological activity of casuarine and its derivatives towards a wide range of glycosidases and a molecular modeling study focussed on glucoamylase (GA) which investigates the binding modes of the newly synthesized compounds within the enzyme cavity. The results highlight the prominent structural features of casuarine and its derivatives which make them selective glucoamylase inhibitors.