Pyrrolidine-2,3,4-tricarboxylic anhydrides: I. Organocatalytic synthesis and fusion of pyrrole ring by the action of p-fluorobenzylamine

N -Boc-glycine effectively catalyzes 1,3-dipolar cycloaddition of maleic anhydride to N -benzylidene α-amino acid esters, which leads to the formation of pyrrolidine-2,3,4-tricarboxylic anhydrides. The subsequent opening of the anhydride fragment in the adducts by the action of p -fluorobenzylamine is regioselective, and it involves recyclization to produce polysubstituted octahydropyrrolo[3,4- b ]pyrroles. The newly synthesized fused pyrrolidines inhibit enzymatic activity of thrombin (factor IIA) in vitro .