Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls.

Rotational correlation time is a key parameter for Organic Radical Contrast Agents (ORCA) for MRI. Design of polycyclic systems with incorporated nitroxide moieties in which rotation of the radical separately from the framework is impossible is one of the ways to improve properties of ORCA. Feasibility of the synthesis of rigid 3b,4,5,6,6a,7-hexahydropyrrolo[2',3':3,4]pyrrolo[1,2- c ][1,2,3]triazole and 3b,4,5,6,6a,7-hexahydropyrrolo[2',3':3,4]pyrrolo[1,2- b ]pyrazole ring systems with incorporated nitroxide moiety from 2-alkynyl-substituted pyrrolidine nitroxides was studied. These nitroxides have been prepared via intramolecular Huisgen cycloaddition or intramolecular alkylation in 2-pyrazolyl derivativatives prepared by Michael addition-cyclocondensation of corresponding alkynones with hydrazine. The reduction kinetics by ascorbate showed that the formation of the rigid tricyclic framework does not lead to a significant increase in stability of the radical center to chemical reduction.