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

Abstract

Rotational correlation time is a key parameter for organic radical contrast agents (ORCA) for magnetic resonance imaging (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 derivatives prepared by Michael addition-cyclocondensation of the 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.