PEG-modified aziridines for stereoselective synthesis of water-soluble fulleropyrrolidines

Abstract

Diastereoselective synthesis of water-soluble fullerene compounds bearing a pharmacophore pyrrolofullerene-2′,5′-dicarboxylate unit is reported. The stereocontrol of the product configuration is achieved through stereospecificity of two consecutive concerted reactions: electrocyclic aziridine ring opening followed by 1,3-dipolar cycloaddition of the resulting azomethyne ylide. The solubility in water (up to 20 μM through direct dissolution) is secured by introducing a polyethylene glycol (PEG) hydrophilic pendant. The structure and molecular-mass distribution of the resulting PEGylated fulleropyrrolidines are exhaustively characterized by ¹H, ¹³C NMR and HRMS. According to absorbance spectroscopy, AFM and DLS studies, the synthesized compound tends to aggregate in aqueous media forming associates of ca. 4–9 nm radius surrounded by a solvation shell resulting in an effective hydrodynamic diameter of ca. 90 nm. In view of notable solubility in water, well-defined chemical structure and resemblance to the compounds with known anti-HIV activity, the synthesized PEGylated diethyl trans-pyrrolofullerene-2′,5′-dicarboxylate might be an attractive candidate for biological evaluation.