Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation

Polycyclic spirobarbiturates containing a pyrrolizidine moiety were synthesized via a one-pot three-component 1,3-dipolar cycloaddition reaction of alloxan, ʟ-proline and <i>N</i>-substituted maleimides. The reaction stereoselectivity was found to depend on the nature of substituents in the maleimide: in most cases the <i>endo</i>-isomer is the main (or only) product, but for some <i>N</i>-arylmaleimides the <i>exo</i>-product is predominant. The proposed mechanism is discussed, and the products were characterized by detailed spectral analysis. The configuration of the stereocenters was determined by X-ray diffraction analysis (XRD) for two adducts, followed by Hirshfeld surface analysis. The antiproliferative effect of the synthesized compounds against cancer cell lines was assessed.