Polycyclic spirobarbiturates containing a pyrrolizidine moiety were synthesized via a one-pot three-component 1,3-dipolar cycloaddition reaction of alloxan, ʟ-proline and N -substituted maleimides. The reaction stereoselectivity was found to depend on the nature of substituents in the maleimide: in most cases the endo -isomer is the main (or only) product, but for some N -arylmaleimides the exo -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.
Puzyrkov et al. (Tue,) studied this question.