Molecular Diversity via Tetrasubstituted Alkenes Containing a Barbiturate Motif: Synthesis and Biological Activity.
The synthesis of a molecularly diverse library of tetrasubstituted alkenes containing a barbiturate motif is described. Base-induced condensation of  N  1 -substituted pyrimidine-2,4,6(1 H ,3 H ,5 H )-triones with 5-(bis(methylthio)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione gave 3-substituted 5-(methylthio)-2 H -pyrano[2,3- d ]pyrimidine-2,4,7(1 H ,3 H )-triones ('pyranopyrimidinones'), regioselectively. A sequence of reactions involving ring-opening of the pyran moiety, displacement of the methylthio group with an amine, re-formation of the pyran ring, and after its final cleavage with an amine, gave tetrasubstituted alkenes (3-amino-3-(2,4,6-trioxotetrahydropyrimidin-5(2 H )-ylidene)propanamides) with a diversity of substituents. Cleavage of the pyranopyrimidinones with an aniline was facilitated in 2,2,2-trifluoroethanol under microwave irradiation. Compounds were tested against  Escherichia coli ,  Staphylococcus aureus , the yeast  Schizosaccharomyces pombe,  and the pathogenic fungus  Candida albicans . No compounds exhibited activity against  E. coli , whilst one compound was weakly active against  S. aureus . Three compounds were strongly active against  S. pombe , but none was active against  C. albicans .
Al-Sheikh A, Begum M, Zhang B, Lewis RA, Allenby NEE, Waddell PG, Golding BT