Nanoparticles of manganese oxides as efficient catalyst for the synthesis of pyrano[2,3-d]pyrimidine derivatives and their complexes as potent protease inhibitors

Novel pyrano[2,3-d] pyrimidine derivatives were synthesized via the three-component reaction of thiophene-2-carbaldehyde, malononitrile and barbituric or thiobarbituric acid in the presence of Mn₂O₃ nanoparticles. This method has been found to be eco-friendly and economical. Compound 1 was used as a precursor for the synthesis of new pyranopyrimidine derivatives 2–5. Moreover, 7-amino-2,3,4,5-tetrahydro-4-oxo-5-(thiophen-2-yl)-2-thioxo-1H-pyrano[2,3-d]pyrimidine-6-carboxamide 4 was then converted into another set of novel compounds 6–8. On the other hand, a series of Mn(II) complexes with pyrano[2,3-d]pyrimidine derivatives have been prepared. The synthesized compounds and its complexes were characterized by elemental analysis, magnetic and spectroscopic methods (IR, XRD, SEM, TEM, ¹³C, ¹HNMR) as well as thermal analysis. The spectrophotometric determinations suggest a distorted octahedral geometry for all complexes. The organic compounds and its chelates as inhibitors exhibited remarkable effects on the enzyme activity of an extracellular toxic protease, KB76 from Brevibacterium otitidis as well as against different bacterial and fungal strains. Graphical abstract: .