New catalyst for synthesis of cyclic nucleosides: Insights into silyl-Hilbert-Johnson reaction, ADME survey, dynamic simulation and molecular docking studies targeting HCV

We report in this paper a low-price catalyst, perchloric acid-doped natural phosphate (PAc@NP), that increases the efficiency of the glycosylation process for the synthesis of cyclic nucleosides using reflux conditions. Most current methods use expensive catalysts as a suitable alternative, which can be achieved by using sustainable development goals to develop antiviral agents against the hepatitis C virus. The PAc@NP catalyst was highly stable and efficient throughout three cycles, delivering product yields in the range of 84 % and 60 %. Molecular docking results demonstrated that compounds 2a, 2b and 2c had higher binding energies −7.2 kcal/mol, −8 kcal/mol, and − 7.7 kcal/mol compared to the reference medicine ribavirin. Hence, ADME analysis verifies the favorable pharmacokinetic properties of the synthesized compounds, which is evidence of their promising activity as new antiviral agents. MD simulations of 100 ns showed the greatest dynamic stability of Complex-2 when interacting with the 2KU0 target protein. Such an outcome predicts Complex-2 as the most prospective lead inhibitor and justifies the promoted approach in this particular case of therapeutic research, emphasizing the HCV-related drug development.