Synthesis, NMR spectroscopic characterization, DFT calculations, and molecular docking of new substituted phenolic and pyranopyran derivatives obtained from triacetic acid lactone

Two substituted phenolic and pyranopyran derivatives named ethyl 2-(2-acetyl-3‑hydroxy-5-methyl phenyl) acetate (6) and ethyl 2- (4E-2,7- dimethyl-5-oxo- 1H, 5H-pyrano[4,3-b]pyran-4-ylidene) acetate (7) have synthesized from the condensation of triacetic acid lactone (TAL) (4-hdroxy-6-methyl-pyran-2-one 1 with 2-amino-pyridine 2 in refluxing ethanol for 6 h. The structures of 6 and 7 have been elucidated based on spectral data (¹H NMR, ¹³C NMR, and mass spectrometry). The ¹H NMR and ¹³C NMR spectra of the phenolic compound 6 taken in CDCl₃ showed that it may exist under the enolic structure form in the liquid phase. NMR spectroscopy data reveal that 7 adopts an E-configuration. Representative mechanisms explaining the formation of 6 and 7 have been proposed and discussed. Moreover, the ¹³C and ¹H NMR chemical shifts are relatively well reproduced at the B3LYP/6–311++G(d,p) level of theory. Second-order perturbation theory analysis of the Fock matrix showed that the strongest interactions in 6 and 7 are those involved π→ π* and n → π*. Molecular docking of 6 and 7 into the binding sites of α-glucosidase, α-amylase, human peroxiredoxin 5, and SARS-CoV-2 main protease (M^pro) investigation indicate that the inhibitions are thermodynamically favorable and that 6 and 7 may act strong inhibitor towards the reported targets. ADMET and druglikeness investigations show that 6 and 7 may act as potential drug candidates.