Quantum Mechanical Spectral Analysis and Aldose Reductase Inhibition Evaluation of Synthetic New Pyrrolopyrazinones

The Maillard reaction, known as the condensation of reduced sugars with amino acids, can be a great source of pyrroles for the discovery of bioactive compounds. In the present study, using glucose and l-alanine, two new pyrrolopyrazinones (1a and 1b) were obtained. Subsequently, two more new pyrrolopyrazinones (2a and 2b) were prepared by further hydrolyzing the methyl ester into carboxylic acid. The structures of the pyrrolopyrazinones were determined by interpretation of 1D and 2D NMR and HRESIMS data as well as computational calculation of ECD Cotton effects. Moreover, the broad ¹H NMR peak shapes observed in the pyrrolopyrazinones were accurately resolved to the presence of long-range couplings, including allylic ⁴ J and homoallylic ⁵ J couplings, by employing quantum mechanics-driven ¹H iterative full spin analysis (QM-HiFSA). The four pyrrolopyrazinones were evaluated for their biological efficacy in the treatment of diabetes in terms of their structural elements, including carboxyl functional groups. As a result, all four compounds were found to be moderately effective in inhibiting aldose reductase and also in proliferating mesenchymal stem cells.