Synthesis, spectroscopic characterization, crystal structure, DFT calculations and Hirshfeld surface analysis of 3-acetyl-30-N2, N2-dimethyl-1′, 3′, 5′-triazine-2′, 4′-diamine of substituted 18β-Glycyrrhetinic compound

Abstract

18β-glycyrrhetinic acid (GA) compounds, exhibiting good biological activity, are widely present in drug molecules. Many literatures reported on antitumor activity of derivatives of 18β-GA, and some of these compounds showed better anti-tumor activity than 18β-GA itself and Gefitinib. The compound 1 that one of the 18β-glycyrrhetinic acid compounds (4-amino-6-(dimethylamino)-1,3,5-triazin-2-yl)methyl (2S,6aS,8aR,12bR)-10-acetoxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxylate was designed and synthesized, and the structure was characterized by spectroscopic techniques including UV-vis, FT-IR, Raman, NMR(1H,13C) and HRMS. The precise structure of 1 were analyzed using single-crystal X-ray diffraction and showed interesting intermolecular NH…O and NH...N hydrogen bonding which was the most important factor in the crystal stacking interaction. The molecular structure was further calculated using density functional theory (DFT), which were compared with the X-ray diffraction value. The results of the conformational analysis indicate that the molecular structure optimized by DFT were consistent with the crystal structures determined by single crystal X-ray diffraction. The molecular electrostatic potential and frontier molecular orbitals of the title compound were further investigated by DFT, and some physicochemical properties of the compound are revealed. In additional, the intermolecular interactions in the crystal were investigated through the Hirshfeld surface analysis to understand the characteristics of the close contacts, and the 2D-fingerprint plot data exposed that a significant contributions to the crystal packing are from N…H/H…N contacts.