Synthesis of Some Acyclonucleosides Analogs of 1,4-Benzothiazine and Their Sulfonates Derivatives: Crystal Structure, Spectroscopic Characterization, DFT Calculations, Hirshfeld Surface Analysis, and Molecular Docking With Mycobacterium tuberculosis

Ten acyclonucleoside analogs of 1,4-benzothiazine and their sulfone derivatives (3a,b–8a,b) were synthesized using alkylation reactions under phase-transfer catalysis (PTC) conditions. The reactions were conducted under optimized conditions, with reaction times ranging from 1.5 to 2 h and yields varying between 70% and 76%. All the synthesized products were characterized using ¹H and ¹³C-NMR spectroscopy. Additionally, the structures of compounds 4a, 6b, 7a, and 8b were confirmed through single-crystal X-ray diffraction analysis. Spectral data were also calculated using density functional theory (DFT) at the B3LYP/6–311++G(d,p) level and compared with experimental results to better understand the non-binding intermolecular interactions in the solid-state crystal packing. Two-dimensional (2D) and three-dimensional (3D) Hirshfeld surface analyses were performed to identify the closest atomic contacts in the studied molecules. The structures of compounds 4a, 6b, 7a, and 8b were optimized and evaluated for their HOMO and LUMO energies, along with their corresponding orbital representations. A strong correlation was observed between the experimental and calculated results. Finally, molecular docking studies of compounds 4a, 6b, 7a, and 8b were performed to investigate their binding patterns with inhibitory targets from the Protein Data Bank (PDB: 4P8K-A chain: DprE1: decaprenylphosphoryl-β-D-ribose-2′-epimerase) from Mycobacterium tuberculosis , using the AutoDock Vina program.