Synthesis of novel pregnane-diosgenin prodrugs via Ring A and Ring A connection: A combined experimental and theoretical studies

•Novel pregnane-diosgenin prodrugs have been synthesized.•Compounds are identified by 1H, 13C NMR, FT-IR, UV and ESI-MS.•Intramolecular interactions in prodrugs are analyzed by AIM approach.•Global and local reactivity helps to indentify reactivity of pregnane-diosgenin prodrugs.•From NLO point of view, these compounds may be used as NLO materials.

Novel pregnane-diosgenin prodrugs have been synthesized. The route involved preparation of 3β-25R-spirost-5ene 3yl-benzoate-2-carboxylic acid (2) by the esterification of diosgenin (1) with phthalic anhydride. The pregnane-diosgenin prodrugs 5 & 6 were synthesized by treating 3β-25R-spirost-5ene 3yl-benzoate-2-carboxylic acid (2) with 3β-hydroxy16α-methoxy pregn-5-ene-20-one (3) and 3β-hydroxypregn-5, 16-diene-20-one (4) respectively. The synthesized compounds have been characterized with the help of spectroscopic techniques like 1H, 13C NMR, FT-IR, UV–visible spectroscopy and mass spectrometry. Density functional theory (DFT) with B3LYP functional and 6-31G (d, p) basis set has been used for the Quantum chemical calculations. UV–Vis spectra of the synthesized compounds were also recorded and electronic properties such as frontier orbitals and band gap energies were calculated by TD-DFT approach. Intramolecular interactions have been identified by AIM approach and vibrational wavenumbers have been calculated using DFT method. The reactivity and reactive site within the synthesized prodrugs were examined with reactivity descriptors (global and local). Dipole moment, polarizability and first static hyperpolarizability were calculated to get a better insight of the properties of synthesized prodrugs. The probable reaction paths of prodrugs were calculated with molecular electrostatic potential (MEP) surface analysis.

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