One pot synthesis of novel pregnane-sulphur prodrugs, spectroscopic investigation, conformational analysis, chemical reactivity, Fukui function and their mathematical model

• Published in: Journal of molecular structure 2020-02, Vol.1201, p.127136, Article 127136
• Main Authors: Sethi, Arun, Singh, Ranvijay Pratap, Pathak, Rachana, Shukla, Dolly, Amandeep, Yadav, Priyanka
• Format: Article
• Language: English
• Subjects: 16-DPA; Lewis acids; Mathematical model; Reactivity descriptors; Thia-Michael addition
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2019.127136

Novel sulphur derivatives have been synthesized for the first time from 16-Dehydropregnenolone acetate (16-DPA) by adopting thia-Michael addition reaction yielding 2-[(3β-acetoxy) pregn–5-ene-20-one −16 –thio] propanoic acid, 2-[(3β-acetoxy) pregn–5-ene-20-one–16–thio] ethanoic acid, 3β-acetoxy 16α-(2-hydroxyethylthio)-pregn-5-ene-20-one and 3β-acetoxy-16β-(2-amino phenylthio)-pregn-5-ene-20-one. All the compounds were characterized with the help of 1H, 13C NMR, FT-IR spectroscopy and mass spectrometry. The molecular geometry and vibrational frequency of these compounds were calculated in ground state by density functional theory (DFT/B3LYP) using 6-31G (d, p) basis set. Conformational analysis of all the compounds was carried out to determine the most stable conformation. The electronic properties such as HOMO-LUMO energy were calculated by using time dependent density functional theory (TD-DFT). The topological parameters-electron density (ρBCP), Laplacian of electron density (∇2ρ(rBCP)), energy parameters-kinetic electron energy density (GBCP), potential electron density (VBCP) and the total electron energy density (HBCP) at the bond critical points (BCP) were analyzed by ‘Atoms in molecules’ AIM theory. Local reactivity descriptors like Fukui functions (fk+, fk−, fk0), local softness (sk+, Sk−, Sk0) and local electrophilicity indices (ωk+, ωk−, ωk0) analysis were performed to find out the reactive sites within the molecules. Molecular electrostatic potential of the synthesized compounds were also determined. Lastly a nonlinear mathematical model has been proposed and analyzed to study the effect of catalysts on these reactions. Local and global stability analysis of the mathematical model along with the persistence of the system was checked using theory of nonlinear ordinary differential equations. [Display omitted] •. Novel sulphur containing pregnane 3, 4, 5 and 6 have been synthesized.•. Compounds were characterized with the help of 1H, 13C NMR, FT-IR and ESI-MS.•. Global and local reactivity of all compounds have been calculated.•. AIM and MEP have also been calculated.•. Local and global stability analysis of the mathematical model has been carried out.