Expeditious synthesis of isolated steroids-fluorine prodrugs, their single crystal X-ray crystallography, DFT studies and mathematical modeling

Abstract

In the present research article, we have synthesized novel steroidal-fluorine prodrugs using cholesterol (1), stigmasterol (4) and hydrocortisone acetate (7) isolated from the flowers of Allamanda violacea. These isolated compounds were converted into their fluorinated prodrugs Cholest-5-en-3β-yl-2-fluoro-benzoate (2), Cholest-5-en-3β-yl- 4-fluoro-benzoate (3), 24α-ethylcholest-5, 22E-dien-3β-yl-2-fluoro benzoate (5), 24α-ethylcholest-5, 22E-dien-3β-yl-4- fluoro benzoate (6), 11, 17-dihydroxy-21-(2-fluoro benzoyloxy)-pregn-4-en-3, 20-dione (8) and 11, 17-dihydroxy-21- (4-fluoro benzoyloxy)-pregn-4-en-3, 20-dione (9). We also synthesized fluorinated prodrugs 25R-spirost-5-en-3β-yl-2- fluoro-benzoate (11) and 25R-spirost-5-en-3β-yl-4-fluoro-benzoate (12) from diosgenin (10) a steroidal sapogenin. The structure and stereochemistry of 25R-spirost-5-en-3β-yl-4-fluoro-benzoate (12) was confirmed with help of single crystal X-ray crystallography. The characterizations of compounds have been carried out with the help of 1H, 13C NMR, FT-IR spectroscopy and mass spectrometry. Density functional theory (DFT) with 6-31G (d, p) basis set and B3LYP functional has been used for the quantum chemical calculations. Global reactivity descriptors have also been calculated to find the electrophilicity and nucleophilicity of a molecule. Dipole moment, polarizability and first static hyperpolarizability have been calculated to get NLO properties of synthesized prodrugs. 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 is checked using theory of nonlinear ordinary differential equations.