Isolation of brassicasterol, its synthetic prodrug-crystal structure, stereochemistry and theoretical studies

• Brassicasterol (compound 1) is reported for the first time from Allamanda violacea.
• Its structure was further proved by synthesizing its prodrug (2) with naproxen by Steglich esterification.
• Single crystal X-ray of (2) confirmed structures of (1) and (2) and stereochemistry of (2).
• NBO analysis explained stability of both (1) and (2) through hyperconjugative interactions.
• HOMO–LUMO energy gaps were calculated with time dependent-DFT.

In the present study brassicasterol (1), was isolated from the chloroform extract of the flowers of Allamanda violacea and identified with the help of different spectroscopic techniques like 1H, 13C, 2D NMR (1H–1H COSY), IR, UV and mass spectrometry. A novel prodrug was synthesized by carrying out esterification of brassicasterol (1) with the well known drug naproxen using Steglich esterification to give 3β-(2-(6-methoxynaphthalene-2yl) propionoxy) 24 methyl cholest-5, 22-dien (2). Compounds 2 was subjected to single crystal X-ray diffraction technique and crystallized out in monoclinic form having P21 space group and stabilized by CH–π interactions. Structure and stereochemistry of compound 2 was established with the help of modern spectroscopic techniques like 1H NMR, IR, UV, mass spectrometry as well as with single crystal X-ray diffraction.Molecular geometry and vibrational frequencies of compounds 1 and 2 were calculated by density functional method (DFT/B3LYP) using 6-31G (d, p) basis set, bond parameters and IR frequencies were correlated with the experimental data. 1H and 13C chemical shifts of compound 1 and 1H chemical shifts of compound 2 were calculated with GIAO method and correlated with experimental data. Hyperconjugative interactions were studied with the help of natural bond order analysis (NBO). Electronic properties of both the compounds such as HOMO–LUMO energies were measured with the help of time dependent DFT method.

Brassicasterol (compound 1) was isolated and chemically transformed into 3β-(2-(6-methoxynaphthalene-2yl) propionoxy) 24 methyl cholest-5, 22-dien (compound 2). Crystal structure of compound 2 not only helped in confirming the structure of compound 1 but it also helped in establishing stereochemistry of both the compounds. DFT studies of both the compounds were carried out using density functional method (DFT/B3LYP) with 6-31G (d, p) basis set.Figure optionsDownload as PowerPoint slide