MEDT Study, hemisynthesis via regioselective ring opening of α-Himachalene-Epoxides, ADME survey and docking studies designed to target coronavirus and HIV-1

• Published in: Journal of molecular liquids Vol. 394; p. 123707
• Main Authors: Ajlaoui, Rahhal El, Raji, Houria, Ouardi, Mahmoud El, Chakroun, Ahmed, Zeroual, Abdellah, Syed, Asad, Bahkali, Ali H., Elgorban, Abdallah M., Verma, Meenakshi, Benharref, Ahmed, Varma, Rajender S.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.01.2024
• Subjects: Epoxidation; Epoxide ring opening; MEDT; Parr functions; Regioselectivity; Epoxidation; Parr functions; Epoxide ring opening; Regioselectivity; MEDT
• ISSN: 0167-7322; 1873-3166
• DOI: 10.1016/j.molliq.2023.123707

•The two diepoxide-α-himachalenes 6 and 7, exhibit regio- and stereospecificity in their opening epoxidation reaction.•The best interaction was predicted by the Parr functions and the energy study to be between the C13 carbon and the hydride.•Via kinetic and thermodynamic control, alcohol 8 is synthesized.•Alcohol (9) and β -himachalene (1) have greater affinities for the coronavirus and HIV-1, respectively. The ring-opening reaction of the two diepoxides, α-himachalenes 6 and 7, with aluminum lithium hydride (LiAlH4) in ether produced the title compounds C15H24O2 sesquiterpene alcohol. Both experimentally and conceptually, the regio- and stereospecificity of this ring opening reaction were investigated using the Molecular Electron Density Theory (MEDT). The Parr functions and the energy study correctly predicted the best interaction to be between the C13 carbon and the hydride, as evidenced by the attained regio- and stereo-specificity revealed through the experimental research. Moreover, the alcohol 8 is obtained from a kinetic and thermodynamic control while the alcohol 9 is obtained only by a kinetic control, in the maximum conformity with the findings of the experiments. In addition, the performed docking calculations to examine the coronavirus and HIV-1 activities of the products 1–9 revealed that alcohol 9 has a higher affinity against coronavirus while β-himachalene 1 against the HIV-1.