A MEDT Study of the Mechanism and Selectivities of the non- Catalyzed and the Lewis Acid Catalyzed Diels-Alder Reaction between R-Carvone and Isoprene -Molecular Docking Analysis: Anti-HIV-1 Activity

Abstract

Abstract The non-catalyzed and Lewis acid (LA) catalyzed Diels-Alder (DA) reaction between R-(-)-carvone 1R and isoprene 2 has been studied within Molecular Electronic Density Theory (MEDT) by using DFT calculations at the B3LYP/6-311 + + G(d,p) computational level. Analysis of the theoretical reactivity indices at the ground state of the reagents indicates that carvone 1R plays the role of an electrophile whereas isoprene 2 should be regarded as nucleophile participating in a polar process. The presence of the LA catalyst significantly increases the electrophilicity ω of carvone 1R , resulting in improved reactivity and selectivities in the LA catalyzed DA reaction. The presence of the LA catalyst significantly reduces the activation Gibbs free energy by increasing the polarity of the DA reaction. The computed relative Gibbs free energies clearly demonstrate a high degree of region- and stereoselectivity in this LA catalyzed DA reaction, which is consistent with the experimental findings. Through an examination of the Electron Localization Function (ELF), it became evident that the LA catalyzed DA reaction follows a non-concerted two-stage one-step mechanism. Finally, docking analysis was conducted for cycloadducts 3 and 4 , docked them to the main protease of HIV-1 (5W4Q and 1A8O), and their binding was compared to the antiviral drug Azidothymidine (AZT). The results indicated that cycloadduct 3 exhibited lower binding energies than AZT, suggesting a significant potential for anti-HIV activity.