Tetraenone A: A New β-Ionone Derivative from Tetraena aegyptia .

In this study, the chemical investigation of Tetraena aegyptia (Zygophyllaceae) led to the identification of a new megastigmene derivative, tetraenone A ((2 S , 5 R , 6 R , 7 E )-2-hydroxy-5,6-dihydro-β-ionone) ( 1 ), along with (3 S , 5 R , 6 S , 7 E )-3-hydroxy-5,6-epoxy-5,6-dihydro-β-ionone- ( 2 ), 3,4-dihydroxy-cinnamyl alcohol-4-glucoside ( 3 ), 3β,19α-dihydroxy-ursan-28-oic acid ( 4 ), quinovic acid ( 5 ), p -coumaric acid ( 6 ), and ferulic acid ( 7 ), for the first time. The chemical structures of 1 - 7 were confirmed by analysis of their 1D and 2D NMR and HRESIMS spectra and by their comparison with the relevant literature. The absolute configurations of 1 and 2 were assigned based on NOESY interactions and ECD spectra. Conformational analysis showed that 1 existed exclusively in one of the two theoretically possible chair conformers with a predominant s-trans configuration for the 3-oxobut-1-en-1-yl group with the ring, while the half-chair conformer had a pseudo-axial hydroxy group that was predominant over the other half-chair conformation. Boat conformations were not among the most stable conformations, and the s-trans isomerism was in favor of s-cis configuration. In silico investigation revealed that 1 and 2 had more favorable binding interactions with M pro rather than with TMPRSS2. Accordingly, molecular dynamic simulations were performed on the complexes of compounds 1 and 2 with M pro to explore the stability of their interaction with the target protein structure. Compounds 1 and 2 might offer a possible starting point for developing covalent inhibitors of M pro of SARS-CoV-2.