Theoretical insight into the on-water catalytic effect in the biogenesis of triterpene dimers: from one-step to two-step hetero Diels-Alder reactions

The reaction for the formation of the xuxuarine A alpha triterpene dimer in an aqueous medium was studied using the ONIOM/CPCM-X scheme at the ONIOM(M06-2X/6-31G(d,p):PM6) level of theory, along with the inclusion of one and two explicit water molecules. The results show that the geometry of the water molecules in the complex of reactants switches the mechanism from a one-step to a two-step hetero Diels-Alder (HDA) reaction. The reaction begins with a Michael addition assisted by water, which is the rate-limiting step. Then, nucleophilic addition-protonation involving nucleophilic attack at the positive carbon center of the carbonyl group takes place. The two-step mechanism has an activation free energy that is 4.7 kcal mol(-1) lower than the one-step mechanism, providing evidence of an alternative two-step water-assisted reaction for the biogenic origin of triterpene dimers.

Automated summary

The study found that the geometry of water molecules plays a key role in switching the mechanism from a one-step to a two-step reaction for the formation of xuxuarine A alpha triterpene dimer, with the Michael addition being the rate-limiting step. Additionally, the two-step mechanism has a lower activation free energy than the one-step mechanism, providing evidence of a water-assisted alternative reaction for the biogenic origin of triterpene dimers.