Electronic and structural features of lanosterol in the 14α-demethylation

14α-demethylation is the reaction which leads directly to norlanosterol from lanosterol, and is carried out exclusively by lanosterol structure. To discover the features, which make lanosterol a unique molecule able to undergo this demethylation, the electronic and energetic parameters of lanosterol and other structurally related steroids, were calculated. Local and global parameters were analyzed, in order to insight into the reactivity and selectivity of every molecule studied. Electrostatic potential maps were used to find differences of selectivity in each molecule, along with total energy and hardness, discovering the differences in reactivity. Lanosterol shows specific orientation and unique shape of electrostatic potential map, which does not appear in other structures, except epilanosterol, because it differs only in the orientation of a hydroxyl group, therefore they present many similarities but many differences also. For this reason, epilanosterol has a similar shape of electrostatic potential map, but not its orientation. Aoyama et al. have found, three essential structural features in lanosterol to be demethylated, which generate a specific electrostatic potential map, the hydroxyl group on C-3, the position of the double bound between C8 and C9 on cycle B, and the side chain double bond. Our study agrees with some biochemical studies, which reveal that there are three key features essential for substrate recognition by the enzyme P-45014DM. We think the present study is an alternative methodology to find features which are related with some parameters obtained via theoretical calculations.