Aromatization within the putative bio-medical action mechanism of berberine and related cationic alkaloids with double iso-quinolinoid skeleton. A theoretical study

In the putative mechanism of action for berberin, to prevent DNA replicatio n the first step is aromatization. The aromatization process, via dehydroge nation has been studied for a series of compounds related to berberine. In contrast to the covalent dehydrogenation, which is endothermic, the aromati zation under ionic conditions was found to be exothermic. The availability of the hydride for ionic aromatization was indicated by the effective HOMO of berberine and related compounds. The results indicate that in the aromat ization process the ease of hydride ion removal parallels the stabilization s energy of the aromatic compounds to be formed. Comparing the nucleophilic additions to the pi -system, the LUMO energy values suggested a greater ac cessibility of the N(+) heterocycles in comparison to the polycycle aromati c hydrocarbons. (C) 2001 Elsevier Science B.V. AR rights reserved.