The dissociation and tautomerization equilibria of hypericin: Alkyl protected hydroxyl derivatives

3-Benzyl-, 3,4-dibenzyl-, 3,4-dibenzyl-1,6,8,13-tetramethyl-, and 1,6,8, 13-tetramethyl hypericin were synthesized by alkylation and dealkylation procedures starting from hypericin. The pK(a) value correlation of these derivatives allowed the unequivocal assignment of the protonation and deprotonation pK(a) values of hypericin. Thus, for hypericin the pK(a) of about -6 was assigned to the C=O groups, that of about 2 to the deprotonation of one hydroxyl group in the bay-positions 3/4, and that of about 9 was found to be characteristic of the bay-peri-diphenolate ion. None of the changes in the spectra characteristic of changes in the tautomeric equilibria could be found for these derivatives. Thus, it was concluded that the undisturbed peripheral hydroxyl groups of hypericin have to be present to allow for tautomeric changes.