Interactions and photoreactivity of 8-alkoxypsoralens with thymine. A model approach.

Abstract

Abstract— To investigate the interactions and the photoreactions in solution between thymine and psoralen, model compounds have been synthesized in which a thymine molecule is linked to a psoralen ring by a polymethylene bridge. Two series of compounds have been studied and compared as models for the two major drugs 5‐MOP and 8‐MOP. We report here the results obtained in the 8‐alkoxypso‐ralen series. In water, intramolecular ring‐ring stacking interactions were evidenced using UV and 1H NMR spectroscopies. In organic solvents such as ethanol, these interactions disappear completely. The photoreactivity of the models was examined in relation to their ground state interaction properties. in water and in ethanol. Slow photolysis of the pyrone ring of psoralen occurs whatever the length of the linking chain (3 to 12 methylenes). No intramolecular thymine‐psoralen photoaddition nor psoralen photodimerization were observed. These results are discussed with regards to the behavior of the 5‐alkoxy models which lead selectively to the 3,4 psoralen‐thymine photoadduct.