Effect of Substitution on the 2+2 Cycloaddition Reaction of Phenylpropanoids

Formation of the cyclobutane products truxillic and truxinic acid within the plant cell wall could occur by photocycloaddition or possibly by enzyme-mediated radical coupling. Model precursors were synthesized and the mode of formation of the cyclobutane products was investigated. Modeling studies suggested that all the model compounds with the exception of the 2-hydroxylated diester contained the correct geometry for photocyclization and this was confirmed by irradiation. Delocalization of the unpaired electron was measured by ESR and the photochemical reaction rates were compared with the partial atomic orbital population of the singly occupied molecular orbital. It was observed that the 3-hydroxylated derivative had almost no delocalization to C8 and the lowest reaction rate. The rate of reaction increased with increasing extent of methoxylation. Incubation with silver oxide or with peroxidase failed to induce intramolecular dimerization. These results suggest that the biological mode of formation of truxillic and truxinic acid is the most likely via light-catalyzed 2+2 cycloaddition.