A novel hydroxylation of aromatics in a flavin-initiated chain reaction

Article abstract of DOI:10.1016/S0040-4020(01)81330-2

In aqueous acidic solutions, the 5-ethyl-3-methyllumiflavinium cation 5 was spontaneously transformed into the dihydroflavin pseudobase radical 6 and the flavosemiquinone 7. In attacking an aromatic like phenylalanine, 6 was mainly reconverted to 5 which, ultimately, could lead to an anaerobic accumulation of 7 in yields of 95 ± 5%. In the immediate presence of O₂ and/or H₂O₂, 7 was rapidly and continuously reoxidized to 5 which, consequently, gave a continued production of 6 increasing the hydroxylating ability of the system. The oxidants also had a second distinct effect in converting an intermediate X in a chain reaction to further increase the yields of hydroxyphenylalanines. As illustrated by the results obtained with O₂ and H₂O₂ under comparable conditions, the efficiency of this chain reaction proved to be significantly influenced by the nature of the oxidant. These new findings imply that hydroxyl radicals arising in a homolysis of the O-O bond in a dihydroflavin hydroperoxide should not be taken for granted as the primary attacking species in the hydroxylation of an aromatic. From a practical point of view it is noticed that the hydroxylating ability of the new flavin / H₂O₂ system surpasses that of any other known, flavin-free chemical system.