Dopamine beta-hydroxylase, a fascinating mammalian copper-containing monooxygenase: enzymatic and biomimetic studies of the O-atom transfer catalysis

This paper summarizes our recent studies on the mechanism of O-atom transfer to a benzylic C-H bond promoted by dopamine beta -hydroxylase (DBH) and its biomimetic models. We demonstrate that it is possible to carry out parallel and comparative studies on enzyme (DBH) and its biomimetic models with the same substrate: 2-aminoindane (1). It was chosen because its two stereogenic centers, both in benzylic positions, make it very powerful for studying the stereochemistry of an O-atom transfer reaction. DBH-catalyzed hydroxylation of 1 exclusively produced 14% of trans(1S,2S)-2-amino-1-indanol 4a (93% e.e.). Studies with stereospecifically deuterium labeled 2-aminoindanes (1R,2S)-2 and (1S,2S)-3 showed that the formation of 4a was the result of an overall process with retention of configuration where an O-atom is stereospecifically inserted in the trans pro-S position of the substrate. Addition of 1 and (+/-)2 to 2-vinylpyridine gave 2-X-IndPY2 ligands 5 and 6, which were transformed into copper(I) and (II) complexes (7)(PF6) and (8)(CF3SO3), respectively. Reaction with dioxygen led to new complexes in which an O-atom transfer to a benzylic C-H bond has been performed in the same manner as that of DBH. With deuterium labeled cis-2-d-IndPY2 ligand 6, we demonstrated that the reaction occurs by a stereospecific process with retention of configuration. In both cases (enzymatic vs. biomimetic) the O-atom transfers occur in a two-step process involving radical intermediates. (C) 2001 Academie des sciences / Editions scientifiques et medicales Elsevier SAS.