ELECTROCHEMICAL OXIDATION OF N-ACYLDOPAMINES AND REGIOSELECTIVE REACTIONS OF THEIR QUINONES WITH N-ACETYLCYSTEINE AND THIOUREA

The metabolism of catechols often involves their oxidation to quinones and subsequent nucleophilic addition reactions with sulfur-containing compounds, Adducts formed during these reactions may play important r oles in many biological systems, We have studied the electrochemical o xidation of N-acetyldopamine (NADA) and N-beta-alanyldopamine (NBAD) i n the presence of two sulfur-centered nucleophiles, N-acetylcysteine ( NACS SH) and thiourea (TU), and have characterized the adducts and rea ction pathways, NADA and NBAD react similarly, but their adducts with NACySH and TU were formed regioselectively, NACySH yields mainly B-add ucts and TU only 6-adducts, The NACySH adducts are oxidized more easil y than the parent N-acyldopamine, and their oxidations are chemically reversible, However, the TU adducts are more difficult to oxidize, and their oxidation products undergo further chemical reactions, An intra molecular base catalysis mechanism for adduct formation with NACySH is proposed, which facilitates removal of the proton from the sulfhydryl group of NACySH and directs formation of the B-adduct via a 1,6-Micha el addition reaction, The absence of a proton on the thioureylene sulf ur atom leads to formation of the 6-thioureylene adduct via a 1,4-Mich ael addition reaction of TU. This mechanism is consistent with the for mation of other sulfur-centered adducts of catechols previously report ed in the literature. (C) 1998 Academic Press.