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 roles in many biological systems. We have studied the electrochemical oxidation of N-acetyldopamine (NADA) and N-beta-alanyldopamine (NBAD) in the presence of two sulfur-centered nucleophiles, N-acetylcysteine (NACySH) and thiourea (TU), and have characterized the adducts and reaction pathways. NADA and NBAD react similarly, but their adducts with NACySH and TU were formed regioselectively. NACySH yields mainly 5-adducts and TU only 6-adducts. The NACySH adducts are oxidized more easily 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 intramolecular 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 5-adduct via a 1,6-Michael addition reaction. The absence of a proton on the thioureylene sulfur atom leads to formation of the 6-thioureylene adduct via a 1,4-Michael addition reaction of TU. This mechanism is consistent with the formation of other sulfur-centered adducts of catechols previously reported in the literature.
Huang
X
X
Agricultural Research Service, Kansas State University, Manhattan, Kansas 66506, USA.
Xu
R
R
Hawley
M D
MD
Hopkins
T L
TL
Kramer
K J
KJ
D000111:Acetylcysteine / Q000737:chemistry; D000818:Animals; D004298:Dopamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D004563:Electrochemistry; D006801:Humans; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D010084:Oxidation-Reduction; D011809:Quinones / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013890:Thiourea / Q000737:chemistry
D011809:Quinones; D013438:Sulfhydryl Compounds; C006374:N-acetyldopamine; C038990:N(beta)-alanyldopamine; D013890:Thiourea; D004298:Dopamine; D000111:Acetylcysteine