Non-oxidative decarboxylation of glycine derivatives by a peroxidase.
Under anaerobic, peroxide-free conditions (pH 5.5, 25 degrees C), horseradish peroxidase (HRP) catalyzes the rapid, non-oxidatve decarboxylation of N-alkyl-N-phenylglycine derivatives to the corresponding N-alkyl-N-methylanilines in 100% yield. When the reaction is conducted in D2O buffer, the product contains a single deuterium in the methyl group. The reactions are very fast compared to the oxidative decarboxylation of the same substrates under standard peroxidatic conditions (i.e., hydrogen peroxide added, air present) and in fact are inhibited by peroxide and oxygen. To account for these unprecedented observations, we propose a cyclic mechanism in which ferric HRP abstracts an electron from the substrate, giving an aminium ion intermediate that decarboxylates; protonation of the resulting alpha-aminoradical on carbon gives an aminium ion that is reduced by ferrous HRP to complete the cycle.
Totah
Rheem A
RA
Department of Medicinal Chemistry, University of Kansas, Lawrence 66045-7582, USA.
Hanzlik
Robert P
RP
D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics
C467420:N-isopropyl-N-phenylglycine; D006735:Horseradish Peroxidase; D005998:Glycine