Pyrrole formation from 4-hydroxynonenal and primary amines.
The reaction of trans-4-hydroxy-2-nonenal (4-HNE) with primary amines was investigated to elucidate chemistry that may clarify the nature of its physiological covalent binding with protein-based primary amino groups. Such binding of 4-HNE, generated endogenously from lipid peroxidation, appears to be a pathophysiologic factor in the modification of low-density lipoprotein and perhaps other instances. We now show that 4-HNE reacts with primary amines in aqueous acetonitrile at pH 7.8 to afford after workup, in 14-23% yield, the corresponding pyrroles, which were characterized by independent synthesis from 4-oxononanal. Additional, mostly unstable adducts are also formed, some of which eventually "age" to the pyrrole. Hydride reduction after initial adduct formation permits the isolation of more stable materials, one of which has been identified as the reduced amine Michael addition product. Pyrrole formation may constitute a physiologically important reaction of 4-hydroxyalkenals.
Sayre
L M
LM
Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106.
Arora
P K
PK
Iyer
R S
RS
Salomon
R G
RG
D000447:Aldehydes / Q000737:chemistry*; D000588:Amines / Q000737:chemistry; D001596:Benzylamines / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D010627:Phenethylamines / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry
D000447:Aldehydes; D000588:Amines; D001596:Benzylamines; D010627:Phenethylamines; D011758:Pyrroles; D013438:Sulfhydryl Compounds; C027576:4-hydroxy-2-nonenal