Synthesis of the four stereoisomers of 2,3-epoxy-4-hydroxynonanal and their reactivity with deoxyguanosine.
2,3-Epoxy-4-hydroxynonanal (EHN) is a potential product of lipid peroxidation that gives rise to genotoxic etheno adducts. We have synthesized all four stereoisomers of EHN and individually reacted them with 2'-deoxyguanosine. In addition to 1,N(2)-etheno-2'-deoxyguanosine, 12 stereoisomeric products were isolated and characterized by (1)H NMR and circular dichroism spectroscopy. The stereochemical assignments were consistent with selective NOE spectra, vicinal coupling constants, and molecular mechanics calculations. Reversed-phase HPLC conditions were developed that could separate most of the adduct mixture.
Department of Chemistry, Center in Molecular Toxicology, Vanderbilt University, VU Station B 351822, Nashville, Tennessee, 37235-1822, USA.
Katya V
KV
Petrova
Donald F
DF
Stec
Markus
M
Voehler
Carmelo J
CJ
Rizzo
D000447:Aldehydes / Q000138:chemical synthesis*; D003849:Deoxyguanosine / Q000737:chemistry*; D004852:Epoxy Compounds / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism
D000447:Aldehydes; D004852:Epoxy Compounds; C066899:2,3-epoxy-4-hydroxynonanal; D003849:Deoxyguanosine
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