Structural characterization of adducts formed in the reaction of 2,3-epoxy-4-hydroxynonanal with deoxyguanosine

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Abstract
Six adducts were isolated by reverse-phase high-performance liquid chromatography from the reaction of deoxyguanosine at 50.degree. C in pH 7.0 buffer with the epoxide of trans-4-hydroxy-2-nonenal, a major .alpha.,.beta.-unsaturated aldehyde from lipid peroxidation. These adducts were designated as adducts 1-6. Structures of these adducts were fully characterized by spectroscopic methods such as UV, proton NMR, MS, and CD and by chemical reactions. Adduct 1 was previously identified as 1,N2-ethenodeoxyguanosine. Adducts 2, 3, 5, and 6 are four diastereomeric 1,N2-ethanodeoxyguanosine derivatives possessing two five-membered fused rings at the 1- and N2-positions of guanine. The systematic name of these adducts is 3-(2-deoxy-.beta.-D-erythro-pentofuranosyl)-3,5,5a,7,8,8a-hexahydro-8-hydroxy-7-pentyl-10H-furo[2'',3'':4,5]imidazo[1,2-a]-purin-10-one. Acid hydrolysis of adducts 5 and 6 yielded the corresponding guanine products which were identical in all respects except having opposite CD. Similar results were obtained with adducts 2 and 3 suggesting they are two pairs of enantiomers. The stereochemical characteristics of these adducts were elucidated. Adduct 4 was characterized by spectroscopic methods and chemical reactions as 3-(2-deoxy-.beta.-D-erythro-pentofuranosyl)-5,9-dihydro-7-(1,2-dihydroxyheptyl)-9H-imidazo[1,2-a]purin-9-one, a 1,N2-ethenodeoxyguanosine derivative. Upon mild base treatment, adducts 2, 3, 5, and 6 were readily converted to adduct 1. The mechanisms for the formation of these adducts and the conversion of adducts 2, 3, 5, and 6 to adduct 1 are discussed.