Mechanisms of formation of adducts from reactions of glycidaldehyde with 2'-deoxyguanosine and/or guanosine.
Convenient synthesis of rac-glycidaldehyde from rac-but-3-ene-1,2-diol and (R)-glycidaldehyde from D-mannitol are described. (R)-Glycidaldehyde (1) reacts with guanosine in water (pH 4-11, faster reaction at higher pH) to give initially 6(S)-hydroxy-7(S)-(hydroxymethyl)-3-(beta-D-ribofuranosyl)-5,6,7- trihydroimidazo[1,2-alpha]purin-9(3H)-one (7a) and 6(S),7(R)-dihydroxy-3-(beta-D-ribofuranosyl)-5,6,7,8- tetrahydropyrimido[1,2- alpha]purin-10(3H)-one (8a). The former decomposes to 7-(hydroxymethyl)-5,9-dihydro-9-oxo-3-(beta-D-ribofuranosyl)imidazo[1,2- alpha]purine (3a), 5,9-dihydro-9-oxo-3-(beta-D-ribofuranosyl)imidazo[1,2-alpha]purine (5a, 1,N2-ethenoguanosine), and formaldehyde, while the latter adduct is relatively stable. The position of the hydroxymethyl group on the imidazo ring of 7-(hydroxymethyl)-5,9-dihydro-9-oxo-3-(beta-D-ribofuranosyl)imidazo-[1,2 - alpha]purine was proved by 13C NMR analysis of adducts derived from [1-15N]guanosine and [amino-15N]guanosine. At longer reaction times, the adduct 7,7'-methylenebis[5,9-dihydro-9-oxo-3-(beta-D-ribofuranosyl)imidazo[1,2- alpha]purine (4a) is formed from guanosine and glycidaldehyde. The structure analysis of this adduct was also aided by 13C NMR analysis of the 15N-labeled adduct derived from [1-15N]guanosine. Analogous adducts were obtained from the reaction between glycidaldehyde and deoxyguanosine. Mechanisms of formation of the adducts from glycidaldehyde and guanosine/deoxyguanosine are proposed and supported by model studies with simple amines. The formaldehyde produced in the reactions described reacts with guanosine to give the known adduct N2-(hydroxymethyl)guanosine (9).
Golding
B T
BT
Department of Chemistry, University of Newcastle upon Tyne, UK.
Slaich
P K
PK
Kennedy
G
G
Bleasdale
C
C
Watson
W P
WP
D000447:Aldehydes / Q000138:chemical synthesis* / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D002273:Carcinogens / Q000737:chemistry; D003432:Cross-Linking Reagents; D018736:DNA Adducts / Q000096:biosynthesis* / Q000737:chemistry; D003849:Deoxyguanosine / Q000737:chemistry*; D004852:Epoxy Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D006151:Guanosine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
D000447:Aldehydes; D000588:Amines; D002273:Carcinogens; D003432:Cross-Linking Reagents; D018736:DNA Adducts; D004852:Epoxy Compounds; D014867:Water; D006151:Guanosine; D003849:Deoxyguanosine; C007871:glycinaldehyde