MECHANISMS OF FORMATION OF ADDUCTS FROM REACTIONS OF GLYCIDALDEHYDE WITH 2'-DEOXYGUANOSINE AND OR GUANOSINE/

Convenient syntheses of rac-glycidaldehyde from rac-but-3-ene-1,2-diol and (R)-glycidaldehyde from D-mannitol are described. (R)-Glycidaldeh yde (1) reacts with guanosine in water (pH 4-11, faster reaction at hi gher pH) to give initially oxy-7(S)-(hydroxymethyl)3-(beta-D-ribofuran osyl)-5 ,6,7-trihydroimidazo[1,2-a]purin-9(3H)-one (7a) and 6(S), ,6,7 ,8-tetrahydropyrimidoll[1,2-a]purin-10(3H)-one (8a). The former decomp oses to -oxo-3-(beta-D-ribofuranosyl)imidazol[1,2-a]purine (3a), 9-oxo -3-(beta-D-ribofuranosyl)imidazo[1,2-a]purine (5a, 1,N-2-ethenoguanosi ne), and formaldehyde, while the latter adduct is relatively stable. T he position of the hydroxymethyl group on the imidazo ring of -oxo-3-( beta-D-ribofuranosyl)imidazo-[1,2-a]purine was proved by C-13 NMR anal ysis of adducts derived from [1-N-15]guanosine and [amino-N-15]guanosi ne. At longer reaction times, the adduct -3-(beta-D-ribofuranosyl)imid azo[1,2-a]purine[(4a) is formed from guanosine and glycidaldehyde. The structure analysis of this adduct was also aided by C-13 NMR analysis of the N-15-labeled adduct derived from [1-N-15]guanosine. Analogous adducts were obtained from the reaction between glycidaldehyde and deo xyguanosine. Mechanisms of formation of the adducts from glycidaldehyd e and guanosine/deoxyguanosine are proposed and supported by model stu dies with simple amines. The formaldehyde produced in the reactions de scribed reacts with guanosine to give the known adduct N-2-(hydroxymet hyl)guanosine (9).