Mechanisms of Formation of Adducts from Reactions of Glycidaldehyde with 2'-Deoxyguanosine and/or Guanosine
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- 作者：Bernard T. Golding ; Pritpal K. Slaich ; Gordon Kennedy ; Christine Bleasdale ; and William P. Watson
- 刊名：Chemical Research in Toxicology
- 出版年：1996
- 出版时间：January 1996
- 年：1996
- 卷：9
- 期：1
- 页码：147 - 157
- 全文大小：386K
- 年卷期：v.9,no.1(January 1996)
- ISSN：1520-5010
文摘
Convenient syntheses of rac-glycidaldehydefrom rac-but-3-ene-1,2-diol and(R)-glycidaldehyde from D-mannitol are described.(R)-Glycidaldehyde (1) reacts with guanosinein water(pH 4-11, faster reaction at higher pH) to give initially6(S)-hydroxy-7(S)-(hydroxymethyl)-3-(
le">-D-ribofuranosyl)-5,6,7-trihydroimidazo[1,2-a]purin-9(3H)-one(7a) and6(S),7(R)-dihydroxy-3-(le">-D-ribofuranosyl)-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10(3H)-one(8a). The former decomposes to7-(hydroxymethyl)-5,9-dihydro-9-oxo-3-(le">-D-ribofuranosyl)imidazo[1,2-a]purine(3a),5,9-dihydro-9-oxo-3-(le">-D-ribofuranosyl)imidazo[1,2-a]purine(5a, 1,N2-ethenoguanosine),andformaldehyde, while the latter adduct is relatively stable. Theposition of the hydroxymethylgroup on the imidazo ring of7-(hydroxymethyl)-5,9-dihydro-9-oxo-3-(le">-D-ribofuranosyl)imidazo[1,2-a]purine was proved by 13C NMRanalysis of adducts derived from [1-15N]guanosineand[amino-15N]guanosine. At longerreaction times, the adduct7,7'-methylenebis[5,9-dihydro-9-oxo-3-(le">-D-ribofuranosyl)imidazo[1,2-a]purine[(4a) is formed from guanosine and glycidaldehyde. The structure analysis of this adduct was also aided by13C NMR analysis of the 15N-labeled adduct derived from [1-15N]guanosine.Analogous adducts were obtained from thereaction between glycidaldehyde and deoxyguanosine. Mechanisms offormation of the adductsfrom glycidaldehyde and guanosine/deoxyguanosine are proposed andsupported by modelstudies with simple amines. The formaldehyde produced in thereactions described reactswith guanosine to give the known adductN2-(hydroxymethyl)guanosine(9).
le">-D-ribofuranosyl)-5,6,7-trihydroimidazo[1,2-a]purin-9(3H)-one(7a) and6(S),7(R)-dihydroxy-3-(le">-D-ribofuranosyl)-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10(3H)-one(8a). The former decomposes to7-(hydroxymethyl)-5,9-dihydro-9-oxo-3-(le">-D-ribofuranosyl)imidazo[1,2-a]purine(3a),5,9-dihydro-9-oxo-3-(le">-D-ribofuranosyl)imidazo[1,2-a]purine(5a, 1,N2-ethenoguanosine),andformaldehyde, while the latter adduct is relatively stable. Theposition of the hydroxymethylgroup on the imidazo ring of7-(hydroxymethyl)-5,9-dihydro-9-oxo-3-(le">-D-ribofuranosyl)imidazo[1,2-a]purine was proved by 13C NMRanalysis of adducts derived from [1-15N]guanosineand[amino-15N]guanosine. At longerreaction times, the adduct7,7'-methylenebis[5,9-dihydro-9-oxo-3-(le">-D-ribofuranosyl)imidazo[1,2-a]purine[(4a) is formed from guanosine and glycidaldehyde. The structure analysis of this adduct was also aided by13C NMR analysis of the 15N-labeled adduct derived from [1-15N]guanosine.Analogous adducts were obtained from thereaction between glycidaldehyde and deoxyguanosine. Mechanisms offormation of the adductsfrom glycidaldehyde and guanosine/deoxyguanosine are proposed andsupported by modelstudies with simple amines. The formaldehyde produced in thereactions described reactswith guanosine to give the known adductN2-(hydroxymethyl)guanosine(9).