4,6-diamino-5-formamidopyrimidine

One-electron oxidation of the adenine moiety of DNA and 2 -deoxyadenos-ine (dAdo) (45) gives rise to related purine radical cations 46 that may undergo either hydration to generate 8-hydroxy-7,8-dihydroadenyl radicals (47) or deprotonation to give rise to the 6-aminyl radicals 50. The formation of 8-oxo-7,8-dihydro-2 -deoxyadenosine (8-oxodAdo) (48) and 4,6-diamino-5-formamidopyrimidine (FapyAde) (49) is likely explained in terms of oxidation and reduction of 8-hydroxy-7,8-dihydroadenyl precursor radicals 47, respectively [90]. Another modified nucleoside that was found to be generated upon type I mediated one-electron oxidation of 45 by photoexcited riboflavin and menadione is 2 -deoxyinosine (51) [29]. The latter nucleoside is likely to arise from deamination of 6-aminyl radicals (50). Overall, the yield of formation of 8-oxodAdo 48 and FapyAde 49 upon one-electron oxidation of DNA is about 10-fold-lower than that of 8-oxodGuo 44 and FapyGua 43, similar to OH radical mediated reactions [91]. 

Greenberg MM, Hantosi Z, Wiederholt CJ, Rithner CD (2001) Studies on N4-(2-deoxy-D-pentofura-nosyl)-4,6-diamino-5-formamidopyrimidine (FAPYdA) and N6(2-deoxy-D-pentofuranosyl)-6-diamino-5-formamido-4-hydroxyprimidine (FAPYdG). Biochemistry 40 15856-15861 Greenstock CL, Dunlop I (1973) Pulse radiolysis studies of nitrofurans Chemical radiosensitization. Radiat Res 56 428-440... 

Diamino-5-formamidopyrimidine (in general also with respect to dAdo, Ado and DNA)... 

Figure 22.5. Representatives of the major oxidative base damage. The 8-oxoguanine is also known as 8-hydroxyguanine due to isomerization. FaPy-G, 2,6-diamino-4-hydroxy-5-formamidopyrimidine FaPy-A, 2,6-diamino-5-formamidopyrimidine.

Fig. 8.3. An example of a gas chromatogram of the base-damage to DNA after exposure to hydroxyl radicals (generated radiolytically) - study of the trimethyl-silylated acidic hydrolysate of the modified DNA (modified from Dizdaroglu, 1988 with permission). Peaks I, phosphoric acid II, thymine III and Ilia, cytosine IV and IVa adenine V and Va guanine I uracil 2 5,6-dihydrothymine 3 5-hydroxy-5,6-dihydrothymine 4 5-hydroxyuracil 5 5-hydroxy-5,6-dihydrouracil 6 5-hydroxycytosine 7 cis-thymine glycol 8 /ra .s-thymine glycol 9 5,6-dihydroxyuracil 10 4,6-diamino-5-formamidopyr-imidine 11 8-hydroxyadenine 12 2,6-diamino-4-hydroxy-5-formamidopyrimidine 13...

Substituted purines may arise in mixtures with 9-substituted derivatives from direct alkylation of purine anions. They are best prepared however by Traube syntheses. Thus formylation of 4,5-diamino-6-benzylthiopyrimidine and ethylation of the formyl derivatives gave a formamidopyrimidine which readily cyclized to 6-benzylthio-7-ethylpurine in the presence of potassium carbonate (B-68MI40901, p. 31). The derivative is clearly a ready source of 7-substituted adenines by reaction with ammonia or amines, or of 7-substituted purines by dethiation with Raney nickel. 7-Methylguanine has also been obtained from 7-methyl-guanosine, sodium borohydride and aniline at pH 4.5 (B-78MI40903, p. 615). 

Treatment of DNA with hydrogen peroxide or other free radical-generating systems (snch as xanthine/xanthine oxidase) can also result in the formation of an imidazole ring-opened derivative of guanine, designated 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FaPy) (26). This lesion is prominent... 

A new synthesis of 6-sulfanylpurin-2-amine (thioguanine, 2) utilizes thiation and ring closure of 2,6-diamino-5-formamidopyrimidin-4-ol in one step with phosphorus pentasulfide in pyridine. ... 

A mixture of 2,6-diamino-5-formamidopyrimidin-4-ol (20 g, 0.12 mmol) and P Sk, (70 g, 0.32 mmol) was suspended in pyridine (600 mL), and the solution was refluxed for 8 h. The excess pyridine was distilled off under reduced pressure using a water bath as the source of heat. H O (800 mL) was added to the residue, and the mixture was allowed to stand for 12 h. The precipitate was filtered and dissolved in boiling 15% aq NHj (1 L). The solution was treated witli charcoal and filtered. The boiling filtrate was neutralized with IlOAc. The solution was allowed to cool and the product was filtered and further purified by precipitaiion from boiling aq NH3 yield 9.6 g (48%) colorless needles mp >300 C. 

Coste F., Ober M., Carell T., Boiteux S., Zelwer C., Castaing B., Structural basis for the recognition of the FapydG lesion (2,6-diamino-4-hydroxy-5-formamidopyrimidine) by the Fpg DNA glycosylase, J. Biol. Chem., 2004,279,44074-44083. 

Douki, T., Martini, R., Ravanat, J.L., Turesky, R.J., and Cadet, J. (1997) Measurement of 2,6-diamino-4-hydroxy-5-formamidopyrimidine and 8-oxo-7,8-dihydroguanine in isolated DNA exposed to y radiation in aqueous solution. Carcinogenesis, 18, 2385-2891. 

---