Radicals deoxyuridin

Other degradation products of the cytosine moiety were isolated and characterized. These include 5-hydroxy-2 -deoxycytidine (5-OHdCyd) (22) and 5-hydroxy-2 -deoxyuridine (5-OHdUrd) (23) that are produced from dehydration reactions of 5,6-dihydroxy-5,6-dihydro-2 -deoxycytidine (20) and 5,6-dihydroxy-5,6-dihydro-2 -deoxyuridine (21), respectively. MQ-photosen-sitized oxidation of dCyd also results in the formation of six minor nucleoside photoproducts, which include the two trans diastereomers of AT-(2-de-oxy-/j-D-eryf/iro-pentofuranosyl)-l-carbamoyl-4 5-dihydroxy-imidazolidin-2-one, h/1-(2-deoxy-J8-D-crythro-pentofuranosyl)-N4-ureidocarboxylic acid and the a and [5 anomers of N-(2-deoxy-D-eryfhro-pentosyl)-biuret [32, 53]. In contrast, formation of the latter compounds predominates in OH radical-mediated oxidation of the pyrimidine ring of dCyd, which involves preferential addition of OH radicals at C-5 followed by intramolecular cyclization of 6-hydroperoxy-5-hydroxy-5,6-dihydro-2 -deoxycytidine and subsequent generation of the 4,6-endoperoxides [53]. 

In the second example, the protected dibromovinyl deoxyuridine 3-247 was transformed into a 2 l-mixture of the desired spirocompounds 3-249 and 3-250 in 57 % yield using standard radical conditions with (TMS)3SiH. In addition, 25 % of a E/Z-mixture of 3-251 was obtained (Scheme 3.64). 

The kinetics of the reaction of 2 -deoxyuridin-L-yl radicals (11) with thiols, with superoxide release from the peroxyl radical (13) generated, have been reported. Radical (11) is produced by photolysis of precursor (10). When the radical is produced in the presence of thiols, (12) is formed. Second-order kinetics were found for the reactions with thiols. Peroxyl radical (13) is formed in the presence of oxygen. This undergoes heterolytic fragmentation to the superoxide anion O2 and cation (14), which ultimately leads to 2-deoxyribonolactone (15). 

In the y-radiolysis, similar reactions are expected to occur as discussed above for the Ura system. Here, however, about equal amounts of OH and 02 -are formed initially and thus the latter will play an even larger role on the way to the products, and thus it is even more difficult to come up with a well-substantiated reaction scheme. An interesting product is 5, 6-cyclo-5-hydroxy-5,6-dihydro-2 -deoxyuridine. Its formation is discussed below in the context of the reactions of alkyl radicals. 

Chatgilialoglu C, Gimisis T (1998) Fate of the C-1 peroxyl radical in the 2 -deoxyuridine system. Chem Commun 1249-1250... 

Chatgilialoglu C, Gimisis T, Guerra M, Ferreri C, Emanuel CJ, Horner JH, Newcomb M, Pedulli GF (1998) Spectra and structure of the 2 -deoxyuridin-1 -yl radical. Tetrahedron Lett 39 3947-3950... 

Emanuel CJ, Newcomb M, Ferreri C, Chatgilialoglu C (1999) Kinetics of 2 -deoxyuridine-T-yl radical reactions. J Am Chem Soc 121 2927-2928... 

The DNA bases most easily reduced are T and C, the reduction potentials of which are very similar [26]. It is therefore expected that excess electron migration through DNA occurs via a hopping mechanism involving all base pairs (C-G and T-A) and the radical anions C and T as stepping stones. We focused our work on 5-pyrenyl-2 -deoxyuridine (Py-dU) and 5-pyrenyl-2 -deoxycytidine (Py-dC) as nucleoside models for ET in DNA. Photoexcitation of the pyrenyl group results in... 

Dussault and coworkers described the preparation of allylstannanes (116, 117) as part of their synthetic studies (equation 93)731. It is interesting to note the preferred geometries of the products which appear to be dependent on the nature of the stannane employed. In this last example, Yu and Oberdorfer reported the use of free-radical hydrostannylation in their preparation of (tributylstannyl)vinyl-substituted 2-deoxyuridine derivatives (e.g. 118) for use in halogenation and radiohalogenation reactions (equation 94)733. 

The thymidine derivatives (146) and (147) undergo cleavage of a C-C bond on irradiation. These reactions are typical Norrish Type I processes and provide a route to study C-3 -DNA radicals. Hydrogen abstraction by the radicals yields a 1 1 mixture of the threo and erythro derivatives (148). The reactions from the P-isomers (146) are generally more efficient than from the a-isomer (147). A study of the photochemical reactivity of the deoxyuridine derivative (149) has been reported. This novel compound is an electron-accepting nucleo base. It has been used as a means of cleaving DNA. The photochemical fission occurs specifically at the 5 -G of 5 GG3 sequences. 

Hydration of the thymidine radical cation leads to the predominant formation of the oxidizing 6-hydroxy-5,6-dihydrothymid-5-yl radical whereas deprotonation mostly generates the methyl-centered radical (Fig. 4). As already pointed out, these two pyrimidine radicals are also produced upon reaction with OH. However, the methyl-centered radical represented only 5% of base radicals when produced by OH while it corresponds to 30% of the thymidine radicals produced upon one-electron oxidation. Type I photosensitization of 2 -deoxy-cytidine leads to the formation of the 6-hydroxy-5,6-dihydro-2 -deoxycytidil-5-yl radical also produced upon reaction with OH. Additional oxidative pathways involve the formation of 2-deoxyribonolactone and free cytosine as well as production of 2 -deoxyuridine as the result of deprotonation ofthe pyrimidine radical cation at Cl and NH2 group, respectively. 

The repair of carbohydrate radicals vithin polynucleotides can proceed with remarkable stereoselectivity, as demonstrated for hydrogen transfer from both 2-mercaptoethanol and dithiothreitol to deoxyuridin-l -yl radials within single-and double-stranded oligonucleotides (Scheme 3.3, Reactions (3.21a) and (3.21j8)) [56]. 

Romieu, A., Bellon, S., Gasparutto, D., and Cadet, J. (2000) Synthesis and UV photolysis of oligodeoxynucleotides that contain 5-(phenyl-thiomethyl)-2 -deoxyuridine a specific photolabile precursor of 5-(2 -deoxyuridilyl)methyl radical. Org. Lett., 2,1085-1088. 

Inactivation of the reductase by 2 -azido-2 -deoxyuridine 5 -diphosphate (26, Fig. 56) is accompanied by loss of the tyrosyl radical (Thelander et al., 1976)... 

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