2 -Deoxyuridine 6-substituted 2 -deoxyuridines

Thiazolylzinc halides have been employed as nucleophiles in Negishi couplings [12-14]. 2-Thiazolylzinc chloride was prepared by deprotonation of thiazole followed by treatment with ZnCl2. Subsequent Negishi coupling of thiazolylzinc chloride with 5-iodo-2 -deoxyuridine 8 elaborated the 5-substituted pyrimidine nucleoside 9 with the assistance of one equivalent of ZnCl2 [14]. 

Application of this reaction to 2, 2-anhydrouridine (LXXXVII) led to a 3-substituted nucleoside (CIV) which, upon acylation followed by reduction with Raney nickel, yielded 3-deoxyuridine (CV, R = uracilyl). Reductive cleavage of CV, by the sodium-liquid ammonia procedure,72 afforded 3-deoxy-D-en/fAro-pentose ( 3-deoxy-D-ribose ), a result which establishes position 3 as the site originally containing the ethylthio function. The authors suggest,248 as a plausible route to CIV, the initial formation of the anion CII, followed by formation of the 2,3-anhydride structure. The anhydride (CIII) is then attacked, at C3, by the ethanethiol ion, to yield... 

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. 

Photochemical reaction in acetonitrile of 2 -deoxyuridine 5 -phosphate with the halo-heteroarenes 2-iodothiophene, 2-iodofuran, l-methyl-2-iodopyrrole and 3-iodothiophene affords the C-5 heteroaryl substituted nucleotides518.6-Aryluridines have been prepared by irradiation of 6-iodouridines in benzene, anisole, thiophene, Af-methylpyrrole or 2-methyl-furan in the presence of triethylamine519. 

The third synthetic application is demonstrated by alkenylation of 5-iodouracil and 5-iodouridine [Eq.(15)]. These iodides were allowed to couple with alkenyl(difluoro)methylsilanes to afford 5-alkenyl-substituted uracils and uridines, respectively, which are potent antitumor or antiviral agents. It is noteworthy that unprotected 5-iodo-2-deoxyuridine could be converted into the corresponding cross-... 

A new series of 5-carboranyl-substituted-2 -deoxyuridine (25a) and deoxy-thymidine (25b) derivatives containing a range of alkyl spacers has been prepared to access a more effective use of boron neutron capture therapy. Evaluation of these derivatives as substrates for the human thymidine kinases TKl and TK2 showed that a decrease in the length of the spacer (from 8 methylene units to 4) between the carborane moiety and the pyrimidine base resulted in better substrate characteristics. 

The triphosphate of 5-formyldUTP (111) has been prepared and its incorporation by several DNA polymerases has been studied. It was found to be incorporated well in place of TTP and could also substitute dCTP to some extent. The preparation of 5-azidoUTP (112) from UTP has been described. The analogue was found to be an inhibitor of CPasell. 2 -Deoxyuridine-5 -triphosphate labelled at the C5 position with the dye methylene blue has been prepared and incorporated into oligonucleotides or DNA fragments by tailing with terminal transferase. " ... 

AflBnity Labellii. —Of a large number of 5-substituted-2 -deoxyuridine 5 -mono-phosphates prepared as potential inhibitors of thymidylate kinase, 5-formyl-dUMP was found to be a potent non-competitive inhibitor of the enzyme from calf thymus, and 5-azidomethyl-dUMP irreversibly inactivated both this enzyme and the enzyme from Ehrlich ascites tumour cells. Protection by cofactor addition could only be demonstrated for the latter case, however. 5-Iodoacetamidomethyl-dUMP (68) irreversibly inactivates the tumour enzyme more rapidly than the calf thymus enzyme, and protection could also be demonstrated in this case it has therefore been claimed that (68) is isozyme-specific for the tumour enzyme. ... 

The reaction of deoxyuridine with nitrile oxides gives products of apparent electrophilic substitution, but these probably arise by ring opening of a cycloadduct. ... 

Pyrimidine nucleosides are readily attacked by electrophiles, such as Hg(II) acetate in the pyrimidine 5-position. The anion is subsequently changed to halide. Thus 2 -deoxyuridine has been mercurated by Hg(OAc)2 in aqueous methanol and coupled with iodobenzene or substituted derivatives on heating with diglyme in a Pd-mediated reaction with formation of 5-aryl derivatives (366) (Scheme 86). The acetate is used for solubility reasons (84TL2431). 

The structural basis of phosphoramide mustard crosslinking to guanosines in an oligonucleotide has been studied both in vitro and by computer simulation. The effects of 5-fluorouridine and 5-fluoro-2 -deoxyuridine substitution into synthetic RNA and DNA have been studied. Destabilisation of duplex oligo-deoxynucleotides but stabilisation of oligoribonucleotides was found upon the analogue substitution for uridine in the parent duplexes. ... 

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