5-Chloro-2 -deoxyuridine

Effect of 3-Aminobenzamide on CHO Cells Replicating in Medium Containing Chloro-Deoxyuridine... 

O Neill JP, Heartlein MW, Preston RJ (1983) Sister chromatid exchanges and gene mutations are induced by the replication of 5-bromo- and 5-chloro-deoxyuridine substituted DNA. Mutat Res 109 259-270... 

Zwanenburg TSB, Mullenders LHF, Natarajan AT, Zeeland AA van (1984) DNA-lesions, chromosomal aberrations and Gj delay in CHO cells cultured in medium containing bromo-or chloro-deoxyuridine. Mutat Res 127 155-168... 

The 5-chloro, 5-bromo and 5-iodo derivatives of uracil are base analogues of thymine and, in cellular systems, can replace the latter in DNA u >. Furthermore, 5-iodo-2 -deoxyuridine is an antiherpes agent currently used for treatment of ocular herpes keratitis. By contrast, 5-fluorouracil can replace uracil in RNA, and, together with 5-fluoro-2 -deoxyuridine, is employed in tumour chemotherapy. All the foregoing are also known mutagens, and 5-bromouracil and its deoxyriboside are widely employed in studies on mutagenesis U9). 

The crystal structure of 5-chloro-2-deoxyuridine [CLDOUR] has a very simple pattern with two infinite chains (Fig. 17.21). One is through the O -H groups, and the other through the minor component of a three-center bond formed by 0(30-H. It strongly resembles a carbohydrate hydrogen-bonding pattern. A very simple scheme is also formed by 2-chloro-2 -deoxyuridine [CDURID] with a short finite chain and a separate link from the primary alcohol (Fig. 17.22). 

CAFFCD. l,3,7-Trimethyl-2,6-purine-dione hydrochloride dihydrate, caffeine hydrochloride dihydrate [C8HuN402+, Cl , 2(H20)]. Mercer A, Ttotter J (1978) Acta Crystallogr, Sect B 34 450 CDURID. 2 -Chloro-2 -deoxyuridine (QHuCU Oj). Suck D, Saenger W, Hobbs J (1972) Biochem Biophys Acta 259 157... 

The synthesis of 5-(2-chloro-l-fluoroethyl)-2 -deoxyuridine by chlorofluorination with diethyl-aminosulfur trifluoride/A-chlorosuccinirnide has also been described.687... 

An interesting stereoselective synthesis of the anomerlc 5-mercapto-2 -deoxyuridines has recently been reported. When 5-acetylmercapto-2,4-0-bis-(trlmethvlsilyl)uracll and the blocked chloro sugar were fused at 100-110° for 15-20 minutes, only the p-isomer of the blocked compound could be Isolated from the reaction. However, when the reaction was carried out in benzene solution at 37° for 90 hours, only the a-isomer was isolated. ... 

The earliest mechanistic studies utilizing alternate substrates were first reported in 1976 by Thelander and co-workers on the inactivation of RDPR by 2 -chloro-2 -deoxyuridine 5 -diphosphate (CIUDP) and the cytidine analog, CICDP (9). 

A procedure for the conversion of uridine to 5 -chloro-5 -deoxyuridine without the need for protection of 0-2 or 0-3 involves the treatment of the nucleoside with iV-chlorodiisopropylamine and TPP, followed by hydrolysis of the resultant 5 -chlorinated 2, 3 -0-triphenylphosphorane. ... 

A simple two-stage conversion of nucleosides to their corresponding 5-deoxy nucleosides involves sequential treatment with thionyl chloride in HMPT, giving the 5 -chloro-5 -deoxy derivatives which were then reduced with tri-butyltin hydride and a,a -azobis(isobutyronitrile) in dry THF. In this way 5 -deoxyadenosine, 5 -deoxyuridine, 5 -deoxythymidine, 5 -deoxytoyomycin, 5 -deoxysangivamycin, 2, 3, 5 -trideoxyadenosine, 3 5 -dideoxyadenosine, and 9-(5 -deoxy-jS-D-arabinofuranosyl)adenine were prepared. ... 

Azido and 3 -amino analogues of 2 -deoxy-5-substituted uridine and cytidine, together with 3 -amino-5 -fluoro-thymidine, have been prepared by standard procedures using 3 -0-mesyl ester intermediates the most active anti-cancer compounds were the 3 -amino-5-fluoro analogues of 2 -deoxyuridine and 2 -deoxycytidine cuid the 3 -amino analogue of 2 -deoxycytidine.An alternative doubleinversion sequence at C-3 using a 3 -chloro-3 -deoxyxylo-nucleo-side intermediate has been described for the preparation of 3 -... 

Cyclouridine, 39B, 322 5-Bromo-2 -deoxyuridine, 31B, 183 1 i3-D-Arabinofuranosyl-5-bromouracil, 39B, 324 5-Bromouridine, 31B, 183 2 -Chloro-2 -deoxyuridine, 38B, 455 5-Chloro-2 -deoxyuridine, 39B, 324 5-Chlorouridine, 37B, 248 -Fluoro-2 -deoxy-/3-uridine, 29, 710 -Iodo-2 -deoxyuridine, 30B, 204 -lodouridine, 35B, 276... 

Trimethylsilyl chloride reacted with the nucleoside 2, 3 -orthoester (405) to give either 3 -0-acetyl-2,2 -anhydro-l-jS-D-arabinofuranosyluracil or 3 -0-acetyl-2 -chloro-2 -deoxyuridine, depending on the solvent and conditions used (Scheme 137). ° Two groups have reported the reaction of derivatives of 2,3-anhydro-j8-... 

Internal standard 5-chloro-2 -deoxyuridine (11.5, m/z 261, cone voltage 35 V)... 

When a series of 8-substituted adenosines was treated with thionyl chloride in HMPA, the corresponding 5 -chloro- 5 -deoxy compounds were obtained in moderate to good yields. When 2 -deoxyuridine was treated with benzoyl chloride in DMF, 5 -chloro-2 ,5 -dideoxyuridine was formed slowly, whereas the same reagents in the presence of MCPBA gave rapid chlorination of the heterocycle to give 5-chloro-2 -deo3qruridine. Several other similar cases were also reported. The unsaturated compound (56), and Its (. -isomer. 

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