3 -Deoxy-3 -fluoro-3- thymidine

C. Wodarski, J. Eisenbarth, K. Weber, M. Henze, U. Haberkorn, M. Eisenhut, Synthesis of 3 -deoxy-3 -[F-18]fluoro-thymidine with 2,3 -anhydro-5 -0-(4,4 -dimethoxytrityl)thymidine, J. Label. Compds Radiopharm. 43 (2000) 1211-1218. 

Luxen A, Guillaume M, Melega WP et al (1992). Production of 6-[18P]fluoro-L-dopa and its metabolism in vivo - a critical review. Nucl Med Biol 19 149 Machula HJ, Blocher A, Kuntzch M et al (2000). Simplified labeling approach for synthesizing 3[Pg.149]

Epoxide 8 (Scheme 2) has been opened by fluoride ion with good rcgioselectivity affording mosdy (25 1) fluoride 9 which was converted into 3 -deoxy-3 -fluoro-thymidine. The very similar epoxide 10 has been treated with titanium reagents (e.g. ( PrO)2TiF2) to get the fluorinated product analogous to 9, but in lower yield. A number of conditions have been evaluated for opening... 

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 -... 

Fig. 14. Effect of 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine (5-FdUMP) on the synthesis of RNA and DNA. 5-FU is incorporated into RNA whereas 5-FdUMP inhibits thymidilate synthetase competitively and blocks DNA synthesis. The conversion of thymidine (dTr) into thymidilate (dTMP) by means of thymidine kinase is only a subsidary routine to thymidilate which can become important, however, under certain conditions such as in developing pollen (page 185). U = uridine triphosphate, Tr = thymidine, TMP = thymidine monophosphate = thymidilate, TDP = thymidine diphosphate, TTP = thymidine triphosphate, 5-F = 5-fluoro, d = deoxy, 1 = thymidine kinase, 2 = thymidilate synthetase.

The 2 -chloro and 2 -bromo congeners of either 748 (FIAC) or 758 (FMAU) are more cytotoxic than FIAC and FMAU, suggesting that these chloro and bromo nucleosides, in contrast to the 2 -fluoro compounds, are comparatively better substrates for deoxycytidine kinase of human lymphocytes than the substrates for viral-specific thymidine kinase. The disposition of the 2 -fluoro group may also be important from the biological viewpoint. It should be noted that the structural difference between RNA and DNA is at the 2 -position. The ribo type of analog (738) of FIAC is 10 times less effective in suppression of HSV replication than is FIAC. Thus Fox, and Watanabe and coworkers concluded that the 2 - up fluorine disposition and the species of the substituent at C-5 are the two important factors influencing antiviral activity. Nevertheless, the mechanism of action of 2 -deoxy-2 -fluorocytidine (737) on certain herpes viruses, including HSV-1... 

Condensation of LXVIa (R = p-toluyl) with monomercurithymine (prepared from 1-acetylthymine) produces a mixture of acylated nucleoside anomers (LXVlb and LXVIc, R = thyminyl) which are separated and de-esterified to thymidine and a-thymidine. Similarly, reaction of N-acetylcytosinemercury (LV) with LXVIa (R = p-chlorobenzoyl) yields the a and ft anomers of acylated 2-deoxycytidine which, after separation and deacylation, are converted smoothly to 2-deoxycytidine (LXVlb, R = H, R = cytosinyl) and its a anomer (LXVIc). In like manner, 2-deoxy-5 -fluoro-uridine and -cytidine were synthesized, along with their... 

I. J., and Harris, A. L. (1995) Increased sensitivity to the prodrug 5 -deoxy-5-fluorouridine and modulation of 5-fluoro-2 -deoxyuridine sensitivity in MCF-7 cells transfected with thymidine phosphorylase. Br. J. Cancer 72, 669-675. 

Treatment of carbocyclic 5 -0-trltyl-3 -epi-thymidine with DAST led not only to the expected carba-3 -deoxy-3 -fluorothymldine, but also to the 4 -fluoro-3 -deoxy isomer and the 3 ,4 -alkene.i ... 

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