3 -Fluorinated nucleosides

Finally, recent developments on research into the first C-F bond forming enzyme are summarized. The fluorinase enzyme isolated from Streptomyces cat-tleya catalyzes the formation of 5 -fluoro-5 -deoxyadenosine from S-adenosyl-L-methionine and fluoride. The substrate specificity and subsequent transformation of the fluorinated nucleoside to fluoroacetic acid and to fluoro threonine are discussed. 

One of the rare fluorinated products found in nature is a fluorinated nucleoside called nucleocidine (4 -fluoro-5-(9-sulfamoyladenosine). This compound has been isolated from microbial cultures (cf. Chapter 4). ... 

Fluorine substitution in nucleosides and nucleic bases resulted in stronger interaction between lanthanides and ligands as compared with unsubstituted nucleosides and nucleic bases. The analysis of the fine structure of the bands, based upon the selection rules for the symmetry allowed transitions enabled the understanding of ligand field symmetry in Pr(III) and Nd(III) complexes of fluorinated nucleosides and nucleic bases. The stepwise complexation of Pr(III) Nd(III) was studied by the red shift of the absorption band which indicated a decrease in Ln-O distance in the complex due to the substitution of water by the fluorinated nucleoside ligand. 

A unique method for the introduction of fluorine via an ester-type linkage has been used for the preparation of fluorinated nucleosides.It consi.sts of the treatment of 2,3 -anhydro nucleosides with hydrogen fluoride in the presence of aluminum trifluoride in dioxane at temperatures between 150 and 200 The yields are in the range of 30-40%. With potassium... 

Figure 7,2 Structures of antitumor fluorinated nucleoside analogues.

Figure 7.3 Structures of antiviral fluorinated nucleoside analogues.

Biological Activity of Fluorinated Nucleosides and Correlations with Their Conformations... 

Herdewijn, P., Van Aerschot, A. and Kerremans, L. (1989) Synthesis of nucleosides fluorinated in the sugar moiety. The application of diethylaminosulfur trifluoride to the synthesis of fluorinated nucleosides. Nucleosides Nucleotides, 8, 65-96. 

Takamatsu, S., Katayama, S., Hirose, N., et al. (2002) Convenient synthesis of fluorinated nucleosides with perfluoroalkanesulfonyl fluorides. Nucleosides, Nucleotides, Nucleic Acids, 21, 849-861. 

For recent fluorinated nucleosides reviews, see (a) Meng, W-D. and Qing F-L. (2006) Fluori-nated nucleosides as antiviral and antitumor agents. Current Topics in Medicinal Chemistry, 6, 1499-1528 (b) Qing, F-L. and Qiu, X-L. (2007) Synthesis of gem-difluoromethylated sugar nucleosides. In Current Fluoroorganic Chemistry, ACS Symposium Series 949, pp. 305-322 and references cited therein. 

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