Mj. Egron et al., SYNTHESIS AND ANTINEOPLASTIC PROPERTIES OF 3'-DEOXY-3'-FLUOROKETONUCLEOSIDE DERIVATIVES - CORRELATIONS BETWEEN STRUCTURE AND BIOLOGICAL-ACTIVITY, Carbohydrate research, 248, 1993, pp. 143-150
Three fluoroketonucleosides (6, 8, and 11) have been synthesized by di
rect oxidation of the fluoro precursors. The presence of the highly el
ectronegative fluorine atom in the alpha position to the carbonyl grou
p favours hydration leading to the gem-diol form so that the beta-elim
ination process to afford 6 and 8 was made difficult and failed in the
case of the difluoro compound 11. The biological activity of compound
s 6, 8, and 11 was tested on human peripherical blood lymphocytes stim
ulated by PHA, and on RAJI and DAUDI cells. The IC50 values showed tha
t, surprisingly, the 3'-enopyranosyl-2'-uloses 6 and 8 have much bette
r antineoplastic activities than their 2'-enopyranosyl-4'-ulose analog
ues 14 and 15 obtained previously. Moreover, compound 11, which is dif
luorinated at C-3' and C-6' but does not have a C=C-C=O group in its s
tructure, is also very active. These results emphasize the important b
iological role played by the fluorine atom in this family of compounds
and suggest a peculiar mechanism of action which is until now unspeci
fied.