THE SYNTHESIS OF DIFLUORO AND TRIFLUORO ANALOGS OF PYRIMIDINE DEOXYRIBONUCLEOSIDES - A NOVEL-APPROACH USING ELEMENTAL FLUORINE

The preparation of some novel fluorodeoxy nucleosides in good yields b y the fluorination of unsaturated intact nucleosides with elemental fl uorine at -78-degrees-C in mixtures of chloroform, ethanol and fluorot richloromethane is described. This is the first example of the fluorin ation of an intact nucleoside by elemental fluorine and represents a c onsiderable step forward in the use of the element in the synthesis of bioactive species. Thus, we were able to obtain 2',3'-dideoxy-beta-D- ribofuranosyl)-5-fluorouracil (6), ',3'-difluoro-beta-D-ribofuranosyl) -5-fluorouracil (7), eoxy-2-fluoro-beta-D-ribofuranosyl)-5-fluorouraci l (8), 3'-difluoro-beta-D-ribofuranosyl)-5-fluorocytosine (10), 2',3'- dideoxy-5-fluorouridine (11), -2'-fluoro-beta-D-arabinofuranosyl)-5-fl uorouracil (12), -tri-O-acetyl-beta-D-ribofuranosyl)-5-fluorouracil (1 2), 5-di-O-acetyl-beta-D-ribofuranosyl)-5-flourouracil (14) and (5R,6S )-and ntofuranosyl)-diffluoro-5,6-dihydro-5-methyluracil (16 and 17) b y a series of fluorinations and deprotections. From the products we ha ve obtained, it is clear that (at least in these fluorinations) the ad dition of the fluorine is in a cis mode.