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 by the fluorination of unsaturated intact nucleosides with elemental fluorine at -78-degrees-C in mixtures of chloroform, ethanol and fluorotrichloromethane is described. This is the first example of the fluorination of an intact nucleoside by elemental fluorine and represents a considerable step forward in the use of the element in the synthesis of bioactive species. Thus, we were able to obtain 1-(2',3'-difluoro-2',3'-dideoxy-beta-D-ribofuranosyl)-5-fluorouracil (6), 1-(2',3'-didehydro-2',3'-dideoxy-2',3'-difluoro-beta-D-ribofuranosyl)-5-fluorouracil (7), 1-(2',3'-didehydro-2',3'-dideoxy-2-fluoro-beta-D-ribofuranosyl)-5-fluorouracil (8), 1-(2',3'-dideoxy-2',3'-difluoro-beta-D-ribofuranosyl)-5-fluorocytosine (10), 2',3'-dideoxy-5-fluorouridine (11), 1-(2',3'-dideoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-fluorouracil (12), 1-(2',3',5-tri-O-acetyl-beta-D-ribofuranosyl)-5-fluorouracil (12), 1-(2-deoxy-3,5-di-O-acetyl-beta-D-ribofuranosyl)-5-flourouracil (14) and (5R,6S)-and (5S,6R)-1-(3',5'-anhydro-2-deoxy-beta-D-threo-pentofuranosyl)-diffluoro-5,6-dihydro-5-methyluracil (16 and 17) by a series of fluorinations and deprotections. From the products we have obtained, it is clear that (at least in these fluorinations) the addition of the fluorine is in a cis mode.