The synthesis of difluoro and trifluoro analogues of pyrimidine deoxyribonucleosides: a novel approach using elemental fluorine

Article abstract of DOI:10.1016/0022-1139(94)03070-7

The preparation of some novel fluorodeoxy nucleosides in good yields by the fluorination of unsaturated intact nucleosides with elemental fluorine at -78 deg 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'-didehydro-2',3'-dideoxy-β-D-ribofuranosyl)-5-fluorouracil (6), 1-(2',3'-didehydro-2',3'-dideoxy-2',3'-difluoro-β-D-ribofuranosyl)-5-fluorouracil (7), 1-(2',3'-didehydro-2',3'-dideoxy-2-fluoro-β-D-ribofuranosyl)-5-fluorouracil (8), 1-(2',3'-dideoxy-2',3'-difluoro-β-D-ribofuranosyl)-5-fluorocytosine (10), 2',3'-dideoxy-5-fluorouridine (11), 1-(2',3'-dideoxy-2'-fluoro-β-D-arabinofuranosyl)-5-fluorouracil (12), 1-(2',3',5'-tri-O-acetyl-β-D-ribofuranosyl)-5-fluorouracil (13), 1-(2-deoxy-3,5-di-O-acetyl-β-D-ribofuranosyl)-5-fluorouracil (14) and (5R,6S)- and (5S,6R)-1-(3',5'-anhydro-2-deoxy-β-D-threo-pentofuranosyl)-difluoro-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.