New method for the preparation of 3'- and 2'-O-phosphoramidites of 2'- and 3'-difluoromethyluridine derivatives.
Hydrogenation of 2'-deoxy-2'-difluoromethylene-5'-O-dimethoxytrityluridine (1) and 3'-deoxy-3'-difluoromethylene-5'-O-dimethoxytrityluridine (7), gave the corresponding 2'- and 3'-difluoromethyluridine derivatives 2a and 8a. Detritylation of compounds 2a, 2b and 8a, 8b resulted in the formation of 1-(2-deoxy-2-C-difluoromethyl-beta-D-arabino-pentofuranosyl)uracil (3a) and 1-(3-deoxy-3-C-difluoromethyl-beta-D-xylo-pento furanosyl)- uracil (9a) as well as corresponding minor isomers 3b and 9b. Compounds 3a and 3b were also obtained from 2'-deoxy-2'-difluoromethylene-3',5'-O-(tetraisopropyldisiloxane-1,3-diyl)uridine (4). Finally, phosphitylation of 2a and 8a provided the title 2'- and 3'-O-phosphoramidites 6 and 10.
Serafinowski
Pawel J
PJ
CRC Centre for Cancer Therapeutics at the Institute of Cancer Research, Sutton, Surrey, UK. p.serafinowski@icr.ac.uk
Brown
Catherine A
CA
D009943:Organophosphorus Compounds / Q000138:chemical synthesis*; D013057:Spectrum Analysis; D014466:Ultraviolet Rays; D014529:Uridine / Q000031:analogs & derivatives*
D009943:Organophosphorus Compounds; C434331:phosphoramidite; D014529:Uridine