Synthesis of acyclic nucleotide analogues possessing a difluoromethylene phosphonyl group at the side chain

A synthetic approach to a new type of acyclic nucleotide analogues 8 and 9 was examined. The design was based on acyclic modification of MRS 2179, a P2Y₁-antagonist, and replacement of one of two phosphate groups characterized by MRS 2179 with an isosteric difluoromethylenephosphonyl group. The nucleotide analogues 8 and 9 were enantio-divergently prepared as their ester-protecting derivatives from a highly differentiated 1,5-pentanediol derivative possessing a difluoromethylenephosphonyl group at the 3-position.