Synthesis of 1,1-difluoro-5-(1H-9-purinyl)-2-pentenylphosphonic acids and the related methano analogues. Remarkable effect of the nucleobases and the cyclopropane rings on inhibitory activity toward purine nucleoside phosphorylase

A series of 1,1-difluoro-5-(1 H -9-purinyl)-2-pentenylphosphonic acids, ( E )- 2a,b and ( Z )- 2a,b , as well as the related methano analogues (±) -3a,b and (±) -4a,b were prepared for evaluation of their PNP inhibitory activities. The cyclopopane ring and the hypoxanthine residue were found to increase the profile of inhibitory activity. The IC 50 and K i values of difluoro{(1 R ∗,2 S ∗)-2-[2-(6-oxo-6,9-dihydro-1 H 9-purinyl)ethyl]cyclopropyl}methylphosphonic acid (±) -3b toward PNP purified from Cellulomonas sp. were determined to be 70 nM and 8.8nM, respectively.