Analogues of acylonucleoside diphosphates. The synthesis of a series of diphosphonate derivatives of pyrimidines and purines

Abstract

The synthesis of a series of (hydroxy)(phosphonomethyl)phosphorylmethoxyalkoxy-pyrimidines and -purines is described. The diphosphonate unit was introduced into suitably functionalised alcohols by use of the reagent (diethoxyphosphinoyl)methyldiethoxyphosphine 13. Mitsunobu coupling of the alcohols 18 and 20 with 1-hydroxypyrimidines and 9-hydroxypurines provided a general route to the protected derivatives 23–26, 31, 32, 36, 37, 40 and 41. Conventional deprotection techniques afforded the pyrimidines 3-8 and purines 9–12 in good overall yields. The antiviral activity of this series of compounds is recorded.