Synthesis of Racemic 5-Substituted 1-(2,3-Dihydroxypropyl)-6-azauracils and Their Isosteric Isomers

Abstract

Acyclic nucleoside analogues of antiviral DHPA and HPMPA have been prepared. Coupling of silylated 6-azauracils with benzyl glycidyl ether and stannic chloride followed by the deprotection with boron trichloride gave 1-(2,3-dihydroxypropyl)-6-azauracils (3) in good overall yields. Reaction of silylated 6-azauracil and epichlorohydrin with or without catalytic stannic chloride afforded 1-(2-chloro-3-hydroxypropyl)-6-azauracil (4a) and 1-(3-chloro-2-hydroxypropyl)-6-azauracil (6a) respectively. Coupling of silylated 6-azaisocytosine under the same reaction conditions provided 1-(2,3-dihydroxypropyl)-6-azaisocytosine (9) and 1-(2-chloro-3-hydroxypropyl)-6-azaisocytosine (10) respectively. None of the compounds exhibited significant antiviral activity against herpes simplex viruses.