Stereospecific synthesis of isomeric 4-substituted 9-(2,3-dihydroxybutyl)adenines

Abstract

Reduction of ethyl 2,3-O-isopropylidene-D-tartrate with sodium borohydride afforded (4S, 5S)-2,2-dimethyl-1,3-dioxolane-4,5-dimethanol (Va) which was benzoylated to give monobenzoyl derivative Vd and further transformed into p-toluensulfonyl derivative Ve. Reaction of the compound Ve with sodium salt of adenine followed by methanolysis gave 2,3-O-isopropylidene derivative Vf which on acid hydrolysis afforded 9-(2S, 3S)-(2,3,4-trihydroxybutyl)adenine (Ia). The enantiomer IIa was obtained from 3,4-O-isopropylidene-D-mannitol via (4R, 5R)-2,2-dimethyl-1,3-dioxolane-4,5-dimethanol (VIa) using the same procedure. Reaction of compounds Vf and VIf with p-toluenesulfonyl chloride afforded 4-O-p-toluenesulfonyl derivatives Vg and VIg. These compounds were also obtained from Va and VIa via di-p-toluenesulfonyl derivatives Vc and VIc by reaction with sodium salt of adenine. Treatment of compounds Vg and VIg with sodium iodide gave 4-iodo derivatives Vh and VIh which on reaction with tri-n-butyltin hydride, followed by acid hydrolysis, afforded enantiomeric threo-2,3-dihydroxybutyl derivatives Ib andIIb. Compounds Vg and VIg on treatment with sodium azide, subsequent catalytic hydrogenation of the intermediates Vj and VIj and acid hydrolysis afforded enantiomeric threo-9-(4-amino-2,3-dihydroxybutyl)adenines (Ic,IIc).