Branched-chain sugar nucleosides. Synthesis of 3′- C-ethyl (and 3′- C-butyl)uridine

Abstract

Syntheses of 3′- C-ethyl(and 3′- C-butyl)uridine ( 13 and 15) are described. Addition of ethyl (and butyl)magnesium bromide or the corresponding alkyllithiums to 1,2:5,6-di- O-isopropylidene-α- d- ribo-hexofuranos-3-ulose ( 1) gave 3- C-ethyl (and 3- C-butyl)-1,2:5,6-di- O-isopropylidene-α- d-allofuranose ( 2 and 3). Selective hydrolysis of 2 and 3, followed by periodate cleavage of the 5,6-diol and subsequent reduction, yielded the diols 6 and 7. Selective benzoylation of the latter compounds afforded 5- O-benzoyl-3- C-ethyl(and 3- C-butyl)-1,2- O-isopropylidene-α- d-ribofuranose ( 8 and 9). Hydrolysis of the latter compounds, followed by acetylation, yielded anomeric mixtures of branched-chain sugar triacetates 10 and 11. These were condensed with bis(trimethylsilyl)uracil and the products deacylated with methanolic ammonia to afford in high yield the title nucleosides 13 and 15.