C-4′-Branched-chain sugar nucleosides: synthesis of isomers of psicofuranine

Abstract

Photoamidation of 3- O-acetyl-1,2:5,6-di- O-isopropylidene-α- d- erythro-hex-3-enofuranose ( 1) afforded 3- O-acetyl-4- C-carbamoyl-1,2:5,6-di- O-isopropylidene-α- d-gulofuranose ( 2) and 3- O-acetyl-3- C-carbamoyl-1,2:5,6-di- O-isopropylidene- d-α-allofuranose ( 3) in 65 and 26% yields, respectively (based on consumed 1). Treatment of 2 with 5% hydrochloric acid in methanol yielded the spiro lactone 5, which was deacetylated to yield 7. Reduction of 5 with sodium borohydride afforded 4- C-(hydroxymethyl)-1,2- O-isopropylidene-α- d-gulofuranose ( 9) in 79% yield. Oxidation of 9 with sodium metaperiodate afforded a dialdose that was reduced with sodium borohydride to give 4- C-(hydroxymethyl)-1,2- O-isopropylidene-α- d- erythro-pentofuranose ( 11) in 88% yield. Treatment of the acetate 12, derived from 11, with trifluoroacetic acid, followed by acetylation, afforded the branched-chain sugar acetate 14. Condensation of the glycosyl halide derived from 14 with N 6-benzoyl- N 6, 9-bis-(trimethylsilyl)adenine yielded an equimolar anomeric mixture of protected nucleosides 15 and 16 in 40% yield. Treatment of the latter compounds with sodium methoxide in methanol afforded 9-[4- C-(hydroxymethyl)-β- d- erythro-pentofuranosyl]-adenine ( 17) and the α- d anomer 18. The structure of 3 was determined by correlation with the known 5,3′-hemiacetal of 3- C-(hydroxymethyl)-1,2- O-isopropylidene-α,α′- d- ribo-pentodialdose ( 25).