C4'-Branched-chain surgar nucleosides: synthesis of isomers of psicofuranine.
Photoamidation of 3-O-acetyl-1,2:5,6-di-O-isopropylidene-alpha-D-erythro-hex-3-enofuranose (1) afforded 3-O-acetyl-4-C-carbamoyl-1,2:5,6-di-O-isopropylidene-alpha-D-gulofuranose (2) and 3-O-acetyl-3-C-carbamoyl-1,2:5,6-di-O-isopropylidene-D-alpha-allofuranose (3) in 65 and 26% yields, respectively (based on consumed 1). Treatment of 2 and 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-alpha-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-alpha-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 N6-benzoyl-N6,9-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)-beta-D-erythro-pentofuranosyl] adenine (17) and the alpha-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-alpha,alpha'-D-ribo-pentodialdose (25).
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D008722:Methods; D009705:Nucleosides / Q000138:chemical synthesis*; D009904:Optical Rotation; D013055:Spectrophotometry, Infrared
D000900:Anti-Bacterial Agents; D009705:Nucleosides; D000241:Adenosine