| Abstract: |
A potentially versatile crystalline intermediate, 5-(5-deoxy-β-D-erythro-pent-4-enofuranosyl)-1, 3-dimethyluracil (7), was synthesized in seven steps from pseudouridine in 67% overall yield. Pseudouridine was sequentially methylated to 1, 3-dimethylpseudouridine (1), acetonated to 2, and iodinated to 3 with methyltriphenoxyphosphonium iodide. After O-deisopropylidenation to 4 followed by acetylation, the product 5 was treated with AgF in pyridine. Crystalline 4′, 5′-olefin 2′, 3′-diacetate 6 was obtained, which was saponified with NH3/MeOH to give 7. When 2′, 3′-O-isopropylidene-5′-O-mesyl-1, 3-dimethylpseudouridine (8) was treated with AgF the 5′-deoxy-5′-fluoro C-nucleoside 9 was obtained. Treatment of 8 with t-BuOK in Me2SO afforded 5-[(3R, 4R)- 2, 3-dihydroxy-4, 5-epoxy-2, 3-O-isopropylidene-1-penten-1-yl]-1, 3-dimethyluracil (10), which was further converted into 1, 3-dimethyl-5-[(3R, 4R)-4, 5-O-isopropylidene-1-nitrilo-3, 4, 5-trihydroxy-5-hexen-6-yl]uracil (11) by treatment with NaCN in Me2SO. Reaction of 6 with HgCl2 in acetone afforded racemic 5-(4-acetoxy-5-methylfuran-2- yl)-1, 3-dimethyluracil (12). Deacetylation of 12 gave 1, 3-dimethyl-5-(5-methyl-4-oxo-4, 5-dihydrofuran-2-yl)uracil (13). Treatment of 6 with methanol in the presence of acetic acid afforded 5-(2, 3-di-O-acetyl-5-deoxy-4-methoxy- d-D-ribofuranosyl)-1, 3-dimethyluracil (14) and the isomeric α-L-lyxo nucleoside 15 in 76.5 and 13.5% yield, respectively. Acid-catalyzed addition of the 4′, 5′-double bond with 1, 2, 4-triazole occurred smoothly, giving rise to crystalline 5-[2, 3-di-O-acetyl-5-deoxy-4-(1H-1, 2, 4-triazol-1-yl)-β-D-ribofuranosyl]-1, 3-dimethyluracil (16) and its α-L lyxo isomer 17. © 1988, American Chemical Society. All rights reserved. |
