Synthesis of Pyrimidine 1′,3′-Anhydro-β-d-psico- and -sorbo-furanosyl Nucleosides

Abstract

A novel approach for the synthesis of pyrimidine 1′,3′-anhydro-β-d-psico- and -sorbo-furanosyl nucleosides 2 and 3, ­respectively, has been developed. The approach described here ­employs a readily available O ²,3′-anhydro-β-d-fructofuranosyl­uracil (1) as a key starting compound.

Key words

pyrimidine nucleosides - hexofuranosides - anhydro ­derivatives

References

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5

Note that the structure of compound 16 in ref. 4 was erroneously described to 1-(1,3-anhydro-β-d-psicofura-nosyl)thymine. Single-crystal X-ray analysis showed that compound 16 actually is methyl 1-deoxy-1-(N ¹-thyminyl)-β-d-psicofuranoside: (Roivainen, J.; Reuter, H.; Mikhailopulo, I. A., unpublished). The structures of the anhydro nucleosides 9, 12, and 13 have been proved by X-ray analyses (Roivainen, J. A.; Reuter, H.; Mikhailopulo, I. A., unpublished).

13

The ¹H NMR and ¹³C MNR data for the psicoside 3 are in agreement with those previously published. [3b]

15

1-(1,3-Anhydro-β-d-psicofuranosyl)uracil (2): amorphous powder; UV (MeOH): λ_max = 257 nm (ε 9500), λ_min = 227 (ε 2700) nm. ¹H NMR (500.13 MHz, DMSO-d ₆): δ_TMS = 7.44 (d, 1 H, J _5,6 = 7.99 Hz, H6), 5.63 (d, 1 H, H5), 5.25 (d, 1 H, J _{3 ′ ,4 ′} = 3.91 Hz, H3′), 5.21 (br s, 1 H, 4′-OH), 5.00 (d, 1 H, J _{1 ′ ,1 ′′} = 8.13 Hz, H1′), 4.82 (br t, 1 H, J = 4.10 Hz, 6′-OH), 4.57 (d, 1 H, H1′′), 4.07 (ddd, 1 H, J _{4 ′ ,5 ′} = 8.59 Hz, J _{5 ′ ,6 ′} = 2.0 Hz, J _{5 ′ ,6 ′′} = 5.68 Hz, H5′), 4.03 (br m, 1 H, H4′), 3.75 (br d, 1 H, J _{6 ′ ,6 ′′} = 12.9 Hz, H6′), 3.50 (br m, 1 H, H6′′) ppm. ¹³C NMR (125.77 MHz, DMSO-d ₆): δ_TMS = 163.22 (C4), 149.24 (C2), 141.60 (C6), 101.96 (C5), 90.85 (C2′), 86.84 (C3′), 83.30 (C5′), 77.83 (C1′), 69.65 (C4′), 60.57 (C6′) ppm. Anal. Calcd for C₁₀H₁₂N₂O₆: C, 46.88; H, 4.72; N, 10.93. Found: C, 46.77; H, 4.63; N, 10.90.

16

1-(1,3-Anhydro-β-d-sorbofuranosyl)uracil (4): amorphous powder; UV (MeOH): λ_max = 256 nm (ε 9900), λ_min = 227 nm (ε 2800). ¹H NMR (500.13 MHz, (DMSO-d ₆): δ_TMS = 11.39 (br s, 1 H, N ³H), 7.40 (d, 1 H, J _5,6 = 8.05 Hz, H6), 5.73 (d, 1 H, H5), 5.60 (d, 1 H, J = 4.42 Hz, 4′-OH), 5.17 (s, 1 H, J _{3 ′ ,4 ′} < 0.5 Hz, H3′), 5.04 (d, 1 H, J _{1 ′ ,1 ′′} = 8.28 Hz, H1′), 4.80 (t, 1 H, J = 5.70 Hz, 6′-OH), 4.57 (d, 1 H, H1′′), 4.42 (m, 1 H, J _{4 ′ ,5 ′} = 3.35 Hz, J _{5 ′ ,6 ′} = 5.54 Hz, J _{5 ′ ,6 ′′} = 5.88 Hz, H5′), 4.10 (br t, 1 H, H4′), 3.74 (ddd, 1 H, J _{6 ′ ,6 ′′} = 11.60 Hz, H6′), 3.63 (ddd, 1 H, H6′′) ppm. ¹³C NMR (125.77 MHz, DMSO-d ₆): δ_TMS = 163.23 (C4), 149.65 (C2), 141.68 (C6), 102.45 (C5), 92.96 (C2′), 91.40 (C3′), 84.92 (C5′), 78.61 (C1′), 70.91 (C4′), 58.79 (C6′). Anal. Calcd for C₁₀H₁₂N₂O₆: C, 46.88; H, 4.72; N, 10.93. Found: C, 46.75; H, 4.61; N, 10.88.

17

1-[3,4-Anhydro-1,6-di-O-(4-monomethoxy)-trityl-β-d-psicofuranosyl]uracil (10): amorphous powder; UV (MeOH): λ_max = 231.5 nm (ε 26900), λ_max = 263 nm (ε 9000), λ_min = 225 nm (ε 23500), λ_min = 255 nm (ε 8800). ¹H NMR (500.13 MHz, DMSO-d ₆): δ_TMS = 11.35 (s, 1 H, N ³H), 7.71 (d, 1 H, J _5,6 = 8.14 Hz, H6), 5.47 (d, 1 H, H5), 4.92 (d, 1 H, J _{3 ′ ,4 ′} = 2.54 Hz, H3′), 4.56 (t, 1 H, J _{5 ′ ,6 ′} = J _{5 ′ ,6 ′′} = 4.26 Hz, H5′), 3.92 (d, 1 H, J _{4 ′ ,5 ′} < 0.5 Hz, H4′), 3.61 (d, 1 H, J _{1 ′ ,1 ′′} = 9.29 Hz, H1′), 3.16 (d, 1 H, H-1′′), 3.19 (d, H6′ and H6′′) ppm. ¹³C NMR (125.77 MHz, DMSO-d ₆): δ_TMS = 163.14 (C4), 150.47 (C2), 141.64 (C6), 100.63 (C5), 63.21 (C1′), 95.92 (C2′), 57.37 (C3′), 56.12 (C4′), 79.83 (C5′), 62.65 (C6′) ppm. Anal. Calcd for C₅₀H₄₄N₂O₈: C, 74.98; H, 5.54; N, 3.50. Found: C, 74.83; H, 5.50; N, 3.42.