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DOI: 10.1055/s-0029-1217364
The Application of Mitsunobu Cyclization for the Synthesis of 2′,3′-Dideoxy-C-Nucleosides Designed as Didanosine Analogues
Publication History
Publication Date:
12 June 2009 (online)
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Abstract
The synthesis of new 2′,3′-dideoxy-C-nucleosides structurally related to didanosine has been achieved. Their preparation involved condensation of a suitably substituted, lithiated 2- or 4-picoline with 2′,3′-dideoxy-5′-benzylribonolactone, followed by borohydride reduction of the resulting hemiacetals, intramolecular Mitsunobu cyclization of the derived diols, formation of the pyrazolo[3,4-c] or [4,3-b]pyridine ring-system and subsequent removal of the protecting groups.
Key words
C-nucleosides - heterocycles - pyrazolo[3,4-c]pyridine - pyrazolo[4,3-b]pyridine - dideoxynucleosides
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References and Notes
1,6-Dihydro-3-(2,3-dideoxy-β-d-ribofuranosyl)-7H-pyrazolo[3,4-c]pyridin-7-one (15): mp 270-272 ˚C (CH2Cl2-MeOH); ¹H NMR (400 MHz, CD3OD): δ = 1.88-2.02 (m, 1 H, H-3′), 2.08-2.25 (m, 2 H, H-2′, H-3′), 2.28-2.40 (m, 1 H, H-2′), 3.63 (dd, 1 H, H-5′, J5 ′ ,4 ′ = 5.48 Hz, J5 ′ ,5 ′ = 11.35 Hz), 3.70 (dd, 1 H, H-5′, J5 ′ ,4 ′ = 4.30 Hz, J5 ′ ,5 ′ = 11.35 Hz), 4.13-4.22 (m, 1 H, H-4′), 5.22 (t, 1 H, H-1′, J1 ′ ,2 ′ = 7.04 Hz), 6.87 (d, 1 H, H-4, J4,5 = 6.65 Hz), 6.95 (d, 1 H, H-5, J5,4 = 6.65 Hz). ¹³C NMR (50 MHz, CD3OD): δ = 28.54 (C-3′), 32.97 (C-2′), 65.59 (C-5′), 77.27 (C-1′), 81.94 (C-4′), 101.72 (C-4), 125.69 (C-3α), 125.93 (C-5), 134.94 (C-7α), 148.07 (C-3), 156.55 (C-7). Anal. Calcd for C11H13N3O3: C, 56.16; H, 5.57; N, 17.86. Found: C, 56.01; H, 5.69; N, 17.68
151,4-Dihydro-3-(2,3-dideoxy-β-d-ribofuranosyl)-7H-pyrazolo[4,3-b]pyridin-7-one (30): Oil. ¹H NMR (400 MHz, CD3OD): δ = 2.00-2.23 (m, 3 H, 2 × H-3′, 1 × H-2′), 2.35-2.46 (m, 1 H, H-2′), 3.71 (dd, 1 H, H-5′, J5 ′ ,4 ′ = 3.13 Hz, J5 ′ ,5 ′ = 11.74 Hz), 3.89 (dd, 1 H, H-5′, J5 ′ ,4 ′ = 2.74 Hz, J5 ′ ,5 ′ = 11.74 Hz), 4.22-4.29 (m, 1 H, H-4′), 5.29 (t, 1 H, H-1′, J1 ′ ,2 ′ = 7.04 Hz), 6.26 (d, 1 H, H-6, J6,5 = 7.04 Hz), 7.77 (d, 1 H, H-5, J5,6 = 7.04 Hz). ¹³C NMR (50 MHz, CD3OD): δ = 28.46 (C-3′), 34.19 (C-2′), 69.95 (C-5′), 77.95 (C-1′), 81.76 (C-4′), 110.23 (C-6), 128.49 (C-3α), 134.58 (C-7α), 138.77 (C-5), 142.86 (C-3), 171.12 (C-7). Anal. Calcd for C11H13N3O3: C, 56.16; H, 5.57; N, 17.86. Found: C, 56.38; H, 5.39; N, 17.99