SYNTHESIS OF SOME 2′- AND 3′-FLUOROALKYL SUBSTITUTED NUCLEOSIDES AND OLIGONUCLEOTIDES

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• All the NMR spectra were recorded in DMSO-d6 and UV spectra in 95% EtOH. 3a NMR δH 3.02 (m, 1H, H-2′), 3.63 (m, 3H, H-4′, H-5′, H-5″), 4. 33 (t, 1H, H-3′ J = 7.69 Hz), 4.95 (bs, 1H, 5′ -OH), 5.61 (d, 1H, H-6, J = 8.12 Hz), 5.83 (d, 1H, 3′ -OH, J = 7.25 Hz), 6.02 (t of d, 1H, CF2H, JHF = 45.6 Hz, JHH = 4.47 Hz), 6.21 (d, 1H, H-1′, J = 7.75 Hz) 7.84 (d, 1H, H-6, J = 8.12 Hz), 11.41 (bs, 1H, NH); δC 51.60 (t, JC-F = 19 Hz, C-2′), 57.96 (C-5′), 66.31 (C-3′), 81.04 (C-1′), 83.84 (C-4′), 100.44 (C-5), 114.54 (t, JC-F = 240 Hz, CF2H), 140.18 (C-6), 149.31 (C-2), 162.13 (C-4); δF −117.17 (1F, d (JFF = 292 Hz) of d (JHgem-F = 54.6 Hz), −121.46 (1F, d (JFF = 292 Hz) of d (JHgem-F = 53.53 Hz); UV λmax 259 nm ϵmax 6468, λmin 229 nm ϵmin 1564; Observed FAB MS 279.0770, [C10H12F2N2O5 + H]+ requires 279.0793. 3b NMR δH 2.89 (m, 1H, H-2′), 3.59 (m, 2H, H-5′, H-5″), 3.85 (m, 1H, H-4′), 4. 36 (d, 1H,-3′, J = 4.48 Hz), 5.12 (bs, 1H, 5′-OH), 5.69 (d, 1H, H-5, J = 8.13 Hz), 5.79 (bs, 1H, 3′-OH), 6.33 (d, 1H, H-1′, J = 8.53 Hz), 6.19 (t of d, 1H, CF2H, JHF = 55.4 Hz, JHH = 6.80 Hz), 7.85 (d, 1H, H-6, J = 8.13 Hz), 11.32 (bs, 1H, NH); δF −114.58 (1F, d (JFF = 295 Hz) of q (JHgem-F = 54.1 Hz, JH2′-F = 10.0 Hz), −123.51 (1F d (J FF = 295 Hz) of q (JHgem-F = 55.9 Hz, JH2′-F = 14.3 Hz); UV λmax 260 nm ϵmax 7426, λmin 230 nm ϵmin 1098; Observed FAB MS 279.0702, [C10H12F2N2O5 + H]+ requires 279.0793. 6a NMR δH2.87 (m, 1H, H-3′), 3. 57 (m, 2H, H-5′, H-5″), 4.30 (m, 2H, H-2′, H-4′), 5.32 (bs, 1H, 5′-OH), 5.71(m, 3H, H-1′, 2′-OH, H-5), 6.31 (t of d, 1H, CF2H, JHF = 49.08 Hz, JHH = 6.88 Hz), 7.84 (d, 1H, H-6, J = 8.16 Hz), 11.34 (bs, 1H, NHi);); δC C-2′), 49.38 (t, JC-F = 19.5 Hz, C-3′), 60.58 (C-5′), 76.90 (C-4′), 87.96 (C-1′), 102.40 (C-5), 116.96 (t, JC-F = 251 Hz, CF2H), 140.69 (C-6), 150.92 (C-2), 163.03 (C-4); δF −112.08 1F d (JFF = 294 Hz) of q (JHgem-F = 55.55 Hz, JH-3′-F = 11.57 Hz), −116.75 1F d (JFF = 294 Hz) of q (JHgemF = 56.3 Hz, JH-3-F = 15.08 Hz); UV λmax 260 nm ϵmin 8778 λmin 229 nm ϵmin 3436; Observed ES MS 279.0802, [C10H12F2N2O5 + H]+ requires 279.0793. 6b NMR δH 2.73 (m, 1H, H-3′), 3.52 (m, 1H, H-5′), 3.75 (m, 1H, H-5″), 4. 34 (m, 3H, H-2′, H-4′, 5′-OH), 5.61 (d, 1H, J = 8.24 Hz, H-5), 5.68 (bs, 2H, 3′-OH, H-1′), 6.20 (t, JHF = 56.1 Hz of d JHH = 5.28 Hz, 1H, CF2H), 7.98 (d, 1H, H-6, J = 8.24 Hz), 11.30 (bs, 1H, NH); δF −116.03 1F d (JFF = 290 Hz) of q (JHgem-F = 55.6 Hz, JH3-F = 10.06 Hz), −122.70 1F d (JFF = 290 Hz) of q (JHgem-F = 57.1 Hz, JH3′-F = 18.7 Hz); UV λmax 262 nm ϵmax 8885 ϵmin 230 nm ϵmin 2020; Observed FAB MS 301.0600, [C10H12F2N2O5 + Na]+ requires 301.0612. 3a - 2D NOESY showed a cross peak between H-2′ and H-4′ and at the same time the lack of a cross peak between H-2′ and H-5′. There was also a cross peak between H-6 and CF2H. This is only possible if the H-2′ proton is on the α face. 3b - 2D NOESY showed a cross peak between H-2′ and H-5 and at the same time the lack of a cross peak between H-2′ and H-4′. This is only possible if the H-2′ proton is on the β face. 6a - 2D NOESY showed a cross peak between between H-5′ and CF2H. and at the same time the lack of a cross peak between H-3′ and H-5′. There was also a cross peak between H-6 and CF2H. This is only possible if the H-3′ proton is on the α face. 6b - 2D NOESY showed a cross peak between H-4′ and CF2H and at the same time the lack of a cross peak between H-5′ and CF2H. There was also a cross peak between H-3′ and H-6. This is only possible if the H-3′ proton is on the β face
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• NMR δH 1.05–1.14H (m, 14H, iPr), 2.59 (m, 1H, H-2′), 2.72 (t, 2H, J = 5.50 Hz, OCH2 CH 2CN), 3.45 (m, 2H, iPr), 3.51 (m, 2H, H-5′, H-5″), 3.73 (s, 6H, OCH3), 4.04 (m, 3H, OCH 2CH2CN, H-4′), 4.67 (m, 1H, H-3′), 5.31 (d, 1H, H-5, J = 9.13 Hz), 6.10 t (JHF = 56 Hz) of m, 1H, CF2H), 6.30(m, 1H, H-1′), 6.87–7.42 (m, 13H, trityl), 7.65 (2 d, unresolved, H-6), 11.39 (bs, 1H, NH); δF− 117.9 (d of m, 1F, CF2H), −122.2 (d of m, 1F, CF2H) δP 150.18 (s), 150.64 (s); Observed FAB MS 779.3050, [C40H47F2N4O8P‒H] requires 779.3021. 10 NMR δ H , (1.21, m, 14H, iPr), 2.88 (t, 2H, J = 6.82 Hz, OCH2 CH 2CN), 2.99 (m, 1H, H-3′), 3.48(m, 4H, H-5′, H-5″, iPr), 3. 71 (s, 6H, OCH3), 4.04 (m, 3H, OCH 2CH2CN, H-4′), 4.51 (m, 1H, H-2′), 5.59 (d, 1H, H-5, J = 8.11 Hz), 5.89 (d, 1H, H-1′, J = 5.62 Hz), 6.18 t (JHF = 48.5 Hz) of m, 1H, CF2H), 6.82–7.45 (m, 13H, trityl), 7.55 (d, 1H, H-6, J = 8.11 Hz), 11.34 (s, 1H, NH); δF −112.58–(−114.86) (m, 1F, CF2H) −117.11– (−118.99) (m, 1F, CF2H); δP 152.502 (s), 152.409 (s); Observed FAB MS 779.3063, [C40H47F2N4O8P-H] requires 779.3021
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• Brown , C. A. , Barnes , C. L. and Serafinowski , P. J. 1999 . Nucleosides & Nucleotides , 18 ( 6&7 ) : 1249 – 1250 .
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