Job/Unit: O43642
/KAP1
Date: 11-02-15 15:50:45
Pages: 10
M. J. Damha et al.
FULL PAPER
tion mixture was then stirred at room temperature for 30 min. This
solution was cooled to 0 °C, TMSOTf (0.37 mL, 2.02 mmol) was
added dropwise, and the solution stirred overnight at room tem-
perature. The reaction mixture was neutralized with NaHCO3. Af-
ter aqueous workup, the resulting residue was purified by column
chromatography (0.5–6% MeOH/CH2Cl2) to afford the protected
nucleosides 9a–c. The protected nucleosides were then deprotected
with saturated ammonia in methanol for 16–24 h at room tempera-
ture. The solvent was evaporated and the products purified by col-
umn chromatography (5–10% MeOH/CH2Cl2) to afford the pure
1,3-oxathiane nucleosides 10a–c as white solids.
(dd, JH-H = 4.5, JH-H = 7.5 Hz, 1 H, H-4Ј), 7.48 (m, 2 H, Bz), 7.55
(d, JH-H = 1.0 Hz, 1 H, H-6), 7.61 (m, 1 H, Bz), 8.09 (m, 2 H, Bz),
8.35 (br. s, 1 H, NH) ppm. 13C NMR (CDCl3, 125 MHz): δ = 12.8
(CH3), 30.2 (C-5Ј), 52.6 (C-4Ј), 62.9 (C-6Ј), 64.5 (C-7Ј), 111.4 (C-
5), 128.5 (Bz), 129.4 (Bz), 129.8 (Bz), 133.4 (Bz), 136.4 (C-6), 150.0
(C-2), 163.0 (C-4), 166.0 (C=O) ppm. β isomer (34%): 1H NMR
(CDCl3, 500 MHz): δ = 1.97 (d, JH-H = 1.0 Hz, 3 H, CH3), 2.04
(q, JH-H = 2.0 Hz, 1 H, H-5Ј), 2.21 (m, 1 H, H-5ЈЈ), 3.79 (td, JH-H
= 2.0, JH-H = 12.0 Hz, 1 H, H-6Ј), 4.41 (ddd, JH-H = 2.5, JH-H
=
4.0, JH-H = 12.5 Hz, 1 H, H-6ЈЈ), 4.52 (m, 1 H, H-7Ј), 4.63 (m, 1
H, H-7ЈЈ), 5.33 (dd, JH-H = 4.5, JH-H = 6.0 Hz, 1 H, H-2Ј), 6.08
(dd, JH-H = 3.0, JH-H = 12.0 Hz, 1 H, H-4Ј), 7.24 (d, JH-H = 1.0 Hz,
1 H, H-6), 7.48 (m, 2 H, Bz), 7.61 (m, 1 H, Bz), 8.09 (m, 2 H, Bz),
8.35 (br. s, 1 H, NH) ppm. 13C NMR (CDCl3, 125 MHz): δ = 12.6
(CH3), 32.1 (C-5Ј), 53.7 (C-4Ј), 65.2 (C-7Ј), 68.9 (C-6Ј), 112.3 (C-
5), 128.4 (Bz), 129.4 (Bz), 129.9 (Bz), 133.3 (Bz), 135.6 (C-6), 149.9
(C-2), 162.8 (C-4), 165.9 (C=O) ppm. HRMS (ESI+): calcd. for
C17H18N2O5SNa [M + Na]+ 385.0834; found 385.0831.
1-(2-Benzoyloxymethyl-1,3-oxathian-4-yl)cytosine (9a): Yield 54%.
1
Rf (9% MeOH/CH2Cl2) = 0.33. α isomer (64%): H NMR ([D4]-
MeOH, 500 MHz): δ = 2.22 (m, 2 H, H-5Ј, H-5ЈЈ), 3.88 (m, 1 H,
H-6Ј), 4.13 (dt, JH-H = 5.0, JH-H = 12.5 Hz, 1 H, H-6ЈЈ), 4.50 (m,
1 H, H-7Ј), 4.77 (dd, JH-H = 7.5, JH-H = 12.0 Hz, 1 H, H-7ЈЈ), 5.56
(dd, JH-H = 4.0, JH-H = 7.5 Hz, 1 H, H-2Ј), 6.01 (m, 2 H, H-4Ј, H-
5), 7.50 (m, 2 H, Bz), 7.64 (m, 1 H, Bz), 8.07 (td, JH-H = 1.0, JH-H
= 7.5 Hz, 2 H, Bz), 8.12 (d, JH-H = 7.5 Hz, 1 H, H-6) ppm. 13C
NMR ([D4]MeOH, 125 MHz): δ = 29.3 (C-5Ј), 53.8 (C-4Ј), 62.9
(C-6Ј), 64.7 (C-7Ј), 76.7 (C-2Ј), 94.0 (C-5), 128.2 (Bz), 129.3 (Bz),
129.5 (Bz), 133.1 (Bz), 142.7 (C-6), 156.3 (C-2), 165.9 (C-4), 166.0
1-(2-Hydroxymethyl-1,3-oxathian-4-yl)thymine (10b): Yield 89%. Rf
(9% MeOH/CH2Cl2) = 0.17. α isomer (65%): 1H NMR ([D6]-
DMSO, 500 MHz): δ = 1.84 (d, JH-H = 1.0 Hz, 3 H, CH3), 2.07
(m, 1 H, H-5Ј), 2.20 (m, 1 H, H-5ЈЈ), 3.49 (m, 1 H, H-7Ј), 3.62 (m,
1 H, H-7ЈЈ), 3.86 (m, 1 H, H-6Ј), 3.98 (m, 1 H, H-6ЈЈ), 5.17 (m, 1
H, OH), 5.21 (dd, JH-H = 5.0, JH-H = 6.5 Hz, 1 H, H-2Ј), 5.82 (dd,
JH-H = 5.0, JH-H = 7.5 Hz, 1 H, H-4Ј), 7.81 (d, JH-H = 1.5 Hz, 1
H, H-6), 11.39 (br. s, 1 H, NH) ppm. 13C NMR ([D6]DMSO,
125 MHz): δ = 12.6 (CH3), 29.4 (C-5Ј), 52.3 (C-4Ј), 63.1 (C-6Ј),
63.8 (C-7Ј), 80.1 (C-2Ј), 110.0 (C-5), 137.9 (C-6), 150.8 (C-2), 164.1
(C-4) ppm. β isomer (35%): 1H NMR ([D6]DMSO, 500 MHz): δ =
1.79 (d, JH-H = 1.0 Hz, 3 H, CH3), 2.07 (m, 1 H, H-5Ј), 2.20 (m, 1
H, H-5ЈЈ), 3.49 (m, 1 H, H-7Ј), 3.78 (m, 2 H, H-6Ј, H-7ЈЈ), 4.21
(ddd, JH-H = 2.0, JH-H = 3.5, JH-H = 11.5 Hz, 1 H, H-6ЈЈ), 5.06
(dd, JH-H = 5.0, JH-H = 6.0 Hz, 1 H, H-2Ј), 5.17 (m, 1 H, OH),
(C=O, Bz) ppm.
β
isomer (36%): 1H NMR ([D4]MeOH,
500 MHz): δ = 1.99 (dq, JH-H = 2.0, JH-H = 13.0 Hz, 1 H, H-5Ј),
2.22 (m, 1 H, H-5ЈЈ), 3.88 (m, 1 H, H-6Ј), 4.37 (ddd, JH-H = 2.5,
JH-H = 4.0, JH-H = 12.5 Hz, 1 H, H-6ЈЈ), 4.50 (m, 1 H, H-7Ј), 4.58
(dd, JH-H = 5.5, JH-H = 11.5 Hz, 1 H, H-7ЈЈ), 5.43 (dd, JH-H = 4.5,
JH-H = 6.0 Hz, 1 H, H-2Ј), 6.01 (m, 1 H, H-5), 6.17 (dd, JH-H
=
2.5, JH-H = 11.5 Hz, 1 H, H-4Ј), 7.50 (m, 2 H, Bz), 7.64 (m, 1 H,
Bz), 7.72 (d, JH-H = 7.5 Hz, 1 H, H-6), 8.07 (td, JH-H = 1.0, JH-H
= 7.5 Hz, 2 H, Bz) ppm. 13C NMR ([D4]MeOH, 125 MHz): δ =
31.8 (C-5Ј), 54.8 (C-4Ј), 65.2 (C-7Ј), 68.7 (C-6Ј), 81.5 (C-2Ј), 95.5
(C-5), 128.2 (Bz), 129.3 (Bz), 129.5 (Bz), 133.1 (Bz), 141.8 (C-6),
156.0 (C-2), 165.7 (C-4), 166.0 (C=O) ppm. HRMS (ESI+): calcd.
for C16H17N3O4SNa [M + Na]+ 370.0837; found 370.0831.
5.93 (dd, JH-H = 3.0, JH-H = 12.0 Hz, 1 H, H-4Ј), 7.61 (d, JH-H
=
1.0 Hz, 1 H, H-6), 11.39 (br. s, 1 H, NH) ppm. 13C NMR ([D6]
DMSO, 125 MHz): δ = 12.4 (CH3), 31.5 (C-5Ј), 53.7 (C-4Ј), 63.9
(C-7Ј), 68.4 (C-6Ј), 85.2 (C-2Ј), 110.8 (C-5), 137.2 (C-6), 150.5 (C-
2), 163.9 (C-4) ppm. HRMS (ESI+): calcd. for C10H14N2O4SNa [M
+ Na]+ 281.0572; found 281.0572.
1-(2-Hydroxymethyl-1,3-oxathian-4-yl)cytosine (10a): Yield 86%.
1
Rf (16% MeOH/CH2Cl2) = 0.27. α isomer (63%): H NMR ([D4]-
MeOH, 500 MHz): δ = 2.22 (m, 2 H, H-5Ј, H-5ЈЈ), 3.69 (m, 1 H,
H-7Ј), 3.80 (m, 1 H, H-6Ј), 3.86 (dd, JH-H = 6.0, JH-H = 12.0 Hz,
1 H, H-7ЈЈ), 4.06 (dt, JH-H = 5.0, JH-H = 12.5 Hz, 1 H, H-6ЈЈ), 5.21
(dd, JH-H = 4.5, JH-H = 6.0 Hz, 1 H, H-2Ј), 5.88 (t, JH-H = 5.0 Hz,
1-(2-Benzoyloxymethyl-1,3-oxathian-4-yl)-5-fluorocytosine
(9c):
1
Yield 72%. Rf (9% MeOH/CH2Cl2) = 0.31. α anomer (67%): H
NMR ([D4]MeOH, 500 MHz): δ = 2.25 (m, 2 H, H-5Ј, H-5ЈЈ), 3.92
(ddd, JH-H = 4.0, JH-H = 7.5, JH-H = 12.0 Hz, 1 H, H-6Ј), 4.13
(ddd, JH-H = 4.0, JH-H = 6.0, JH-H = 12.5 Hz, 1 H, H-6ЈЈ), 4.51 (m,
1 H, H-7Ј), 4.78 (dd, JH-H = 7.5, JH-H = 12.0 Hz, 1 H, H-7ЈЈ), 5.59
(dd, JH-H = 4.0, JH-H = 7.0 Hz, 1 H, H-2Ј), 5.97 (td, JH-H = 1.5,
JH-H = 6.5 Hz, 1 H, H-4Ј), 7.51 (m, 2 H, Bz), 7.65 (m, 1 H, Bz),
8.07(m,2H,Bz),8.24(d,JHF=6.5 Hz,1H,H-6) ppm.13CNMR([D4]-
MeOH, 125 MHz): δ = 29.0 (C-5Ј), 54.3 (C-4Ј), 62.9 (C-6Ј), 64.7
(C-7Ј), 76.5 (C-2Ј), 126.9 (C-6, JCF 32.5 Hz), 128.2 (Bz), 129.3 (Bz),
133.1 (Bz), 138.0 (C-5), 155.0 (C-2), 158.1 (C-4, JCF = 17.1 Hz),
166.0 (C=O) ppm. β anomer (33%): 1H NMR ([D4]MeOH,
500 MHz): δ = 2.01 (dq, JH-H = 2.5, JH-H = 13.5 Hz, 1 H, H-5Ј),
2.25 (m, 1 H, H-5ЈЈ), 3.87 (td, JH-H = 2.0, JH-H = 12.0 Hz, 1 H, H-
6Ј), 4.37 (ddd, JH-H = 2.5, JH-H = 4.0, JH-H = 12.5 Hz, 1 H, H-6ЈЈ),
4.51 (m, 1 H, H-7Ј), 4.58 (dd, JH-H = 5.5, JH-H = 11.5 Hz, 1 H, H-
1 H, H-4Ј), 6.06 (d, JH-H = 8.0 Hz, 1 H, H-5), 8.31 (d, JH-H
=
7.5 Hz, 1 H, H-6) ppm. 13C NMR ([D4]MeOH, 125 MHz): δ = 28.7
(C-5Ј), 54.9 (C-4Ј), 62.9 (C-6Ј), 63.6 (C-7Ј), 79.8 (C-2Ј), 94.1 (C-5),
144.4 (C-6), 153.4 (C-2), 163.8 (C-4) ppm. β isomer (37%): 1H
NMR ([D4]MeOH, 500 MHz): δ = 1.99 (dq, JH-H = 2.5, JH-H
=
13.0 Hz, 1 H, H-5Ј), 2.22 (m, 1 H, H-5ЈЈ), 3.47 (m, 1 H, H-7Ј), 3.69
(m, 1 H, H-7ЈЈ), 3.80 (m, 1 H, H-6Ј), 4.35 (ddd, JH-H = 2.5, JH-H
= 4.0, JH-H = 12.0 Hz, 1 H, H-6ЈЈ), 5.09 (dd, JH-H = 4.0, JH-H
=
5.5 Hz, 1 H, H-2Ј), 6.03 (d, JH-H = 7.5 Hz, 1 H, H-5), 6.10 (dd, JH-
= 3.0, JH-H = 11.5 Hz, 1 H, H-4Ј), 7.81 (d, JH-H = 7.5 Hz, 1 H,
H
H-6) ppm. 13C NMR ([D4]MeOH, 125 MHz): δ = 31.8 (C-5Ј), 54.7
(C-4Ј), 63.6 (C-7Ј), 63.7 (C-6Ј), 84.7 (C-2Ј), 95.4 (C-5Ј), 142.9 (C-
6), 153.9 (C-2), 164.1 (C-4) ppm. HRMS (ESI+): calcd. for
C9H13N3O3SNa [M + Na]+ 266.0575; found 266.0569.
1-(2-Benzoyloxymethyl-1,3-oxathian-4-yl)thymine (9b): Yield 68%. 7ЈЈ), 5.43 (dd, JH-H = 4.0, JH-H = 6.0 Hz, 1 H, H-2Ј), 6.14 (ddd,
Rf (9% MeOH/CH2Cl2) = 0.64. α isomer (66%): 1H NMR (CDCl3, JH-H = 2.0, JH-H = 3.0, JH-H = 12.0 Hz, 1 H, H-4Ј), 7.51 (m, 2 H,
500 MHz): δ = 2.00 (d, JH-H = 1.0 Hz, 3 H, CH3), 2.21 (m, 2 H, Bz), 7.65 (m, 1 H, Bz), 7.92 (d, JHF = 7.0 Hz, 1 H, H-6), 8.07 (m,
H-5Ј, H-5ЈЈ), 3.93 (ddd, JH-H = 3.5, JH-H = 7.0, JH-H = 12.5 Hz, 1
H, H-6Ј), 4.16 (ddd, JH-H = 3.5, JH-H = 7.0, JH-H = 12.5 Hz, 1 H, 55.3 (C-4Ј), 65.2 (C-7Ј), 68.6 (C-6Ј), 81.5 (C-2Ј), 125.9 (C-6, JCF
2 H, Bz) ppm. 13C NMR ([D4]MeOH, 125 MHz): δ = 31.6 (C-5Ј),
=
H-6ЈЈ), 4.52 (m, 1 H, H-7Ј), 4.86 (dd, JH-H = 8.0, JH-H = 12.0 Hz, 29.1 Hz), 128.2 (Bz), 129.3 (Bz), 133.1 (Bz), 138.0 (C-5), 154.7 (C-
1 H, H-7ЈЈ), 5.46 (dd, JH-H = 4.5, JH-H = 8.0 Hz, 1 H, H-2Ј), 6.00 2), 158.1 (C-4, JCF = 17.1 Hz), 165.9 (C=O) ppm. HRMS (ESI+):
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0