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B.-S. Jeong et al. / Tetrahedron: Asymmetry 16 (2005) 3795–3801
(m, 1H), 7.48–7.41 (m, 3H), 6.15 (t, 1H, J = 6.5 Hz),
4.69–4.54 (m, 2H), 4.43–4.29 (m, 2H), 3.22–3.12 (m,
1H), 2.44–2.31 (m, 1H), 2.24 (s, 3H); 13C NMR
(100 MHz, CDCl3) d 171.5, 166.2, 163.6, 155.3, 144.3,
133.9, 130.1, 129.4, 128.9, 102.8, 101.0, 97.2, 90.1,
76.1, 75.9, 65.3, 65.0, 42.3, 42.1, 25.2; HRMS (EI): calcd
62.6, 40.6, 40.4; HRMS (EI): calcd (C9H12O3N3F)
229.0864, found 229.0866.
4.2.16. (ꢀ)-1-(2,3-Dideoxy-3-fluoroapio-a-D-furanosyl)-
cytosine 15b. Compound 14b (65 mg, 0.17 mmol) was
converted to 15b (39 mg, 98%) as a white solid according
(C18H18O5N3F) 375.1231, found 375.1229. Compound
to the same procedure used for the preparation of 15a:
20
20
14b: Rf = 0.15 (EtOAc only); ½aꢁD ¼ ꢀ72:9 (c 0.33,
Rf = 0.09 (CH2Cl2/MeOH = 8:1); mp 207 ꢁC; ½aꢁD ¼
24
CHCl3); 1H NMR (400 MHz, CDCl3) d 9.24 (br s,
1H), 8.04–8.02 (m, 2H), 7.94 (d, 1H, J = 7.5 Hz), 7.62–
7.58 (m, 1H), 7.48–7.44 (m, 3H), 6.25 (dd, 1H, J = 7.1,
1.6 Hz), 4.67–4.53 (m, 3H), 4.22 (dd, 1H, J = 35.0,
11.1), 2.85–2.62 (m, 2H), 2.26 (s, 3H); 13C NMR
(100 MHz, CDCl3) d 171.5, 166.1, 163.6, 155.5, 144.2,
134.0, 130.1, 129.3, 128.9, 102.1, 100.3, 96.8, 88.6,
77.0, 76.7, 64.9, 64.6, 41.9, 41.7, 25.2; HRMS (EI): calcd
(C18H18O5N3F) 375.1231, found 375.1232.
ꢀ78:0 (c 0.32, MeOH) {lit.5 ½aꢁD ¼ ꢀ75:8 (c 0.50,
MeOH)}; UV (H2O) kmax 270.3 nm (pH 7), 279.0 nm
(pH 2), 270.6 nm (pH 11); 1H NMR (400 MHz,
DMSO-d6) d 7.54 (d, 1H, J = 7.4 Hz), 7.11–7.03 (m,
2H), 6.03 (dd, 1H, J = 7.6, 2.5 Hz), 5.71 (d, H, J =
7.4 Hz), 5.24 (t, 1H, J = 5.7 Hz), 4.25 (dd, 1H, J =
20.9, 10.9 Hz), 3.94 (dd, 1H, J = 34.5, 10.9 Hz), 3.67–
3.58 (m, 2H), 2.62–2.07 (m, 2H); 13C NMR (100 MHz,
CD3OD) d 166.6, 157.2, 141.2, 141.1, 104.6, 102.8,
94.5, 87.9, 76.2, 75.9, 62.7, 62.5, 40.9, 40.7; HRMS
(EI): calcd (C9H12O3N3F) 229.0864, found 229.0863.
4.2.14. (ꢀ)-1-(30-O-Benzoyl-2,3-dideoxy-3-fluoroapio-b-
D-furanosyl)thymine (16a) and (ꢀ)-1-(30-O-Benzoyl-2,3-
dideoxy-3-fluoroapio-a-D-furanosyl)thymine 16b. Com-
pound 9 (400 mg, 1.5 mmol) was converted to 16a
(221 mg, 45%) and 16b (200 mg, 41%) as a white solid
according to the same procedure used for the prepara-
tion of 12a and 12b. Compound 16a: Rf = 0.38 (n-hex-
4.2.17. (ꢀ)-1-(2,3-Dideoxy-3-fluoroapio-b-D-furanosyl)-
thymine 17a. To a solution of 16a (180 mg, 0.52 mmol)
in MeOH (20 ml) was added sodium methoxide
(25 wt % solution in methanol, 0.2 ml) at room temper-
ature and the mixture was stirred for 3 h. The reaction
mixture was neutralized by the addition of several pieces
of dry ice and concentrated. The residue was purified by
silica gel column chromatography (CH2Cl2/MeOH =
1
ane/EtOAc = 1:1); H NMR (400 MHz, CDCl3) d 8.27
(br s, 1H), 8.06–8.03 (m, 2H), 7.63–7.59 (m, 1H), 7.49–
7.45 (m, 2H), 7.11 (d, 1H, J = 0.96 Hz), 6.14 (t, 1H,
J = 6.9 Hz), 4.73–4.57 (m, 2H), 4.42–4.23 (m, 2H),
2.87–2.80 (m, 1H), 2.53–2.47 (m, 1H), 1.92 (d, 3H,
J = 0.96 Hz); 13C NMR (100 MHz, CDCl3) d 166.2,
164.3, 150.7, 136.5, 134.0, 130.1, 129.5, 128.9, 111.6,
103.0, 101.2, 88.9, 75.9, 75.7, 65.4, 65.1, 40.9, 40.6,
12.8. Compound 16b: Rf = 0.30 (n-hexane/EtOAc =
10:1) to give 17a (85 mg, 68%) as a white solid: Rf =
20
0.45 (CH2Cl2/MeOH = 10:1); mp 181 ꢁC ½aꢁD ¼ ꢀ11:8
(c 0.11, MeOH); UV (H2O) kmax 266 nm (pH 7),
1
268 nm (pH 2), 268 nm (pH 11); H NMR (400 MHz,
DMSO-d6) d 11.31 (br s, 1H), 7.56 (d, 1H, J =
1.0 Hz), 6.14 (dd, 1H, J = 8.1, 6.4 Hz), 5.26 (br t, 1H),
4.21 (dd, 1H, J = 35.0, 10.5 Hz), 3.98–3.90 (m, 1H),
3.73–3.66 (m, 2H), 2.50–2.27 (m, 2H), 1.78 (d, 3H,
J = 1.0 Hz); 13C NMR (100 MHz, CD3OD) d 165.4,
151.2, 137.3, 110.7, 105.4, 103.6, 87.6, 75.3, 75.0, 63.0,
62.7, 39.5, 39.3, 11.3; HRMS (EI): calcd (C10H13N2O4F)
244.0860, found 244.0860.
1
1:1); H NMR (400 MHz, CDCl3) d 8.22 (br s, 1H),
8.06–8.03 (m, 2H), 7.64–7.60 (m, 1H), 7.50–7.46 (m,
2H), 7.35 (d, 1H, J = 1.1 Hz), 6.32 (dd, 1H, J = 7.8,
2.6 Hz) 4.70–4.53 (m, 2H), 4.54–4.47 (m, 1H), 4.04
(dd, 1H, J = 34.0, 11.1 Hz) 2.80–2.53 (m, 1H), 2.53–
2.47 (m, 1H), 1.95 (d, 3H, J = 0.96 Hz); 13C NMR
(100 MHz, CDCl3) d 166.2, 164.4, 150.9, 135.4, 134.1,
130.2, 129.3, 129.0, 111.5, 102.2, 100.4, 85.8, 75.9,
75.7, 64.9, 64.6, 41.5, 41.3, 13.1.
4.2.18. (ꢀ)-1-(2,3-Dideoxy-3-fluoroapio-a-D-furanosyl)-
thymine 17b. Compound 16b (100 mg, 0.29 mmol)
was converted to 17b (60 mg, 86%) as a white solid
according to the same procedure used for the prepara-
4.2.15. (+)-1-(2,3-Dideoxy-3-fluoroapio-b-D-furanosyl)-
cytosine 15a. To a solution of 14a (60 mg, 0.16 mmol)
in MeOH (4 ml) was added sodium methoxide (25 wt %
solution in methanol, 0.1 ml) at room temperature and
the mixture was stirred for 2 h. The reaction mixture
was neutralized with methanol saturated with HCl gas
and concentrated. The residue was purified by silica
gel column chromatography (CH2Cl2/MeOH = 8:1) to
tion of 17a: Rf = 0.43 (CH2Cl2/MeOH = 10:1); mp
20
153 ꢁC ½aꢁD ¼ ꢀ14:8 (c 0.11, MeOH); UV (H2O) kmax
268 nm (pH 7), 268 nm (pH 2), 266 nm (pH 11); 1H
NMR (400 MHz, DMSO-d6) d 11.30 (br s, 1H), 7.39
(d, 1H, J = 1.0 Hz), 6.08 (dd, 1H, J = 7.8, 3.0 Hz), 5.27
(br t, 1H), 4.30–4.22 (m, 1H), 3.89 (dd, 1H, J = 33.9,
10.9 Hz), 3.68–3.59 (m, 2H), 2.64–2.49 (m, 1H), 2.23–
2.17 (m, 1H), 1.77 (d, 3H, J = 373 1.0 Hz); 13C NMR
(100 MHz, CD3OD) d 165.4, 151.2, 136.5, 110.2, 104.6,
102.9, 86.3, 75.7, 75.4, 62.8, 62.5, 40.2, 40.0, 11.6; HRMS
(EI): calcd (C10H13N2O4F) 244.0860, found 244.0859.
give 15a (34 mg, 93%) as a white solid: Rf = 0.11
20
(CHCl2/MeOH = 8:1); mp 85 ꢁC; ½aꢁD ¼ þ48:7 (c 0.17,
24
MeOH) {lit.5 ½aꢁD ¼ þ41:1 (c 0.48, MeOH)}; UV
(H2O) kmax 271.3 nm (pH 7), 278.6 nm (pH 2),
1
270.8 nm (pH 11); H NMR (400 MHz, DMSO-d6) d
7.60 (d, 1H, J = 7.4 Hz), 7.16–7.08 (m, 2H), 6.10 (t,
1H, J = 7.5 Hz), 5.70 (d, 1H, J = 7.4 Hz), 5.23 (t, 1H,
J = 5.8 Hz), 4.19 (dd, 1H, J = 35.0, 10.4 Hz), 3.94 (dd,
1H, J = 22.0, 10.4 Hz), 3.71–3.63 (m, 2H), 2.48–2.18
(m, 2H); 13C NMR (100 MHz, CD3OD) d 166.5,
157.3, 141.5, 105.3, 103.6, 95.4, 88.4, 75.3, 75.0, 62.9,
Acknowledgments
We are grateful to Drs. E. Fogassy and J. Balint at
Technical University of Budapest (Hungary) for their
determination of optical purity through chiral HPLC.