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I. Krizmanic et al. / Tetrahedron 59 (2003) 4047–4057
4054
3300 (s), 3210 (s), 1640 (s), 1620 (s), 1540 (s), 1450 (s), 1400
(m), 1300 (m), 1265 (s), 1205 (m); 1H NMR (DMSO-d6) d/
ppm: 7.82 (d, 2H, J¼8.0 Hz, Ts-b), 7.71 (brd, 2H, J¼7.3 Hz,
H-6 and NH), 7.57 (brs, 1H, NH), 7.18 (d, 2H, J¼8.0 Hz,
Ts-c), 6.21 (d, 1H, J¼3.3 Hz, H-10),0 5.88 (d, 1H, J¼7.3 Hz,
H-5), 5.51 (brd, 2H, J¼3.3 Hz, OH-20and OH-30), 5.05 (t, 1H,
J¼5 Hz, OH-50), 4.02 (brs, 1H, H-2 ), 3.88 (brs,0 1H, H-300),
3.78 (brs, 1H, H-40), 3.57 (brt, 2H, J¼4.7 Hz, H-5a and H-5b)
2.30(s, 3H, CH3-Ts); 13C NMR (DMSO-d6) d/ppm: 162.85 (s,
C-4), 153.20 (s, C-2), 143.04 (d, C-6), 141.27 (s, Ts-d), 140.49
(s, Ts-a), 128.30 (d, Ts-c), 127.98 (d, Ts-b), 95.18 (d, C-5),
87.49 (d, C-10), 86.03 (d, C-40), 76.59 (d, C-30), 74.37 (d, C-20),
61.28 (t, C-50), 21.06 (q, CH3 –Ts); Anal. calcd for
C16H20N4O6S (Mr¼396.41): C 48.36, H 5.25, N 14.08%;
found: C 48.48, H 5.09, N 14.13%.
added to a stirred solution of p-toluensulfonamide 2
(549 mg, 3.2 mmol) and sodium hydride (70 mg, 55% in
oil, 1.6 mmol) in dimethylformamide (7 mL). The mixture
was stirred at 1108C for 3 h, and evaporated to dryness. The
residue was purified by preparative chromatography
(EtOAc/acetone/EtOH/H2O 15:3:2:2) yielding 204 mg
(32%) of N 2-tosylarabinoisocytidine 7, as solid foam.
(b) To a stirred solution of p-toluensulfonamide 2 (2.84 g,
16.6 mmol) and DBU (2.5 mL, 16.6 mmol) in dry aceto-
nitrile (11 mL), 2,20-anhydro-1-(b-D-arabinofuranosyl)ura-
cil 6 (1.88 g, 8.3 mmol) was added. The reaction mixture
was refluxed for 72 h, cooled and treated with a small
amount of methanol. The starting material was filtered off,
and the filtrate was evaporated. The residue was purified by
preparative chromatography on a funnel (CH2Cl2/MeOH
9:1), yielding 1.62 g (49%) of N1-{1-[3,4-dihydroxy-5-
(hydroxymethyl)tetrahydro-2-furanyl]-4-oxo-1,4-dihydro-
2-pyrimidinyl}-4-methyl-1-benzenesulfonamide (7), in the
form solid foam: Rf¼0.81 (EtOAc/acetone/EtOH/H2O
4:1:1:1); UV (MeOH) lmax/nm: 227, 243, and 265 (sh),
Crystals for X-ray. The compound 3 sample was dissolved
in hot methanol, and after storage at 188C, for 48 h, gave
colorless crystals (prisms).
4.4.3. 4-Imino-N 2-[({3-[(dimethylamino)carbonyl]-2-
pyridinyl(sulfonyl)amino]-1-(b-D-arabinofuranosyl)pyri-
midine 5. To a mixture of 2-aminosulfonyl-3-(N,N-dimethyl-
log 1/dm3 mol21 cm21: 4.08, 4.08, and 3.83; IR (KBr) nmax
/
cm21: 3582 (s), 3511 (s), 3286 (s), 2921 (m), 1690 (s), 1598
(s), 1468 (m), 1365 (m), 1296 (s), 1121 (s), 1101 (s), 1064
aminocarbonyl)pyridine13
4
(175 mg, 0.8 mmol) and
1
dimethylformamide (3 mL), sodium hydride (35 mg, 55% in
oil, 0.8 mmol) and 2,20-anhydro-1-(b-D-arabinofuranosyl)-
cytosine hydrochloride 1 (105 mg, 0.4 mmol) were added
under stirring. The mixture was stirred at room temperature
for 2 h and evaporated. The residue was purified by
preparative chromatography (CH2Cl2/MeOH 3:1) yielding
131 mg (82%) of N3,N3-dimethyl-2-[({1-[3,4-dihydroxy-5-
(hydroxymethyl)tetrahydro-2-furanyl]-4-imino-1,4-dihydro-
2-pyrimidinyl}amino)sulfonyl]nicotinamide (5), as white
crystals: mp¼1908C; Rf¼0.59 (CH2Cl2/MeOH 3:1); UV
(MeOH) lmax/nm: 232 and 270 (sh), log 1/dm3 mol21
cm21: 4.32 and 3.89; IR (KBr) nmax/cm21: 3340 (s, br),
3200 (s), 2910 (m), 1641 (s, br), 1550 (m), 1480 (s), 1410
(m), 1380 (m), 1160 (m), 1112 (s); 1H NMR (DMSO-d6) d/
ppm: 8.53 (d, 1H, J¼4.3 Hz, H-6–Py), 7.75 (d, 1H,
J¼7.7 Hz, H-6), 7.70 (d, 1H, J¼7.0 Hz, H-4–Py), 7.50
(dd, 1H, J¼4.3, 7.0 Hz H-5–Py), 7.36 (brs, 1H, NH), 7.15
(brs, 1H, NH), 6.21 (t, 1H, J¼4.3 Hz H-10), 5.87 (d, 1H,
J¼7.7 Hz, H-5), 5.52 (brd, 2H, J¼3.3 Hz, OH-20and OH-
30), 5.04 (brs, 1H, OH-50), 4.06 (brs, 1H, H-20), 3.89 (brs,
1H, H-30), 3.79 (brs, 1H, H-40), 3.58 (brs, 2H, 2H-50) 2.93 (s,
3H, CH3–N), 2.73 (s, 3H, CH3–N); 13C NMR (DMSO-d6)
d/ppm: 168.03 (s, CvO–Py), 162.61 (s, C-4), 156.26 (s,
C-2–Py), 153.64 (s, C-2), 148.87 (d, C-6–Py), 142.90 (d,
C-6), 136.34 (d, C-4–Py), 131.41 (s, C-3–Py), 125.45 (0d,
C-5–Py), 95.41 (d, C-5), 87.37 (d, C-10), 85.84 (d, C-4 ),
76.27 (d, C-30), 74.76 (d, C-20), 61.08 (t, C-50), 38.48 (q,
CH3–N), 34.47 (q, CH3–N). Anal. calcd for C17H22N6O7S
(Mr¼454.47): C 36.58, H 5.47,N 15.14%; found: C 36.86, H
5.54, N 15.18%.
(s), 1009 (s); H NMR (DMSO-d6) d/ppm: 10.63 (brs, 1H,
NH), 7.79 (d, 2H, J¼8 Hz, Ts-b), 7.76 (d, 1H, J¼8.3 Hz,
H-6), 7.36 (d, 2H, J¼8.0 Hz, Ts-c), 6.01 (d, 1H, J¼3.7 Hz
H-10), 5.89 (d, 1H, J¼8.3 Hz, H-5), 5.58 (brs, 1H, OH-20),
5.00 (brs, 1H, OH-30), 5.00 (br s, 1H, OH-50), 3.97 (brs, 1H,
H-20), 3.86 (brs, 1H, H-30), 3.78 (d, 1H, J¼2.9 Hz, H-40),
3.57 (pd, 2H, J¼5.3 Hz, H-5a0 and H-5b0 ) 2.36 (s, 3H, CH3–
Ts); 13C NMR (DMSO-d6) d/ppm: 159.28 (s, C-4), 148.58
(s, C-2), 143.09 (s, Ts-d), 142.95 (d, C-6), 139.49 (s, Ts-a),
129.75 (d, Ts-c), 125.86 (d, Ts-b), 1002.53 (d, C-5), 87.61 (d,
C-10), 86.43 (d, C-40), 75.80 (d, C-3 ), 74.95 (d, C-20), 60.89
(t, C-50), 21.09 (q, CH3–Ts). Anal. calcd for C16H19N3O7S x
2H2O (Mr¼433.45): C 44.34, H 5.23, N 9.69%; found: C
44.02, H 4.77, N 9.61%.
4.4.6. 50-O-Trityl-2,30-anhydro-1-(2-deoxy-b-D-threo-
pentofuranosyl)thymine 8. Following the reported pro-
cedure for the synthesis of 2,30-anhydro-1-(2-deoxy-5-O-
trityl-b-D-threo-pentofuranosyl)-6-methyluracil,15b trityl-
ation and subsequent mesylation afforded 30-mesyl-50-O-
trityl-thymidine (70%), which was converted into 2,30-
anhydro derivative 8 by treatment with DBU/CH3CN
(82%). The product 4-methyl-10-[(trityloxy)methyl]-8,11-
dioxa-2,6-diazatricyclo[7.2.1.02,7]dodeca-3,6-dien-5-one
(8) was isolated as a white solid: m.p.¼229–2308C (lit.15c
mp¼226–2278C).
4.4.7. 2,30-Anhydro-1-(2-deoxy-b-D-threo-pentofurano-
syl)thymine 12. The starting material 10-(hydroxy-
methyl)-4-methyl-8,11-dioxa-2,6-diazatricyclo(7.2.1.02,7
-
(dodeca-3,6-dien-5-one (12) was prepared by treatment of
30-mesylthymidine with DBU/CH3CN in 65% yield;
mp¼230–2318C (lit.16b 235–2378C).
4.4.8. 50-O-t-Butyldimethylsilyl-2,30-anhydro-1-(2-deoxy-
b-D-threo-pentofuranosyl)thymine 13. Synthesis of 10-
({[1-(tert-butyl)-1,1-dimethylsilyl]oxy}methyl)-4-methyl-
8,11-dioxa-2,6-diazatricyclo[7.2.1.02,7]dodeca-3,6-dien-5-
one (13) was achieved by treatment of 30-mesyl-50-TBDMS
4.4.4. 2,20-Anhydro-1-(b-D-arabinofuranosyl)uracil 6.
The product 3-hydroxy-2-(hydroxymethyl)-2,3,3a,9a-tetra-
hydro-6H-furo(2,3-d(pyrimido(2,1-b(oxazol-6-one (6) was
isolated in quantitative yield.14 The resulting white solid
had mp¼2348C (lit.14 mp¼234–2378C).
4.4.5. N 2-Tosylarabinoisocytidine 7. (a) 2,20-Anhydro-1-
(b-D-arabinofuranosyl)uracil 6 (362 mg, 1.6 mmol) was