5440
M. Koszytkowska-Stawiꢀnska, W. Sas / Tetrahedron Letters 45 (2004) 5437–5440
14. Madec-Lougerstay, R.; Florent, J.-C.; Monneret, C.
J. Chem. Soc., Perkin Trans. 1 1999, 1369–1376.
15. We named nucleosides B as aza-analogues of ganciclovir
due to the structural similarity of sugar mimics B and
parent ganciclovir, independently of the kind of base.
16. Iley, J.; Moreira, R.; Rosa, E. J. Chem. Soc., Perkin Trans.
2 1991, 563–570.
17. Lopes, F.; Moreira, R.; Iley, J. Bioorg. Med. Chem. 2000,
8, 707–716.
18. The pivaloyloxymethyl group is met frequently in many
prodrugs; for example, see: Refs. 16,17; Calheiros, T.; Iley,
J.; Lopes, F.; Moreira, R. Bioorg. Med. Chem. Lett. 1995,
CHCl3/MeOH were used as eluting solvents) or by
crystallization (3ab0) to yield the corresponding nucleoside
3. Crude 3ac0 was submitted to deprotection with conc.
NH3 (aq) in methanol.
ꢀ
25. Koszytkowska-Stawinska, M.; Sas, W. J. Chem. Res. (S)
1996, 162–163.
26. Mironiuk-Puchalska, E.; Kołaczkowska, E.; Sas, W.
Tetrahedron Lett. 2002, 43, 8351–8354.
27. The derivative C was formed when 7b was treated with
TMSOTf itself, BF3ÆOEt2, or AlCl3 in MeCN. The
explanation for how C arises will be reported in a full
paper.
ꢀ ꢀ
5, 937–940; Anastasi, C.; Quelever, G.; Burlet, S.; Garino,
28. Nucleoside 10a was obtained by the procedure employed
for the synthesis of 3ac0.23 10b was obtained in similar way
as 3bd0 but TMSOTf was replaced by tin(IV) chloride. 10a
(flash chromatography: CH2Cl2/MeOH, 98/2, v/v; 71%,
foam). dH (200 MHz, CDCl3): 1.18 (s, 18H), 3.06 (s, 3H),
4.32 (m, 5H), 5.49 (s, 2H), 7.55 (m, 4H), 7.90(m, 2H), 8.17
(d, 3J ¼ 7:6, 1H), 8.78 (bs, 1H); dC (50MHz, CDCl 3):
27.26, 38.89, 41.85, 56.67, 58.42, 62.04, 97.77, 127.74,
129.22, 132.94, 133.51, 148.41, 155.75, 163.00, 178.05; IR
(KBr), m (cmꢀ1): 3308, 2976, 2932, 1732, 1696, 1676, 1556,
1484, 1340, 1312, 1276, 1252, 1148; HRMS (ESI, MeOH):
565.2327 calcd for C26H37N4O8S (M+H)þ, found
565.2346. 10b (flash chromatography CHCl3/acetone, 98/
2, v/v, 44%, foam) dH (200 MHz, CDCl3): 1.08 (m, 18H),
2.96 (s, 3H), 4.27 (m, 5H), 5.28 (s, 2H), 5.75 (s, 2H), 7.45
(m, 5H), 8.43 (s, 1H), 8.74 (s, 1H), 9.26 (bs, 1H); dC
(50MHz, CDCl 3): 27.07, 38.72, 41.98, 52.05, 56.08, 61.93,
67.83, 121.36, 128.51, 128.62, 135.46, 143.54, 149.87,
151.02, 151.16, 153.17, 177.84; IR (KBr), m (cmꢀ1): 2976,
1732, 1616, 1588, 1472, 1340, 1284, 1212, 1148; HRMS
(ESI, MeOH): 641.2364 calcd for C28H38N6O8NaS
(M+Na)þ, found 641.2380.
C.; Souard, F.; Krus, J.-L. Curr. Med. Chem. 2003, 10,
1825–1843; Calogeropoulou, T.; Detsi, A.; Lekkas, E.;
Koufaki, M. Curr. Med. Top. Chem. 2003, 3, 1467–
1495.
19. All new compounds were fully characterized by HRMS,
1
IR, H and 13C NMR spectroscopy.
€
20. Vorbuggen, H.; Ruh-Pohlenz, C. Handbook of Nucleoside
Synthesis; John Wiley: New York, 2001; pp 29–33 and
110–140.
€
€
21. Bohringer, M.; Roth, H.-J.; Hunziker, J.; Gobel, M.;
Krishnan, R.; Giger, A.; Schweizer, B.; Schreiber, J.;
Leumann, C.; Eschenmoser, A. Helv. Chim. Acta 1992, 75,
1416–1477; Wright, G. E.; Dudycz, L. W. J. Med. Chem.
€
1984, 27, 175–181; Tarkoy, M.; Bolli, M.; Schweizer, B.;
Leumann, C. Helv. Chim. Acta 1993, 76, 481–510;
Augustyns, K.; Rozenski, J.; Van Aerschot, A.; Janssen,
G.; Herdewijn, P. J. Org. Chem. 1993, 58, 2977–2982;
Shoning, K.-V.; Scholz, P.; Wu, X.; Guntha, S.; Delgado,
G.; Krishnamurthy, R.; Eschenmoser, A. Helv. Chim.
Acta 2002, 85, 4111–4153.
€
22. Thomson, S. A.; Josey, J. A.; Cadilla, R.; Gaul, M. D.;
Hassman, C. F.; Luzzio, M. J.; Pipe, A. J.; Reed, K. L.;
Ricca, D. J.; Wiethe, R. W.; Noble, S. A. Tetrahedron
1995, 51, 6179–6194.
23. Zou, R.; Robins, M. J. Can. J. Chem. 1987, 65, 1436–1437;
Robins, M. J.; Zou, R.; Guo, Z.; Wnuk, S. F. J. Org.
Chem. 1996, 61, 9207–9212; Dalpozzo, R.; DeNino, A.;
Maiuolo, L.; Procopio, A.; De Munno, G.; Sindona, G.
Tetrahedron 2001, 57, 4035–4038.
29. Heating 10a with conc. NH3 (aq) and MeOH in a sealed
tube at 70 °C for 24 h afforded after solvent removal, a
residue, which was purified by flash chromatography
(acetone/MeOH/NH3 (aq), 6/1/0.4, v/v/v) giving 11a (mp
212–222 °C dec.). dH (200 MHz, DMSO-d6): 3.06 (s, 3H),
3.44 (m, 4H), 3.79 (m, 1H), 4.90(m, 2H), 5.19 (s, 2H), 5.76
3
(d, 3J ¼ 7:4, 1H), 7.22 (2H, br s, 2H), 7.63 (d, J ¼ 7:4,
1H); dC (50MHz, DMSO- d6): 39.94, 55.49, 59.57, 62.04,
94.60, 143.88, 155.63, 165.81; IR (KBr), m (cmꢀ1): 3504,
3428, 3348, 3140, 1680, 1616, 1512, 1320, 1148; HRMS
(ESI, MeOH): 293.0914 calcd for C9H17N4O5S (M+H)þ,
found 293.0925.
24. General procedure for synthesis of azaacyclic nucleosides
3: A mixture of the pyrimidine base (2.0mmol) and BSA
(4.0mmol, 1.0cm ) in dry acetonitrile (10cm 3) was stirred
3
at room temperature under an argon atmosphere for 1 h,
then a solution of 2 (1.0mmol) in acetonitrile (1 cm 3) and
TMSOTf (1.66 mmol) were added successively. For the
synthesis of purine nucleosides 3d0,e0 the molar ratio of
base/BSA/2/TMSOTf was 2/5.7/1.0/1.66, respectively. The
reaction mixture was left for 24 h at room temperature,
then CHCl3 (50cm 3) and a saturated solution of sodium
carbonate (1 cm3) were added successively. The mixture
was stirred for 1 h, then filtered through a Celite pad. The
organic phase was separated, washed with water, brine
and dried with anhydrous magnesium sulfate. The crude
nucleosides were purified by flash chromatography (SiO2,
200-400 mesh, various mixtures of CHCl3/acetone or
30. Compound 10b was hydrogenated in MeOH in the
presence of 10% Pd/C under ambient pressure at room
temperature for 2 d, then treated with ammonia as above
to yield after flash chromatography 11b (CHCl3/MeOH,
9:1, v/v, 73%, mp 240–242 °C). dH (200 MHz, DMSO-d6):
3.10(s, 3H), 3.47 (m, 4H), 3.82 (m, 1H), 5.00(t, 3J ¼ 5:4,
2H), 5.65 (s, 2H), 7.36 (bs, 2H), 8.13 (s, 1H), 8.19 (s, 1H);
dC (50MHz, DMSO- d6): 39.97, 51.47, 59.50, 61.93, 118.34,
140.29, 149.05, 152.67, 156.08; IR (KBr), m (cmꢀ1): 3324,
3160, 1664, 1600, 1332, 1152; HRMS (ESI, MeOH):
317.1027 calcd for C10H17N6O4S (M+H)þ, found
317.1042.