F. Seela et al. / Tetrahedron 63 (2007) 3471–3482
3481
8ꢂ2.5 cm, CH2Cl2–CH3OH 4:1), furnishing a colorless
solid. Crystallization from MeOH–CH2Cl2 afforded slightly
pink crystals (120 mg, 81%); mp 188 ꢀC (dec.); TLC: Rf
(CH2Cl2–CH3OH 4:1) 0.45. UV (MeOH): lmax(3) 344
1H NMR (DMSO-d6): 1.76–1.81 (m, 2H, CH2); 1.98 (m,
1H, Ha-C(20)); 2.19–2.33 (m, 3H, CH2, Hb-C(20)); 2.59–
2.64 (t, J¼6.7 Hz, 2H, CH2); 2.83 (s, 1H, C^CH), 3.63
(m, 2H, H2-C(50)); 3.86 (m, 1H, H-C(40)); 4.23 (m, 1H, H-
C(30)); 5.10 (m, 1H, OH-C(50)); 5.25 (m, 1H, OH-C(30));
5.93 (s, 1H, H-C(7)); 6.25 (t, J¼6.10 Hz, 1H, H-C(10));
8.51 (s, 1H, H-C(6)); 11.1 (s, 1H, H-N(7)). Anal. Calcd for
C16H19N3O4 (317.34): C, 60.56; H, 6.03; N, 13.24. Found:
C, 60.46; H, 6.04; N, 13.08.
1
(3100), 274 (3800), 227 (21,500). H NMR (DMSO-d6):
3.61–3.82 (m, 2H, H2-C(50)); 3.94–3.99 (m 3H, H-C(40),
H-C(20), H-C(30)); 5.00 (s, 1H, OH-C(50)); 5.23 (s, 1H,
OH-C(30)); 5.48 (s, 1H, OH-C(20)); 5.92 (s, 1H, H-C(10));
6.20 (d, J¼3.4 Hz, 1H, H-C(5)); 7.10 (d, J¼3.4 Hz, 1H, H-
C(6)); 8.81 (s, 1H, H-C(4)); 11.16 (br s, 1H, H-N(7)).
Anal. Calcd for C11H13N3O5 (267.24): C, 49.44; H, 4.90;
N, 15.72. Found: C, 49.22; H, 5.10; N, 15.55.
Acknowledgements
We thank Mrs. Simone Budow for measuring some of the
NMR spectra and Mr. Gabiele De Paoli for his help in fluo-
rescence measurement. Financial support by ChemBiotech
is gratefully acknowledged.
4.1.3.7. 5-(Hept-1,6-diynyl)-20-deoxyuridine (16). To
a
suspension of 5-iodo-20-deoxyuridine (15, 0.5 g,
1.41 mmol) and CuI (54 mg, 0.28 mmol) in anhydrous
DMF (8 mL) were added successively 1,6-heptadiyne
(1.3 g, 14.1 mmol), anhydrous Et3N (283 mg, 2.8 mmol),
and Pd(0)(PPh3)4 (162 mg, 0.14 mmol). The mixture was
stirred at rt for 16 h under argon atmosphere. The reaction
mixture was diluted with MeOH–CH2Cl2 (1:1, 30 mL),
and Dowex 1X8 (100–200 mesh; 0.5 g, bicarbonate form)
was introduced. After additional stirring for 1 h, the mixture
was filtered and the resin washed with MeOH–CH2Cl2 1:1,
50 mL. The combined filtrates were evaporated, and the
residue was purified by FC (silica gel, column 15ꢂ3 cm,
CH2Cl2–MeOH 96:4) affording 16 as a colorless amorphous
solid (0.34 g, 76%). TLC: Rf (CH2Cl2–MeOH 9:1) 0.50. UV
(MeOH): lmax(3) 229 (14,500), 292 (14,800). 1H NMR
(DMSO-d6): 1.69–1.73 (m, 2H, CH2); 2.14–2.47 (m, 6H,
2CH2, H2-C(20)); 2.87 (s, 1H, C^CH); 3.63 (m, 2H, H2-
C(50)); 3.83 (m, 1H, H-C(40)); 4.27 (m, 1H, H-C(30)); 5.15
(m, 1H, OH-C(50)); 5.29 (m, 1H, OH-C(30)); 6.15 (m, 1H,
H-C(10)); 8.19 (s, 1H, H-C(6)); 11.62 (s, 1H, H-N(7)).
Anal. Calcd for C16H18N2O5 (318.12): C, 60.37; H, 5.70;
N, 8.80. Found: C, 60.26; H, 5.75; N, 8.85.
References and notes
1. Callis, P. R. Annu. Rev. Phys. Chem. 1983, 34, 329–357.
2. Ward, D. C.; Reich, E. J. Biol. Chem. 1969, 244, 1228–1237.
3. Seela, F.; Steker, H.; Driller, H.; Bindig, U. Liebigs Ann. Chem.
1987, 15–19.
4. Seela, F.; Steker, H. Liebigs Ann. Chem. 1984, 1719–1730.
5. Seela, F.; Chen, Y.; Bindig, U.; Kazimierczuk, Z. Helv. Chim.
Acta 1994, 77, 194–202.
6. (a) Lindahl, T. Nature 1993, 362, 709–715; (b) Wierzchowski,
J.; Wielgus-Kutrowska, B.; Shugar, D. Biochim. Biophys. Acta
1996, 1290, 9–17.
7. Winkeler, H.-D.; Seela, F. Liebigs Ann. Chem. 1984, 708–721.
8. Seela, F.; Chen, Y. Helv. Chim. Acta 1997, 80, 1073–1086.
9. Seela, F.; Zulauf, M.; Sauer, M.; Deimel, M. Helv. Chim. Acta
2000, 83, 910–927.
10. Okamoto, A.; Tanaka, K.; Fukuta, T.; Saito, I. J. Am. Chem.
Soc. 2003, 125, 9296–9297.
11. Okamoto, A.; Tanaka, K.; Saito, I. J. Am. Chem. Soc. 2004,
126, 9458–9463.
4.1.3.8.
3-(2-Deoxy-b-D-erythro-pentofuranosyl)-6-
pentyn-1-yl-furo[2,3-d]pyrimidin-3H-2-one (17). To a
solution of compound 16 (200 mg, 0.63 mmol) in Et3N–
MeOH (3:7, 30 mL) was added CuI (21 mg, 0.11 mmol)
and the mixture was refluxed for 6 h. The solvent was evap-
orated in vacuo and the crude product was purified by FC
(silica gel, column 15ꢂ3 cm, CH2Cl2–MeOH, 95:5) to
give a colorless amorphous solid (180 mg, 90%); TLC: Rf
(CH2Cl2–MeOH 9:1) 0.45. UV (MeOH): lmax(3) 244
12. Woo, J.; Meyer, R. B., Jr.; Gamper, H. B. Nucleic Acids Res.
1996, 24, 2470–2475.
13. Secrist, J. A., III; Barrio, J. R.; Leonard, N. J.; Weber, G.
Biochemistry 1972, 11, 3499–3506.
14. Srivastava, S. C.; Raza, S. K.; Misra, R. Nucleic Acids Res.
1994, 22, 1296–1304.
15. Zhang, W.; Rieger, R.; Iden, C.; Johnson, F. Chem. Res.
Toxicol. 1995, 8, 148–156.
16. (a) Kasai, H.; Goto, M.; Ikeda, K.; Zama, M.; Mizuno, Y.;
Takemura, S.; Matsuura, S.; Sugimoto, T.; Goto, T.
Biochemistry 1976, 15, 898–904; (b) Sattsangi, P. D.;
Leonard, N. J.; Frihart, C. R. J. Org. Chem. 1977, 42, 3292–
3296.
1
(10,000), 331 (5600). H NMR (DMSO-d6): 1.79 (m, 2H,
CH2); 2.04 (m, 1H, Ha-C(20)); 2.23 (m, 2H, CH2); 2.26
(m, 1H, Hb-C(20)); 2.73 (t, J¼7.4 Hz, 2H, CH2); 2.84 (s,
1H, C^CH); 3.35 (m, 2H, H2-C(50)); 3.89 (m, 1H, H-
C(40)); 4.22 (m, 3H, H-C(30)); 5.13 (m, 1H, OH-C(50));
5.28 (1H, OH-C(30)); 6.16 (t, J¼6.10 Hz, 1H, H-C(10));
6.47 (s, 1H, H-C(5)); 8.68 (s, 1H, H-C(4)).
17. Bazin, H.; Zhou, X.-X.; Glemarec, C.; Chattopadhyaya, J.
Tetrahedron Lett. 1987, 28, 3275–3278.
18. Seela, F.; Bussmann, W. Tetrahedron 1985, 41, 935–940.
19. Inoue, Y.; Kuramochi, T.; Imakubo, K. Chem. Lett. 1981,
1161–1164.
20. (a) Sugiyama, T.; Schweinberger, E.; Kazimierczuk, Z.;
Ramzaeva, N.; Rosemeyer, H.; Seela, F. Chem.—Eur. J.
2000, 6, 369–378; (b) Yip, K.-F.; Tsou, K.-C. J. Org. Chem.
1975, 40, 1066–1070.
21. (a) Seela, F.; Lindner, M.; Glac¸on, V.; Lin, W. J. Org. Chem.
2004, 69, 4695–4700; (b) Lin, W.; Li, H.; Ming, X.; Seela, F.
Org. Biomol. Chem. 2005, 3, 1714–1718; (c) Bhat, G. A.;
4.1.3.9.
3-(2-Deoxy-b-D-erythro-pentofuranosyl)-
3,7-dihydro-6-pentyn-1-yl-pyrrolo[2,3-d]pyrimidin-2-one
(7d). Compound 17 (200 mg, 0.62 mmol) was dissolved in
concd aqueous NH3 (30 mL) and the reaction mixture was
stirred at rt overnight. The resulting solution was concen-
trated and the residue applied to FC (silica gel, column
15ꢂ3 cm, CH2Cl2–MeOH 9:1) to give 7d as a colorless
foam (184 mg, 92%). TLC: Rf (CH2Cl2–MeOH 9:1) 0.21.
UV (MeOH): lmax 229 (24,600), 262 (4000), 343 (4000).