PAPER
Synthesis of 5¢-Deoxytubercidin and Its Analogues
1445
13C NMR (100 MHz, CDCl3): d = 19.3, 20.7, 20.9, 73.7, 74.7, 78.6,
1H NMR (400 MHz, DMSO-d6): d = 1.27 (d, J = 6.0 Hz, 3 H,
CHCH3), 3.85–3.91 (m, 2 H, H-3¢, 4¢), 4.36 (s, 1 H, H-2¢), 5.08 (br
s, 1 H, 3¢-OH), 5.30 (br s, 1 H, 2¢-OH), 6.01 (d, J = 4.4 Hz, 1 H, H-
1¢), 6.61 (d, J = 4.0 Hz, 1 H, H-5), 7.01 (br s, 2 H, 4-NH2), 7.26 (d,
J = 3.6 Hz, 1 H, H-6), 8.06 (s, 1 H, H-2).
86.5, 106.5, 115.1, 124.0, 150.6, 152.0, 152.7, 169.7, 170.0.
4-Amino-5-iodo-7-(5-deoxy-b-D-ribofuranosyl)-7H-pyrro-
lo[2,3-d]pyrimidine (4a); Typical Procedure
A solution of 8a (18.2 g, 37.9 mmol) in methanolic ammonia
(MeOH saturated with NH3 at 0 °C, 360 mL) was placed in an au-
toclave and stirred at 130 °C for 12 h. After cooling, the mixture was
concentrated to dryness and the residue was purified over a silica
gel column (CH2Cl2–MeOH, 20:1) to afford 4a; yield: 11.5 g
(81%); white crystals; Rf = 0.51 (CH2Cl2–MeOH, 15:1); mp 242–
243 °C.
13C NMR (100 MHz, DMSO-d6): d = 19.9 (C-5¢), 74.6 (C-2¢), 75.7
(C-3¢), 79.6 (C-4¢), 88.3 (C-1¢), 100.9 (C-5), 103.7 (C-4a), 122.5 (C-
6), 151.2 (C-7a), 152.6 (C-2), 158.3 (C-4).
HRMS (ESI): m/z calcd for [M + H]+ C11H14N4O3: 251.1139; found:
251.1134.
1H NMR (400 MHz, DMSO-d6): d = 1.27 (d, J = 6.4 Hz, 3 H,
CHCH3), 3.85 (m, 1 H, H-3¢), 3.92 (m, 1 H, H-4¢), 4.39 (d, J = 3.6
Hz, 1 H, H-2¢), 5.10 (s, 1 H, 3¢-OH), 5.32 (s, 1 H, 2¢-OH), 6.00 (d,
J = 5.2 Hz, 1 H, H-1¢), 6.67 (br s, 2 H, 4-NH2), 7.61 (s, 1 H, H-6),
8.11 (s, 1 H, H-2).
13C NMR (100 MHz, DMSO-d6): d = 20.0 (C-5¢), 53.1 (C-5), 74.3
(C-2¢), 75.5 (C-3¢), 80.2 (C-4¢), 88.0 (C-1¢), 104.1 (C-4a), 127.9 (C-
6), 151.3 (C-7a), 153.0 (C-2), 158.1 (C-4).
Supporting Information for this article is available online at
Acknowledgment
This work was supported by the Chinese Ministry of Education, the
NSF of China (No. 20972086, 20962009), and SRFDP (No.
20090002110060).
HRMS (ESI): m/z calcd for [M + Na]+ C11H13IN4O3 + Na:
398.9925; found: 398.9923.
References
4-Amino-5-bromo-7-(5-deoxy-b-D-ribofuranosyl)-7H-pyrro-
lo[2,3-d]pyrimidine (4b)
Compound 4b was prepared as described for 4a starting from 8b
(19.5 g, 45.1 mmol); yield: 11.9 g (80%); white crystals; Rf = 0.45
(CH2Cl2–MeOH, 15:1); mp 254–255 °C.
1H NMR (400 MHz, DMSO-d6): d = 1.27 (d, J = 6.4 Hz, 3 H,
CHCH3), 3.85 (m, 1 H, H-3¢), 3.92 (m, 1 H, H-4¢), 4.39 (t, J = 10.8,
5.6 Hz, 1 H, H-2¢), 5.11 (d, J = 5.2 Hz, 1 H, 3¢-OH), 5.34 (d, J = 5.2
Hz, 1 H, 2¢-OH), 6.03 (d, J = 5.2 Hz, 1 H, H-1¢), 6.80 (br s, 2 H, 4-
NH2), 7.59 (s, 1 H, H-6), 8.12 (s, 1 H, H-2).
13C NMR (100 MHz, DMSO-d6): d = 20.0 (C-5¢), 74.3 (C-2¢), 75.5
(C-3¢), 80.2 (C-4¢), 87.97 (C-1¢), 88.03 (C-5), 101.9 (C-4a), 122.6
(C-6), 150.7 (C-7a), 153.5 (C-2), 157.9 (C-4).
(1) Sagar, S.; Kaur, M.; Minneman, K. P. Mar. Drugs 2010, 8,
2619.
(2) (a) Seela, F.; Peng, X. H. Curr. Top. Med. Chem. 2006, 6,
867. (b) Seela, F.; Peng, X. H.; Budow, S. Curr. Org. Chem.
2007, 11, 427. (c) Taylor, E. C.; Kuhnt, D.; Shih, C.; Rinzel,
S. M.; Grindey, G. B.; Barredo, J.; Jannatipour, M.; Moran,
R. G. J. Med. Chem. 1992, 35, 4450.
(3) Changelian, P. S.; Flanagan, M. E.; Ball, D.; Kent, C. R.;
Borie, D. C. Science 2003, 302, 875.
(4) (a) Nakamura, G. J. Antibiot. 1961, 14A, 90. (b) Nishimura,
H.; Katagiri, K.; Sato, K.; Mayama, M.; Shimaoka, N. T.
J. Antibiot. 1956, 9A, 60. (c) Ohkuma, K. J. Antibiot. 1961,
14A, 343.
(5) Kazlauskas, R.; Murphy, P. T.; Wells, R. J.; Baird-Lambert,
J. A.; Jamieson, D. D. Aust. J. Chem. 1983, 36, 165.
(6) Mitchell, S. S.; Pomerantz, S. C.; Concepción, G. P.; Ireland,
C. M. J. Nat. Prod. 1996, 59, 1000.
(7) Cook, A. F.; Holman, M. J. Nucleosides Nucleotides 1984,
4, 401.
(8) (a) Phillis, J. W.; Smith-Barbour, M. Life Sci. 1993, 53, 497.
(b) Davies, L. P.; Cook, A. F. Life Sci. 1995, 56, PL345.
(c) Ugarkar, B. G.; DaRe, J. M.; Kopcho, J. J.; Browne, C.
E. III.; Schanzer, J. M.; Wiesner, J. B.; Erion, M. D. J. Med.
Chem. 2000, 43, 2883.
(9) (a) Kazimierczuk, Z.; Revankar, G. R.; Robins, R. K.
Nucleic Acids Res. 1984, 12, 1179. (b) Ramasamy, K.;
Imamura, N.; Robins, R. K.; Revankar, G. R. Tetrahedron
Lett. 1987, 28, 5107. (c) Ramasamy, K.; Imamura, N.;
Robins, R. K.; Revankar, G. R. J. Heterocycl. Chem. 1988,
25, 1893.
HRMS (ESI): m/z calcd for [M + Na]+ C11H13BrN4O3 + Na:
351.0063; found: 351.0051.
4-Amino-5-chloro-7-(5-deoxy-b-D-ribofuranosyl)-7H-pyrro-
lo[2,3-d]pyrimidine (4c)
Compound 4c was prepared as described for 4a starting from 8c
(15.0 g, 38.7 mmol); yield: 9.14 g (83%); white crystals; Rf = 0.42
(CH2Cl2–MeOH, 15:1); mp 245–246 °C.
1H NMR (400 MHz, DMSO-d6): d = 1.27 (d, J = 6.4 Hz, 3 H,
CHCH3), 3.85 (m, 1 H, H-3¢), 3.91 (m, 1 H, H-4¢), 4.37 (t, J = 11.2,
5.6 Hz, 1 H, H-2¢), 5.10 (d, J = 5.2 Hz, 1 H, 3¢-OH), 5.33 (d, J = 5.6
Hz, 1 H, 2¢-OH), 6.03 (d, J = 5.2 Hz, 1 H, H-1¢), 6.87 (br s, 2 H, 4-
NH2), 7.54 (s, 1 H, H-6), 8.11 (s, 1 H, H-2).
13C NMR (100 MHz, DMSO-d6): d = 19.9 (C-5¢), 74.3 (C-2¢), 75.5
(C-3¢), 80.2 (C-4¢), 87.9 (C-1¢), 100.8 (C-4a), 103.9 (C-5), 120.0 (C-
6), 150.3 (C-7a), 153.7 (C-2), 157.7 (C-4).
(10) (a) Lüpke, U.; Seela, F. Chem. Ber. 1979, 112, 3526.
(b) Seela, F.; Muth, H.-P.; Bindig, U. Synthesis 1988, 670.
(c) Seela, F.; Westermann, B.; Bindig, U. J. Chem. Soc.,
Perkin Trans. 1 1988, 697. (d) Rosemeyer, H.; Seela, F.
Helv. Chim. Acta 1988, 71, 1573. (e) Seela, F.; Kretschmer,
U. J. Heterocycl. Chem. 1990, 27, 479. (f) Seela, F.;
Soulimane, T.; Mersmann, K.; Jürgens, T. Helv. Chim. Acta
1990, 73, 1879.
(11) (a) Ugarkar, B. G.; Castellino, A. J.; DaRe, J. M.; Kopcho, J.
J.; Schanzer, J. M.; Erion, M. D. J. Med. Chem. 2000, 43,
2894. (b) Ugarkar, B. G.; Castellino, A. J.; DaRe, J. M.;
Ramirez-Weinhouse, M.; Kopcho, J. J.; Rosengren, S.;
Erion, M. D. J. Med. Chem. 2003, 46, 4750.
HRMS (ESI): m/z calcd for [M + H]+ C11H14ClN4O3: 285.0749;
found: 285.0737.
4-Amino-7-(5-deoxy-b-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyri-
midine (4d)
To a solution of 4b (1.65 g, 4.59 mmol) in THF (50 mL) and MeOH
(25 mL) was added 20% Pd(OH)2/C (1.00 g, 1.42 mmol). After stir-
ring at r.t. for 5 h under H2 atmosphere, the mixture was filtered, and
concentrated to dryness. The residue was purified over a silica gel
column (CH2Cl2–MeOH, 10:1) to afford 4d; yield: 999 mg (87%);
pale yellow oil; Rf = 0.29 (CH2Cl2–MeOH, 15:1).
Synthesis 2011, No. 9, 1442–1446 © Thieme Stuttgart · New York