5054
Y. Aubin et al. / Tetrahedron 63 (2007) 5050–5055
(CH3). Anal. Calcd for C12H14ClN5O2: C, 48.74; H, 4.77; N,
23.68. Found: C, 49.03; H, 4.73; N, 23.71.
61.0 (CH2), 52.9 (CH), 43.7 (CH), 30.7 (CH2), 24.0 (CH),
16.8 (CH3), 6.6 (2ꢂCH2). Anal. Calcd for C15H20N6O2: C,
56.95; H, 6.37; N, 26.56. Found: C, 57.29; H, 6.41; N, 26.67.
4.1.9. ((1S,2R,4R,5R)-4-(6-(Cyclopropylamino)-9H-
purin-9-yl)-1-methyl-6-oxa-bicyclo[3.1.0]hex-2-yl)me-
thanol (D)-1a. A mixture of (+)-10 (200 mg, 0.712 mmol)
and cyclopropylamine (1 mL) in dry THF (10 mL) was
stirred at rt for 3 h, and the reaction mixture was evaporated
in vacuo. The resulting residue was purified by column chro-
matography using gradients methylene chloride/methanol as
the eluent to give the corresponding 6-cyclopropylamino
carbanucleoside (+)-1a (198 mg, 92%) as a white foam.
[a]2D5 +24.7 (c 1, CHCl3). IR (neat): n 3298, 3121,
Acknowledgements
We are thankful to Dr. R. Faure for NOESY and HMBC
experiments. We thank P. Fournier for the English language
revision of the manuscript.
References and notes
1
1662 cmꢀ1. H NMR (300 MHz, CDCl3): d 8.43 (s, 1H),
1. (a) Agrofolio, L. A.; Challaud, S. R. Acyclic, Carbocyclic and
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Med. Res. Rev. 1995, 15, 497–531.
3. Forselectedrecentsynthesesandreferencescited therein see:(a)
Moon, H. R.; Lee, H. J.; Kim, K. R.; Lee, K. M.; Lee, S. K.; Kim,
H. O.; Chun, M. W.; Jeong, L. S. Bioorg. Med. Chem. Lett. 2004,
14, 5641–5644; (b) Kim, J. W.; Choi, B. G.; Hong, J. H. Bull.
Korean Chem. Soc. 2004, 25, 1812–1816; (c) Zhu, X.-F.;
Nydegger, F.; Gossauer, A. Helv. Chim. Acta 2004, 87, 2245–
2265; (d) Gonzalez-Moa, M. J.; Besada, P.; Teijeira, M.;
Teran, C.; Uriate, E. Synthesis 2004, 543–548; (e) Quadrelli,
P.; Scrocchi, R.; Caramella, P.; Rescifina, A.; Piperno, A.
Tetrahedron2004, 60, 3643–3651;(f)Yang,Y.-Y.;Meng, W.-D.;
Qing, F.-L. Org. Lett. 2004, 6, 4257–4259; (g) Hegedus, L. S.;
Cross, J. J. Org. Chem. 2004, 69, 8492–8495; (h) Wang, J.;
Jin, Y.; Rapp, K. L.; Bennett, M.; Schinazi, R. F.; Chu, C. K.
J. Med. Chem. 2005, 48, 3736–3748; (i) Meillon, J.-C.; Griffe,
L.; Storer, R.; Gosselin, G. Nucleosides Nucleotides Nucleic
8.05 (s, 1H), 6.35 (br s, 1H), 5.09 (t, J¼8.2 Hz, 1H), 3.86
(m, 2H), 3.54 (s, 1H), 3.01 (br s, 1H), 2.33 (m, 2H), 1.56
(s, 3H), 1.55–1.42 (m, 1H), 0.90 (m, 2H), 0.62 (m, 1H).
13C NMR (75 MHz, CDCl3): d 155.8 (C), 153.2 (CH),
149.0 (C), 138.1 (CH), 119.4 (C), 64.5 (C), 63.7 (CH),
61.5 (CH2), 53.5 (CH), 43.8 (CH), 30.7 (CH2), 23.7 (CH),
16.3 (CH3), 7.3 (2ꢂCH2). Anal. Calcd for C15H19N5O2: C,
59.79; H, 6.36; N, 23.24. Found: C, 60.02; H, 6.39; N, 23.02.
4.1.10. ((1S,2R,4R,5R)-4-(6-Amino-9H-purin-9-yl)-1-
methyl-6-oxa-bicyclo[3.1.0]hex-2-yl)methanol (D)-1b. A
solution of (+)-8 (200 mg, 0.66 mmol) and saturated metha-
nolic ammonia (10 mL) was stirred in a flask fitted with a rub-
ber stopper at rt for 10 h. After evaporation of the solvent in
vacuo, the residue was purified by column chromatography
using gradients petroleum ether/ethyl acetate as the eluent
to give adenosine carbanucleoside (+)-1b (157 mg, 91%) as
a white solid. Mp 162 ꢁC. ee¼99%, determined by chiral
HPLC (Chiralcel OD-H, hexane/2-PrOH 9:1, 1 mL/min,
UV and CD detection at 254 nm, 25 ꢁC, Rt(+)¼21.37,
Rt(ꢀ)¼25.09, k(+)¼6.01, k(ꢀ)¼7.23, alpha¼1.20 and
Rs¼1.36). [a]2D5 +26.9 (c 1, MeOH/CHCl3 1:1). IR (KBr):
n 3273, 3109, 1671 cmꢀ1. 1H NMR (500 MHz, DMSO-d6):
d 8.15 (s, 1H), 8.11 (s, 1H), 7.26 (br s, 2H), 4.99 (t,
J¼8.2 Hz, 1H), 4.67 (t, J¼4.9 Hz, 1H), 3.70 (s, 1H), 3.67
(td, J¼10.2, 5.8 Hz, 1H), 3.47 (td, J¼10.2, 5.8 Hz, 1H),
2.34–2.22 (m, 2H), 1.48 (s, 3H), 1.29 (dt, J¼11.8, 8.9 Hz,
1H). 13C NMR (75 MHz, DMSO-d6): d 156.2 (C), 152.7
(CH), 149.7 (C), 138.5 (CH), 118.8 (C), 64.5 (C), 63.8
(CH), 61.0 (CH2), 53.7 (CH), 43.8 (CH), 30.7 (CH2), 16.8
(CH3). Anal. Calcd for C12H15N5O2: C, 55.16; H, 5.79; N,
26.80. Found: C, 55.32; H, 5.83; N, 26.99.
ꢀ
Acids 2005, 24, 695–699; (j) Garcıa, M. D.; Caaman˜o, G.;
ꢀ
Fernandez, F.; Lopez, C.; De Clercq, E. Synthesis 2005, 925–
932; (k) Lee, J. A.; Moon, H. R.; Kim, H. O.; Kim, K. R.; Lee,
K. M.; Kim, B. T.; Hwang, K. J.; Chun, M. W.; Jacobson,
K. A.; Jeong, L. S. J. Org. Chem. 2005, 70, 5006–5013; (l)
Roy, A.; Schneller, S. W.; Keith, K. A.; Hartline, C. B.; Kern,
E. R. Bioorg. Med. Chem. 2005, 13, 4443–4449; (m) Jin,
Y. L.; Hong, J. H. Bull. Korean Chem. Soc. 2005, 26, 1366–
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2005, 26, 1520–1524; (o) Kim, A.; Hong, J. H. Bull. Korean
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Gage, J. L.; Priour, A.; Savela, G.; Miller, M. J. J. Org. Chem.
4.1.11. ((1S,2R,4R,5R)-4-(2-Amino-6-(cyclopropyl-
amino)-9H-purin-9-yl)-1-methyl-6-oxa-bicyclo[3.1.0]-
hexan-2-yl)methanol (D)-1c. Derivative (ꢀ)-11 was
converted to the 2-amino-6-cyclopropylamino carbanucleo-
side (155 mg, 83%) as a white foam (+)-1c, according to
the same procedure used in the preparation of (+)-1a except
stirring at 50 ꢁC for 2 h. [a]D25 +12.7 (c 1, MeOH/CHCl3 1:1).
€
2006, 71, 4164–4169; (q) Ludek, O. R.; Kramer, T.; Balzarini,
J.; Meier, C. Synthesis 2006, 1313–1324; (r) Garcıa, M. D.;
1
IR (neat): n 3299, 3185, 1668 cmꢀ1. H NMR (300 MHz,
ꢀ
ꢀ
DMSO-d6): d 7.66 (s, 1H), 7.30 (br d, J¼4.82 Hz, 1H),
5.82 (br s, 2H), 4.75 (ddd, 9.3, 8.3, 1.0 Hz, 1H), 4.63 (t,
J¼5.1 Hz, 1H), 3.64 (ddd, J¼11.9, 6.2, 5.8 Hz, 1H), 3.61
(d, J¼0.8 Hz, 1H), 3.44 (ddd, J¼10.7, 6.0, 5.1 Hz, 1H),
3.03 (br s, 1H), 2.29–2.06 (m, 2H), 1.45 (s, 3H), 1.18 (dt,
J¼12.0, 9.3 Hz, 1H), 0.68–0.61 (m, 2H), 0.59–0.53 (m,
2H). 13C NMR (75 MHz, DMSO-d6): d 160.4 (C), 156.1
(C), 151.5 (C), 134.7 (CH), 113.4 (C), 64.2 (C), 63.8 (CH),
Caaman˜o, O.; Fernandez, F.; Abeijon, P.; Blanco, J. M.
Synthesis 2006, 73–80; (s) Gosselin, G.; Griffe, L.; Meillon,
J.-C.; Storer, R. Tetrahedron 2006, 62, 906–914.
4. (a) Comin, M. J.; Rodriguez, J. B.; Russ, P.; Marquez, V. E.
Tetrahedron 2003, 59, 295–301; (b) Paoli, L.; Piccini, S.;
Rodriguez, M.; Sega, A. J. Org. Chem. 2004, 69, 2881–2883;
(c) Ishikura, M.; Matsumoto, K.; Murakami, A. Heterocycles
2004, 64, 241–248.