320
M. Leuck et al. / Tetrahedron Letters 45 (2004) 317–320
Med. Chem. Lett. 1996, 6, 2247–2252; (e) Gryaznov, S. M.;
Letsinger, R. L. Tetrahedron Lett. 1993, 34, 1261–1264; (f)
mixture was filtered and concentrated to give 250 mg
(87%) of the nitrophenylester 4 as a light yellow foam,
which was used as a crude product in subsequent
reactions. 1H NMR (300 MHz, CD3CN) 8.28–8.21 (m,
3H), 7.72–7.70 (m, 1H), 7.46–7.42 (m, 2H), 7.35–7.13 (m,
10H), 6.88–6.84 (m, 4H), 5.40 (s, 2H), 3.76 (s, 6H), 3.33 (q,
J ¼ 6:6 Hz, 2H), 3.02 (t, J ¼ 6:4 Hz, 2H), 2.94–2.90 (m,
2H), 2.83–2.79 (m, 2H), 1.66–1.52 (m, 4H), 1.48–1.32 (m,
4H). MS (FAB) m=z 819 [M+H]þ.
€
Hovinen, J.; Guzaev, A.; Azhayev, A.; Lonnberg, H.
Tetrahedron 1994, 50, 7203–7218; (g) Avino, A.; Garcia,
~ꢀ
R. G.; Albericio, F.; Mann, M.; Wilm, M.; Neubauer, G.;
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Petrie, C. R.; Reed, M. W.; Adams, A. D.; Meyer, R. B.
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Adams, H.; Hudson, D.; Cook, R. M. Bioconjugate Chem.
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ꢁ
10. CPG 500 A with an aminohexyl spacer (5.0 g) was
5. Vu, H.; Joyce, N.; Rieger, M.; Walker, D.; Goldknopf, I.;
Schmaltz Hill, T.; Jayaraman, K.; Mulvey, D. Bioconju-
gate Chem. 1995, 6, 599–607.
6. Cain, B. F. J. Org. Chem. 1976, 41, 2029–2031.
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Tetrahedron Lett. 1990, 31, 6729–6732; (b) Kuijpers, W.
H. A.; Kuyl-Yeheskiely, E.; van Boom, J. H.; van Boeckel,
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suspended in DMF (13 mL) and Et3N (0.5 mL). Nitro-
phenyl ester 4 (250 mg, 305 lmol) was dissolved in DMF
(4.0 mL) and added to the suspension, which was then left
overnight on an orbital shaker at room temperature. The
CPG was washed with DMF/Et3N 9/1 (v/v), DMF, EtOH,
acetonitrile, and EtOAc in multiple 20 mL portions. The
CPG was finally treated with commercially available Cap
A (Ac2O/THF) and Cap B (1-methylimidazole/pyridine/
THF) synthesis solutions for 2h and washed with THF,
EtOH/pyridine 9/1 (v/v), EtOH, acetonitrile, and EtOAc.
The loading was determined to be 36.0 lmol/g by a
photometric (497 nm) DMT loading assay.
8. The synthesis of 3 was conducted according to Bigg, D. C.
H.; Lesimple, P. Synthesis 1992, 277–278.
9. The amide 3 (200 mg, 0.334 mmol) was reacted in 1.5 mL
EtOAc with succinic anhydride (40 mg, 0.401 mmol) in the
presence of Et3N (46 lL, 0.327 mmol) and 4-dimethyl-
aminopyridine (10 mg, 0.084 mmol) for 2h at 50 °C. The
mixture was concentrated and redissolved in CH2Cl2. The
solution was extracted with 10% aqueous citric acid and
water, dried over Na2SO4, and concentrated to a foam.
The residue was redissolved in 1,4-dioxane (3 mL) and
pyridine (70 lL) and reacted with 4-nitrophenol (50 mg,
0.358 mmol) and 1,3-dicyclohexylcarbodiimide (94 mg,
0.456 mmol) at room temperature overnight. The reaction
11. Woo, S. L.; Fung, S. Solid support reagents for the
synthesis of 30-nitrogen containing polynucleotides. PCT
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58993.
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yak, R.; Spiess, E.; Andrus, A. Tetrahedron Lett. 1990, 31,
7269–7272.