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DOI: 10.1055/s-2003-41406
Synthesis of Novel Phosphoramidite Building Blocks from Pentaerythritol
Publication History
Publication Date:
28 August 2003 (online)
Abstract
The synthesis of four types of phosphoramidites containing various protecting groups (DMTr, TBDMS, Lev) has been achieved starting from pentaerythritol. The protecting groups can be deprotected selectively in an orthogonal manner.
Key words
protecting groups - chemoselectivity - alcohols - DNA - oligonucleotides
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References
Reaction conditions and selected spectroscopic data. 1: CEP-Cl (297 µL, 1.34 mmol) was added to a solution of 6 (560 mg, 0.537 mmol) and DIPEA (187 µL, 1.074 mmol) in THF (6 mL). The reaction mixture was stirred at room temperature for 80 min and then 5% NaHCO3 solution and EtOAc were added. The organic layer was separated, dried over MgSO4, and concentrated under reduced pressure. Purification by flash chromatography provided 1 as a colorless oil (236 mg, 0.190 mmol, 35%). 1H NMR (300 MHz, CDCl3): δ = 7.27-7.14 (m, 27 H), 6.72-6.68 (m, 12 H), 4.11 (q, J = 6.7 Hz, 2 H), 3.75 (s, 18 H), 3.39-3.23 (m, 8 H), 2.23 (t, J = 6.3 Hz, 2 H), 2.03 (s, 2 H), 1.31-1.22 (m, 4 H), 1.09 (d, J = 6.7 Hz, 6 H), 0.95 (d, J = 6.7 Hz, 6 H); 13C NMR (75.5 MHz, CDCl3): δ = 157.7, 144.7, 135.8, 129.7, 127.8, 127.1, 126.0, 112.5, 85.1, 62.3, 57.7, 54.7, 42.5, 24.1, 24.0, 13.7; 31P NMR (121.5 MHz, CDCl3): δ = 148.9; HR-ESIMS (m/z): [M + Na]+ calcd for C77H83N2O11PNa, 1243.5852; found, 1243.5807. 2: Reaction of CEP-Cl (166 µL, 0.74 mmol), 9 (319.7 mg, 0.37 mmol), and DIPEA (260 µL, 1.48 mmol) in THF (4 mL) for 90 min, followed by the workup described above, provided 2 as a yellow oil (302.8 mg, 0.29 mmol, 77%). 1H NMR (300 MHz, CDCl3): δ = 7.24 (d, J = 7.2 Hz, 4 H), 7.17-7.09 (m, 14 H), 6.67 (d, J = 8.4 Hz, 8 H), 4.02 (q, J = 10.7 Hz, 2 H), 3.68 (s, 12 H), 3.66-3.37 (m, 6 H), 3.17-3.14 (m, 4 H), 2.50 (t, J = 7.0 Hz, 2 H), 2.35 (t, J = 6.3 Hz, 2 H), 2.28 (t, J = 6.7 Hz, 2 H), 2.05 (s, 3 H), 1.21 (t, J = 5.7 Hz, 4 H), 1.05 (d, J = 6.7 Hz, 6 H), 0.94 (d, J = 6.7 Hz, 6 H); 13C NMR (75.5 MHz, CDCl3): δ = 172.5, 158.8, 145.2, 136.2, 130.5, 128.4, 127.9, 126.8, 117.9, 113.2, 86.0, 61.6, 60.6, 55.4, 43.3, 43.1, 38.0, 30.0, 28.0, 24.8, 24.7, 14.4; 31P NMR (121.5 MHz, CDCl3): δ = 150.2; HR-FABMS
(m/z): [M + H]+ calcd for C61H72N2O11P, 1039.4874; found, 1039.4877. 3: Reaction of CEP-Cl (74 µL, 0.33 mmol), 10 (141 mg, 0.222 mmol), and DIPEA (77 µL, 0.445 mmol) in THF (6 mL) for 30 min, followed by the workup described above, provided 3 as a yellow oil (114 mg, 0.135 mmol, 61%). 1H NMR (300 MHz, CDCl3): δ = 7.40-7.38 (m, 2 H), 7.29-7.26 (m, 7 H), 6.82 (d, J = 8.7 Hz, 4 H), 4.17-4.12 (m, 4 H), 3.78 (s, 6 H), 3.73-3.65 (m, 2 H), 3.61-3.51 (m, 2 H), 3.15 (s, 2 H), 2.68 (t, J = 6.5 Hz, 4 H), 2.56 (t, J = 6.3 Hz, 2 H), 2.48 (t, J = 6.5 Hz, 4 H), 2.16 (s, 6 H), 1.25 (d, J = 6.7 Hz, 2 H), 1.16 (d, J = 6.7 Hz, 6 H), 1.10 (d, J = 6.7 Hz, 6 H); 13C NMR (75.5 MHz, CDCl3): δ = 205.8, 171.8, 158.0, 158.0, 144.2, 135.3, 135.0, 129.7, 127.7, 127.4, 127.3, 126.3, 117.2, 112.6, 112.5, 85.8, 85.5, 62.6, 61.6, 61.4, 60.2, 57.9, 57.7, 54.7, 46.9, 43.5, 42.7, 42.5, 37.3, 30.5, 29.3, 27.3, 24.2, 24.1, 22.1, 20.7, 19.9, 19.8; 31P NMR (121.5 MHz, CDCl3): δ = 150.7; HR-FABMS (m/z): [M + Na]+ calcd for C45H59N2O11PNa, 857.3754; found, 857.3759. 4: Reaction of CEP-Cl (114 µL, 0.518 mmol), 12 (134.8 mg, 0.207 mmol), and DIPEA (144 µL, 0.828 mmol) in THF (4.2 mL) for 90 min, followed by the workup described above, provided 4 as a yellow oil (86.2 mg, 0.101 mmol, 50%). 1H NMR (300 MHz, CDCl3): δ = 7.41-7.38 (m, 2 H), 7.29-7.17 (m, 7 H), 6.79 (d, J = 8.9 Hz, 4 H), 4.11-4.09 (m, 2 H), 3.76 (s, 6 H), 3.70-3.52 (m, 8 H), 3.12 (s, 2 H), 2.66-2.64 (m, 2 H), 2.53-2.45 (m, 4 H), 2.15 (s, 3 H), 1.14 (d, J = 6.8 Hz, 6 H), 1.08 (dd, J
1 = 6.7, J
2
= 1.4 Hz, 6 H), 0.08 (d, J = 1.1 Hz, 9 H), -0.03 (d, J = 2.4 Hz, 6 H); 13C NMR (75.5 MHz, CDCl3): δ = 205.9, 171.9, 157.9, 144.6, 135.7, 129.7, 127.2, 126.1, 117.2, 112.5, 85.3, 63.2, 61.0, 60.4, 57.7, 54,7, 45.0, 42.6, 42.5, 37.4, 29.4, 27.3, 25.3, 24.2, 24.1, 19.9, 19.8, 17.7, -6.12; 31P NMR (121.5 MHz, CDCl3): δ = 150.3, 150.1; HR-FABMS (m/z): [M + Na]+ calcd for C46H67N2O9PSiNa, 873.4251; found, 873.4252.