N. Ciliberti et al. / Bioorg. Med. Chem. 15 (2007) 3065–3081
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1H NMR (CDCl3) d (ppm): 0.81 (t, 3H, J = 6.7 Hz,
CH3); 0.94–1.15 (m, 8H, 4 · CH2); 1.18–1.30 (m, 28H,
TIPDS) 1.35–1.65 (m, 2H, CH2CH2CO); 2.10–2.21 (m,
2H, CH2CO); 3.70–3.81 (m, 1H, H40); 3.92–4.15 (m,
2H, H50, H500); 4.30–4.41 (m, 1H, H30); 5.51–5.62 (m,
1H, H20); 6.15 (d, 1H, J = 6.4 Hz, H10); 6.59 (d, 1H,
J = 13.6 Hz, vinyl); 7.35 (d, 1H, J = 13.6 Hz, vinyl);
7.46 (s, 1H, H6); 9.25 (br s, 1H, NH).
2 · CH2); 1,85 (s, 3H, CH3); 2.10–2.23 (m, 2H, CH2CO);
3.69–3.78 (m, 1H, H40); 3.90–4.12 (m, 2H, H50, H500);
4.34–4.45 (m, 1H, H30); 5.42–5.53 (m, 1H, H20); 6.16
(d, 1H, J = 6.6 Hz, H10); 7.22 (s, 1H, H6); 8.03 (br s,
1H, NH).
MALDI-TOFMS: m/z 607.5 Da (M+Na)+; 623.8 Da
(M+K)+. C32H48N2O8Si2 requires 584.86.
MALDI-TOFMS: m/z 739.9 Da (M+Na)+; 755.7 Da
5.2.8. 1-[20-O-Dodecanoyl-30,50-O-(1,1,3,3-tetraisopropyl-
disiloxane-1,3-diyl)-b-D-arabinofuranosyl]thymine (6g).
Yield 95%; yellow oil.
(M+K)+.C31H53BrN2O8Si2 requires 716.25.
5.2.4. 1-[20-O-Decanoyl-30,50-O-(1,1,3,3-tetraisopropyl-
disiloxane-1,3-diyl)-b-D-arabinofuranosyl]-5(E)-(2-bromo-
vinyl)uracil (5e). Yield 69%; colourless solid (mp: 235–
238 ꢂC).
1H NMR (CDCl3) d (ppm): 0.87 (t, 3H, J = 6.1 Hz,
CH3); 0.89–1.13 (m, 28H, TIPDS); 1.12–1.38 (m, 16H,
8 · CH2); 1.39–1.71 (m, 2H, CH2CH2CO); 1.85 (s, 3H,
CH3); 2.09–2.37 (m, 2H, CH2CO); 3.69–3.88 (m, 1H,
H40); 3.90–4.15 (m, 2H, H50, H500); 4.41–4.47 (m, 1H,
H30); 5.43–5.58 (m, 1H, H20); 6.16 (d, 1H, J = 6.5 Hz,
H10); 7.24 (s, 1H, H6); 9.15 (br s, 1H, NH).
1H NMR (CDCl3) d (ppm): 0.88 (t, 3H, J = 6.6 Hz,
CH3); 1.02–1.17 (m, 12H, 6 · CH2); 1.23–1.26 (m,
28H, TIPDS); 1.42–1.58 (m, 2H, CH2CH2CO); 2.21 (t,
2H, J = 7.4 Hz, CH2CO); 3.79–3.98 (m, 1H, H40);
4.06–4.12 (m, 2H, H50, H500); 4.39–4.50 (m, 1H, H30);
5.58–5.69 (m, 1H, H20); 6.23 (d, 1H, J = 6.3 Hz, H10);
6.66 (d, 1H, J = 13.6 Hz, vinyl); 7.43 (d, 1H,
J = 13.6 Hz, vinyl); 7.52 (s, 1H, H6); 9.86 (br s, 1H, NH).
MALDI-TOFMS: m/z 683.8 Da (M+H)+; 705.4 Da
(M+Na)+; 721.4 Da (M+K)+. C34H62N2O8Si2 requires
682.40.
5.3. General procedure for the synthesis of the N-Boc-
aminoacyl derivatives 5h–m
MALDI-TOFMS: m/z 768.1 Da (M+Na)+; 783.4 Da
(M+K)+. C33H57BrN2O8Si2 requires 744.28.
To a stirred solution of the selected N-Boc amino
acid derivative (0.25 mmol) in dry CH2Cl2 (3.5 mL),
5.2.5. 1-[20-O-Octanoyl-30,50-O-(1,1,3,3-tetraisopropyl-
disiloxane-1,3-diyl)-b-D-arabinofuranosyl]thymine (6d).
Yield 50%; yellow oil.
compound
3
(150 mg, 0.25 mmol) and DMAP
(3 mg, 0.03 mmol) were added under argon atmo-
sphere. To the solution, cooled at 0 ꢂC, was then
added N,N0-dicyclohexylcarbodiimide (DCC, 68 mg,
0.33 mmol) and the resulting mixture was reacted at
25 ꢂC for 3–5 h. After this period, the N,N0-dic-
yclohexylurea (DCU), deriving by the reaction, was
filtered off and the solvent was evaporated to dryness.
The resulting residue was dissolved in EtOAc
(15 mL), washed with HCl 0.5 N (10 mL), saturated
NaHCO3 (10 mL), and finally with brine (10 mL).
After drying over anhydrous Na2SO4, the solvent
was evaporated to give, in all cases, the pure 20-O-
aminoacyl derivatives as white foams, in almost
quantitative yield (98–100%).
1H NMR (CDCl3) d (ppm): 0.88 (t, 3H, J = 6.5 Hz, CH3);
1.00–1.19 (m, 10H, 5 · CH2); 1.21–1.41 (m, 28H, TIPDS);
1.43–1.78 (m, 2H, CH2CO); 1.92 (s, 3H, CH3); 3.76–3.81
(m, 1H, H40); 3.95–4.28 (m, 2H, H50, H500); 4.40–4.52 (m,
1H, H30); 5.50–5.60 (m, 1H, H20); 6.23 (d, 1H, J = 6.5 Hz,
H10); 7.29 (s, 1H, H6); 8.12 (br s, 1H, NH).
MALDI-TOFMS: m/z 650.0 Da (M+Na)+; 665.3 Da
(M+K)+. C30H54N2O8Si2 requires 626.34.
5.2.6. 1-[20-O-Decanoyl-30,50-O-(1,1,3,3-tetraisopropyl-
disiloxane-1,3-diyl)-b-D-arabinofuranosyl]thymine (6e).
Yield 58%; yellow oil.
5.3.1. 1-[20-O-(N-Boc-4-aminobuanoyl)-30,50-O-(1,1,3,3-
tetraisopropyldisiloxane-1,3-diyl)-b-D-arabinofuranosyl]-
5(E)-(2-bromovinyl)uracil (5h). 1H NMR (400 MHz,
CDCl3) d (ppm): 0.99–1.12 (m, 28H, TIPDS); 1.49 (s,
9H, t-Bu); 1.75–1.81 (m, 2H, CH2CH2CO); 2.25–2.30
(m, 2H, CH2CO); 3.05–3.11 (m, 1H, CHH–N); 3.22–
3.29 (m, 1H, CHH–N); 3.86–3.88 (m, 1H, part of
ABX system, H40); 4.01 (dd, 1H, part of ABX system,
JAB = 13.6 Hz, JAX = 2.4 Hz, H50); 4.17–4.20 (m, 1H,
part of ABX system, H500); 4.31–4.35 (m, 1H, H30);
4.80 (br s, 1H, NH–Boc); 5.74–5.76 (m, 1H, H20); 6.14
(d, 1H, J = 6.0 Hz, H10); 6.68 (d, 1H, J = 13.6 Hz, vi-
nyl); 7.47 (d, 1H, vinyl); 7.68 (s, 1H, H6); 8.68 (br s,
1H, NH).
1H NMR (CDCl3) d (ppm): 0.78–0.89 (m, 3H, CH3);
1.00–1.18 (m, 28H, TIPDS); 1.14–1.19 (m, 14H,
7 · CH2); 1.85 (s, 3H, CH3); 2.01–2.48 (m, 2H, CH2CO);
3.65–3.74 (m, 1H, H500); 3.83–4.45 (m, 3H, H50, H40,
H30); 5.42–5.51 (m, 1H, H20); 6.17 (d, 1H, J = 6.4 Hz,
H10); 7.20 (s, 1H, H6); 8.50 (br s, 1H, NH).
MALDI-TOFMS: m/z 677.5 Da (M+Na)+; 693.7 Da
(M+K)+. C32H58N2O8Si2 requires 654.37.
5.2.7. 1-[20-O-Pentanoyl-30,50-O-(1,1,3,3-tetraisopropyl-
disiloxane-1,3-diyl)-b-D-arabinofuranosyl]thymine (6f).
Yield 68%; yellow oil.
1H NMR (CDCl3) d (ppm): 0.77 (t, 3H, J = 5.5 Hz,
CH3); 0.87–1.12 (m, 28H, TIPDS); 1.15–1.65 (m, 4H,
MALDI-TOFMS: m/z 798.9 Da (M+Na)+; 814.1 Da
(M+K)+. C32H54BrN3O10Si2 requires 775.25.