M. Romero et al. / Carbohydrate Research 341 (2006) 2883–2890
2889
1H), 7.18–7.38 (m, 5H); 13C NMR (100 MHz, CDCl3): d
21.8, 22.0, 64.6 (JCP = 6.1 Hz), 66.6, 70.2 (JCP
7.6 Hz), 72.8, 73.0 (JCP = 10.6), 80.5 (JCP = 7.6 Hz),
119.3, 119.2 (JCP = 6.1 Hz), 125.2, 129.8; 31P NMR
(121 MHz, CDCl3): d ꢀ12.0 ppm; MS (EI-mode) m/z
332, (M+ 26%); FAB-HRMS m/z Calcd for
C14H21O7P [M+H]+: 333.1103. Found: 333.1101.
J = 17.6, 2.8 Hz), 5.78 (m, 2H), 7.18–7.41 (m, 10H);
13C NMR (100 MHz, CDCl3): d 36.4, 38.6, 61.6, 62.9
(JCP = 6.1 Hz), 68.8, 70.3 (JCP = 10.6 Hz), 70.5
(JCP = 9.1 Hz), 70.9, 74.2 (JCP = 11.7 Hz), 82.3
(JCP = 10.7 Hz), 82.7 (10.7 Hz); 115.3, 118.4, 118.8,
119.5, 125.5, 130.0, 133.6; 31P NMR (121 MHz, CDCl3):
d ꢀ11.6, ꢀ11.3; MS m/z 313, (M+H, 4%); FAB-HRMS
m/z Calcd for C14H17O6P [M+H]+: 313.0841. Found:
313.0851.
=
4.3.2. (SP,4S,5R,10S)-4-(1-Hydroxy-2-isopropoxy-ethyl)-
5-hydroxy-2-oxo-2-phenoxy-1,3,2-dioxaphosphorinane (10).
Syrup (57%); [a]D ꢀ29.7 (c 0.8, CHCl3); 1H NMR
(400 MHz, CDCl3): d 1.16 (d, 3H, J = 6.0 Hz), 1.18 (s,
3H, J = 6.0 Hz), 2.91 (br, 1H), 3.56 (dd, 1H, J = 9.9,
4.2 Hz), 3.64 (m, 2H), 3.99 (m, 1H), 4.24 (m, 1H), 4.33–
4.57 (m, 3H), 7.16–7.37 (m, 5H); 13C NMR (100 MHz,
CDCl3): d 22.0, 22.1, 64.7 (JCP = 6.8 Hz), 67.4, 70.5
(JCP = 5.7 Hz), 71.4 (JCP = 5.7 Hz), 73.0, 83.2
(JCP = 5.7 Hz), 120.0, 125.7, 130.1; 31P NMR (121 MHz,
CDCl3): d ꢀ11.3 ppm; MS (EI-mode) m/z 332 (M+
15%); HRMS (FAB-mode) m/z Calcd for C14H21O7P
[M+H]+: 333.1103. Found: 333.1109.
4.5. General procedure for the nucleobase-coupling
reaction
The nucleobase (0.72 mmol) and 1,1,1,3,3,3-hexamethyl-
disilazane (2 mL) were stirred at 100 °C for 8 h. The
reaction mixture was cooled to room temperature and
cyclic phosphate (0.6 mmol) and TMSOTf (0.92 mmol)
in freshly distilled acetonitrile were added. The reaction
mixture was then stirred until the disappearance of the
respective starting material. The reaction mixture was
treated with a diluted aq soln NaHCO3 (30 mL). The
aq layer was extracted three times with CH2Cl2
(50mL), the organic phase was dried with MgSO4, con-
centrated in vacuo and the residue was purified by col-
umn chromatography on silica gel (230–400 mesh).
4.4. General procedure for the allylation reaction of 1,2-
O-isopropylidene xylo- and ribofuranose derivatives
A solution of 1,2-O-isopropylidene xylo- and ribofura-
nose derivatives (2.0 mmol) in 50 mL of dry CH2Cl2 at
0 °C was treated with allyltrimethylsilane (3.0 mmol)
and BF3ÆOEt2 (3.0 mmol) (for the six-membered ring
phosphates, 10.0 mmol of allyltrimethylsilane and
BF3ÆOEt2 were used). The reaction mixture was warmed
to room temperature over 4 h. The reaction mixture was
treated with satd aq NaHCO3 (50 mL). The aq layer was
extracted three times with CH2Cl2 (50 mL). The organic
phase was dried with MgSO4, concentrated in vacuo and
the residue was purified by column chromatography on
silica gel (230–400 mesh).
4.5.1. (RP,4R,5R,10S,2R)-4[1-(5-Iodouracil)-1,2-O-iso-
propylidene-ethyl]-5-hydroxy-2-oxo-2-phenoxy-1,3,2-di-
oxaphosphorinane (12). Syrup (88%); [a]D +10.7 (c 0.9,
1
CHCl3); H NMR (400 MHz, CDCl3/CD3OD): d 1.51
(s, 3H), 1.58 (s, 3H), 4.17 (td, 1H, J = 10.4, 4.4 Hz),
4.22 (td, 1H, J = 10.0, 2.8 Hz), 4.37 (ddd, 1H,
J = 24.0, 10.0, 4.4 Hz), 4.57 (ddd, 1H, J = 5.6, 3.2,
2.0 Hz), 4.78 (dt, 1H, J = 9.6, 2.0 Hz), 6.33 (d, 1H,
J = 5.6 Hz), 7.24–37 (m, 5H), 7.50 (s, 1H), 7.91 (s,
1H); 13C NMR (75 MHz, CDCl3/CD3OD): d 27.8,
27.1, 61.6 (JCP = 4.6 Hz), 69.0, 70.6 (JCP = 6.8 Hz),
80.9 (JCP = 7.9 Hz), 81.2 (JCP = 6.8 Hz), 83.4, 131.1,
119.5 (JCP = 4.5 Hz), 125.4, 129.7, 143.8, 149.8, 150.4,
160.5; 31P NMR (121 MHz, CDCl3): d ꢀ11.7 ppm;
FAB-HRMS m/z Calcd for C18H21IN2O9P [M+H]+:
567.0029. Found: 567.0027.
4.4.1. (2S,3R,4R,5R)-2-Allyl-4-(benzyloxy)-5-((benzyl-
oxy)methyl)-tetrahydrofuran-3-ol (4a, major stereoiso-
mer). Syrup (80%); [a]D ꢀ20.2 (c 1.0, CHCl3); 1H
NMR (300 MHz, CDCl3): d 2.38 (m, 1H), 2.48 (m,
1H), 3.70 (m, 3H), 3.87 (dd, 1H, J = 5.2, 2.4 Hz), 3.99
(dd, 1H, J = 4.4, 2.2 Hz), 4.23 (m, 1H), 4.49–4.62 (m,
4H), 5.08 (2H, m), 5.84 (1H, m), 7.18–7.41 (10H, m);
13C NMR (75 MHz, CDCl3): d 38.0, 68.7, 71.7, 73.3,
79.0, 79.1, 83.8, 85.2, 117.3, 127.3, 127.4, 127.5, 127.6,
128.1, 128.2, 134.1, 137.7. Anal. Calcd for C22H26O4:
C, 74.55; H, 7.39. Found: C, 74.51; H, 7.38.
4.5.2. (RP,4R,5R,10S,2R)-4[1-(Thymidine)-1,2-O-isoprop-
ylidene-ethyl]-5-hydroxy-2-oxo-2-phenoxy-1,3,2-dioxaphos-
phorinane (13). Syrup (85%); [a]D +19.2 (c 1.0,
1
CHCl3); H NMR (400 MHz, CDCl3): d 1.48 (s, 3H),
1.52 (s, 3H), 1.91 (s, 3H), 4.21 (td, 1H, J = 13.0,
1.2 Hz), 4.41 (ddd, 1H, J = 24.2, 10.4, 4.8 Hz), 4.49
(m, 1H), 4.59 (dt, 1H, J = 10.4, 1.2 Hz), 4.91 (m, 1H),
4.96 (d, 1H, J = 4.0 Hz), 6.13 (d, 1H, J = 3.2 Hz),
7.16–7.35 (m, 2H), 7.42 (d, 1H, J = 1.2 Hz), 10.61 (s,
1H); 13C NMR (75 MHz, CDCl3): d 12.6, 27.3, 28.0,
62.1 (JCP = 4.6 Hz), 70.9 (JCP = 6.9 Hz), 81.8
(JCP = 9.0 Hz), 83.3 (JCP = 7.9 Hz), 85.2, 111.3, 114.6,
119.7, 125.4, 129.9, 135.3, 151.7, 164.3; 31P NMR
4.4.2. (RP)-1-Allyl-1-desoxy-2-O-isopropoxy-3,5-O-phen-
oxyphosphoryl-a-D-ribofuranose (11a and 11b 76/24,
respectively). Data reported as a mixture of stereoiso-
mers: Syrup (86%); 1H NMR (400 MHz, CDCl3): d
2.29–2.46 (m, 4H), 3.84 (m, 2H), 3.95 (m, 2H), 4.19–
4.49 (m, 8H), 5.01 (d, 2H, J = 17.6 Hz), 5.15 (dd, 2H,