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S. Kralıkova et al. / Tetrahedron 62 (2006) 9742–9750
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9747
read from expanded records. The exchange of hydroxyl
protons for deuterium was carried out using several drops of
tetradeuterioacetic acid. Assignments of signals in 13C NMR
spectra were accomplished on the basis of J-modulated
spectra (APT) enabling to discriminate between C, CH,
CH2, and CH3 signals, and in some cases confirmed by 1H,
J¼7.6, 3.9, 2.4 Hz, H-40), 4.16 (1H, J¼13.0, 2.4 Hz, H-50),
3.95 (4H, q, J¼7.0 Hz, 2ꢁOCH2), 1.41 (3H, s, CH3), 1.26
(3H, s, CH3), 1.15 (3H, t, J¼7.0 Hz, OCH2CH3), 1.09
(3H, t, J¼7.0 Hz, OCH2CH3); dC (125.7 MHz, DMSO)
165.22, 133.82, 129.70 (2), 129.57, 128.97 (2), 112.57,
104.79, 79.52 (d, J¼12.7 Hz), 78.00, 71.30, 66.32 (d,
J¼165.0 Hz), 62.48 (d, J¼6.8 Hz), 62.21 (d, J¼6.8 Hz),
27.19, 26.94, 16.44 (d, J¼5.9 Hz), 16.38 (d, J¼4.4 Hz).
Compound 7b: dH (500 MHz, DMSO) 8.02 (2H, m, ortho-
Ar-H), 7.70 (1H, m, para-Ar-H), 7.56 (2H, meta-Ar-H),
5.85 (1H, br s, OH), 5.90 (1H, d, J¼3.8 Hz, H-10), 4.96
(1H, dd, J¼8.5, 5.1 Hz, H-30), 4.90 (1H, dd, J¼5.1,
3.8 Hz, H-20), 4.43 (1H, dt, J¼8.5, 2.7, 2.7 Hz, H-40), 3.99
(1H, J¼13.0, 2.7 Hz, H-50), 4.05 (4H, q, J¼7.0 Hz,
2ꢁOCH2), 1.42 (3H, s, CH3), 1.26 (3H, s, CH3), 1.22 (3H,
t, J¼7.0 Hz, OCH2CH3), 1.21 (3H, t, J¼7.0 Hz, OCH2CH3);
dC (125.7 MHz, DMSO) 165.48, 134.16, 129.82 (2), 129.35,
129.25 (2), 112.68, 104.79, 78.20 (d, J¼2.4 Hz), 77.15,
72.24 (d, J¼9.8 Hz), 68.68 (d, J¼6.8 Hz), 62.10 (d,
J¼6.8 Hz), 27.06, 26.91, 16.69 (d, J¼5.9 Hz), 16.62 (d,
J¼5.9 Hz). For 1H and 13C NMR data see Tables 1–3.
1
13C-correlated HMQC spectra. The H and 13C NMR data
are summarized in Tables 1–3.
4.2. (5RS)-3-O-Benzoyl-1,2-O-isopropylidene-D-ribo-
furanos-5-C-ylphosphonate (7a, 7b)
The 1,2:5,6-di-O-isopropylidene-a-D-allofuranose18
3
(13.01 g, 50 mmol) was treated with benzoylcyanide
(7.21 g, 55 mmol) and triethylamine (0.695 mL, 5 mmol)
in acetonitrile (60 mL) at 0 ꢀC under exclusion of moisture
(TLC in T-1) overnight. The reaction mixture was quenched
by addition of methanol (5 mL) and the solvent was evapo-
rated in vacuo. The residue was dissolved in chloroform and
the organic layer was washed several times with water. After
evaporation of solvent, the benzoyl derivative 4 was treated
with 60% aqueous acetic acid (600 mL) at 50 ꢀC for 3 h
(TLC in T-1 and C-1). The acid was evaporated in vacuo,
the residue was taken into chloroform (300 mL), and the
organic layer was washed with saturated aqueous solution
of NaCl (250 mL). The layers were separated by centrifuga-
tion, the organic layer was washed with water (4ꢁ250 mL),
dried over anhydrous Na2SO4, and evaporated. The residue
was dissolved in 70% aqueous acetone (650 mL) and to
this solution, saturated aqueous solution of sodium periodate
(12.84 g, 60 mmol) was added at 0 ꢀC. Resulting solution
was stirred for 8 h at rt (TLC in C-1) and, after cooling the
mixture in an ice bath, the suspension was filtered through
Celite. Filtration cake was washed with acetone, and the
combined filtrates were evaporated. The residue was re-dis-
solved in acetone (200 mL) and the rest of sodium iodate
was filtered off. Crude aldehyde 6 was co-distilled with
dry toluene, dissolved in dichloromethane (50 mL), and
treated with diethyl phosphite (7.74 mL, 60 mmol) and tri-
ethylamine (2.78 mL, 20 mmol) at 80 ꢀC for 24 h (TLC in
T-1 and C-1). The solvent was evaporated in vacuo and the
crude epimeric phosphonates 7a and 7b were purified on
silica gel using elution with a linear gradient of ethyl acetate
in toluene. Yield: 1.27 g (5%) of 7a, 1.82 g (7%) of 7b, and
10.72 g (42%) of the mixture of 7a and 7b. HR-FAB calcd
for C19H28O9P (M+H)+: 431.1471; found: 431.1470. Com-
pound 7a: nmax (KBr) 3430 (w, br, OH), 3243 (m, OH),
3072 (w, C–H), 2986 (m, CH3), 2876 (w, CH3), 1251 (s,
P]O), 1219 (m), 1206 (m), 1131 (s, COCOC), 1032 (vs,
POC), 1480 (w, OCH2CH3), 1602 (w), 1584 (w), 1492
(w), 1452 (w), 1731 (m, C]O), 1724 (s, C]O), 1275 (s,
C]O), 1217 (s, C(CH3)2), 1098 (m, COCOC), 1002 (m),
688 (w) cmꢂ1. Compound 7b: nmax (KBr) 3506 (w, br,
OH), 3272 (m, OH), 3066 (w, C–H), 2992 (m, CH3), 2871
(w, CH3), 1256 (s, P]O), 1236 (s, P]O), 1219 (m), 1206
(m), 1152 (s, COCOC), 1033 (vs, POC), 1601 (w), 1583
(w), 1492 (w), 1452 (w), 1731 (m, C]O), 1720 (s,
C]O), 1711 (s, C]O), 1282 (s, C]O), 1100 (s, COCOC),
999 (m), 692 (w) cmꢂ1. Compound 7a: dH (500 MHz,
DMSO) 8.01 (2H, m, ortho-Ar-H), 7.65 (1H, m, para-
Ar-H), 7.54 (2H, meta-Ar-H), 6.10 (1H, br s, OH), 5.91
(1H, d, J¼3.9 Hz, H-10), 5.20 (1H, dd, J¼7.6, 5.6 Hz,
H-30), 4.88 (1H, dd, J¼5.6, 3.9 Hz, H-20), 4.63 (1H, ddd,
4.3. (4R)-Diethyl-[1,3-di-O-acetyl-2-O-benzoyl-D-
erythrofuranos-4-yl]phosphonate (10)
Periodic acid dihydrate (0.99 g, 4.35 mmol) was added to a
solution of phosphonate 7a (1.25 g, 2.9 mmol) in 50% aque-
ous dioxane (20 mL), and the reaction mixture was heated at
60 ꢀC in the dark for 1–3 days (TLC in C-1). The solution was
treated with Dowex 1ꢁ2 in acetate form (10 mL) under stir-
ring for 10 min to remove periodate and iodate anions, the
resin was filtered off, washed with 50% dioxane (30 mL),
and the combined filtrates were evaporated. The residue
was co-distilled several times with water to remove acetic
acid, and finally treated with 0.1 M TEAB (30 mL) for
20 min. The aqueous solution was evaporated to dryness,
the crude 9b was co-distilled with methanol (3ꢁ50 mL),
dried with pyridine (3ꢁ10 mL), and treated with acetic anhy-
dride (1.21 mL, 12.8 mmol) and DMAP (20 mg) in pyridine
(12 mL) overnight (TLC in C-1). The reaction mixture was
quenched by addition of water (1 mL) at 0 ꢀC, the solvent
was evaporated in vacuo, and the crude product 10 was puri-
fied on silica gel byelution with a lineargradient of acetone in
toluene. Yield: 940 mg (73%, yellow oil) of 10 (b-anomer).
HR-FAB calcd for C19H26O10P (M+H)+: 445.1264; found:
445.1273. dH (500 MHz, CDCl3) 8.04 (2H, m, ortho-Ar-H),
7.62 (1H, m, para-Ar-H), 7.48 (2H, meta-Ar-H), 6.34 (1H,
d, J¼1.4 Hz, H-10), 5.90 (1H, ddd, J¼14.2, 8.0, 4.7 Hz,
H-30), 5.64 (1H, dd, J¼4.7, 1.4 Hz, H-20), 4.44 (1H, dt,
J¼8.0, 0.9 Hz, H-40), 4.20 (4H, q, J¼7.0 Hz, 2ꢁOCH2),
2.15 (3H, s, OAc), 2.01 (3H, s, OAc), 1.35 (6H, t,
J¼7.0 Hz, 2ꢁOCH2CH3); dC (125.7 MHz, CDCl3) 169.21,
169.06, 164.89, 133.72, 129.79 (2), 128.71, 128.58 (2),
98.31, 75.41, 74.11, 70.51, 64.57 (d, J¼5.9 Hz), 63.41 (d,
1
J¼5.9 Hz), 16.40 (2C, d, J¼5.9 Hz), 20.91, 20.33. For H
and 13C NMR data see Tables 1–3.
4.4. (4R)-Ethyl-[1-(adenin-9-yl)-1-deoxy-b-D-erythro-
furanos-4-yl]phosphonate (12b)
6-N-Benzoyladenine (598 mg, 2.5 mmol) in hexamethyl-
disilazane (HMDS) (25 mL, 118 mmol) was refluxed in the
presence of chlorotrimethylsilane (2.5 mL, 20 mmol) under