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D. F. Ewing et al. / Tetrahedron 59 (2003) 941–945
white powder of the corresponding dialdehyde. Without
further purification the dialdehyde was dissolved in freshly
distilled tetrahydrofuran (5 mL), and treated with a yellow
solution of methyltriphenylphosphine bromide (1.3 g,
3.66 mmol) and potassium tert-butoxide (0.41 g,
3.66 mmol) in toluene (50 mL) at 608C under argon. After
1 h, the mixture was cooled at room temperature, washed
with a saturated solution of ammonium chloride (2£30 mL),
dried over MgSO4, evaporated to a yellow syrup and
purified by column chromatography (hexane–ethyl acetate,
9:1) to afford bis-(4-methoxyphenyl)phenylmethanol
(29.3 mg, 10%) and the protected nucleoside 9 (0.25 g;
158.9 (21C, trityl). Anal. calcd for C32H33O5N3: C, 77.22;
H, 6.16; N, 7.79. Found: C, 71.25; H, 6.19; N, 7.82. HRMS
(ESI) (MþNaþ) calcd for C32H33O5N3Na: 562.2333, found
562.2318.
3.2.6. 1-{1-[1-(Hydroxymethyl)prop-2-enyloxy]prop-2-
enyl}thymine (1). An aqueous solution of acetic acid
(80%, 65 mL) was added to 8 (0.5 g, 1.01£1023 mol). After
1 h at 508C, the mixture was co-evaporated with methanol
and purified by column chromatography (ethyl acetate–
methanol, 49:1) to afford 1 (0.22 g., 86%) as an oil; Rf 0.4
(dichloromethane–methanol, 95:5); 1H NMR (CDCl3) d
1.90 (3H, s, CH3), 3.62 (2H, m, H-50a, H-50b), 4.06 (1H, m,
H-40), 5.38 (1H, d, J¼10.5 Hz, H-30-CH2), 5.44 (1H, d,
J¼1.4 Hz, J¼10.5 Hz, H-30-CH2), 5.45 (1H, d, J¼17.2 Hz,
H-30-CH2), 5.57 (1H, dt, J¼1.4, 17.2 Hz, H-20 –CH2), 5.73
(1H, m, H-30), 5.82 (1H, dq, J¼3.5, 10.5,0 17.2 Hz, H-20 –
CH2), 6.31 (1H, dt, J¼1.7, 3.6 Hz, H-1 ), 7.21 (1H, d,
J¼1.2 Hz, H-6), 9.70 0(1H, bs, NH); 13C NMR (CDCl3) d
12.5 (CH3), 64.9 (C-5 ), 79.7 (C-40), 81.5 (C-10), 111.8 (C-
5), 120.0 (C-20 –CH2), 121.2 (C-30 –CH2), 132.8 (C-30),
133.2 (C-20), 136.0 (C-6), 151.2 (C-2), 163.7 (C-4). Anal.
calcd for C12H16O4N2: C, 57.13; H, 6.39; N, 11.10. Found:
C, 57.12; H, 6.43; N, 11.15. HRMS (ESI) (MþNaþ) calcd
for C12H16O4N2Na: 275.1012, found 275.1008.
1
51%) as a foam; Rf 0.5 (hexane–ethyl acetate, 1:1); H
NMR (CDCl3) d 3.07 (1H, dd, J¼3.2, 10.4 Hz, H-50a), 3.35
(1H, dd, J¼8.2, 10.4 Hz, H-50b), 3.91 (1H, m, H-40), 5.30
(1H, s, H-30 –CH2), 5.35 (1H, d, J¼5.6 Hz, H-30 –CH2), 5.44
(1H, dt, J¼1.4, 10.4 Hz, H-20 –CH2), 5.61 (1H, dt, J¼1.4,
17.1 Hz, H-20 –CH2), 5.74 (1H, d, J¼7.9 Hz, H-5), 5.75
(1H, m, H-30), 5.84 (1H, qd, J¼3.6, 10.5, 17.1 Hz, H-20),
6.26 (1H, dt, J¼1.5, 3.6 Hz, H-10), 7.53–7.25, 3.81 (21H, m,
trityl), 7.43 (1H, d, J¼7.9 Hz, H-6), 8.64 (1H, bs, NH); 13C
NMR (CDCl3) d 66.3 (C-50), 78.8 (C-40), 80.7 (C-10), 103.5
(C-5), 119.6 (C-20 –CH2), 121.2 (C-30 –CH2), 133.2 (C-30),
133.9 (C-20), 141.2 (C-6), 151.5 (C-2), 164.0 (C-4), 55.6,
86.7, 113.5, 127.3, 128.2, 128.6, 130.5, 136.2, 136.4, 145.1,
158.9 (21C, trityl). Anal. calcd for C32H32O6N2: C, 71.09;
H, 5.97; N, 5.18. Found: C, 71.05; H, 5.95; N, 5.22. HRMS
(ESI) (MþNaþ) calcd for C32H32O6N2Na: 563.2140, found
563.2158.
3.2.7. 1-{1-[1-(Hydroxymethyl)prop-2-enyloxy]prop-2-
enyl}uracil (2). An aqueous solution of acetic acid (80%,
65 mL) was added to 9 (0.5 g, 9.15£1024 mol). After 1 h at
room temperature, the mixture was co-evaporated with
methanol and purified by column chromatography (ethyl
acetate–methanol, 49:1) to afford 2 (0.21 g., 95%) as a
solid; mp 1128C; Rf 0.6 (dichloromethane–methanol, 95:5);
1H NMR (CDCl3) d 3.59 (1H, dd, J¼7.7, 12.0 Hz, H-50a),
3.67 (1H, dd, J¼3.6, 12.0 Hz, H-50b), 4.09 (1H, m, H-40),
5.38 (1H, d, J¼10.4 Hz, H-30 –CH2), 5.44 (1H, dt, J¼1.2,
10.4 Hz, H-30 –CH2), 5.46 (1H, d, J¼17.4 Hz, H-30 –CH2),
5.58 (1H, dt, J¼1.2, 17.2 Hz, H-20 –CH2), 5.74 (1H, m,
H-30), 5.75 (1H, d, 0J¼8.1 Hz, H-5), 5.83 (1H, dq, J¼3.7,
10.5, 17.1 Hz, H-2 –CH2), 6.32 (1H, dt, J¼1.6, 3.7 Hz,
3.2.5. 1-{1-[1-(4,40-Dimethoxytrityloxymethyl)prop-2-
enyloxy]prop-2-enyl}cytosine (11). A solution of 1,2,4-1-
H-triazole (0.57 g, 9.66 mmol) and POCl3 (0.17 mL,
2.02 mmol) in acetonitrile (6 mL) was cooled at 08C. Et3N
(1.1 mL, 9.24 mmol) was then added and the mixture stirred
for 30 min at room temperature. A solution of 9 (0.5 g,
9.25£1024 mol) in acetonitrile (3 mL) was added and the
resulting heterogeneous mixture stirred overnight at room
temperature. Et3N (0.9 mL) and H2O (0.4 mL) were added
to give a homogeneous solution which was stirred for
15 min, dissolved in dichloromethane (15 mL), washed with
a saturated solution of Na2CO3 (2£15 mL), dried over
MgSO4 and evaporated to give a yellow powder of the
1,2,4-triazolyl derivative 10. Without further purification 10
was dissolved in dioxane (6.5 mL) and added to an aqueous
solution of ammonia (30%) (2.15 mL) and set aside
overnight at room temperature. The subsequent mixture
was evaporated under reduced pressure and purified by
column chromatography (ethyl acetate–methanol, 13:1) to
afford 11 (0.44 g; 88%) as a white powder; mp 1048C; Rf 0.3
(dichloromethane–methanol, 95:5); 1H NMR (CDCl3) d
3.02 (1H, dd,0 J¼3.0, 10.3 Hz, H-50a), 3.31 (1H, dd, J¼8.2,
10.3 Hz, H-50b), 3.94 (1H, m, H-40), 5.26 (1H, dt, J¼0.8,
10.2 Hz, H-3 –CH2), 5.32 (1H, dt, J¼0.8, 17.2 Hz, H-30 –
CH2), 5.35 (1H, dt, J¼1.5, 10.5 Hz, H-20 –CH2), 5.54 (1H,
dt, J¼1.5, 17.1 Hz, H-20 –CH2), 5.60 (1H, m, H-30), 5.63
(1H, d, J¼7.3 Hz, H-5), 5.86 (1H, qd, J¼3.6, 010.5, 17.1 Hz,
H-20), 6.41 (1H, dt, J¼1.8, 3.6 Hz, H-1 ), 7.63 (1H,
J¼7.3 Hz, H-6), 7.45–7.22, 3.81 (21H, m, trityl); 13C
NMR (CDCl3) d 66.5 (C-50), 78.5 (C-40), 81.3 (C-10), 96.2
(C-5), 118.6 (C-20 –CH2), 120.5 (C-30 –CH2), 133.7 (C-30),
134.9 (C-20), 142.3 (C-6), 157.3 (C-2), 166.3 (C-4), 55.6,
86.6, 113.5, 127.2, 128.6, 128.6, 130.5, 136.3, 136.5, 145.3,
H-10), 7.44 (1H, d, J¼8.1 Hz, H-6), 9.91 (1H, bs, NH); 13
C
NMR (CDCl3) d 65.3 (C-50), 80.6 (C-40), 81.3 (C-10), 103.3
(C-5), 120.3 (C-20 –CH2), 121.0 (C-30 –CH2), 133.3 (C-30),
133.5 (C-20), 141.4 (C-6), 151.6 (C-2), 164.5 (C-4). Anal.
calcd for C11H14O4N2: C, 55.46; H, 5.92; N, 11.76. Found:
C, 55.43; H, 5.95; N, 11.78. HRMS (ESI) (MþNaþ) calcd
for C11H14O4N2Na: 261.0864, found 261.0851.
3.2.8. 1-{1-[1-(Hydroxymethyl)prop-2-enyloxy]prop-2-
enyl}cytosine (3). An aqueous solution of acetic acid
(80%, 65 mL) was added to 9 (0.5 g, 9.27£1024 mol). After
1 h at room temperature, the mixture was co-evaporated
with methanol and purified by column chromatography
(ethyl acetate–methanol, 3:1) to afford 3 (0.20 g, 91%) as a
white powder; mp 488C, Rf 0.3 (dichloromethane–
methanol, 80:20); 1H NMR (CDCl3) d 3.54 (1H, dd,
J¼8.0, 12.0 Hz, H-50a), 3.66 (1H, dd, J¼3.2, 12.0 Hz, H-
50b), 4.06 (1H, m, H-40), 5.31 (1H, d, J¼10.5 Hz, H-30 –
CH2), 5.35 (1H, dt, J¼1.3, 10.5 Hz, H-30 –CH2), 5.41 (1H,
d, J¼17.2 Hz, H-30 –CH2), 5.48 (1H, dt, J¼1.3, 17.2 Hz,
H-20 –CH2), 5.73 (1H, m, H-30), 5.81 (1H, dq, J¼3.8, 10.5,
17.2 Hz, H-20-CH2), 5.88 (1H, d, J¼7.1 Hz, H-5), 6.38 (1H,
dt, J¼1.6, 3.7 Hz, H-10), 7.48 (1H, d, J¼8.1 Hz, H-6); 13C