2182
S. Guillarme et al. / Tetrahedron 59 (2003) 2177–2184
DBU (26.5 mg, 0.174 mmol) in acetonitrile (7 mL), in the
same experimental conditions as for 11c, led to 11d
(495 mg, 1.37 mmol, 79%) as a yellow oil after column
chromatography (silica gel, CH2Cl2/EtOAc: 8/2!6/4): IR
(neat, cm21) 3490, 1747, 1697, 1660, 1250, 1180; 1H NMR
(CDCl3) d 7.92 (m, 2H, arom), 7.65 (m, 1H, arom), 7.50 (m,
2H, arom), 7.26 (q, 1H, CH, J¼1.2 Hz), 4.2 (q, 2H, CH2–O,
J¼7.1 Hz), 4.09 (dd, 2H, CH2–N, J¼3.9, 6.7 Hz), 3.92 (dt,
1H, CH2–O, J¼5.4, 11.5 Hz), 3.79 (ddd, 1H, CH2–O,
J¼4.2, 7.4, 11.5 Hz), 3.01 (m, 1H, CH), 2.67 (br s, 1H, OH),
1.95 (d, 3H, CH3, J¼1.2 Hz), 1.29 (t, 3H, CH3, J¼7.1 Hz);
13C NMR (CDCl3) d 171.9 (CvO), 168.7 (C6H5CO), 163.0
(CvO), 150.5 (CvO), 141.2 (CH), 135.1 (quat C), 131.4
(CH), 130.4 (CH), 129.9 (CH), 110.8 (quat C), 61.5
(CH2–O), 60.1 (CH2–O), 47.2 (CH2–N), 46.2 (CH),
14.1 (CH3), 12.4 (CH3). Anal. calcd for C18H20N2O6,
0.2H2O: C, 59.40; H, 5.65; N, 7.70. Found: C, 59.42; H,
5.73; N, 7.95.
acetyl-6-O-(diphenylcarbamoyl)guanine (307 mg, 0.790
mmol), dimethyl itaconate 8 (187 mg, 1.18 mmol) and
K2CO3 (9.1 mg, 0.077 mmol) in DMF (3 mL) was stirred
for 60 h at room temperature. After removal of the solvent
under reduced pressure, the residue was purified by column
chromatography (silica gel, CH2Cl2/EtOAc: 2/8!1/9) to
afford 12b (270 mg, 0.494 mmol, 63%) as a white solid:
mp 68–708C; IR (KBr, cm21) 3502, 3264, 1741, 1621,
1590, 1550, 1492; 1H NMR (CDCl3) d 8.01 (br s, 1H, NH),
7.96 (s, 1H, CH), 7.46–7.24 (m, 10H, arom), 4.58 (dd, 1H,
CH2–N, J¼7.4, 14.3 Hz), 4.45 (dd, 1H, CH2–N, J¼5.4,
14.3 Hz), 3.69 (s, 3H, CH3), 3.67 (s, 3H, CH3), 3.45 (m, 1H,
CH), 2.68 (d, 2H, CH2, J¼6.1 Hz), 2.56 (s, 3H, CH3);
13C NMR (CDCl3) d 172.1 (CvO), 171.1 (CvO), 156.2
(quat C), 155.2 (quat C), 152.2 (CvO), 150.4 (CvO),
144.5 (CH), 141.7 (quat C), 129.2–126.3 (CH), 120.5
(quat C), 52.6 (CH3), 52.1 (CH3), 44.3 (CH2–N), 41.3
(CH), 33.3 (CH2), 25.1 (CH3). Anal. calcd for C27H26N6O7:
C, 59.34; H, 4.80; N, 15.38. Found: C, 59.01; H, 4.82; N,
15.15.
4.1.6. Dimethyl 2-(6-N-benzoyladenin-9-ylmethyl) succi-
nate 12a and dimethyl 2-(6-N-benzoyladenin-7-yl-
methyl) succinate 12a0. A solution of 6-N-benzoyladenine
(235 mg, 0.983 mmol), dimethyl itaconate 8 (233 mg,
1.475 mmol) and K2CO3 (11.5 mg, 0.098 mmol) in DMF
(4 mL) was heated at 808C for 24 h. The mixture was
evaporated under reduced pressure and both compounds
were separated by column chromatography (silica gel,
CH2Cl2/EtOAc: 1/9!0/1) to give successively isomer 12a0
(36.9 mg, 0.093 mmol, 9%) as a white solid then isomer 12a
(231.7 mg, 0.583 mmol, 59%) as a white solid.
4.1.8. Dimethyl 2-(4-N-benzoylcytosin-1-ylmethyl) suc-
cinate 12c. A solution of 4-N-benzoylcytosine (250 mg,
1.16 mmol), dimethyl itaconate 8 (275 mg, 1.73 mmol) and
DBU (212 mg, 1.39 mmol) in DMF (3.5 mL) was stirred for
40 h at room temperature. The mixture was evaporated
under reduced pressure and the crude product was purified
by column chromatography (silica gel, CH2Cl2/EtOAc:
75/25!4/6) to give 12c (370 mg, 0.991 mmol, 58%) as a
white solid: mp 132–1338C; IR (KBr, cm21) 3479, 1727,
1660, 1625, 1554, 1486, 1251; 1H NMR (CDCl3) d 8.69 (br
s, 1H, NH), 7.89 (m, 2H, arom), 7.79 (d, 1H, CH, J¼
7.9 Hz), 7.63 (m, 1H, arom), 7.53 (d, 1H, CH, J¼7.9 Hz),
7.48 (m, 2H, arom), 4.19 (d, 2H, CH2–N, J¼5.5 Hz), 3.71
(s, 3H, CH3), 3.70 (s, 3H, CH3), 3.44 (m, 1H, CH), 2.85 (dd,
1H, CH2, J¼5.3, 17.1 Hz), 2.72 (dd, 1H, CH2, J¼6.3,
17.1 Hz); 13C NMR (CDCl3) d 173.2 (CvO) (2 signal
overlap), 172.0 (CvO), 163.1 (C6H5CO), 150.5 (CH),
133.6 (quat C), 133.5 (CH), 129.4 (CH), 128.1 (CH), 97.0
(CH), 52.9 (CH3), 52.5 (CH3), 52.1 (CH2–N), 40.2 (CH),
34.1 (CH2). Anal. calcd for C18H19N3O6: C, 57.90; H, 5.13;
N, 11.26. Found: C, 57.75; H, 5.12; N, 11.13.
Compound 12a. Mp 109–1118C; IR (KBr, cm21) 3440,
3158, 3100, 1734, 1660; 1H NMR (CDCl3) d 9.09 (br s, 1H,
NH), 8.80 (s, 1H, CH), 8.07 (s, 1H, CH), 8.05 (d, 2H, arom,
J¼7.0 Hz), 7.62 (m, 1H, arom), 7.53 (m, 2H, arom), 4.70
(dd, 1H, CH2–N, J¼7.1, 14.1 Hz), 4.53 (dd, 1H, CH2–N,
J¼5.6, 14.1 Hz), 3.71 (s, 3H, CH3), 3.70 (s, 3H, CH3), 3.51
(m, 1H, CH), 2.74 (dd, 1H, CH2, J¼6.4, 17.0 Hz), 2.69 (dd,
1H, CH2, J¼6.4, 17.0 Hz); 13C NMR (CDCl3) d 172.3
(CvO), 171.3 (CvO), 164.8 (C6H5CO), 152.8 (CH), 152.3
(quat C), 150.0 (quat C), 147.7 (CH), 133.7 (quat C), 132.9
(CH), 129.0 (CH), 128.0 (CH), 122.8 (quat C), 52.7 (CH3),
52.3 (CH3), 44.2 (CH2–N), 41.5 (CH), 33.4 (CH2). Anal.
calcd for C19H19N5O5: C, 57.43; H, 4.82; N, 17.62. Found:
C, 57.17; H, 4.83; N, 17.33.
4.1.9. Dimethyl 2-(3-N-benzoylthymin-1-ylmethyl) suc-
cinate 12d. Reaction from 3-N-benzoylthymine (92 mg,
0.4 mmol), dimethyl itaconate 8 (63.3 mg, 0.4 mmol) and
DBU (6.1 mg, 0.04 mmol) in acetonitrile (2 mL), in the
same experimental conditions as for 11d, led to 12d (99 mg,
0.255 mmol, 64%) as a yellow oil after column chroma-
Compound 12a0. Mp 61–628C; IR (KBr, cm21) 3446, 3060,
3012, 1733, 1637; 1H NMR (CDCl3) d 15.5 (br s, 1H, NH),
8.34 (s, 1H, CH), 8.23 (d, 2H, arom), 8.12 (s, 1H, CH), 7.54
(m, 1H, arom), 7.49 (m, 2H, arom), 5.15 (dd, 1H, CH2–N,
J¼7.1, 13.7 Hz), 4.91 (dd, 1H, CH2–N, J¼7.3, 13.7 Hz),
3.78 (m, 1H, CH), 3.72 (s, 3H, CH3), 3.62 (s, 3H, CH3), 2.78
(dd, 1H, CH2, J¼4.3, 17.1 Hz), 2.60 (dd, 1H, CH2, J¼6.9,
17.1 Hz); 13C NMR (CDCl3) d 179.0 (C6H5CO), 171.6
(CvO), 170.7 (CvO), 158.1 (quat C), 149.9 (quat C),
146.6 (CH), 141.6 (CH), 136.5 (quat C), 131.8 (CH), 128.8
(CH), 127.7 (CH), 114.6 (quat C), 52.0 (CH3), 51.6 (CH3),
47.4 (CH2–N), 42.0 (CH), 32.2 (CH2). Anal. calcd for
C19H19N5O5: C, 57.43; H, 4.82; N, 17.62. Found: C, 57.73;
H, 4.84; N, 17.46.
tography (silica gel, CH2Cl2/EtOAc: 9/1): IR (neat, cm21
)
3068, 3006, 1753, 1699, 1654, 1253, 1176; 1H NMR
(CDCl3) d 7.93 (m, 2H, arom), 7.65 (m, 1H, arom), 7.50 (m,
2H, arom), 7.21 (s, 1H, CH), 4.04 (dd, 1H, CH2–N, J¼8.0,
14.0 Hz), 3.97 (dd, 1H, CH2–N, J¼7.4, 14.0 Hz), 3.71 (s,
3H, CH3), 3.69 (s, 3H, CH3), 3.26 (m, 1H, CH), 2.76 (dd,
1H, CH2, J¼6.6, 17.0 Hz), 2.70 (dd, 1H, CH2, J¼6.3,
17.0 Hz), 1.96 (s, 3H, CH3); 13C NMR (CDCl3) d 172.6
(CvO), 171.8 (CvO), 168.8 (CvO), 163.0 (C6H5CO),
160.0 (CvO), 140.6 (CH), 135.0 (quat C), 131.5 (CH),
130.5 (CH), 129.1 (CH), 110.7 (quat C), 52.6 (CH3), 52.1
(CH3), 49.7 (CH2–N), 40.5 (CH), 33.5 (CH2), 12.4 (CH3).
Anal. calcd for C19H20N2O7: C, 58.76; H, 5.19; N, 7.21.
Found: C, 58.37; H, 5.17; N, 7.01.
4.1.7. Dimethyl 2-(2-N-acetyl-6-O-(diphenylcarbamoyl)-
guanin-9-ylmethyl) succinate 12b. A solution of 2-N-