E. Coutouli-Argyropoulou, S. Trakossas / Tetrahedron 67 (2011) 1915e1923
1919
CH2OH), 76.9 (C-50), 112.1 (C-5), 139.2(C-6), 150.8 (C-2), 162.7 (C-4);
MS (m/z, %): 452 [(MþH)þ, 100%]. Anal. Calcd for C25H45N3O4: C,
66.48; H, 10.04; N, 9.30. Found: C, 66.26; H, 10.21; N, 9.25.
2990, 2910, 2860, 1595, 1560, 1450, 1390, 1230, 1050 cmꢁ1; 1H NMR:
d
2.10 (br, 1H, OH), 2.23 (dt, J¼12.1, 8.0 Hz, 1H, 40-H), 2.51 (ddd, J¼12.1,
9.5, 6.7 Hz, 1H, 40-H), 2.62 (s, 3H, NeCH3), 3.62 (dd, J¼12.0, 4.8 Hz, 1H,
CH2OH), 3.72e3.86 (m, 2H, CH2OH and 30-H), 3.99 (s, 3H, OCH3), 4.01 (s,
3.3.2. (30RS,50RS)-5-(50-Hydroxymethyl-20-methyl isoxazolidin-30-yl)-1,3-
dioctyluracil (4a). This compound was obtained from nitrone 2a in 30%
yield as an oil; IR (liquid film): nmax 3450, 3050, 2920, 2850, 1675, 1630,
3H, OCH3), 4.25e4.35 (m, 1H, 50-H), 8.30 (s, 1H, 6-H); 13C NMR:
d 38.0
(C-40), 43.6 (NeCH3), 54.0 and 54.7 (OCH3), 63.6 and 64.5 (C-30 and
CH2OH), 77.5 (C-50),112.9 (C-5),156.8 (C-6),164.7 (C-2),169.0 (C-4); MS
(m/z, %): 278 [(MþNa)þ, 100]. Anal. Calcd for C11H17N3O4: C, 51.76; H,
6.71; N, 16.46. Found: C, 51.58; H, 6.65; N, 16.66.
1450, 1340, 1250, 1230, 1030 cmꢁ1; 1H NMR:
d 0.80e0.95 (m, 6H, CH3),
1.17e1.41 (m, 20H, CH2CH2(CH2)5CH3), 1.52e1.70 (m, 4H,
CH2CH2(CH2)5CH3), 1.90 (br, 1H, OH), 2.14 (ddd, J¼12.4, 8.0, 5.2 Hz, 1H,
40-H), 2.58 (dt, J¼12.4, 8.0 Hz, 1H, 40-H), 2.71 (s, 3H, NeCH3), 3.63 (dd,
J¼12.0, 5.1 Hz, 1H, CH2OH), 3.71e4.02 (m, 6H, CH2CH2(CH2)5CH3,
CH2OH and 30-H), 4.12e4.21 (m, 1H, 50-H), 7.33 (s, 1H, 6-H); 13C NMR:
3.3.7. (30RS,50SR)-5-[(20-Benzyl-50-hydroxymethyl)isoxazolidin-30-
yl]-2,4-dimethoxypyrimidine (15b) and (30RS,50RS)-5-[(20-benzyl-
50-hydroxymethyl)isoxazolidin-30-yl]-2,4-dimethoxypyrimidine (16b).
These compounds were obtained from nitrone 14b as a oily mixture
in a ratio 2:1 and 85% total yield and they were characterized only
d
14.0 (CH3), 22.6, 26.5, 27.0, 27.6, 29.0, 29.1, 29.2, 31.6 and 31.7
(CH2(CH2)6CH3), 37.3 (C-40), 41.6, 49.9 and 53.5 (CH2(CH2)6CH3 and
NeCH3), 63.9 (C-30 and CH2OH), 78.2 (C-50), 112.1 (C-5), 139.2 (C-6),
150.9 (C-2), 162.6 (C-4), 166.7 (C]O); MS (m/z, %): 452 [(MþH)þ,100%].
Anal. Calcd for C25H45N3O4: C, 66.48; H, 10.04; N, 9.30. Found: C, 66.48;
H, 9.87; N, 9.50.
by their 1H NMR spectrum; 1H NMR:
d 1.98 (br, OH), 2.05 (ddd,
J¼12.7, 7.7, 5.7 Hz, 40-H of 15b), 2.21 (dt, J¼12.2, 7.6 Hz, 1H, 40-H of
16b), 2.58 (ddd, J¼12.2, 8.1, 6.9 Hz, 1H, 40-H of 16b), 2.81 (dt, J¼12.7,
8.3 Hz, 40-H of 15b), 3.62 (dd, J¼12.0, 4.8 Hz, 1H, CH2OH), 3.54e4.01
(overlapped s and m, OCH3, CH2C6H5, CH2OH and 30-H of 16b), 3.99
(s, OCH3), 4.01 (s, OCH3), 4.08 (apparent t, SJ¼16 Hz, 30-H of 16b),
4.22e4.31 (m, 1H, 50-H of 16b), 4.33e4.41 (m, 1H, 50-H of 15b),
7.19e7.37 (m, CH2C6H5), 8.41 (s, 6-H of 16b), 8.43 (s, 6-H of 15b).
3.3.3. (30RS,50SR)-5-[(20-Benzyl-50-hydroxymethyl)isoxazolidin-30-
yl]-1,3-dioctyluracil (3b). This compound was obtained fromnitrone
2b in 55% yield as an oil; IR (liquid film): nmax 3450, 3050, 2920, 2850,
1675, 1630, 1450, 1330, 1210, 1110, 1020 cmꢁ1; 1H NMR:
d 0.80e0.98
(m, 6H, CH3), 1.15e1.43 (m, 20H, CH2CH2(CH2)5CH3), 1.50e1.75 (m,
4H, CH2CH2(CH2)5CH3), 2.01 (dt, J¼12.6, 6.4 Hz, 1H, 40-H), 2.30 (br,
1H, OH), 2.88 (dt, J¼12.6, 8.4 Hz, 1H, 40-H), 3.57 (dd, J¼11.6, 5.5 Hz,
1H, CH2OH), 3.63e3.78 (m, 3H, CH2CH2(CH2)5CH3 and CH2OH),
3.84e3.93 (m, 3H, CH2CH2(CH2)5CH3 and CH2C6H5), 4.05 (d,
J¼13.7 Hz,1H, CH2C6H5), 4.15 (dd, J¼8.4, 6.4 Hz,1H, 30-H), 4.39e4.49
(m,1H, 50-H), 7.27e7.32 (m, 5H, CH2C6H5), 7.39 (s,1H, 6-H); 13C NMR:
3.4. Mesylation reactions of hydroxymethyl isoxazolidines,
3, 4, 15, 16
General procedure. Hydroxymethyl isoxazolidine 3 or 4 or 15 or
16 (2 mmol) was dried by addition and evaporation with dry tol-
uene three times. Next, it was dissolved in dry pyridine (3 ml) and
mesylchloride (2.4 mmol) was added under an argon atmosphere
at 0 ꢀC. The reaction mixture was stirred at room temperature until
the completion of the reaction (1e2 h). Then the pyridine was
evaporated and the residue was chromatographed on a silica gel
column with a mixture of hexane/ethyl acetate (2:1 for the re-
actions of 3a, 4a,1:1 for the reactions of 3b,15a,16a,15b,16b) as the
eluent.
d
14.0 (CH3), 22.5, 26.4, 26.8, 26.9, 27.5, 29.1, 29.2, 31.6 and 31.7
(CH2(CH2)6CH3), 37.7 (C-40), 41.8, and 49.9 (CH2(CH2)6CH3), 61.2, 61.9
and 64.5 (C-30, CH2C6H5 and CH2OH), 77.3 (C-50), 112.5 (C-5), 127.4,
128.7, 128.8 and 136.8 (CH2C6H5), 139.4 (C-6), 150.8 (C-2), 162.5 (C-
4); MS (m/z, %): 550 [(MþNa)þ, 100]. Anal. Calcd for C31H49N3O4: C,
70.55; H, 9.36; N, 7.96. Found: C, 70.33; H, 9.21; N, 8.07.
3.3.4. (30RS,50RS)-5-[(20-Benzyl-50-hydroxymethyl)isoxazolidin-30-
yl]-1,3-dioctyluracil (4b). This compound was obtained from
nitrone 2b in 20% yield only as a mixture with 3b; 1H NMR:
3.4.1. (30RS,50SR)-5-[20-Methyl-50-((methylsulfonyloxy)methyl)iso-
xazolidin-30-yl]-1,3-dioctyluracil (5a). This compound was obtained
from 3a in 87% yield as an oil; IR (liquid film): nmax 2920, 2845,
d
0.80e0.98(m, CH3),1.15e1.45 (m, CH2CH2(CH2)5CH3),1.50e1.80(m,
1690, 1650, 1455, 1350, 1175, 1060 cmꢁ1; 1H NMR:
d 0.80e0.95 (m,
CH2CH2(CH2)5CH3), 2.01 (dt, J¼12.6, 6.4 Hz, 40-H of 3b), 2.17 (ddd,
J¼12.4, 7.8,4.8 Hz, 40-Hof4b), 2.58(dt, J¼12.4, 7.8 Hz, 40-Hof4b), 2.88
(dt, J¼12.6, 8.4 Hz, 40-H of 3b), 3.51e3.80 (m, CH2CH2(CH2)5CH3 and
CH2OH), 3.84e3.93 (m, CH2CH2(CH2)5CH3 and CH2C6H5), 4.05 (d,
J¼13.7 Hz, CH2C6H5), 4.10e4.20 (m, 30-H and 50-H of 4b), 4.39e4.49
(m, 50-H of 3b), 7.20e7.40 (m, CH2C6H5 and 6-H).
6H, CH3), 1.17e1.40 (m, 20H, CH2CH2(CH2)5CH3), 1.55e1.75 (m, 4H,
CH2CH2(CH2)5CH3), 1.91 (dt, J¼12.8, 6.2 Hz, 1H, 40-H), 2.68 (s, 3H,
NeCH3), 2.89e2.96 (m, 1H, 40-H), 3.05 (s, 3H, SO2CH3), 3.61e3.95
(m, 5H, CH2CH2(CH2)5CH3 and 30-H), 4.18 (dd, J¼11.0, 4.5 Hz, 1H,
CH2OSO2CH3), 4.31 (dd, J¼11.0, 7.0 Hz, 1H, CH2OSO2CH3), 4.45e4.61
(m, 1H, 50-H), 7.32 (s, 1H, 6-H); 13C NMR:
d 13.97, 13.98 (CH3), 22.5,
22.6, 26.5, 27.0, 27.5, 29.0, 29.1, 29.2, 31.6 and 31.7 (CH2(CH2)6CH3),
37.7 and 38.1 (C-40 and SO2CH3), 41.5, 44.0 and 50.0 (CH2(CH2)6CH3
and NeCH3), 64.2 and 64.9 (C-30 and CH2OSO2CH3), 74.2 (C-50),
111.6 (C-5), 139.5 (C-6), 150.9 (C-2), 162.5 (C-4); MS (m/z, %): 552
[(MþNa)þ, 100]. Anal. Calcd for C26H47N3O6S: C, 58.95; H, 8.94; N,
7.93. Found: C, 58.88; H, 8.69; N, 8.01.
3.3.5. (30RS,50SR)-5-(50-Hydroxymethyl-20-methylisoxazolidin-30-yl)-
2,4-dimethoxypyrimidine (15a). This compound was obtained from
nitrone 14a in 53% yield as an oil; IR (liquid film): nmax 3600e3100,
1
2950, 2910, 2860, 1595, 1565, 1460, 1390, 1200, 1075, 1015 cmꢁ1; H
NMR: 2.07 (ddd, J¼12.4, 8.5, 5.6 Hz, 1H, 40-H), 2.62 (s, 3H, NeCH3),
2.70 (br, 1H, OH), 2.77 (dt, J¼12.4, 8.5 Hz, 1H, 40-H), 3.65e3.71 (m, 2H,
CH2OH), 3.80 (t, J¼8.5 Hz, 1H, 30-H), 3.98 (s, 3H, OCH3), 4.01 (s, 3H,
3.4.2. (30RS,50RS)-5-[20-Methyl-50-(methylsulfonyloxy)methyl)iso-
xazolidin-30-yl]-1,3-dioctyluracil (6a). This compound was obtained
from 4a in 85% yield as an oil; IR (liquid film): nmax 2920, 2845,
OCH3), 4.30e4.39 (m, 1H, 50-H), 8.31 (s, 1H, 6-H); 13C NMR:
d 38.3 (C-
40), 43.4 (NeCH3), 54.0 and 54.7 (OCH3), 64.5 and 65.3 (C-30 and
CH2OH), 77.0 (C-50, detected by DEPT), 112.8 (C-5), 156.5 (C-6), 164.7
(C-2), 168.9 (C-4); MS (m/z, %): 278 [(MþNa)þ, 100]. Anal. Calcd for
C11H17N3O4: C, 51.76; H, 6.71; N, 16.46. Found: C, 51.54; H, 6.82; N,
16.65.
1695, 1640, 1455, 1350, 1170, 1080 cmꢁ1; 1H NMR:
d 0.85e0.95 (m,
6H, CH3), 1.17e1.40 (m, 20H, CH2CH2(CH2)5CH3), 1.52e1.77 (m, 4H,
CH2CH2(CH2)5CH3), 2.28 (ddd, J¼12.6, 8.2, 5.5 Hz,1H, 40-H), 2.56 (dt,
J¼12.6, 7.6 Hz, 1H, 40-H), 2.72 (s, 3H, NeCH3), 3.09 (s, 3H, SO2CH3),
3.70e3.80 (m, 2H, CH2CH2(CH2)5CH3), 3.85e3.98 (m, 3H,
CH2CH2(CH2)5CH3 and 30-H), 4.22e4.44 (m, 3H, CH2OSO2CH3 and
3.3.6. (30RS,50RS)-5-(50-Hydroxymethyl-20-methylisoxazolidin-30-yl)-
2,4-dimethoxypyrimidine (16a). This compound was obtained from
nitrone 14a in 36% yield as an oil; IR (liquid film): nmax 3600e3100,
50-H), 7.31 (s, 1H, 6-H); 13C NMR:
d
14.0 (CH3), 22.6, 26.5, 27.0, 27.6,
29.0, 29.1, 29.2, 31.6 and 31.7 (CH2(CH2)6CH3), 37.6 and 37.8 (C-40