3920
Y.-C. Shih, T.-C. Chien / Tetrahedron 67 (2011) 3915e3923
chromatography (Hex/EtOAc¼8:2, Rf¼0.31) to give the product
(12b, oil, 84%). 1H NMR (CDCl3, 400 MHz)
7.50e7.46 (m, 7H, Ph),
(CH3), ꢁ5.4 (CH3); MS (ESI) m/z 573 (100) (Mꢁ1); HRMS calcd for
C30H45N2O7Si (Mꢁ1): 573.2996. Found: 573.2994.
d
7.34e7.27 (m, 3H, Ph), 5.69 (s, 1H, 5-H), 5.49 (d, 1H, J¼1.1 Hz, 10-H),
5.18 (dd, 1H, J¼1.3 and 6.5 Hz, 20-H), 5.15 (d, 1H, J¼13.8 Hz, CH2),
5.09 (d, 1H, J¼13.8 Hz, CH2), 4.85 (dd, 1H, J¼4.2 and 6.4 Hz, 30-H),
4.06e4.02 (m, 1H, 40-H), 3.85 (dd, 1H, J¼5.7 and 10.6 Hz, 50-H), 3.78
(dd, 1H, J¼7.3 and 10.6 Hz, 50-H), 1.35 (s, 3H, CH3), 1.29 (s, 3H, CH3),
0.90 (s, 9H, CH3), 0.04 (s, 6H, CH3); 13C NMR (CDCl3, 100 MHz)
4.3.12. 50-O-tert-Butyldimethylsilyl-20,30-O-isopropylidene-5-phenyl-
uridine (19a). The reaction was purified by flash column chroma-
tography (Hex/EtOAc¼8:2, Rf¼0.13) to give the product (19a, 77%).
1H NMR (CDCl3, 400 MHz)
d 8.17 (br s, 1H, NH), 7.61 (s, 1H, 6-H),
7.47e7.32 (m, 5H, Ph), 5.93 (d, 1H, J¼3.2 Hz, 10-H), 4.82e4.73 (m,
2H, 20-H, and 30-H), 4.34 (t, 1H, J¼2.8 Hz, 40-H), 3.91e3.77 (m, 2H,
50-H), 1.60 (s, 3H, CH3), 1.37 (s, 3H, CH3), 0.77 (s, 9H, CH3), ꢁ0.03 (s,
d
161.8, 154.4, 151.1, 136.6, 132.6, 130.4 (CH), 129.0 (CH), 128.9 (CH),
128.4 (CH), 128.3 (CH), 127.6 (CH), 113.4, 103.7 (CH), 93.8 (CH), 89.2
(CH), 84.1 (CH), 82.4 (CH), 64.1 (CH2), 44.1 (CH2), 27.0 (CH3), 25.9
(CH3), 25.4 (CH3), 18.4, ꢁ5.2 (CH3), ꢁ5.3 (CH3); MS (ESI) m/z 587
(100) (MþNa); HRMS calcd for C31H40N2O6Si$Na (MþNa):
587.2553. Found: 587.2546.
3H, CH3), ꢁ0.10 (s, 3H, CH3); 13C NMR (CDCl3, 100 MHz)
d 161.9,
149.6, 137.8, 132.2, 128.4 (CH), 128.3 (CH), 128.0 (CH), 115.4 (CH),
114.2, 92.9 (CH), 86.7 (CH), 85.0 (CH), 80.6 (CH), 63.3 (CH2), 27.2
(CH3), 25.7 (CH3), 25.3 (CH3), 18.2, ꢁ5.5 (CH3), ꢁ5.6 (CH3); MS (ESI)
m/z 475 (100) (Mþ1).
4.3.9. 50-O-tert-Butyldimethylsilyl-20,30-O-isopropylidene-N3-(p-me-
thoxybenzyl)-6-phenyluridine (13a). The reaction was purified by
flash column chromatography (Hex/EtOAc¼8.5:1.5, Rf¼0.20) to
give the product (13a, oil, 69%). 1H NMR (CDCl3, 400 MHz)
4.3.13. 50-O-tert-Butyldimethylsilyl-20,30-O-isopropylidene-5-(p-me-
thoxyphenyl)uridine (19b). The reaction was purified by flash
column chromatography (Hex/EtOAc¼6.5:3.5, Rf¼0.25) to give
d
7.48e7.46 (m, 7H, Ph), 6.85 (d, 2H, J¼8.6 Hz, Ph), 5.69 (s, 1H, 5-
the product (19b, 61%). 1H NMR (CDCl3, 400 MHz)
d 8.87 (br s, 1H,
H), 5.51 (d, 1H, J¼1.1 Hz, 10-H), 5.21 (dd, 1H, J¼1.2 and 6.4 Hz, 20-
H), 5.11 (d, 1H, J¼13.6 Hz, CH2), 5.05 (d, 1H, J¼13.6 Hz, CH2), 4.89
(dd, 1H, J¼4.2 and 6.4 Hz, 30-H), 4.09e4.05 (m, 1H, 40-H), 3.89 (dd,
1H, J¼5.6 and 10.6 Hz, 50-H), 3.84e3.78 (m, 1H, 50-H), 3.81 (s, 3H,
OCH3), 1.35 (s, 3H, CH3), 1.29 (s, 3H, CH3), 0.91 (s, 9H, CH3), 0.05 (s,
NH), 7.53 (s, 1H, 6-H), 7.39 (d, 1H, J¼8.6 Hz, Ph), 6.90 (d, 1H,
J¼8.6 Hz, Ph), 5.91 (d, 1H, J¼2.6 Hz, 10-H), 4.83 (dd, 1H, J¼2.8 and
6.1 Hz, 30-H), 4.75 (dd, 1H, J¼2.7 and 6.1 Hz, 20-H), 4.32 (d, 1H,
J¼2.8 Hz, 40-H), 3.89 (dd, 1H, J¼2.5 and 11.4 Hz, 50-H), 3.81e3.78
(m, 4H, CH3, and 50-H), 1.60 (s, 3H, CH3), 1.36 (s, 3H, CH3), 0.79 (s,
9H, CH3), ꢁ0.01 (s, 3H, CH3), ꢁ0.07 (s, 3H, CH3); 13C NMR (CDCl3,
6H, CH3); 13C NMR (CDCl3, 100 MHz)
d 161.8, 159.1, 154.2, 151.1,
132.7, 130.8 (CH), 130.4 (CH), 128.9 (CH), 128.8, 128.2 (CH), 113.7
(CH), 113.3, 103.8 (CH), 93.8 (CH), 89.2 (CH), 84.1 (CH), 82.5 (CH),
64.1 (CH2), 55.2 (CH3), 43.5 (CH2), 27.0 (CH3), 25.9 (CH3), 25.4
(CH3), 18.4, ꢁ5.2 (CH3), ꢁ5.3 (CH3); MS (ESI) m/z 617 (100)
(MþNa); HRMS calcd for C32H42N2O7Si$Na (MþNa): 617.2659.
Found: 617.2662.
100 MHz) d 162.2, 159.5, 149.7, 137.1 (CH), 129.6 (CH), 124.6, 115.1,
114.2, 114.0 (CH), 93.0 (CH), 86.7 (CH), 84.9 (CH), 80.7 (CH), 63.4
(CH2), 55.3 (CH3), 27.2 (CH3), 25.8 (CH3), 25.3 (CH3), 18.3, ꢁ5.5
(CH3), ꢁ5.6 (CH3); MS (ESI) m/z 505 (100) (Mþ1), 527 (46)
(MþNa); HRMS calcd for C25H35N2O7Si (Mꢁ1): 503.2214. Found:
503.2212.
4.3.10. 50-O-tert-Butyldimethylsilyl-20,30-O-isopropylidene-N3-
(p-methoxybenzyl)-6-(p-nitrophenyl)uridine (13c). The reaction was
purified by flash column chromatography (Hex/ether¼6:4, Rf¼0.19;
Hex/EtOAc¼8:2, Rf¼0.23) to give the product (13c, 98%). 1H NMR
4.3.14. 50-O-tert-Butyldimethylsilyl-20,30-O-isopropylidene-5-(p-nit-
rophenyl)uridine (19c). The reaction was purified by flash column
chromatography (Hex/EtOAc¼7:3, Rf¼0.28) to give the product
(19c, 38%). 1H NMR (CDCl3, 400 MHz)
d 9.61 (s, 1H, NH), 8.20 (d,
(CDCl3, 400 MHz)
d
8.34 (d, 2H, J¼9.0 Hz, Ph), 7.67 (br d, 2H,
1H, J¼8.8 Hz, Ph), 7.83 (br s, 1H, 6-H), 7.70 (d, 1H, J¼8.8 Hz, Ph),
5.91 (d, 1H, J¼2.6 Hz, 10-H), 4.82 (dd, 1H, J¼2.7 and 6.1 Hz, 20-H),
4.73 (dd, 1H, J¼2.2 and 6.1 Hz, 30-H), 4.40 (d, 1H, J¼2.3 Hz, 40-H),
3.90 (dd, 1H, J¼2.1 and 11.6 Hz, 50-H), 3.80 (dd, 1H, J¼3.3 and
11.6 Hz, 50-H), 1.59 (s, 3H, CH3), 1.36 (s, 3H, CH3), 0.75 (s, 9H, CH3),
ꢁ0.04 (s, 3H, CH3), ꢁ0.11 (s, 3H, CH3); 13C NMR (CDCl3, 100 MHz)
J¼4.8 Hz, Ph), 7.46 (d, 2H, J¼8.6 Hz, Ph), 6.84 (d, 2H, J¼8.6 Hz, Ph),
5.88 (s, 1H), 5.27 (s, 1H), 5.18 (d, 1H, J¼6.5 Hz, 20-H), 5.08 (d, 1H,
J¼13.6 Hz, CH2), 5.02 (d, 1H, J¼13.6 Hz, CH2), 4.88 (dd, 1H, J¼4.3 and
6.3 Hz, 30-H), 4.08e4.04 (m, 1H, 40-H), 3.86 (dd, 1H, J¼5.6 and
10.6 Hz, 50-H), 3.81e3.77 (m, 1H, 50-H), 3.78 (s, 3H, OCH3), 1.36 (s,
3H, CH3), 1.29 (s, 3H, CH3), 0.90 (s, 9H, CH3), 0.06 (s, 6H, CH3); 13C
d
161.7, 149.5, 147.1, 139.4 (CH), 139.1, 128.8 (CH), 123.6 (CH), 114.2,
NMR (CDCl3, 100 MHz)
d
161.2, 159.3, 151.8, 150.7, 148.9, 138.6, 130.8
112.5, 93.6 (CH), 87.1 (CH), 85.3 (CH), 80.7 (CH), 63.4 (CH2), 27.1
(CH3), 25.7 (CH3), 25.2 (CH3), 18.2, ꢁ5.5 (CH3), ꢁ5.6 (CH3); MS
(ESI) m/z 518 (100) (Mꢁ1); HRMS calcd for C24H33N3O8Si (Mꢁ1):
518.1959. Found: 518.1963.
(CH),129.5 (CH),128.5, 124.2 (CH),113.7 (CH), 113.6,104.5 (CH), 94.0
(CH), 89.6 (CH), 84.0 (CH), 82.3 (CH), 64.0 (CH2), 55.2 (CH3), 43.7
(CH2), 27.0 (CH3), 25.9 (CH3), 25.3 (CH3), 18.4, ꢁ5.26 (CH3), ꢁ5.29
(CH3); MS (ESI) m/z 662 (100) (MþNa); HRMS calcd for
C32H41N3O9Si$Na (MþNa): 662.2510. Found: 662.2504.
4.3.15. N-(50-O-tert-Butyldimethylsilyl-20,30-O-isopropylidene-
bofuranosyl)malonamide (15). 1H NMR (CDCl3, 400 MHz)
7.44 (s,
b-D-ri-
d
4.3.11. 50-O-tert-Butyldimethylsilyl-20,30-O-isopropylidene-6-(n-bu-
tyl)-N3-(p-methoxybenzyl)uridine (13i). The reaction was purified
by flash column chromatography (Hex/EtOAc¼8:2, Rf¼0.20) to give
1H, NH), 7.28 (d, 1H, J¼9.1 Hz, NH), 5.85 (d, 1H, J¼9.1 Hz, 10-H), 5.61
(s, 1H, NH), 4.72 (d, 1H, J¼5.9 Hz, 20-H), 4.51 (d, 1H, J¼5.9 Hz, 30-H),
4.31 (s, 1H, 40-H), 3.82e3.74 (m, 2H, 50-H), 3.15 (d, 1H, J¼16.6 Hz,
CH2), 3.09 (d, 1H, J¼16.6 Hz, CH2), 1.53 (s, 3H, CH3), 1.34 (s, 3H, CH3),
0.96 (s, 9H, CH3), 0.17 (s, 3H, CH3), 0.16 (s, 3H, CH3); 13C NMR (CDCl3,
the product (13i, oil, 26%). 1H NMR (CDCl3, 400 MHz)
d 7.40 (d, 2H,
J¼8.7 Hz, Ph), 6.81 (d, 2H, J¼8.7 Hz, Ph), 5.68 (s, 1H, CH), 5.59 (s, 1H,
CH), 5.17 (d, 1H, J¼6.4 Hz, 20-H), 5.0 (d, 1H, J¼13.6 Hz, CH2), 4.93 (d,
1H, J¼13.7 Hz, CH2), 4.88 (dd, 1H, J¼4.3 and 6.4 Hz, 30-H), 4.16e4.12
(m, 1H, 40-H), 3.83 (dd, 1H, J¼5.4 and 10.7 Hz, 50-H), 3.78e3.72 (m,
1H, 50-H), 3.76 (s, 3H, OCH3), 2.51 (t, 2H, J¼7.7 Hz, CH2), 1.64e1.56
(m, 2H, CH2), 1.53 (s, 3H, CH3), 1.46e1.37 (m, 2H, CH2), 1.34 (s, 3H,
CH3), 0.95 (t, 3H, J¼7.3 Hz, CH3), 0.87 (s, 9H, CH3), 0.01 (s, 6H, CH3);
100 MHz)
d 168.1, 167.1, 112.9, 87.3 (CH), 86.7 (CH), 86.6 (CH), 82.2
(CH), 65.2 (CH2), 42.8 (CH2), 26.7 (CH3), 26.0 (CH3), 25.1 (CH3), 18.5,
ꢁ5.3 (CH3). 1H NMR (DMSO-d6, 400 MHz)
d
8.61 (d, 1H, J¼8.5 Hz,
NH), 7.44 (s, 1H, NH), 7.07 (s, 1H, NH), 5.34 (dd, 1H, J¼2.1 and 8.5 Hz,
10-H), 4.62 (dd, 1H, J¼1.6 and 6.3 Hz, 30-H), 4.55 (dd, 1H, J¼2.2 and
6.2 Hz, 20-H), 3.94e3.91 (m, 1H, 40-H), 3.61 (d, 2H, J¼6.0 Hz, 50-H),
3.01 (s, 2H, CH2), 1.43 (s, 3H, CH3), 1.27 (s, 3H, CH3), 0.87 (s, 9H, CH3),
0.06 (s, 3H, CH3), 0.05 (s, 3H, CH3); 13C NMR (DMSO-d6, 100 MHz)
13C NMR (CDCl3, 100 MHz)
d 162.1, 159.0, 154.3, 151.2, 130.5 (CH),
128.9, 113.6 (CH), 113.5, 101.6 (CH), 92.1 (CH), 89.6 (CH), 84.4 (CH),
82.4 (CH), 64.2 (CH2), 55.1 (CH3), 43.3 (CH2), 32.4 (CH2), 29.5 (CH2),
27.2 (CH3), 25.9 (CH3), 25.4 (CH3), 22.1 (CH2), 18.4, 13.6 (CH3), ꢁ5.3
d
168.8, 167.5, 113.0, 85.9 (CH), 85.2 (CH), 84.3 (CH), 82.0 (CH), 63.9
(CH2), 43.8 (CH2), 27.3(CH3), 26.3 (CH3), 25.6 (CH3), 18.5, ꢁ4.8 (CH3),