The Journal of Organic Chemistry
Article
131.4, 129.7, 129.6, 128.8, 118.8, 118.7, 116.9, 86.4, 85.2, 76.6, 66.1,
35.4, 18.2, 18.1, 12.0; IR (neat) ν 3186, 3071, 2942, 2865, 1716, 1692,
1603, 1483, 1463, 1314, 1269, 1248, 1095, 773, 710 cm−1; HR-ESI MS
(m/z) [M + Na]+ calcd for C29H37BrN2O6SiNa 639.150 20, found
1′-(3′,5′-O-(Di-tert-butylsilylene)-2′-deoxy-α,β-D-ribofurano-
side)-6-bromoquinazoline-2,4-(3H)-dione (20α and 20β). Ac-
cording to the general procedure A, the inseparable isomer mixture of
nucleosides 20α and 20β (α/β = 1.8:1.0, 0.164 g, 50%) was obtained
as a white solid after column chromatography on silica gel (hexane/
EtOAc, 8:2) using 6-bromoquinazoline-2,4-(1H,3H)-dione 12 (0.190
g, 0.788 mmol), BSA (0.40 mL, 1.642 mmol), thioglycoside 9 (α/β =
1.0:1.8, 0.350 g, 0.657 mmol), NIS (0.177 g, 0.788 mmol), and
1
639.149 05. 17β: Rf (hexane/EtOAc, 7:3) 0.27; H NMR (2D COSY,
400 MHz, CDCl3) δ 9.79 (s, br, 1H), 8.33 (d, J1 = 2.1 Hz, 1H), 8.06
(d, J1 = 8.0 Hz, 2H), 7.91 (d, J1 = 9.1 Hz, 1H), 7.65 (dd, J1 = 8.7 Hz, J2
= 2.0 Hz, 1H), 7.58 (t, J1 = 7.6 Hz, 1H), 7.45 (t, J1 = 7.6 Hz, 2H), 6.92
(dd, J1 = 9.3 Hz, J2 = 6.3 Hz, 1H, H1′), 5.79−5.76 (m, 1H, H3′), 4.22−
4.11 (m, 3H, H4′, H5′ and H5′), 3.02−2.94 (m, 1H, H2′), 2.30 (dd, J1 =
15.3 Hz, J2 = 6.6 Hz, 1H, H2′), 1.16−1.11 (m, 21H); 13C NMR (100
MHz, CDCl3) δ 166.2, 160.8, 150.2, 138.5, 137.8, 133.5, 131.2, 129.9,
129.6, 128.6, 119.4, 118.6, 117.1, 84.3, 84.2, 73.3, 62.8, 34.2, 18.19,
18.17, 12.1; IR (neat) ν 3187, 3066, 2943, 2865, 1713, 1603, 1485,
1467, 1316, 1270, 1105, 773, 711 cm−1; HR-ESI MS (m/z) [M + Na]+
calcd for C29H37BrN2O6SiNa 639.150 20, found 639.149 48.
1
TMSOTf (71 μL, 0.394 mmol): Rf (hexane/EtOAc, 8:2) 0.23; H
NMR (2D COSY, 400 MHz, CDCl3) 20α, δ 9.77 (s, br, 1H), 8.35 (d,
J1 = 2.5 Hz, 1H), 7.75 (d, J1 = 2.5 Hz, 1H), 7.29 (d, J1 = 9.2 Hz, 1H),
6.45 (dd, J1 = 9.2 Hz, J2 = 6.4 Hz, 1H, H1′), 4.50−4.33 (m, 3H, H3′,
H4′ and H5′), 3.92 (dd, J1 = 9.7 Hz, J2 = 8.9 Hz, 1H, H5′), 3.09−3.02
(m, 1H, H2′), 2.53 (dt, J1 = 12.8 Hz, J2 = 6.5 Hz, 1H, H2′), 1.13−1.06
(m, 18H); 20β, δ 9.80 (s, br, 1H), 8.33 (d, J1 = 2.5 Hz, 1H), 7.73 (d, J1
= 2.5 Hz, 1H), 7.37 (d, J1 = 9.1 Hz, 1H), 6.39 (dd, J1 = 9.6 Hz, J2 = 3.6
Hz, 1H, H1′), 4.81 (q, J1 = 8.8 Hz, 1H, H3′), 4.50−3.37 (m, 1H, H5′),
4.10 (t, J1 = 10.4 Hz, 1H, H5′), 3.71 (ddd, J1 = 10.4 Hz, J2 = 8.9 Hz, J3
= 5.0 Hz, 1H, H4′), 2.90 (ddd, J1 = 6.5 Hz, J2 = 3.5 Hz, J3 = 2.1 Hz, 1H,
H2′), 2.32−2.28 (m, 1H, H2′), 1.13−1.06 (m, 18H); 13C NMR (100
MHz, CDCl3) δ 161.1, 161.0, 149.6, 149.1, 139.9, 139.7, 138.18,
138.15, 131.7, 131.5, 118.3, 118.2, 117.1, 116.9, 116.3, 116.5, 84.9,
84.2, 78.4, 77.6, 76.2, 75.5, 68.2, 67.5, 35.8, 34.4, 27.7, 27.6, 27.4, 27.3,
22.85, 22.82, 20.4, 20.3; IR (neat) ν 2967, 2934, 2893, 2859, 1700,
1603, 1472, 1316, 1052, 826, 772, 749, 426 cm−1; HR-ESI MS (m/z)
[M + Na]+ calcd for C21H29BrN2O5SiNa 519.092 68, found 519.091
74.
1′-(3′-O-p-Methoxybenzoyl-5′-O-triisopropylsilyl-2′-deoxy-
α-D-ribofuranoside)-6-bromoquinazoline-2,4-(3H)-dione (18α)
and 1′-(3′-O-p-Methoxybenzoyl-5′-O-triisopropylsilyl-2′-
deoxy-β-D-ribofuranoside)-6-bromoquinazoline-2,4-(3H)-
dione (18β). According to the general procedure A, the separable
isomer mixture of nucleosides 18α (0.072 g, 30%) and 18β (0.123 g,
50%) was obtained as off-white foams after column chromatography
on silica gel (hexane/EtOAc, 8:2 → 6:4) using 6-bromoquinazoline-
2,4-(1H,3H)-dione 12 (0.109 g, 0.452 mmol), BSA (0.23 mL, 0.942
mmol), thioglycoside 7 (α/β = 1.0:1.8, 0.20 g, 0.377 mmol), NIS
(0.102 g, 0.452 mmol), and TMSOTf (62 μL, 0.226 mmol). 18α: Rf
(hexane/EtOAc, 7:3) 0.38; 1H NMR (2D COSY, 400 MHz, CDCl3) δ
8.69 (s, br, 1H), 8.33 (d, J1 = 2.3 Hz, 1H), 8.02 (d, J1 = 8.8 Hz, 2H),
7.78 (d, J1 = 9.1 Hz, 1H), 7.61 (dd, J1 = 9.1 Hz, J2 = 2.4 Hz, 1H), 7.17
(t, J1 = 7.8 Hz, 1H, H1′), 6.99 (d, J1 = 8.8 Hz, 2H), 5.73 (d, J1 = 7.9 Hz,
1H, H3′), 4.54 (s, 1H, H4′), 4.14 (dd, J1 = 10.8 Hz, J2 = 1.8 Hz, 1H,
H5′), 4.03 (dd, J1 = 10.8 Hz, J2 = 2.1 Hz, 1H, H5′), 3.91 (s, 3H), 3.00−
2.92 (m, 1H, H2′), 2.59 (ddd, J1 = 14.9 Hz, J2 = 7.5 Hz, J3 = 3.2 Hz,
1H, H2′), 1.15−1.12 (m, 21H); 13C NMR (100 MHz, CDCl3) δ 166.1,
164.1, 160.4, 149.8, 138.1, 137.6, 131.8, 131.4, 121.9, 118.9, 118.7,
116.9, 114.1, 86.5, 85.3, 76.3, 66.2, 55.7, 35.5, 18.21, 18.19, 12.0; IR
(neat) ν 2960, 2940, 2866, 1715, 1604, 1462, 1258, 1095, 772, 418
cm−1; HR-ESI MS (m/z) [M + Na]+ calcd for C30H39BrN2O7SiNa
1′-(3′,5′-O-(Tetraisopropylsiloxane-1,3-diyl)-2′-deoxy-α-D-ri-
bofuranoside)-6-bromoquinazoline-2,4-(3H)-dione (21α). Ac-
cording to the general procedure A, the nucleosides 21α (0.139 g,
56%) was obtained as an off-white foam after column chromatography
on silica gel (hexane/EtOAc, 9:1 → 8:2) using 6-bromoquinazoline-
2,4-(1H,3H)-dione 12 (0.120 g, 0.497 mmol), BSA (0.26 mL, 1.035
mmol), thioglycoside 21 (α/β = 1.0:1.8, 0.200 g, 0.414 mmol), NIS
(0.112 g, 0.497 mmol), and TMSOTf (45 μL, 0.248 mmol). 21α: Rf
1
(hexane/EtOAc, 8:2) 0.23; H NMR (2D COSY and ROESY, 500
MHz, CDCl3) δ 9.53 (s, br, 1H), 8.34 (d, J1 = 2.5 Hz, 1H), 7.75 (dd, J1
= 9.1 Hz, J2 = 2.5 Hz, 1H), 7.49 (d, J1 = 9.1 Hz, 1H), 6.68 (dd, J1 = 9.8
Hz, J2 = 6.6 Hz, 1H, H1′), 4.69 (q, J1 = 7.5 Hz, 1H, H3′), 4.29 (sext, J1
= 3.6 Hz, 1H, H4′), 4.02 (dd, J1 = 12.1 Hz, J2 = 3.6 Hz, 1H, H5′), 3.88
(dd, J1 = 12.1 Hz, J2 = 7.0 Hz, 1H, H5′), 2.86−2.79 (m, 1H, H2′),
2.57−2.52 (m, 1H, H2′), 1.11−1.04 (m, 28H); 13C NMR (100 MHz,
CDCl3) δ 160.8, 150.1, 138.5, 137.9, 131.5, 118.6, 117.9, 117.0, 84.3,
84.1, 72.9, 63.5, 36.3, 17.7, 17.62, 17.60, 17.5, 17.4, 17.3, 17.2, 17.1,
13.6, 13.4, 13.1, 12.7, IR (neat) ν 2943, 2867, 1708, 1603, 1483, 1465,
1315, 1143, 1118, 1091, 885, 774, 705 cm−1; HR-ESI MS (m/z) [M +
Na]+ calcd for C25H39BrN2O6Si2Na 621.142 77, found 621.142 73.
1′-(3′-O-Acetyl-5′-O-triisopropylsilyl-2′-deoxy-α-D-
ribofuranoside)quinazoline-2,4-(3H)-dione (29α) and 1′-(3′-O-
Acetyl-5′-O-triisopropylsilyl-2′-deoxy-β-D-ribofuranoside)-
quinazoline-2,4-(3H)-dione (29β). According to the general
procedure A, the separable isomer mixture of nucleosides 29α
(0.065 g, 30%) and 29β (0.116 g, 53%) was obtained as off-white
foams after column chromatography on silica gel (hexane/EtOAc, 8:2
→ 6:4) using quinazoline-2,4-(1H,3H)-dione 24 (0.089 g, 0.547
mmol), BSA (0.28 mL, 1.14 mmol), thioglycoside 5 (α/β = 1.0:1.8,
0.20 g, 0.456 mmol), NIS (0.113 g, 0.502 mmol), and HOTf (16 μL,
0.182 mmol). 29α: Rf (hexane/EtOAc, 7:3) 0.29; 1H NMR (2D
COSY and ROESY, 400 MHz, CDCl3) δ 9.17 (s, br, 1H), 8.22 (dd, J1
= 7.9 Hz, J2 = 1.6 Hz, 1H), 7.73 (d, J1 = 7.8 Hz, 1H), 7.64−7.60 (m,
1H), 7.29−7.25 (m, 1H), 7.05 (t, J1 = 7.8 Hz, 1H, H1′), 5.53 (ddd, J1 =
8.5 Hz, J2 = 4.0 Hz, J3 = 2.5 Hz, 1H, H3′), 4.42 (d, J1 = 2.4 Hz, 1H,
H4′), 4.01 (dd, J1 = 10.8 Hz, J2 = 2.5 Hz, 1H, H5′), 3.96 (dd, J1 = 10.8
Hz, J2 = 2.8 Hz, 1H, H5′), 2.87−2.80 (m, 1H, H2′), 2.54 (ddd, J1 = 14.5
Hz, J2 = 7.6 Hz, J3 = 4.0 Hz, 1H, H2′), 2.14 (s, 3H), 1.16−1.08 (m,
21H); 13C NMR (100 MHz, CDCl3) δ 170.8, 161.9, 150.2, 139.3,
134.6, 129.0, 123.7, 117.0, 116.7, 86.1, 84.6, 75.7, 65.6, 35.1, 21.2,
18.16, 18.14, 12.0; IR (neat) ν 3210, 3065, 2942, 2856, 2363, 2363,
1704, 1687, 1609, 1483, 1386, 1313, 1231, 772, 686 cm−1; HR-ESI MS
(m/z) [M + Na]+ calcd for C24H36N2O6SiNa 499.22403, found
1
669.160 76, found 669.159 57. 18β: Rf (hexane/EtOAc, 7:3) 0.23; H
NMR (2D COSY, 400 MHz, CDCl3) δ 8.94 (s, br, 1H), 8.33 (d, J1 =
2.3 Hz, 1H), 8.01 (d, J1 = 8.8 Hz, 2H), 7.92 (d, J1 = 9.1 Hz, 1H), 7.65
(dd, J1 = 9.0 Hz, J2 = 2.3 Hz, 1H), 6.93 (d, J1 = 8.8 Hz, 1H), 6.89 (dd,
J1 = 9.8 Hz, J2 = 6.5 Hz, 1H, H1′), 5.75−5.72 (m, 1H, H3′), 4.19−4.12
(m, 3H, H4′, H5′ and H5′), 3.88 (s, 3H), 2.99−2.91 (m, 1H, H2′), 2.27
(dd, J1 = 14.1 Hz, J2 = 6.4 Hz, 1H, H2′), 1.20−1.11 (m, 21H); 13C
NMR (100 MHz, CDCl3) δ 165.9, 163.9, 160.5, 149.9, 138.5, 137.9,
132.0, 131.3, 122.0, 119.5, 118.6, 117.2, 113.9, 84.5, 84.3, 73.0, 62.9,
55.6, 34.3, 18.23, 18.21, 12.1; IR (neat) ν 2960, 2940, 2866, 1715,
1605, 1257, 1218, 1065, 772, 417 cm−1; HR-ESI MS (m/z) [M + Na]+
calcd for C30H39BrN2O7SiNa 669.160 76, found 669.159 68.
1′-(3′-O-(N-Acetyl)-glycyl-5′-O-triisopropylsilyl-2′-deoxy-β-
D-ribofuranoside)-6-bromoquinazoline-2,4-(3H)-dione (19β).
According to the general procedure A, nucleoside 19β (0.150 g,
41%) was obtained as an off-white foam after column chromatography
on silica gel (hexane/EtOAc, 1:9 → 0:1) using 6-bromoquinazoline-
2,4-(1H,3H)-dione 12 (0.175 g, 0.726 mmol), BSA (0.37 mL, 1.513
mmol), thioglycoside 8α or 8β (0.30 g, 0.605 mmol), NIS (0.164 g,
0.726 mmol), and TMSOTf (66 μL, 0.363 mmol). 19β: Rf (hexane/
EtOAc, 1:9) 0.24; 1H NMR (2D COSY, 400 MHz, CDCl3) δ 10.06 (s,
1H), 8.19 (d, J1 = 2.5 Hz, 1H), 7.80 (d, J1 = 9.1 Hz, 1H), 7.59 (dd, J1 =
9.1 Hz, J2 = 2.5 Hz, 1H), 6.73 (dd, J1 = 9.3 Hz, J2 = 6.2 Hz, 1H, H1′),
6.45 (t, J1 = 5.3 Hz, 1H), 5.59−5.56 (m, 1H, H3′), 4.08 (d, J1 = 5.4 Hz,
2H), 4.06−4.01 (m, 3H, H4′, H5′ and H5′), 2.90−2.82 (m, 1H, H2′),
2.19 (ddd, J1 = 14.1 Hz, J2 = 6.2 Hz, J3 = 2.1 Hz, 1H, H2′), 2.05 (s,
3H), 1.16−1.07 (m, 21H); 13C NMR (100 MHz, CDCl3) δ 170.7,
169.9, 160.8, 150.2, 138.5, 137.7, 131.0, 119.2, 118.4, 117.0, 84.1, 84.0,
74.0, 62.7, 41.6, 33.9, 22.9, 18.11, 18.09, 12.0; IR (neat) ν 3225, 2943,
2866, 1706, 1603, 1484, 1467, 1187 cm−1; HR-ESI MS (m/z) [M +
Na]+ calcd for C26H38BrN3O7SiNa 634.156 01, found 634.155 05.
J
dx.doi.org/10.1021/jo3014929 | J. Org. Chem. XXXX, XXX, XXX−XXX