H2¢¢); 2.83(1H, m, H3¢); 3.61(1H, dd, JH5¢-H5¢¢ = 13.0, JH5¢-H4¢
=
& 6.4, aCH2CN, bCH2CN); 2.79(1H, m, bH3¢); 2.91(1H, m, aH3¢);
a
a
b
3.2, H5¢); 3.83(2H, m, H5¢¢ & H4¢); 6.00(1H, dd, JH1¢-H2¢¢ = 7.3,
JH1¢-H2¢ = 3.5, H1¢); 7.16-7.34(10H, m o-Ph, p-Ph, H6); 7.49(6H, m,
m-Ph); 8.85(1H, s (br), NH). ES-HRMS; C29H28N2NaO4S requires
523.1667; [M + Na]+ = 523.1666 (0.3 ppm). Elemental analysis:
Calculated for C29H28N2O4S: C, 69.58; H, 5.64; N, 5.60. Found: C,
69.36; H, 5.92; N, 5.48.
3.28(1H, m, H5¢/bH5¢); 3.46(4H, m, CHMe2, CHMe2); 3.56-
a a b a b
3.76(7H, m, H5¢/bH5¢, H5¢¢, H5¢¢, OCH2, OCH2); 3.92(2H,
a
a
m, H4¢, bH4¢); 6.01(2H, m, H1¢, bH1¢); 7.09-7.25(20H, m, o-
aPh, o-bPh, p-aPh, p-bPh, H6, bH6); 7.40(12H, m-aPh, m-bPh);
a
a
b
8.73(2H, s, NH, NH). ES-HRMS; C38H45N4NaO5PS requires
723.2746; [M+Na]+ = 723.2746 (1.0 ppm). Elemental analysis:
Calculated for C38H45N4O5PS: C, 65.12; H, 6.47; N, 7.99. Found:
C, 64.93; H, 6.54; N, 8.01.
3¢-S-Trityl-2¢-deoxy-4N-benzoyl-3¢-thiocytidine
(14C).
(0.31 g, 0.52 mmol, 52%). Rf (EtOAc–n-hexane 3 : 1)
=
1
0.38. H NMR d = 1.86(1H, ddd, JH2¢-H2¢¢ = 13.9, JH2¢-H3¢ = 7.0,
JH2¢-H1¢ = 1.9, H2¢); 2.45(1H, ddd, JH2¢¢-H2¢ = 14.0, JH2¢¢-H3¢ = 10.5,
JH2¢¢-H1¢ = 7.0, H2¢¢); 2.70(1H, m, H3¢); 3.70(1H, m, H5¢); 3.88(2H,
m, H5¢¢, H4¢); 6.00(1H, dd, JH1¢-H2¢¢ = 6.9, JH1¢-H2¢ = 1.8, H1¢);
7.20-7.30(10H, m, o-Ph, p-Ph, H5); 7.45-7.54(9H, m, m-Ph, m-Bz,
p-Bz); 7.88(2H, m, o-Bz); 8.22(1H, d, JH6-H5 = 7.4, H6); 8.66(1H, s
(br), NH). ES-HRMS; C35H31N3NaO4S requires 612.1933; [M +
Na]+ = 612.1918 (2.4 ppm).
3¢-S-Trityl-2¢-deoxy-4N -benzoyl-3¢thiocytidine-5¢-O-[(2-cyano-
ethyl)-(N,N-diisopropyl)]-phosphoramidite (3C)
Performed as described for 2T, but using 14C (0.256 g,
0.43 mmol), 0.25 M ETT solution in MeCN (1.1 mL, 0.28 mmol),
2 - cyanoethyl - N, N, N¢, N¢ - tetraisopropylphosphordiamidite
(0.18 mL, 0.56 mmol) and CH2Cl2 (1.7 mL) instead of acetonitrile.
Purification by flash silica chromatography, eluting with 3 : 2
EtOAc–n-hexane (with 0.5% NEt3), afforded the title compound
as a white amorphous solid. (0.214 g, 0.23 mmol, 62%). Rf
(EtOAc–n-hexane 3 : 1) = 0.52. 31P NMR d = 149.4 & 149.1.
3¢-S-Trityl-2¢-deoxy-6N-benzoyl-3¢-thioadenosine
(14A).
(0.31 g, 0.51 mmol, 51%). Rf (EtOAc–n-hexane 3 : 1) = 0.27.
1H NMR d = 1.99(1H, m, H2¢); 2.32(1H, m, H2¢¢); 3.34(2H,
m, H3¢, H5¢); 3.73(1H, m, H5¢¢); 4.01(1H, m, H4¢); 6.10(1H,
m, H1¢); 7.13-7.23(9H, m, o-Ph, p-Ph); 7.38-7.58(9H, m, m-Ph,
m-Bz, p-Bz); 7.88(1H, s, H2); 7.94(2H, m, o-Bz); 8.57(1H, s,
H8); 9.11(1H, s (br), NH). ES-HRMS; C36H31N5NaO3S requires
636.2045; [M + Na]+ = 636.2047 (0.3 ppm).
a
1H NMR d = 1.02-1.24(25H, 4 ¥ d, J = 6.8, CHMe2,bCHMe2,
b
aH2¢); 1.59(1H, m, H2¢); 2.05(1H, ddd, JH2¢¢-H2¢ = 14.3, JH2¢¢-H3¢
=
9.2, JH2¢¢-H1¢ = 6.9, aH2¢¢); 2.34(1H, m, bH2¢¢); 2.58(4H, m, aCH2CN,
bCH2CN); 2.75(2H, m, bH3¢, aH3¢); 3.36(1H, m, aH5¢/bH5¢);
3.50(4H, m, aCHMe2, bCHMe2); 3.63-3.85(7H, m, aH5¢/bH5¢,
5¢-O-(4,4¢-Dimethoxytrityl)-2¢-deoxy-6N-benzoyl-3¢-thioadenosine
(9A)
aH5¢¢, H5¢¢, OCH2, OCH2); 3.96(2H, m, H4¢, H4¢); 5.91(1H,
b
a
b
a
b
dd, JH1¢-H2¢¢ = 6.7, JH1¢-H2¢ = 2.7, aH1¢); 6.00(1H, dd, J = 6.1 & 4.8,
Performed as described for 12, but using 8A23 (0.863 g, 1.11 mmol),
THF (42 mL), methanol (28 mL), water (6.5 mL), 0.5 M NaOH
(0.133 g, 6.7 mL, 3.33 mmol) and 1 M citric acid (3.5 g, 16.7 mL,
16.7 mmol). Flash silica chromatography was not required. (0.75 g,
bH1¢); 7.18(20H, m, o-aPh, o-bPh, p-aPh, p-bPh, H5, H5); 7.36-
7.47(16H, m, m-aPh, m-bPh, m-aBz, m-bBz); 7.53(2H, p-aBz, p-bBz);
7.81(4H, m, o-aBz, o-bBz); 8.01 & 8.26(2H, 2 ¥ d, JH6-H5 = 7.4 (¥2),
aH6, bH6); 8.51(2H, s, aNH, bNH). ES-HRMS; C44H48N5O5NaPS
requires 812.3012; [M + Na]+ = 812.3051 (4.9 ppm).
a
b
1
1.11 mmol, >99%). Rf (EtOAc) = 0.39. H NMR d = 1.60(1H,
d, J = 7.0, SH3¢); 2.45(1H, ddd, JH2¢-H2¢¢ = 13.8, JH2¢-H3¢ = 10.6,
JH2¢-H1¢ = 7.1, H2¢); 3.06(1H, ddd, JH2¢¢-H2¢ = 13.4, JH2¢¢-H3¢ = 7.0,
JH2¢¢-H1¢ = 2.2, H2¢¢); 3.35(1H, dd, JH5¢-H5¢¢ = 10.9, JH5¢-H4¢ = 3.9, H5¢);
3.50 (1H, dd, JH5¢¢-H5¢ = 10.8, JH5¢¢-H4¢ = 3.0, H5¢¢); 3.70-3.83(7H, m,
3¢-S-Trityl-2¢,3¢-dideoxy-6N -benzoyl-3¢thioadenosine-5¢-O-[(2-
cyanoethyl)-(N,N-diisopropyl)]-phosphoramidite (3A)
OMe, H3¢); 3.97(1H, m, H4¢); 6.34(1H, dd, JH1¢-H2¢ = 7.3, JH1¢-H2¢¢
=
Performed as described for 2T, but using 14A (0.285 g,
0.47 mmol), 0.25 M ETT solution in MeCN (1.2 mL, 0.30 mmol),
2 - cyanoethyl - N, N, N¢, N¢ - tetraisopropylphosphordiamidite
(0.19 mL, 0.60 mmol) and CH2Cl2 (1.7 mL) instead of acetonitrile.
(0.22 g, 0.27 mmol, 58%). Rf (EtOAc–n-hexane 3 : 1) = 0.52. 31P
NMR d = 148.7 & 149.0. 1H NMR d = 0.98-1.10(24H, 4 ¥
d, J = 6.8 (¥2), 6.7 (¥2), aCHMe2, bCHMe2); 1.41(1H, ddd,
2.3, H1¢); 6.70-6.75(4H, m, m-Ar2); 7.18-7.23(7H, m, o-Ar2, m-Ph
& p-Ph); 7.30-7.40(2H, m, o-Ph); 7.45-7.55(3H, m, m-Bz, p-Bz);
7.97(2H, m, o-Bz); 8.25(1H, s, H2); 8.75 (1H, s, H8); 8.95(1H, s
(br), NH). ES-HRMS; C38H35N5O5NaS required 696.2241; [M +
Na]+ found = 696.2257 (2.2 ppm).
3¢-S-Trityl-3¢-thiothymidine-5¢-O-[(2-cyanoethyl)-(N,N-diisopro-
pyl)]-phosphoramidite (3T)
a
JH2¢-H2¢¢ = 14.1, JH2¢-H3¢ = 7.2, JH2¢-H1¢ = 2.3, H2¢); 1.86(1H, ddd,
b
JH2¢-H2¢¢ = 13.7, JH2¢-H3¢ = 7.3, JH2¢-H1¢ = 4.1, H2¢); 2.03(1H, ddd,
Performed as described for 2T, but using 14T (0.489 g,
0.98 mmol), 0.25 M ETT solution in MeCN (2.54 mL, 0.64 mmol),
2 - cyanoethyl - N, N, N¢, N¢ - tetraisopropylphosphordiamidite
(0.4 mL, 1.27 mmol) and MeCN (3.6 mL). Purification by flash
silica chromatography, eluting with 2 : 1 EtOAc–n-hexane (with
0.5% NEt3), afforded the title compound as a white amorphous
solid. (0.382 g, 0.54 mmol, 56%). Rf (EtOAc–n-hexane 3 : 1) = 0.49.
31P NMR d = 149.3 &149.0. 1H NMR d = 0.98-1.11(24H, 4 ¥ d,
a
JH2¢¢-H2¢ = 14.1, JH2¢¢-H3¢ = 9.6, JH2¢¢-H1¢ = 7.0, H2¢¢); 2.17(1H, m,
bH2¢¢); 2.54(4H, m, aCH2CN, bCH2CN); 3.20(2H, m, bH3¢, aH3¢);
3.34(2H, m, aCHMe2/bCHMe2); 3.47(3H, m, aCHMe2/bCHMe2,
aH5¢/bH5¢); 3.60-3.84(7H, m, aH5¢/bH5¢, aH5¢¢, bH5¢¢, aOCH2,
bOCH2); 4.05(2H, m, aH4¢, bH4¢); 6.14(1H, dd, JH1¢-H2¢¢ = 6.8,
JH1¢-H2¢ = 2.5, aH1¢); 6.20(1H, dd, JH1¢-H2¢¢ = 6.8, JH1¢-H2¢ = 3.9, bH1¢);
7.10-7.22(18H, m, o-aPh, o-bPh, p-aPh, p-bPh); 7.41-7.54(18H,
m, m-aPh, m-bPh, m-aBz, m-bBz, p-aBz, p-bBz); 7.93(4H, m, o-
a
b
J = 6.7 (¥3) & 6.8, CHMe2, CHMe2); 1.21(1H, ddd, JH2¢-H2¢¢
=
a
b
aBz, o-bBz); 7.99 & 8.05(2H, 2 ¥ s, H2, H2); 8.63 & 8.93(2H,
14.0, J = 8.4 & 5.2, aH2¢); 1.59(1H, m, bH2¢); 1.79 & 1.80(6H, 2 ¥
d, JMe-H6 = 1.0 & 0.9, aMe, bMe); 1.90(1H, m, aH2¢¢); 2.04(1H, ddd,
JH2¢¢-H2¢ = 14.0, J = 6.0 & 5.0, bH2¢¢); 2.41 & 2.50(4H, 2 ¥ t, J = 6.3
a
b
a
b
2 ¥ s, H8, H8); 8.86 & 8.93(2H, 2 ¥ s, NH, NH). ES-HRMS;
C45H48N7O4NaPS requires 836.3124; [M + Na]+ = 836.3160
(4.3 ppm).
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The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 1463–1470 | 1469
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