NUCLEOSIDES, NUCLEOTIDES AND NUCLEIC ACIDS
7
140.90, 115.88 (q, JCF = 293 Hz), 101.66, 79.03, 76.95, 69.84, 69.72, 67.98, 67.29,
62.02, 55.41, 54.45, 53.52, 36.71, 28.49, 26.37, 25.98; 19F NMR (300 MHz, CD3CN)
δ 87.72; MS (ESI) m/z: [M+H]+ calcd. for C21H34F3N4O7 511.2380, found 511.094.
2-Hydroxymethyl-4-[4,9-dioxa-12-(N-trifluoroacetylamino)dodecyl]-6-(N2-
isobutyrylguanin-9-yl)morpholine(5c): 65% yield, Rf = 0.18 (EtOH/DCM, 1/9);
1H NMR (400 MHz, DMSO-d6) δ 12.04 (br.s, 1H, NH), 11.67 (s, 1H, NH), 9.35
(brt, 1H, J = 5.4 Hz, NH), 8.12 (s, 1H, H8), 5.60 (dd, 1H, J = 10.5, 2.2 Hz, H6ꢀ),
4.80 (br t, 1H, J = 5.6 Hz, 2ꢀ-CH2OH), 3.96–3.87 (m, 1H, H2ꢀ), 3.45–3.23 (m, 10H,
2ꢀ-CH2OH, H3ꢀꢀ, H5ꢀꢀ, H8ꢀꢀ, H10ꢀꢀ), 3.18 (app q, 2H, J = 6.6 Hz, H12ꢀꢀ), 3.03 (br
d, 1H, J = 10.7 Hz, H5ꢀ), 2.82 (br d, 1H, J = 10.4 Hz, H3ꢀ), 2.73 (sep, 1H, J =
6.8 Hz, CH(CH3)2), 2.58–2.37 (m, 4H, H3ꢀ, H1ꢀꢀ), 1.97 (app t, 1H, J = 11.1 Hz,
H5ꢀ), 1.70–1.58 (m, 4H, H2ꢀꢀ, H11ꢀꢀ), 1.52–1.40 (m, 4H, H6ꢀꢀ, H7ꢀꢀ), 1.08 (br.d, 6H, J
= 6.7 Hz, CH(CH3)2); 13C NMR (400 MHz, DMSO-d6) δ 180.65, 156.62 (q, JCF
=
36.0 Hz), 155.27, 148.75, 148.60, 137.85, 120.28, 116.37 (q, JCF = 36.0 Hz), 79.21,
74.26, 70.32, 70.25, 68.43, 67.76, 62.54, 55.65, 54.84, 53.48, 37.16, 35.20, 28.97,
26.81, 26.48, 19.32, 19.28; 19F NMR (300 MHz, CD3CN) δ 87.97; MS (ESI) m/z:
[M+H]+ calcd. for C26H41F3N7O7 620.3020, found 620.369.
2-Hydroxymethyl-4-[4,9-dioxa-12-(N-trifluoroacetylamino)dodecyl]-6-(N4-
benzoylcytozin-1-yl)morpholine (5d): yield 55%; Rf = 0.25 (EtOH/DCM, 1/9); 1H
NMR (400 MHz, DMSO-d6) δ 11.31 (s, 1H, NH), 9.39 (br t, 1H, J = 5.6 Hz, NH),
817 (d, 1H, J = 7.6 Hz, H6), 8.01 (dt, 2H, J = 7.1, 1.7 Hz, Bz), 7.63 (tt, 1H, J = 7.4,
1.4 Hz, Bz), 7.51 (tt, 2H, J = 7.5, 1.4 Hz, Bz), 7.37, (d, 1H, J = 7.6 Hz, H5), 5.71 (dd,
1H, J = 9.4, 2.4 Hz, H6ꢀ), 4.82 (t, 1H, J = 5.8 Hz, 2ꢀ-CH2OH), 3.49 (app t, 1H, J =
5.6 Hz, 2ꢀ-CH2OH), 3.45–3.26 (m, 8H, H3ꢀꢀ, H5ꢀꢀ, H8ꢀꢀ, H10ꢀꢀ), 3.23 (app q, 2H, J =
6.2 Hz, H12ꢀꢀ), 3.01 (br.d, 1H, J = 10.8, H5ꢀ), 2.86 (d, 1H, J = 10.0 Hz, H3ꢀ), 2.41 (t,
2H, J = 7.2 Hz, H1ꢀꢀ), 1.96–1.83 (m, 2H, H3ꢀ, H5ꢀ), 1.74–1.61 (m, 4H, H2ꢀꢀ, H11ꢀꢀ),
1.55–1.44 (m, 4H, H6ꢀꢀ, H7ꢀꢀ); 13C NMR (400 MHz, DMSO-d6) δ 167.76, 163.49,
156.52 (q, JCF = 34.8 Hz), 154.09, 145.95, 133.44, 133.14, 128.80, 127.87, 116.37 (q,
JCF = 286.0 Hz), 96.83, 80.89, 77.39, 70.21, 70.10, 68.35, 67.65, 62.40, 56.60, 54.80,
53.95, 37.06, 28.85, 26.74, 26.35; 19F NMR (400 MHz, DMSO-d6) δ 91.79; MS (ESI)
m/z: [M+H]+ calcd. for C28H39F3N5O7 614.2802, found 614.184.
2-Hydroxymethyl-4-[4,9-dioxa-12-(N-trifluoroacetylamino)dodecyl]-6-
1
(thymin-1-yl)morpholine(5e): yield 60%; Rf = 0.30 (EtOH/DCM, 1/9); H NMR
(300 MHz, DMSO-d6) δ 11.39 (s, 1H, NH), 9.39 (br t, 1H, J = 5.36 Hz, NH), 7.55
(q, 1H, J = 1.1 Hz, H6), 5.58 (br d, 1H, J = 9.7 Hz, H6ꢀ), 4.80 (t, 1H, J = 5.6 Hz,
2ꢀ-CH2OH), 3.74–3.63 (m, 1H, H2ꢀ), 3.51–3.28 (m, 10H, 2c-CH2OH, H3ꢀꢀ, H5ꢀꢀ,
H8ꢀꢀ, H10ꢀꢀ), 3.23 (app q, 2H, J = 6.7 Hz, H12ꢀꢀ), 2.92–2.77 (m, 2H, H3ꢀ, H5ꢀ), 2.42
(br t, 2H, J = 8.1 Hz, H1ꢀꢀ), 2.10 (br.t, 1H, J = 10.7 Hz, H3ꢀ), 1.88 (br t, 1H, J =
10.74 Hz, H5ꢀ), 1.78 (d, 3H, J = 1.1 Hz, CH3), 1.75–1.61 (m, 4H, H2ꢀꢀ, H11ꢀꢀ),
1.54–1.47 (m, 4H, H6ꢀꢀ, H7ꢀꢀ); 13C NMR (300 MHz, DMSO-d6) δ 163.68, 156.19
(q, JCF = 35.7 Hz), 150.11, 136.47, 116.11 (q, JCF = 287.7 Hz), 109.44, 78.79, 76.90,
69.91, 69.79, 68.02, 67.35, 60.06, 55.19, 54.59, 53.53, 36.77, 28.56, 26.32, 26.05,