◦
1
Compound 4c: M.p.: 126.8–127.1 C; H NMR (300 MHz,
CDCl3): d 7.55–7.53 (m, 1H), 6.13 (d, J = 6.7 Hz, 1H), 5.82
(d, J = 8.2 Hz, 1H), 5.38–5.28 (m, 4H), 5.22–5.17 (m, 2H), 4.97
(br, 1H), 4.22–4.21 (m, 1H), 3.75–3.74 (m, 2H), 3.15–3.11 (m,
4H), 2.01–1.99 (m, 8H), 1.47–1.25 (m, 48H), 0.90–0.85 (m, 6H);
13C NMR (75 MHz, CDCl3): d 165.7, 162.9, 155.3, 154.8, 150.9,
139.9, 131.3, 130.8, 130.6, 130.5, 130.4, 130.1, 129.2, 104.0, 86.1,
81.9, 73.5, 73.2, 72.2, 66.5, 66.2, 52.7, 41.7, 41.6, 32.9, 32.2, 30.2,
30.1, 30.0, 29.9, 29.8, 29.7, 29.6, 27.6, 27.5, 27.1, 23.0, 14.5; IR
(neat): 3345, 2925, 2854, 2107, 1708, 1542, 1464, 1384, 1263, 1173,
2¢,3¢-Di-O-(alkylcarbamyl)-5¢-deoxy-5¢-(4-lysylaminomethyl-1H-
1,2,3-triazol-1-yl)uridine (7a–c)
A solution of compound 5, sodium ascorbate (0.2 equiv.),
Cu(OAc)2 (0.2 equiv.), and compound 4a–c (2 equiv.) in CH2Cl2–
H2O (1 : 1, v/v) (0.1 M) was stirred at room temperature for
12 h. The mixture was extracted with CH2Cl2 and washed with
water and brine. The organic layer was dried (Na2SO4) and
evaporated and purified through flash column chromatography
(SiO2, chloroform–MeOH, 30 : 1 to 10 : 1, v/v), then, a yellowish
solid (65–79%) was isolated.
1090, 1061 cm-1; HRMS-FAB (m/z): calcd for C47H81N7NaO7
+
The isolated compound was dissolved in ammonia solution
(28%, aq.) (0.01 M) and the mixture was stirred at 40–45 C for
[M+Na]+, 878.6090; found, 878.6092.
◦
1 d. After quenching with methanol, the solution was lyophilized
and the oilic residue was washed repeatedly and precipitated with
ether, then, a yellowish solid 7a (88%), 7b (quant.), and 7c (quant.)
was isolated.
Na,Ne-Bis(trifluoroacetyl)-L-lysine-N-propargylamide (5)
EDC (3.4 g, 17.7 mmol) and DMAP (2.17 g, 17.7 mmol) were
added to a solution of Na,Ne-bis(trifluoroacetyl)-L-lysine (3.0 g,
8.9 mmol) in DMF (45 ml). After stirring at room temperature
for 30 min, propargyl amine (0.91 ml, 13.3 mmol) was added
and the mixture was stirred for an additional 12 h at room
temperature. After, ethyl acetate was added to the mixture and
it was washed with 1 N HCl (aq.), sat. NaHCO3 (aq.), water,
and brine sequentially. The organic layer was dried (Na2SO4) and
evaporated and purified through re-crystallization in ether, then,
a white solid 5 was is◦olated (2.25 g, 68%).
Compound 7a: M.p. 101.7–102.5 ◦C; 1H NMR (300 MHz,
DMSO-d6) d 8.96 (br, 1H), 7.96 (br, 2H), 7.75 (d, J = 8.0 Hz,
1H), 7.47–7.04 (m, 2H), 5.91 (d, J = 6.3 Hz, 1H), 5.73 (d, J =
7.9 Hz, 1H), 5.30–5.28 (m, 1H), 5.23–5.19 (m, 1H), 4.78 (d, J =
5.3 Hz, 2H), 4.45–4.35 (m, 3H), 3.74 (t, J = 6.1 Hz, 1H), 2.98–
2.89 (m, 4H), 2.77–2.73 (m, 2H), 1.75–1.67 (m, 2H), 1.52–1.47 (m,
2H), 1.37–1.22 (m, 28H), 0.86–0.82 (m, 6H); 13C NMR (75 MHz,
DMSO-d6) d 168.4, 162.9, 158.6, 158.2, 154.6, 154.5, 150.5, 143.8,
123.9, 102.6, 86.9, 80.2, 71.4, 70.6, 52.0, 50.9, 34.9, 31.3, 29.3, 28.8,
28.7, 26.4, 26.3, 22.1, 21.0, 13.9; IR (neat) 3325, 3077, 2956, 2927,
2855, 1678, 1542, 1464, 1266, 1202, 1134 cm-1; HRMS-FAB (m/z)
M.p.: 140.9–142.1 C; 1H NMR (300 MHz, MeOD): d 4.37 (dd,
J = 8.89, 5.78 Hz, 1H), 3.99–3.95 (m, 2H), 3.28–3.26 (m, 2H), 2.59
(t, J = 2.58 Hz, 1H), 1.83–1.74 (m, 2H), 1.62–1.55 (m, 2H), 1.43–
1.37 (m, 2H); 13C NMR (75 MHz, MeOD): d 172.5, 91.5, 80.2,
72.4, 54.9, 40.4, 32.2, 29.5, 29.4, 26.7, 24.0; 19F NMR (282.38 MHz,
MeOD): d 0.004, -0.39; IR (KBr): 3308, 3289, 3098, 2955, 2932,
1707, 1660, 1557, 1451, 1351, 1188, 1167 cm-1; HRMS-FAB (m/z):
calcd for C13H15F6N3NaO3+ [M+Na]+, 398.0910; found, 398.0917.
calcd for C36H63N10O8 [M + H]+, 763.4825; found, 763.4833.
+
Compound 7b: M.p. 208.0–209.0 ◦C; 1H NMR (300 MHz,
DMSO-d6) d 8.93 (s, 1H), 7.96 (br, 2H), 7.75 (d, J = 8.0 Hz,
1H), 7,47–7.04 (m, 2H), 5.91 (d, J = 6.3 Hz, 1H), 5.73 (d, J =
8.0 Hz, 1H), 5.29–5.27 (m, 1H), 5.23–5.21 (m, 1H), 4.78 (d, J =
5.3 Hz, 2H), 4.40–4.35 (m, 3H), 3.72 (t, J = 6.0 Hz, 1H), 2.94 (br,
4H), 2.73 (t, J = 7.5 Hz, 2H), 1.71–1.68 (m, 2H), 1.52–1.47 (m,
2H), 1.37–1.23 (m, 44H), 0.87–0.82 (m, 6H); 13C NMR (75 MHz,
DMSO-d6) d 168.4, 162.8, 158.6, 158.2, 154.6, 150.4, 143.7, 123.8,
115.3, 102.6, 86.9, 80.1, 71.4, 70.5, 52.0, 50.9, 34.5, 31.3, 30.1, 29.0,
28.8, 28.7, 26.4, 22.0, 21.1, 13.9; IR (neat) 3321, 3066, 2923, 2853,
1679, 1540, 1464, 1267, 1202, 1133 cm-1; HRMS-FAB (m/z) calcd
Na-Fmoc-Nx-Pbf-L-arginine-N-propargylamide (6)
After drying the mixture of Na-Fmoc-Nw-Pbf-L-arginine (2.0 g,
3.1 mmol), TBTU (1.2 g, 3.72 mmol), and HOBT (0.5 g, 3.7 mmol)
in vacuo, the mixture was dissolved in dry DMF (25 mL) under Ar
(g) conditions. Adding DIPEA (1.3 ml, 7.4 mmol) and stirring for
30 min at room temperature, propargyl amine (0.26 ml, 3.7 mmol)
was added to the mixture and the mixture was stirred for an
additional 2 h. After, ethyl acetate was added to the mixture and
washed with 1 N HCl (aq.), sat. NaHCO3 (aq.), water, and brine
sequentially. The organic layer was dried (Na2SO4), evaporated
and purified through flash column chromatography (SiO2, hexane–
ethyl acetate, 3 : 2 to ethyl acetate only, v/v), then, a white solid 6
(1.4 g, 65%) was isolated.
for C44H79N10O8 [M + H]+, 875.6077; found, 875.6080.
+
Compound 7c: M.p. 205.8–206.2 ◦C; 1H NMR (300 MHz,
DMSO-d6) d 8.87 (br, 1H), 7.94 (br, 2H), 7.75 (d, J = 7.9 Hz,
1H), 7.47–7.04 (m, 2H), 5.92 (d, J = 6.3 Hz, 1H), 5.73 (d, J =
7.9 Hz, 1H), 5.33–5.30 (m, 5H), 5.23–5.21 (m, 1H), 4.78 (d, J =
5.4 Hz, 2H), 4.40–4.35 (m, 3H), 3.68 (br, 1H), 2.96–2.89 (m, 4H),
2.76–2.71 (m, 2H), 1.98–1.96 (m, 8H), 1.67 (br, 2H), 1.51–1.49 (m,
2H), 1.37–1.23 (m, 52H), 0.86–0.82 (m, 6H); 13C NMR (75 MHz,
DMSO-d6) d 162.9, 154.4, 150.4, 143.7, 141.3, 130.0, 129.6, 123.9,
107.1, 102.4, 86.8, 80.1, 71.4, 70.3, 52.8, 50.4, 46.0, 34.7, 31.9, 31.3,
30.0, 29.2, 29.1, 28.9, 28.8, 28.7, 18.6, 26.6, 26.5, 22.1, 21.5, 13.9;
IR (neat) 3452, 3332, 2925, 2854, 1684, 1529, 1463, 1259, 1214,
M.p.: 128.3–128.9 ◦C; 1H NMR (300 MHz, CDCl3): d 7.74–7.22
(m, 8H), 6.24 (s, 2H), 6.02–6.00 (m, 1H), 4.35–4.32 (m, 3H), 4.15–
4.11 (m, 1H), 3.98 (br, 2H), 3.27 (br, 2H), 2.90 (s, 2H), 2.54 (d,
J = 22.17 Hz, 6H), 2.13 (s, 1H), 2.06 (s, 3H), 1.87 ~ 1.58 (br, 6H),
1.42 (s, 6H); 13C NMR (75 MHz, CDCl3): d 172.1, 159.1, 156.8,
156.6, 144.0, 143.9, 141.5, 138.6, 132.7, 132.5, 128.0, 127.3, 125.3,
125.0, 120.2, 117.9, 86.7, 79.7, 71.6, 67.4, 54.3, 47.3, 43.4, 40.8,
30.8, 29.4, 28.8, 25.5, 19.5, 18.2, 12.7; IR (neat): 3649, 3436, 3309,
2970, 2929, 1718, 1667, 1619, 1549, 1451, 1245, 1104, 1092 cm-1;
HRMS-FAB (m/z): calcd for C37H44N5O6S+ [M+H]+, 686.3007;
found, 686.3015.
+
1137 cm-1; HRMS-FAB (m/z) calcd for C56H99N10O8 [M + H]+,
1039.7642; found, 1039.7654.
2¢,3¢-Di-O-(oleylcarbamyl)-5¢-deoxy-5¢-(4-(2S-2,6-
diguanidinohexanyl)aminomethyl-1H-1,2,3-triazol-1-yl)uridine (8)
Compound 7c (200 mg, 0.19 mmol) and 1,3-di-BOC-2-
(trifluoromethylsulfonyl)guanidine (223 mg, 0.57 mmol) were
294 | Org. Biomol. Chem., 2011, 9, 291–296
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