G. H. Hakimelahi et al. / Bioorg. Med. Chem. 10 (2002) 1321–1328
1327
ꢀ
calcd for C H Cl N O : C, 54.39; H, 3.26; Cl, 22.94;
1
N, 9.06. Found: C, 54.37; H, 3.14; Cl, 22.87; N, 9.11.
(17.0 mg, 0.0147 mmol). After stirring at 25 C for 30
min, CuI (5.0 mg, 0.026 mmol) was added and the mix-
4
10
2
2
2
ꢀ
quenched with NH Cl aqueous solution (20%, 20 mL)
ture was stirred at 50 C for 24 h. The reaction was
1
N -(5-Chloropent-4-ene-2-yne-1-yl)uracil (5). To a solu-
4
tion of 2 (0.600 g, 3.99 mmol) in THF (150 mL) and n-
butylamine (0.590 g, 8.04 mmol), under argon atmo-
sphere, were added cis-1,2-dichloroethene (0.580 g, 6.03
mmol) and Pd(PPh ) (0.23 g, 0.20 mmol). After stirring
and extracted with EtOAc (3 Â 20 mL). The EtOAc
solution was dried over MgSO (s) and filtered. Evap-
4
oration under reduced pressure and purification of the
residue by use of column chromatography (hexanes/
EtOAc=7:3) afforded 7 (0.0393 g, 0.185 mmol) in 66%
3
4
ꢀ
at 25 C for 30 min, CuI (76.0 mg, 0.380 mmol) was
ꢀ
ꢀ
added and the mixture was stirred at 25 C for 10 h. The
reaction was quenched with NH Cl aqueous solution
yield as a white solid: mp 114–116 C; R (hexanes/
f
EtOAc=1:1) 0.33; IR (CH Cl ) n 3054 (CH¼CH),
4
2
2
(
The EtOAc solution was dried over MgSO (s) and fil-
5%, 30 mL) and extracted with EtOAc (3 Â 30 mL).
2360, 2306 (2 CꢁC), 1715 (C¼O),1676 (C¼O), 1450,
À1
1277, 888 cm ; UV (EtOH) l
230 (e 4 017), 262 (e 3
4
max
1
tered. Evaporation under reduced pressure and pur-
ification of the residue by use of column
288); H NMR (CDCl ) d4.70 (s, 2H, CH ), 4.74 (s, 2
3
2
H, CH ), 5.79 (d, J=8.1 Hz, 1 H, C H), 5.99 (d, J=5.13
Hz, 1 H, CH), 6.25 (d, J=5.13 Hz, 1 H, CH), 7.50 (d,
2
5
chromatography (hexanes/EtOAc=6:4) afforded
(
5
0.599 g, 2.79 mmol) in 70% yield as a foam: R (hex-
1
3
J=8.1 Hz, 1 H, C H); C NMR (CDCl ) d 30.88
f
6
3
anes/EtOAc=1:1) 0.38; IR (CH Cl ) n 3381 (NH), 3050
(CH ), 38.65 (CH ), 66.85, 72.51, 81.35, 88.89 (2 CꢁC),
2
2
2
2
(
1
l
CH¼CH), 2986 (ꢁCH), 2359 (CꢁC), 1700 (C¼O),
102.01 (C ), 112.82 (¼CH), 115.07 (¼CH), 140.81 (C ),
2 4
5 6
+
À1
694 (C¼O), 1275, 1131, 864 cm ; UV (EtOH)
150.17 (C ¼O), 161.39 (C ¼O); MS m/z 212 (M ).
12 8 2 2
1
235 (e 17,300), 260 (e 13,250); H NMR (CDCl ) d
Anal. calcd for C H N O : C, 67.92; H, 3.80; N, 13.20.
Found: C, 67.81; H, 3.75; N, 13.20.
max
3
4
.74 (s, 2H, CH ), 5.78 (d, J=8.0 Hz, 1 H, C H), 5.88
2
5
(
CHCl), 7.52(d, J=8.0 Hz, 1 H, C H), 9.21 (br s, 1 H,
d, J=6.0 Hz, 1 H, CH), 6.47 (d, J=6.0 Hz, 1 H,
cis-1,2-(Dimethoxycarbonylmethylthiopropyn-1-yl)ethene
(8). To a solution of 7 (94.2mg, 0.444 mmol) in EtOH
(20 mL) and AcOH (1.26 mL), under argon atmos-
phere, was added methyl thioglycolate (106.4 mg, 1.004
6
1
3
NH); C NMR (CDCl ) d 37.79 (CH ), 81.32, 88.91
3
2
(
1
2
CꢁC), 102.86 (C ), 110.81 (¼CH), 130.77 (¼CCl),
5
42.47 (C ), 150.34 (C ¼O), 163.34 (C ¼O); MS m/z
6
2
4
+
ꢀ
10 (M , Cl-cluster). Anal. calcd for C H ClN O :
9 7 2 2
mmol). After stirring at 25 C for 48 h, the reaction was
quenched with H O (30 mL) and extracted with EtOAc
C, 51.32; H, 3.35; Cl, 16.83; N, 13.30. Found: C, 51.23;
H, 3.30; Cl, 16.95; N, 13.27.
2
(3 Â 20 mL). The aqueous solution contained uracil.
The EtOAc solution was dried over MgSO (s) and fil-
4
1
3
[N -(5-Chloropent-4-ene-2-yne-1-yl)-N -(prop-2-yne-1-
yl)]uracil (6). To a solution of 5 (0.19 g, 0.93 mmol) in
tered. Evaporation under reduced pressure and pur-
ification of the residue by use of column
chromatography (hexanes/EtOAc=9:1) afforded 8 (73.0
CH CN (40 mL) and DBU (0.190 g, 1.22 mmol) was
3
added propargyl bromide (0.140 g, 1.22 mmol). The
ꢀ
mg, 0.234 mmol) in 53% yield as an oil: R (hexanes/
f
reaction mixture was stirred at 45 C for 12h. The
solution was concentrated under reduced pressure and
EtOAc (120 mL) was added. The EtOAc solution was
EtOAc=8:2) 0.64; IR (CH Cl ) n 3062(CH ¼CH),
2
2
À1
2298 (2 CꢁC), 1736 (2C ¼O), 1480, 1200, 878 cm ; UV
max 3
1
(EtOH) l
4 H, 2 CH ), 3.80 (s, 6H, 2CH ), 3.95 (br s, 4 H, 2
225 (e 1 973); H NMR (CDCl ) d 3.27 (s,
washed with NH Cl aqueous solution (5%, 3 Â 90 mL).
4
2 3
+
Then, it was dried over MgSO (s) and filtered. Evap-
4
ꢁCCH ), 5.89 (s, 2H, CH ¼CH); MS m/z 312(M , S-
2
oration under reduced pressure and purification of the
residue by use of column chromatography (hexanes/
EtOAc=7:3) afforded 6 (0.185 g, 0.744 mmol) in 80%
cluster). Anal. calcd for C H O S : C, 53.83; H, 5.16;
1
4
16
4 2
S, 20.52. Found: C, 53.70; H, 5.29; S, 20.67.
yield as a foam: R (hexanes/EtOAc=1:1) 0.53; IR
f
(
1
CH Cl ) n 3304 (ꢁCH), 3089 (CH¼CH), 3058 (CꢁC),
Acknowledgements
2
2
À1
715 (C¼O),1678 (C¼O), 1450, 671 cm ; UV (EtOH)
max 3
1
l
235 (e 15,100), 260 (e 10,941); H NMR (CDCl ) d
For financial support, we thank Academia Sinica and
the National Science Council of Republic of China.
2
CH ), 4.77 (s, 2H, CH ), 5.82(d, J=8.0 Hz, 1 H, C H),
.15 (t, J=4.5 Hz, 1 H, ꢁCH), 4.68 (d, J=4.5 Hz, 2H,
2
2
5
5
CHCl), 7.52(d, J=8.0 Hz, 1 H, C H); C NMR
.87 (d, J=6.0 Hz, 1 H, CH), 6.47 (d, J=6.0 Hz, 1 H,
1
3
6
(
7
CDCl ) d 30.39 (CH ), 38.64 (CH ), 70.75 (ꢁCH),
References and Notes
3
2
2
7.81 (ꢁC),81.49, 88.83 (CꢁC),102.18 (C ), 110.78
5
(
¼CH), 130.76 (¼CCl), 140.64 (C ), 150.39 (C ¼O),
1. (a) Umansky, V.; Rocha, M.; Breitkreutz, R.; Hehner, S.;
Bucur, M.; Erbe, N.; Droge, W.; Ushmorov, A. J. Cell. Bio-
chem. 2000, 78, 578. (b) Meister, A.; Anderson, M. E. Annu.
Rev. Biochem. 1983, 52, 711, and references cited therein.
2. Hoog, J.-O.; Holmgren, A.; D’Silva, C.; Douglas, K. T.;
Seddon, A. P. FEBS Lett. 1982, 138, 59.
6 2
+
1
Anal. calcd for C H ClN O : C, 57.96; H, 3.65;
61.59 (C =O); MS m/z 248 (M , Cl-cluster).
4
1
2
9
2
2
Cl, 14.26; N, 11.27. Found: C, 57.90; H, 3.61; Cl, 14.29;
N, 11.21.
3
4
. Holmgren, A. Curr. Top. Cell. Regul. 1981, 19, 47.
. Fuchs, J. A.; Haller, B.; Tuggle, C. K. Functions of Glu-
1
1
,10 - Diazabicyclo[8.3.1]trideca - 5,12 - diene - 3,7 - diyne -
1,14 - dione (7). To a solution of 6 (72.0 mg, 0.280
tathione (Noble Conf.); Raven: New York, 1983.
5. Davis, N. K.; Greer, S.; Jones-Mortimer, M. C.; Perham,
R. N. J. Gen. Microbiol. 1982, 128, 1631.
mmol) in THF (80 mL) and n-butylamine (1.0 mg, 0.014
mmol), under argon atmosphere, was added Pd(PPh3)4