1042
S. Kotha et al. / Bioorg. Med. Chem. Lett. 15 (2005) 1039–1043
2H). 13C NMR (50.32 MHz, CDCl3): d 43.1, 43.8, 56.6,
118.4, 120.8, 130.4, 131.2, 149.8, 170.2. Mass: m/z
311.2025 (M+Na).
with water, brine and dried over MgSO4. The solvent
was removed under vacuum and the crude product
was purified by silica gel column chromatography using
3% ethyl acetate–petroleum ether as an eluent to give
21 (227 mg, yield 81%) as a colorless solid. Mp: 58–
59 ꢁC.
2.2. Typical experimental procedure for RCM reaction
To a suspension of tetra-allyl barbituric acid 18 (90 mg,
0.313 mmol) in toluene (10 mL), first generation Grubbs
catalyst (25.7 mg, 10 mol %) was added and stirred at
90 ꢁC for 26 h under nitrogen. The solvent was removed
under vacuum and the crude product was purified by sil-
ica gel column chromatography using 5% ethyl acetate–
petroleum ether as an eluent to give 19 (86 mg, yield
95%) as a faint yellow solid.
By using similar procedure, compounds 24, 26 and 33
were synthesized.
2.5. Selected spectral data
1
Compound 21: H NMR (300 MHz, CDCl3): d 2.69 (d,
J = 7.4 Hz, 4H), 3.26 (s, 6H), 5.02–5.11 (m, 4H), 5.45–
5.54 (m, 2H). 13C NMR (75.4 MHz, CDCl3): d 27.9,
42.7, 56.9, 119.9, 130.8, 150.8, 170.5. m/z 236 (M+).
Mp: 52–53 ꢁC. Rf: 0.5 (10% ethyl acetate–petro-
leum ether). IR (CHCl3) mmax: 1692, 1646 cmꢀ1 1H
.
1
NMR (200 MHz, CDCl3): d 2.99 (s, 4H), 4.45 (d,
J = 5.8 Hz, 4H), 5.16–5.29 (m, 4H), 5.64 (s, 2H), 5.72–
5.89 (m, 2H). 13C NMR (50.38 MHz, CDCl3): d 44.1,
44.9, 54.8, 118.8, 127.2, 131.1, 150.3, 171.5. Mass: m/z
260 (M+).
Compound 22: H NMR (300 MHz, CDCl3): d 3.00 (s,
4H), 3.30 (s, 6H), 5.66 (s, 2H). 13C NMR (75.4 MHz,
CDCl3): d 28.8, 45.3, 54.8, 127.2, 151.3, 172.3. m/z 208
(M+).
1
Compound 24: H NMR (300 MHz, CDCl3): d 1.15 (t,
2.3. Typical experimental procedure for allylation of
tetronic acid 5 or thiotetronic acid 6
J = 7 Hz, 6H), 2.67 (d, J = 7.4 Hz, 4H), 4.36 (q,
J = 7 Hz, 4H), 4.97–5.97 (dd, J = 10.3, 6.9 Hz, 4H),
5.36–5.56 (m, 2H). 13C NMR (75.4 MHz, CDCl3): d
12.2, 43.3, 56.7, 120.6, 130.4, 168.8, 178.8. m/z 280 (M+).
To a solution of tetronic acid 5 (150 mg, 1.5 mmol) in
chloroform (10 mL), powdered potassium carbonate
(621 mg, 4.5 mmol) and tetrabutylammonium hydrogen
sulfate (1.5 g, 4.5 mmol) were added. The reaction mix-
ture was cooled to 0 ꢁC and to this cooled solution, allyl
bromide (545 mg, 4.5 mmol) was added dropwise and
the reaction mixture was stirred at 0 ꢁC for 1 h. Then,
the reaction temperature was maintained between 0
and 15 ꢁC till the completion of the reaction (12 h, mon-
itored by TLC) and the reaction mixture was quenched
by addition of water (10 mL). The organic layer was sep-
arated and the aqueous layer was extracted with chloro-
form (3 · 20 mL). The combined organic layer was
washed with water, brine and dried over MgSO4. The
solvent was removed under vacuum and the crude prod-
uct was purified by silica gel column chromatography
using 1% ethyl acetate–petroleum ether as an eluent to
give 28 (99 mg, yield 55%) and 35 (63 mg, 35%) as a col-
orless liquid. Similar procedure was used for the dially-
lation of thiotetronic acid 6.
1
Compound 25: H NMR (300 MHz, CDCl3): d 1.22 (t,
J = 7 Hz, 6H), 2.99 (s, 4H), 4.41 (q, J = 7 Hz, 4H),
5.63 (s, 2H). 13C NMR (75.4 MHz, CDCl3): d 12.1,
43.6, 44.1, 55.8, 126.9, 169.8, 179.4. m/z 253 (M+1).
1
Compound 26: H NMR (300 MHz, CDCl3): d 1.92 (q,
J = 7, 7.5 Hz, 4H), 2.13 (t, J = 7.5 Hz, 4H), 3.29 (d,
J = 5 Hz, 6H), 4.91 (dd, J = 10.5, 6.5 Hz, 4H), 5.60–
5.66 (m, 2H). 13C NMR (75.4 MHz, CDCl3): d 28.8,
36.5, 39.3, 55.7, 115.8, 135.7, 150.3, 171.8. m/z 264 (M+).
Compound 27: 1H NMR (300 MHz, CDCl3): d 2.27 (m,
4H), 2.46 (m, 4H), 3.29 (s, 6H), 5.65 (t, J = 3.2 Hz, 2H).
13C NMR (75.4 MHz, CDCl3): d 25.1, 34.8, 39.4, 53.9,
130.1, 141.5, 172.9. m/z 236 (M+).
1
Compound 28: H NMR (300 MHz, CDCl3): d 2.50 (d,
J = 6.3 Hz, 4H), 4.39 (s, 2H), 5.13–5.20 (m, 2H), 5.59–
5.65 (m, 2H). 13C NMR (75.4 MHz, CDCl3): d 39.1,
54.1, 121.2, 130.2, 203.8, 209.8. m/z 180 (M+).
2.4. Typical experimental procedure for allylation
of 20 to 21
1
Compound 29: H NMR (300 MHz, CDCl3): d 2.63 (d,
To a suspension of 1,3-dimethyl barbituric acid 20
(150 mg, 0.962 mmol) in chloroform (10 mL), powdered
potassium carbonate (796 mg, 5.77 mmol) and BTEAC
(548 mg, 2.41 mmol) were added. The reaction mixture
was cooled to 0 ꢁC and to this ice-cooled stirred solu-
tion, allyl bromide (407 mg, 3.37 mmol) was added
dropwise and the reaction mixture was stirred at 0 ꢁC
for 1 h. Then the reaction mixture was stirred at rt for
24 h. At the conclusion of the reaction (TLC monitor-
ing), the reaction mixture was quenched with addition
of water (10 mL). The organic layer was separated and
the aqueous layer was extracted with chloroform
(3 · 20 mL). The combined organic layer was washed
J = 8 Hz, 4H), 4.32 (s, 2H), 5.68 (s, 2H). 13C NMR
(75.4 MHz, CDCl3): d 35.2, 42.3, 66.3, 127.3, 197.1,
209.1. m/z 152 (M+).
1
Compound 30: H NMR (300 MHz, CDCl3): d 2.40–
2.42 (m, 4H), 3.75 (s, 2H), 5.08–5.12 (m, 4H), 5.54–
5.65 (m, 2H). 13C NMR (75.4 MHz, CDCl3): d 40.9,
41.2, 60.6, 120.7, 130.5, 203.5, 207.7. m/z 196 (M+).
1
Compound 31: H NMR (300 MHz, CDCl3): d 2.77 (s,
4H), 4.02 (s, 2H), 5.62 (s, 2H). 13C NMR (75.4 MHz,
CDCl3): d 39.38, 42.3, 60.1, 127.3, 201.9, 205.01. m/z
168 (M+).