P. Rajan et al. / Bioorg. Med. Chem. Lett. 11 (2001) 215±217
217
with the radical on the m-hydroxyl group we found 83.2
and 87.0 kcal/mol, respectively, for the hydrogen and
non-hydrogen bonded radical, indicating clearly the
importance of 4c in the radical formation.
4. (a) Nakawaza, T.; Ohsawa, K. J. Nat. Prod. 1998, 61, 993.
(b) Graefe, E. U.; Veit, M. Phytomedicine 1999, 6, 239.
5. Duniec, Z.; Robak, J.; Gryglewski, R. Biochem. Pharmacol.
2283, 1983.
6. The hydroxycinnamic acid (10 mmol) is dissolved in 20 mL
of DMF and 1.4 mL (10 mmol) of triethylamine. The solution
is cooled in an ice±water bath and 10 mmol of the amine are
added followed by a solution of 10 mmol of BOP in 20 mL of
The spin population de®ned as N (A)=N � N illus-
S
A"
A#
trates the eect of the N-substituent on the caeoyl
group on the unpaired spin density distribution showing
an additional mesomeric eect with the second aromatic
ꢀ
CH Cl . The mixture is stirred at 0 C for 30 min and then at
2
2
2 2
room temperature for 2 h. CH Cl is removed under reduced
pressure and the solution is diluted with 150 mL of water. The
products are extracted with ethyl acetate. The extract is washed
0
ring oering a positive spin density to the C4 -nucleus
and responsible for the more eective spin delocalisa-
tion and the higher activity of the N-phenyl compound
10 (Scheme 3).
successively with 1 N HCl, water, 1 M NaHCO
4
dried over MgSO , ®ltered and evaporated. The residue is
puri®ed on a silica gel column (eluent: ethyl acetate±petroleum
ether). (Yields are between 65 and 85%.)
and water,
3
This study shows that caeic anilides are strong inhibi-
tors of lipid peroxidation. Further investigation is
needed to evaluate their complete antioxidant pro®le,
safety and detailed structure±activity relationship.
7
. The antioxidant activity of each compound was expressed
as IC50 value, i.e. the concentration in mm necessary to inhibit
TBARS formation by 50%, and was calculated from the cor-
responding log-dose inhibition curve.
8
2
.
1H NMR (400 MHz) spectral data for 4 and 10, respectively:
.83 (3H, s, CH ), 6.20 (1H, d, J=20 Hz, vinyl), 6.70±7.00
3
(
3H, m, arom), 7.30 (1H, d, J 20 Hz); 6.43 (1H, d, J=22 Hz,
vinyl), 6.80±7.50 (8H, m, arom), 7.53 (1H, d, J=22 Hz, vinyl).
. Vedernikova, I.; Proinov, E.; Salahub, D. R.; Haemers, A.
References and Notes
9
1
. (a) Middleton, E. TIPS 1984, 5, 335. (b) Cos, P.; Calomme,
Int. J. Quant. Chem. 1999, 77, 161.
M.; Pieters, M.; Vlietinck, A. J.; Vanden Berghe, D. In Studies in
Natural Products Chemistry; Atta-Ur-Rahman, Ed.; Elsevier
Science: Amsterdam, 2000; Vol. 22, pp 307±341.
10. The electronic structure and geometry parameters of the
compounds in their neutral and radical state were calculated
using the linear combination of Gaussian type orbitals
(LGTCO) Kohn±Sham (KS) DFT program deMon-KS3 (St-
Amant, A.; Salahub, D. R. Chem. Phys. Lett. 1990, 169).
Orbital basis sets of DZVP quality with added polarisation
functions were used (621/41/1*) for C and O atoms and (41/
1*) for H atoms. The auxiliary basis used to ®t the exchange-
correlation potential were as follows: (5,2;5,2) for C, (4,4;4,4)
for O and (5,1;5,1) for H atoms. The geometries were optimised
until both the norm and the local energy gradient and the norm
of the maximal individual gradient fell below 0.0003 a.u. using
the kinetic-energy-density dependent exchange-correlation
scheme PLAP3.
2
. (a) Cuvelier, M. E.; Richard, H.; Berset, C. Biosci. Bio-
technol. Biochem. 1992, 56, 324. (b) Sud'ina, G. F.; Mirzoeva,
O. K.; Pushkaraeva, M. A.; Korshunova, G. A.; Shubatyan,
N. V.; Varfolomeev, S. D. FEBS Lett. 1993, 329, 21. (c)
Ohnishi, M.; Morishita, H.; Iwahashi, H.; Toda, S.; Shiratati,
Y.; Kimura, M.; Kido, R. Phytochemistry 1994, 36, 579. (d)
Nardini, M.; D'Aquino, M.; Tomassi, G.; Gentili, V.; Di
Felici, M.; Scaccini, C. Free Radical Biol. Med. 1995, 19, 541.
(
e) Cuvelier, M. E.; Richard, H.; Berset, C. J. Am. Oil Chem.
Soc. 1996, 73, 645. (f) Yamanaka, N.; Oda, O.; Nagao, S.
FEBS Lett. 1997, 405, 186. (g) Chen, J. H.; Ho, C.-T. J. Agric.
Food Chem. 1997, 45, 2374.
R
11. The radical stability ÁE was calculated as the dierence
3
. (a) Challis, B. C.; Bartlett, C. D. Nature 1975, 254, 532. (b)
between the total energy of the neutral compound and the sum
of the total energy of the related phenolic radical and the H-
radical.
Knekt, P.; Jarvinen, R.; Reunanen, A. L.; Maatela, J. Br.
Med. J. 1995, 312, 478.