Anti-oxidant activities of curcumin and related enones

Article abstract of DOI:10.1016/j.bmc.2005.03.035

The natural product curcumin (diferuloylmethane, 1,7-bis(4-hydroxy-3- methoxyphenyl)-1,6-heptadiene-3,5-dione), obtained from the spice turmeric, exhibits numerous biological activities including anti-cancer, anti-inflammatory, and anti-angiogenesis activities. Some of these biological activities may derive from its anti-oxidant properties. There are conflicting reports concerning the structural/electronic basis of the anti-oxidant activity of curcumin. Curcumin is a symmetrical diphenolic dienone. A series of enone analogues of curcumin were synthesized that included: (1) curcumin analogues that retained the 7-carbon spacer between the aryl rings; (2) curcumin analogues with a 5-carbon spacer; and (3) curcumin analogues with a 3-carbon spacer (chalcones). These series included members that retained or were devoid of phenolic groups. Anti-oxidant activities were determined by the TRAP assay and the FRAP assay. Most of the analogues with anti-oxidant activity retained the phenolic ring substituents similar to curcumin. However, a number of analogues devoid of phenolic substituents were also active; these non-phenolic analogues are capable of forming stable tertiary carbon-centered radicals.

Full text of DOI:10.1016/j.bmc.2005.03.035

Bioorganic & Medicinal Chemistry 13 (2005) 3811–3820
Anti-oxidant activities of curcumin and related enones
Waylon M. Weber,a Lucy A. Hunsaker,b Steve F. Abcouwer,b
Lorraine M. Decka,* and David L. Vander Jagtb,*
aDepartment of Chemistry, University of New Mexico, Albuquerque, NM 87131, USA
bDepartment of Biochemistry and Molecular Biology, University of New Mexico School of Medicine,
Albuquerque, NM 87131, USA
Received 18 January 2005; revised 1 March 2005; accepted 2 March 2005
Available online 12 April 2005
Abstract—The natural product curcumin (diferuloylmethane, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione),
obtained from the spice turmeric, exhibits numerous biological activities including anti-cancer, anti-inflammatory, and anti-angio-
genesis activities. Some of these biological activities may derive from its anti-oxidant properties. There are conflicting reports con-
cerning the structural/electronic basis of the anti-oxidant activity of curcumin. Curcumin is a symmetrical diphenolic dienone. A
series of enone analogues of curcumin were synthesized that included: (1) curcumin analogues that retained the 7-carbon spacer
between the aryl rings; (2) curcumin analogues with a 5-carbon spacer; and (3) curcumin analogues with a 3-carbon spacer (chal-
cones). These series included members that retained or were devoid of phenolic groups. Anti-oxidant activities were determined by
the TRAP assay and the FRAP assay. Most of the analogues with anti-oxidant activity retained the phenolic ring substituents sim-
ilar to curcumin. However, a number of analogues devoid of phenolic substituents were also active; these non-phenolic analogues
are capable of forming stable tertiary carbon-centered radicals.
Ó 2005 Elsevier Ltd. All rights reserved.
1. Introduction
ity,3 possibly owing to its ability to induce apoptosis
by inhibiting the activation of the prosurvival transcrip-
tion factor NFjB.2 Curcumin exhibits anti-inflamma-
tory activity that may be related to its ability to inhibit
up-regulation of COX-2.4 Curcumin has anti-angiogen-
esis activity, which has been ascribed to the ability
of curcumin to irreversibly inhibit CD13/aminopepti-
dase N, a membrane-bound metalloproteinase that is
Curcumin (Fig. 1) is a non-nutritive, non-toxic chemical
in turmeric that has been used for centuries in India and
elsewhere as a dietary spice and as a herbal medicine for
treatment of wounds, jaundice, and rheumatoid arthri-
tis.1 In addition, curcumin inhibits the proliferation of
a variety of tumor cells2 and has anti-metastatic activ-
• H
•
O
O
O
O
OH
OH
HO
HO
OCH
OCH
3
OCH
OCH
3
3
3
Curcumin
Figure 1. Curcumin exists in solution as an equilibrium mixture of the symmetrical dienone and the keto-enol tautomer stabilized by intramolecular
H-bonding.
Keywords: Curcumin; Anti-oxidants.
*
Corresponding authors. Tel.: +1 505 277 5438 (L.M.D.); +1 505 272 5788 (D.L.V.J.); e-mail addresses: ldeck@unm.edu; dlvanderjagt@
salud.unm.edu
0968-0896/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmc.2005.03.035

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W. M. Weber et al. / Bioorg. Med. Chem. 13 (2005) 3811–3820
important in angiogenesis.5a Curcumin also exhibits po-
tent anti-oxidant activity.6 It is unclear whether the anti-
oxidant activity of curcumin is the basis for most of its
reported biological activities.
prepared as shown in Scheme 1. Compounds 2a-i con-
tain two aryl rings separated by an unsaturated seven
carbon spacer having two carbonyls. The aryl rings con-
tain different substituents in various positions on the
ring. These compounds were designed to test the impor-
tance of the type of functional group and location of the
group on the aryl ring. Compounds 2a–i were prepared
following the procedure described by Pabon.10 2,4-Pen-
tanedione was reacted with a substituted benzaldehyde
in an aldol-type reaction to give curcumin (2a) or one
of its analogues 2b–i.
It has been suggested that the anti-oxidant activity of
curcumin depends upon the presence of the phenolic
functional groups.6,7 However, other studies support
the conclusion that the central methylene hydrogens of
curcumin are important for anti-oxidant activity.8 More
recently, it has been demonstrated that both the central
methylene hydrogens and the phenolic hydrogens may
be involved in the mechanism of formation of the phen-
oxy radical, depending upon reaction conditions.9 In the
present study, three series of analogues of curcumin were
synthesized and their anti-oxidant activities were com-
pared using two different procedures. These three series
examined the role of the enone functionality in aryl sys-
tems where the spacer is 7-carbons (as in curcumin), 5-
carbons, or 3-carbons in length (as in a chalcone). In
addition, the importance of ring substituents including
phenolic groups was assessed as well as the importance
of the central methylene hydrogens of curcumin.
Two curcumin analogues, 3a and 3b, were prepared as
shown in Scheme 1. Compounds 3a and 3b contain
two aryl rings separated by a saturated seven carbon
spacer having two carbonyls. These compounds were
designed to test the importance of unsaturation in the
seven carbon spacer. Compounds 3a and 3b were pre-
pared by reduction of 2a and 2b, respectively, as de-
scribed by Venkateswarlu et al.11
Four additional curcumin analogues, 4b, 5b, 6b, and 7b,
were prepared as shown in Scheme 1. Compounds 4b,
5b, 6b, and 7b contain two aryl rings separated by an
unsaturated seven carbon spacer. All four compounds
have either one or two substituents attached to the cen-
tral methylene carbon and were designed to test the
importance of the central methylene hydrogens. Com-
pounds 4b and 5b were prepared from 2b using a base
and an alkyl halide as described by Pederson et al.12
In our hands the disubstituted compound 5b was formed
rather than the monosubstituted compound 7b as
reported by Pederson. Compounds 6b and 7b were pre-
pared following the procedure described by Pabon.10 3-
Methyl-2,4-pentanedione and 3-benzyl-2,4-pentanedione
2. Chemistry
Curcumin exists in equilibrium between the diketo and
keto-enol forms; the keto-enol form is strongly favored
by intramolecular H-bonding9 (Fig. 1). Curcumin is a
relatively simple bis-phenolic compound that can be pre-
pared in a single reaction. The following schemes sum-
marize the procedures used to prepare the three series
of curcumin analogues. Compounds in series 1, which
retain the 7-carbon spacer contained in curcumin, were
O
OH
R1
O
O
OH
R2
R3
f
e
H
CH2C6H5
7b
CH3
6b
1a-i
a
O
O
c
H3C CH3
R1
O
OH
R1
4b
R2
R3
R2
R3
O
O
2a-i
d
b
C6H5H2C CH2C6H5
5b
a: R1=H, R2=OCH3, R3=OH
b: R1,R2,R3=H
R1
O
OH
R1
R2
R3
R2
R3
c:
d:
e:
f:
g:
h:
i:
R1=OCH3, R2,R3=H
R1=H, R2,R3=OCH3
R1,R2=OCH3, R3=H
R1,R2=H, R3=OCH3
R1,R2=H, R3=OH
3a,b
R1,R2=H, R3=N(CH3)2
R1=H, R2=OH, R3=OCH3
Scheme 1. Reagents: (a) CH3C(O)CH2C(O)CH3 (0.5 equiv), B2O3, B(OC4H9)3, nBuNH2, EtOAc; (b) H2, Pd/C, EtOAc; (c) CH3Br (2.0 equiv),
NH4Cl, NaOH, CH2Cl2; (d) C6H5CH2Br (2.0 equiv), NH4Cl, NaOH, CH2Cl2; (e) CH3C(O)CH(CH3)C(O)CH3 (0.5 equiv), B2O3, B(OC4H9)3,
nBuNH2, EtOAc; (f) CH3C(O)CH(CH2C6H5)C(O)CH3 (0.5 equiv), B2O3, B(OC4H9)3, nBuNH2, EtOAc.

W. M. Weber et al. / Bioorg. Med. Chem. 13 (2005) 3811–3820
3813
were reacted with benzaldehyde in an aldol type reaction
to give 6b and 7b, respectively.
rings separated by a saturated five carbon spacer and
were designed to test the importance of unsaturation
and the necessity of a carbonyl in the spacer of series
2 compounds. Compounds 10b and 11b were prepared
by reduction of 9b.11
Compounds in series 2, which contain a 5-carbon
spacer, were prepared as shown in Scheme 2. Com-
pounds 9a–w contain two identical aryl rings separated
by an unsaturated five carbon spacer having a single car-
bonyl whereas compounds 9x and 9y have two different
aryl rings. These compounds were designed to test the
importance of the length of the spacer between the
two aryl rings. Compounds 9a–w were prepared from
acetone and a substituted benzaldehyde in a base cata-
lyzed aldol reaction as described by Masuda et al.13 In
the case of phenolic benzaldehydes, the phenol was pro-
tected with a methoxymethyl group prior to the aldol
reaction and deprotected later to give the free phenol.13
Compounds 9u and 9v were prepared from 9a and 9r,
respectively, by reaction with acetic anhydride as de-
scribed by Ali et al.14 Compounds 9x and 9y were pre-
pared using two consecutive base catalyzed aldol
reactions.13
Compounds 12a and 12b were prepared as shown
in Scheme 2. These compounds contain two identical
aryl rings separated by an unsaturated five carbon
spacer having both a carbonyl and a saturated ring
and were designed to test the importance of a ring in
the spacer. They were synthesized following the proce-
dure of Masuda et al.13 by reaction of a substituted
benzaldehyde with cyclohexanone in a base catalyzed
aldol reaction.
Compound 13b was prepared as shown in Scheme 2.
This compound contains two identical aryl rings sepa-
rated by a five carbon spacer containing both a carbonyl
and two epoxide rings. This compound was designed to
test the importance of an epoxide on the spacer. Com-
pound 13b was synthesized following the procedure of
Yadav and Kapoor15 by the reaction of 9b with tert-but-
yl hydroperoxide.
Compounds 8a, 8c, and 8t were prepared as shown in
Scheme 2. These compounds contain a single aryl ring
with an unsaturated 3-carbon chain and a single car-
bonyl. These compounds were designed to test the neces-
sity of two aryl rings. Compounds 8a, 8c, and 8t were
prepared from excess acetone and a substituted benzal-
dehyde in a base catalyzed aldol reaction following the
procedure of Masuda et al.13
Compounds 15a and 15b were prepared as shown in
Scheme 3. These compounds have an unsaturated five
carbon spacer between two nitrogen containing aryl
rings. These compounds were designed to test the impor-
tance of a heterocyclic ring. Compounds 15a and 15b
were synthesized according to the method of Zelle16 by
the reaction of a pyridinecarboxaldehyde with 1,3-ace-
tonedicarboxylic acid.
Compounds 10b and 11b were prepared as shown in
Scheme 2. These compounds contain two identical aryl
R1
O
R1
R1
R4
O
R1
O
R2
R3
R2
R3
R2
R3
R2
R3
H
CH3
a
b
R5
8a,c,t
12a,b
1a-w
d
c
O
O
R1
R4
O
R6
R9
O
O
10b
+
R2
R3
R7
R8
e
f
R5
R10
OH
13b
9a-y
11b
a: R1,R4,R5,R6,R9,R10=H, R2,R7=OCH3, R3,R8=OH n: R1,R6=CH3, R2,R3,R4,R5,R7,R8,R9,R10=H
b: R1,R2,R3,R4,R5,R6,R7,R8,R9,R10=H
o:
p:
q:
r:
s:
R1,R2,R4,R5,R6,R7,R9,R10=H, R3,R8=Cl
R1,R3,R4,R5,R6,R8,R9,R10=H, R2,R7=Cl
R1,R6=Cl, R2,R3,R4,R5,R7,R8,R9,R10=H
R1,R2,R4,R5,R6,R7,R9,R10=H, R3,R8=OH
R1,R3,R4,R5,R6,R8,R9,R10=H, R2,R7=OH
R1,R6=OH, R2,R3,R4,R5,R7,R8,R9,R10=H
c:
d:
e:
f:
R1,R2,R4,R5,R6,R7,R9,R10=H, R3,R8=OCH3
R1,R3,R4,R5,R6,R8,R9,R10=H, R2,R7=OCH3
R1,R6=OCH3, R2,R3,R4,R5,R7,R8,R9,R10=H
R1,R2,R6,R7=OCH3, R3,R4,R5,R8,R9,R10=H
R1,R4,R5,R6,R9,R10=H, R2,R3,R7,R8=OCH3
R1,R4,R6,R9=OCH3, R2,R3,R5,R7,R8,R10=H
R1,R3,R6,R8=OCH3, R2,R4,R5,R7,R9,R10=H
R1,R3,R5,R6,R8,R10=H, R2,R4,R7,R9=OCH3
R1,R5,R6,R10=OCH3, R2,R3,R4,R7,R8,R9=H
R1,R2,R4,R5,R6,R7,R9,R10=H, R3,R8=CH3
R1,R3,R4,R5,R6,R8,R9,R10=H, R2,R7=CH3
g:
h:
i:
t:
u:
v:
w:
x:
y:
R1,R4,R5,R6,R9,R10=H, R2,R7=OCH3, R3,R8=OC(O)CH3
R1,R2,R4,R5,R6,R7,R9,R10=H, R3,R8=OC(O)CH3
R1,R2,R4,R5,R6,R7,R9,R10=H, R3,R8=C(O)OCH3
R1,R2,R4,R5,R6,R7,R8,R9,R10=H, R3=OCH3
j:
k:
l:
R1,R4,R5,R6,R7,R8,R9,R10=H, R2=OCH3, R3=OH
m:
Scheme 2. Reagents: (a) cyclohexanone (0.5 equiv), NaOH, EtOH, H2O; (b) CH3C(O)CH3 (1.0 equiv), NaOH, EtOH, H2O; (c) CH3C(O)CH3
(0.5 equiv), NaOH, EtOH, H2O; (d) PhCHO, NaOH, EtOH, H2O; (v) H2, Pd/C, EtOAc; (e) Al2O3-KF, (CH3)3COOH, CH3CN, ClCH2CH2Cl.

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W. M. Weber et al. / Bioorg. Med. Chem. 13 (2005) 3811–3820
1.0
0.8
0.6
0.4
0.2
0.0
O
O
O
X
Y
H
X
Y
X
Y
HO2CCH2CCH2CO2H
EtOH
15a,b
2) HCl
3) NaOH
14a,b
series 3
series 2
series 1
a: X=CH, Y=N
X=N, Y=CH
b:
Scheme 3.
Compounds in series 3, called chalcones, which contain
a 3-carbon spacer, were prepared as shown in Scheme 4.
Compounds 17a–h contain two aryl rings separated by
an unsaturated 3-carbon spacer having a single car-
bonyl. These compounds were designed to test the
importance of the length of the spacer and symmetry
in series 3 compounds. Compounds 17a–h were pre-
pared from a substituted benzaldehyde and a substituted
acetophenone in a base catalyzed aldol reaction as de-
scribed by Kohler and Chadwell.17
2a 3a 2g 2i7b 6b
9r9t 12a
17f8a17g 17h 8t
Figure 2. Activities of curcumin and analogues in the TRAP assay. All
compounds were tested in triplicate at 10 lM concentrations, with
Trolox, 10 lM, as reference standard. All of the remaining analogues
were indistinguishable from the blank.
3. Results and discussion
The anti-oxidant activities of curcumin and analogues
(Schemes 1–4) were determined in two standard assays.
Anti-oxidant activity was measured as the ability of the
analogues to react with the preformed radical monoca-
tion of 2,20-azinobis-(3-ethylbenzothiazoline-6-sulfonic
acid) (ABTSÅ+). This assay is also known as the total
radical-trapping anti-oxidant parameter assay (TRAP
assay). Anti-oxidant activity was also measured in the
ferric reducing/anti-oxidant power assay (FRAP assay)
in which the compounds are reacted with ferric tripyr-
idyltriazine complex. In both colorimetric assays, the
vitamin E analogue Trolox was used as a control.
and 12a) also retained phenolic groups, although not
all phenolic analogues were active including 9a, 9s,
and 9y. Active analogues in series 3 (8a, 8t, 17f, 17g,
and 17h) retain phenolic groups.
Most interesting is the activity of analogues that do not
retain phenolic groups. Two analogues in series 1 (6b
and 7b) are dienones, similar to curcumin. However,
both 6b and 7b are devoid of ring substituents but con-
tain a single alkyl group attached to the central meth-
ylene carbon. By comparison, analogue 2b, which has
no ring substituents or an alkyl group attached to the
central methylene carbon, and analogues 4b and 5b,
which are similar to 6b and 7b but with dialkylation of
the central methylene, are inactive. An explanation of
these properties is shown in Figure 3. Curcumin (2a,
Fig. 3, top) has been proposed to form the stable phen-
oxy radical in radical trapping reactions either through
direct abstraction of the phenolic hydrogen, or by way
of initial ionization of an acidic proton from the central
methylene, followed by electron transfer to form a car-
bon-centered radical that can isomerize to the phenoxy
radical.9 The pathway is dictated by reaction conditions.
In the case of analogues 6b and 7b (Fig. 3, bottom), sta-
bilized tertiary carbon-centered radicals can form in the
The results of the TRAP assay of anti-oxidant activity
are shown in Figure 2. There were active compounds
in all three series. Generally, activity was observed with
analogues that retained a phenolic substituent. In series
1, this included 3a, which is the reduced form of curcu-
min (2a) in which both of the enone double bonds have
been reduced. Analogue 3a was the most active com-
pound in the TRAP assay. Clearly, it is not necessary
to retain the enone or dienone structure of curcumin
in order to retain activity. Other phenolic analogues in
series 1 included analogue 2g, where the methoxy groups
of curcumin have been removed, and 2i, which is an iso-
mer of curcumin. Active analogues in series 2 (9r, 9t,
R1
O
R4
O
R1
O
R4
R2
R3
R5
R6
R2
R3
R5
R6
NaOH
H2O,
EtOH
H
CH3
+
1
16
a: R1,R2,R3,R4,R5,R6=H
b: R1,R2,R4,R5,R6=H, R3=COOH
17a-h
c:
d:
e:
f:
g:
h:
R1,R2,R3,R4,R5=H, R6=COOH
R1,R2,R3,R4,R5=H, R6=CN
R1,R2,R3,R5=H, R4,R6=CH3
R1,R4,R5,R6=H, R2=OCH3, R3=OH
R1,R2,R3,R4=H, R5=OCH3, R6=OH
R1,R4=H, R2,R5 = OCH3, R3,R6 = OH
Scheme 4.

W. M. Weber et al. / Bioorg. Med. Chem. 13 (2005) 3811–3820
3815
O
O
C
O
C
O
C
H+
C
C
H
C
H
HO
H
HO
OCH3
OCH3
ABTS
2a
O
O
C
C
C
H
HO
OCH3
O
O
C
O
C
O
C
C
C
H+
C
H
O
H
H
O
OCH3
OCH3
H+
O
C
O
C
O
C
O
C
O
C
O
C
C
R
C
R
C
H
R
ABTS
6b or 7b
Figure 3. Mechanisms of the radical trapping reactions of curcumin (top) and non-phenolic analogues of curcumin (bottom).
reaction of 6b or 7b with ABTS in the TRAP assay. This
is not possible with the dialkylated analogues 4b and 5b.
Analogue 2b likely is inactive because formation of a
secondary carbon-centered radical is less favored than
formation of tertiary radicals.
the TRAP assay. Especially interesting are the results
with analogues 2h and 9l, which are devoid of phenolic
groups. Analogue 2h which is comparable to curcumin
in the FRAP assay, contains dimethylamino groups in
place of phenolic groups in the basic curcumin structure
and contains no other functional groups. This raises the
possibility of developing analogues that are more active
than curcumin. The mechanism of the anti-oxidant
activities of 7b and 2h in the FRAP assay may involve
formation of carbon-centered radicals, however this re-
mains to be investigated.
The FRAP assay measures the ability of a compound to
reduce the ferric tripyridyltriazine complex to the col-
ored ferrous complex. The results of the FRAP assay
of anti-oxidant activities of curcumin and analogues
are shown in Figure 4. The results show similarities as
well as differences compared to the TRAP assay. In ser-
ies 1, curcumin (2a) is most active, and other phenolic
analogues including 3a, 2g, and 2i are active. Likewise,
in series 2 and 3, active analogues 12a, 8a, 17h, and
17f are phenolic compounds that also were active in
the TRAP assay. Analogue 7b, which is devoid of phe-
nolic groups but contains a benzyl group attached to
the central methylene of the curcumin basic structure
and was active in the TRAP assay, is also active in the
FRAP assay whereas the related 6b was active only in
4. Conclusions
We conclude, therefore, that selected analogues of cur-
cumin that are devoid of phenolic groups are active in
both the TRAP assay and the FRAP assay, and that
some of these are active based on their abilities to form
stable carbon-centered radicals. Other analogues that
are devoid of phenolic groups also exhibit activity by

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W. M. Weber et al. / Bioorg. Med. Chem. 13 (2005) 3811–3820
0.25
Uni-Melt apparatus and are uncorrected. NMRspectra
were recorded on a Bruker AC250 NMRspectrometer
in CDCl3 unless otherwise noted. Chemical shifts are
in ppm (d) relative to TMS. High resolution mass spec-
tra were recorded on a Waters APcI MS. Compounds
2a–i, 6b, and 7b were prepared using a modification of
PabonÕs method.10 Compounds 3a, 3b, 10b, and 11b
were prepared following the method of Venkateswarlu
et al.11 Compounds 4b and 5b were prepared following
the method of Pederson et al.12 Compounds 9a–t, 9w,
8a, 8c, 8t, 12a, and 12b were prepared following the
method of Masuda et al.13 Compounds 9u and 9v were
prepared following the procedure of Ali et al.14 Com-
pound 13b was prepared following the method of Yadav
and Kapoor.15 Compounds 15a and 15b were prepared
following the method of Zelle and Su.16 Compounds
17a–h were prepared following the procedure of Kohler
and Chadwell.17
series 3
series 2
series 1
0.20
0.15
0.10
0.05
0.00
2a 3a 2g 2i2h 7b
91l 2a
178f a 17h
Figure 4. Activities of curcumin and analogues in the FRAP assay. All
compounds were tested at 10 lM with Trolox, 1 lM, as reference
standard. All of the remaining analogues were indistinguishable from
the blank.
5.1.1. 1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-
3,5-dione (2a). Orange-yellow solid: mp 182–184 °C
[lit.12 182–183 °C].
mechanisms that must still be determined. Most of the
active analogues of curcumin, however, are able to form
phenoxy radicals, and this is likely the basis of their anti-
oxidant activities. With this set of analogues, we are now
in a position to investigate the role of anti-oxidant activ-
ity in the multiple biological activities reported for
curcumin.
5.1.2. 1,7-Diphenyl-1,6-heptadiene-3,5-dione (2b). Yellow
solid: mp 140–142 °C [lit.12 139–140 °C].
5.1.3. 1,7-Bis(2-methoxyphenyl)-1,6-heptadiene-3,5-dione
(2c). Yellow crystals: mp 121–123 °C [lit.18 mp 121–
122 °C]; 13C NMR :d 55.5, 101.4, 111.1, 120.6, 124.0,
124.7, 128.5, 131.1, 135.6, 158.3, 183.6.
The most extensive recent studies of the biological activi-
ties of curcumin and its analogues have focused on the
anti-angiogenic properties of these compounds.5a–d,37
Curcumin and analogues inhibit activator protein-1
(AP-1) transcription, resulting in the down-regulation
of a number of pro-angiogenic genes.5b Synthetic ana-
logues that are quite far removed from curcumin but
retaining the same ring substituents, including the phe-
nolic functional groups, were shown to be more active
than curcumin in their anti-angiogenic activities involv-
ing cell proliferation and tube formation with human
umbilical vein endothelial cells.5c Other analogues of
curcumin were shown to exhibit anti-cancer activity
against a wide range of cells, and the most active ana-
logues also inhibited angiogenesis;37 this includes a
novel analogue, designated EF24, that was recently
shown to induce apoptosis in a number of breast and
prostate cell lines by a redox-dependent process.5d Inter-
estingly, ER24 does not contain phenolic groups and is
structurally related to the analogues with the 5-carbon
spacer (Scheme 2). It is likely, therefore, that analogues
of curcumin may exhibit a range of activities, not all of
which are related to the anti-oxidant properties of
curcumin.
5.1.4. 1,7-Bis(3,4-dimethoxyphenyl)-1,6-heptadiene-3,5-
dione (2d). Orange solid: mp 129–131 °C [lit.18 128–
130 °C].
5.1.5. 1,7-Bis(2,3-dimethoxyphenyl)-1,6-heptadiene-3,5-
dione (2e). The compound was prepared according to
the method of Pabon10 by the reaction of 2,4-pentanedi-
one and 2,3-dimethoxybenzaldehyde to give a yellow
1
solid: mp 117–120 °C; H NMR: d 3.87 (s, 12H), 5.87
(s, 1H), 6.68 (d, 2H, J = 16.1 Hz), 6.92 (d, 2H, J =
8.2 Hz), 7.05 (t, 2H, J = 8.0 Hz), 7.18 (d, 2H, J =
6.8 Hz), 7.95 (d, 2H, J = 16.1 Hz), 15.88 (s, 1H); 13C
NMR: (DMSO) d 55.7, 60.7, 101.9, 114.6, 118.7, 124.1,
125.1, 128.0, 134.2, 147.7, 152.6, 182.9. Anal. Calcd for
C23H24O6: C, 69.68; H, 6.10. Found: C, 69.43; H, 6.16.
5.1.6. 1,7-Bis(4-methoxyphenyl)-1,6-heptadiene-3,5-dione
(2f). Yellow solid: mp 157–159 °C [lit.18 mp 154–
155 °C]; 13C NMR :d 55.4, 101.2, 114.4, 121.9, 127.9,
129.7, 140.0, 161.2, 183.2.
5.1.7. 1,7-Bis(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione
(2g). Red-orange crystals: mp 226–228 °C [lit.12 mp 223–
224 °C].
5.1.8. 1,7-Bis(4-N,N-dimethylaminephenyl)-1,6-heptadi-
ene-3,5-dione (2h). Purple solid: mp 200–202 °C [lit.19
mp 206 °C].
5. Experimental
5.1. Chemical synthesis
5.1.9. 1,7-Bis(3-hydroxy-4-methoxyphenyl)-1,6-heptadiene-
3,5-dione (2i). Orange-yellow solid: mp 190–192 °C [lit.20
Reagent quality solvents were used without purification.
Melting points were determined on a Thomas–Hoover
1
189–190 °C]; H NMR: (DMSO) d 3.78 (s, 6H), 6.09,

W. M. Weber et al. / Bioorg. Med. Chem. 13 (2005) 3811–3820
3817
(s, 1H), 6.60 (d, 2H, J = 15.9 Hz), 6.49 (d, 2H,
J = 8.9 Hz), 7.11 (m, 4H), 7.47 (d, 2H, J = 15.9 Hz),
9.19 (s, 2H); 13C NMR: d 55.6, 100.9, 112.0, 114.0,
121.2, 121.5, 127.5, 140.2, 146.6, 149.8, 182.8.
5.1.19. 1,5-Bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-
3-one (9a). Yellow solid: mp 84–86 °C [lit.13 82–83 °C].
5.1.20. 1,5-Diphenyl-1,4-pentadien-3-one (9b). Yellow
crystals: mp 110–112 °C [lit.26 112–114 °C].
5.1.10. 1,7-Bis(4-hydroxy-3-methoxyphenyl)-heptane-3,5-
dione (3a). White crystals: mp 93–95 °C [lit.21 92–93 °C].
5.1.21. 1,5-Bis(4-methoxyphenyl)-1,4-pentadien-3-one (9c).
Yellow solid: mp 128–130 °C [lit.26 133–134 °C].
5.1.11. 1,7-Diphenylheptane-3,5-dione (3b). Orange-yel-
low oil [lit.22].
5.1.22. 1,5-Bis(3-methoxyphenyl)-1,4-pentadien-3-one (9d).
Yellow solid: mp 64–65 °C [lit.27 52–54 °C]; 1H NMR: d
3.83 (s, 6H), 6.94 (dd, 2H, J = 8.1 Hz, 2.4 Hz), 7.04 (d,
2H, J = 15.9 Hz), 7.15 (m, 4H), 7.32 (t, 2H, J = 8.0
Hz), 7.68 (d, 2H, J = 16.1 Hz); 13C NMR :d 55.2, 113.2,
116.2, 120.9, 125.5, 129.8, 136.0, 143.0, 159.8, 188.6.
5.1.12. 4,4-Dimethyl-1,7-diphenyl-1,6-heptadiene-3,5-dione
(4b). The compound was prepared according to the
method of Pederson et al.12 by the reaction of 2b with
1
methyl iodide to give yellow oil: H NMR :d 1.46 (s,
6H), 6.77 (d, 2H, J = 15.7 Hz), 7.33 (m, 6H), 7.49 (m,
4H), 7.72 (d, 2H, J = 15.6 Hz); 13C NMR: d 21.1, 60.9,
121.4, 128.5, 128.7, 130.6, 134.1, 144.1, 197.9. Anal.
Calcd for C21H20O2: C, 82.86; H, 6.62. Found: C,
82.54; H, 6.83.
5.1.23. 1,5-Bis(2-methoxyphenyl)-1,4-pentadien-3-one (9e).
Yellow solid: mp 123–124 °C [lit.28 124 °C].
5.1.24. 1,5-Bis(2,3-dimethoxyphenyl)-1,4-pentadien-3-one
(9f). Yellow solid: mp 106–108 °C [lit.29 108 °C]; 13C
NMR: d 55.9, 61.3, 114.1, 119.3, 124.1, 126.8, 129.0,
137.8, 148.7, 153.0, 189.5.
5.1.13. 4,4-Dibenzyl-1,7-diphenyl-1,6-heptadiene-3,5-dione
(5b). The compound was prepared according to the
method of Pederson et al.12 by the reaction of 2b with
benzyl bromide to give 5b as a white solid: mp 182–
183 °C (lit.12 181 °C); 1H NMR: (DMSO) d 3.43 (s,
4H), 7.12 (m, 12H), 7.38 (m, 6H), 7.57 (d, 2H,
J = 15.5 Hz), 7.67 (m, 4H); 13C NMR: d 37.0, 69.3,
123.6, 126.3, 127.8, 128.6, 128.7, 130.0, 130.5, 134.0,
136.3, 142.0, 196.4. Anal. Calcd for C33H28O2: C,
86.81; H, 6.18. Found: C, 86.52; H, 6.24.
5.1.25. 1,5-Bis(3,4-dimethoxyphenyl)-1,4-pentadien-3-one
(9g). Yellow solid: mp 72–75 °C [lit.30 68–70 °C]; 13C
NMR: d 55.9, 109.9, 111.0, 122.9, 123.5, 127.7, 142.8,
149.1, 151.2, 188.4.
5.1.26. 1,5-Bis(2,5-dimethoxyphenyl)-1,4-pentadien-3-one
(9h). Yellow solid: mp 105–106 °C [lit.31 105–106 °C]; 1H
NMR: d 3.79 (s, 6H), 3.85 (s, 6H), 6.88 (m, 4H), 7.11 (d,
2H, J = 2.8 Hz), 7.12 (d, 2H, J = 16.1 Hz), 8.01 (d, 2H,
J = 16.1 Hz); 13C NMR: d 55.8, 56.1, 112.4, 113.1,
117.1, 124.5, 126.3, 137.9, 153.0, 153.4, 189.6.
5.1.14. 4-Methyl-1,7-diphenyl-1,6-heptadiene-3,5-dione (6b).
The compound was prepared according to the method
of Pabon10 by the reaction of 3-methyl-2,4-
pentanedione and benzaldehyde to give an orange
1
solid: mp 154–157 °C; H NMR: d 2.17 (s, 3H), 7.12
(d, 2H, J = 15.5 Hz), 7.38 (m, 6H), 7.58 (m, 4H), 7.74
(d, 2H, J = 15.5 Hz); 13C NMR: d 12.1, 106.2, 120.8,
182.1, 128.8, 129.9, 135.4, 141.3, 182.4. Anal. Calcd
for C20H18O2: C, 82.73; H, 6.25. Found: C, 82.69; H,
6.36.
5.1.27. 1,5-Bis(2,4-dimethoxyphenyl)-1,4-pentadien-3-one
(9i). Yellow solid: mp 138–140 °C [lit.32 138–139 °C]; 13C
NMR: d 55.4, 55.5, 98.3, 105.3, 117.1, 124.1, 130.0,
137.6, 159.9, 162.6, 189.7.
5.1.28. 1,5-Bis(3,5-dimethoxyphenyl)-1,4-pentadien-3-one
(9j). Yellow solid: mp 126–128 °C [lit.33 124.5–125.5 °C];
1H NMR: d 3.80 (s, 12H), 6.49 (s, 2H), 6.73 (d, 4H,
J = 2.0 Hz), 7.00 (d, 2H, J = 15.9 Hz), 7.62 (d, 2H,
J = 15.7 Hz); 13C NMR: d 55.4, 102.7, 106.2, 125.7,
136.8, 143.2, 160.9, 188.6.
5.1.15. 4-Benzyl-1,7-diphenyl-1,6-heptadiene-3,5-dione (7b).
The compound was prepared according to the method
of Pabon10 by the reaction of 3-benzyl-2,4-pentanedione
and benzaldehyde to give a yellow solid: mp 162–164 °C;
1H NMR: d (DMSO) 3.99 (s, 2H), 6.99 (d, 2H,
J = 15.6 Hz), 7.34 (m, 15H), 7.77 (d, 2H, J = 15.2 Hz);
13C NMR: d 30.0, 110.6, 121.0, 125.8, 127.6, 128.3,
128.3, 128.7, 130.1, 134.7, 141.3, 141.6, 183.1. Anal.
Calcd for C26H22O2: C, 85.22; H, 6.05. Found: C,
85.48; H, 6.11.
5.1.29. 1,5-Bis(2,6-dimethoxyphenyl)-1,4-pentadien-3-one
1
(9k). Yellow solid: mp 152–154 °C [lit.28]; H NMR: d
3.90 (s, 12H), 6.57 (d, 4H, J = 8.5 Hz), 7.26 (t, 2H,
J = 8.5 Hz), 7.59 (d, 2H, J = 16.3 Hz), 8.17 (d, 2H,
J = 16.3 Hz); 13C NMR: d 55.8, 103.7, 113.1, 129.0,
130.9, 133.3, 160.0, 192.4.
5.1.16.
1-(4-Hydroxy-3-methoxyphenyl)-1-buten-3-one
(8a). Orange-yellow solid: mp 120–122 °C [lit.23 124–
125 °C].
5.1.30. 1,5-Bis(4-methylphenyl)-1,4-pentadien-3-one (9l).
Yellow solid: mp 174–176 °C [lit.26 171–172 °C].
5.1.17. 1-(4-Methoxyphenyl)-1-buten-3-one (8c). Yellow
solid: mp 71–73 °C [lit.24 72–72.5 °C].
5.1.31. 1,5-Bis(3-methylphenyl)-1,4-pentadien-3-one (9m).
1
Yellow solid: mp 68–72 °C [lit.34]; H NMR: d 2.38 (s,
5.1.18. 1-(2-Hydroxyphenyl)-1-buten-3-one (8t). Yellow
solid: mp 135–137 °C [lit.25 139–140 °C].
6H), 7.06 (d, 2H, J = 15.9 Hz), 7.26 (m, 4H), 7.40 (m,
4H), 7.70 (d, 2H, J = 15.9 Hz); 13C NMR :d 21.3,

3818
W. M. Weber et al. / Bioorg. Med. Chem. 13 (2005) 3811–3820
125.1, 125.4, 128.6, 128.8, 131.1, 134.6, 138.4, 143.1,
188.6.
4H), 7.57 (m, 3H), 7.71 (dd, 2H, J = 15.9, 2.0 Hz); 13C
NMR: d 55.4, 114.4, 123.3, 125.5, 127.4, 128.2, 128.8,
130.0, 130.2, 134.8, 142.6, 143.0, 161.5, 188.6.
5.1.32. 1,5-Bis(2-methylphenyl)-1,4-pentadien-3-one (9n).
Yellow solid: mp 98–100 °C [lit.26 94–96 °C].
5.1.43. 1-(4-Hydroxy-3-methoxyphenyl)-5-phenyl-1,4-penta-
dien-3-one (9y). The compound was prepared according
to the method of Masuda13 by the reaction of 8a with
5.1.33. 1,5-Bis(4-chlorophenyl)-1,4-pentadien-3-one (9o).
1
1
Yellow crystals: mp 184–186 °C [lit.26 191–193 °C]; H
benzaldehyde to give yellow oil: H NMR: d 3.92 (s,
NMR: d 7.00 (d, 2H, J = 15.9 Hz), 7.37 (d, 4H, J = 8.5
Hz), 7.52 (d, 4H, J = 8.5 Hz), 7.66 (d, 2H, J = 15.9 Hz);
13C NMR :d 125.7, 129.2, 129.5, 133.2, 136.4, 141.9, 188.1.
3H), 6.08 (s, 1H), 6.91 (d, 1H, J = 16.1 Hz), 6.93 (d,
2H, J = 8.2 Hz), 7.07 (d, 1H, J = 15.9 Hz), 7.10 (s, 1H),
7.15 (d, 1H, J = 8.0 Hz), 7.38 (m, 2H), 7.59 (m, 2H),
7.67 (d, 1H, J = 15.9 Hz), 7.71 (d, 1H, J = 15.9 Hz); 13C
NMR: d 56.0, 109.8, 114.9, 123.4, 125.3, 127.3, 128.3,
128.8, 130.3, 134.9, 142.8, 143.5, 146.8, 148.3, 188.7.
5.1.34. 1,5-Bis(3-chlorophenyl)-1,4-pentadien-3-one (9p).
Yellow solid: mp 123–125 °C [lit.35 120–121 °C];
13C NMR: d 126.3, 126.6, 127.9, 130.1, 130.3, 134.9,
136.5, 141.8, 188.0.
5.1.44. 1,5-Diphenylpentan-3-one (10b). Clear oil [lit.41].
5.1.35. 1,5-Bis(2-chlorophenyl)-1,4-pentadien-3-one (9q).
Yellow solid: mp 114–116 °C [lit.36 110 °C]; 1H NMR: d
7.04 (d, 2H, J = 16.1 Hz), 7.29 (m, 4H), 7.41 (m, 2H),
7.67 (m, 2H), 8.11 (d, 2H, J = 16.1 Hz); 13C NMR: d
127.0, 127.5, 127.6, 130.1, 131.1, 132.9, 135.3, 139.2,
188.4.
5.1.45. 1,5-Diphenylpentan-3-ol (11b). White solid: mp
47–49 °C [lit.42 45–46 °C]. 13C NMR :d 32.1, 39.2,
70.8, 125.6, 128.3, 142.0.
5.1.46. 2,6-Bis(4-hydroxy-3-methoxybenzylidene)cyclohex-
anone (12a). Yellow solid: mp 177–178 °C [lit.43 179–
181 °C]; 13C NMR :d 23.1, 28.5, 56.0, 113.2, 114.4,
124.4, 128.5, 134.2, 136.9, 146.2, 146.4, 172.8.
5.1.36. 1,5-Bis(4-hydroxyphenyl)-1,4-pentadien-3-one (9r).
Yellow solid: mp 235–237 °C [lit.37 238–239 °C].
5.1.47. 2,6-Bis(benzylidene)cyclohexanone (12b). Yellow
crystals: mp 117–119 °C [lit.44 117 °C].
5.1.37. 1,5-Bis(3-hydroxyphenyl)-1,4-pentadien-3-one (9s).
Brown solid: mp 199–201 °C [lit.37 198–200 °C].
5.1.48. trans,trans-1,2,4,5-Diepoxy-1,5-diphenylpentan-3-
one (13b). White crystals: mp 117–119 °C [lit.45 117–
119 °C].
5.1.38. 1,5-Bis(2-hydroxyphenyl)-1,4-pentadien-3-one (9t).
Yellow solid: mp 156–157 °C [lit.37 155 °C].
5.1.39. 1,5-Bis(4-acetoxy-3-methoxyphenyl)-1,4-pentadien-
3-one (9u). Yellow solid: mp 179–180 °C [lit.38 150 °C];
1H NMR: d 2.31 (s, 6H), 3.87 (s, 6H), 6.98 (d, 2H,
J = 15.9 Hz), 7.06 (d, 2H, J = 8.1 Hz), 7.18 (m, 4H),
7.67 (d, 2H, J = 15.9 Hz); 13C NMR :d 20.7, 56.0,
111.7, 121.4, 123.3, 125.5, 133.7, 141.6, 142.6, 151.4,
168.5, 188.3. Exact mass calcd for C23H22O7: 410.4165,
observed (M+H) 411.1444.
5.1.49. 1,5-Bis(4-pyridyl)-1,4-pentadien-3-one (15a). Yel-
1
low solid: mp 145–146 °C [lit.46 149 °C]; H NMR: d
7.17 (d, 2H, J = 15.9 Hz), 7.42 (d, 4H, J = 5.6 Hz),
7.63 (d, 2H, J = 15.9 Hz), 8.67 (d, 4H, J = 5.6 Hz); 13C
NMR: d 121.9, 128.6, 141.0, 141.6, 150.6, 172.5. Hydro-
chloride salt: yellow solid mp >250 °C; 1H NMR: d D2O
7.54 (d, 2H, J = 16.3 Hz), 7.78 (d, 2H, J = 15.9 Hz), 8.15
(d, 4H, J = 6.6 Hz), 8.70 (d, 4H, J = 6.6 Hz); 13C NMR :
d
193.0.
13C NMR: d D2O 128.2, 136.2, 141.3, 144.2, 154.4,
5.1.40. 1,5-Bis(4-acetoxyphenyl)-1,4-pentadien-3-one (9v).
The compound was prepared by reaction of 9r with ace-
tic anhydride following the procedure of Ali et al.14 to
5.1.50. 1,5-Bis(3-pyridyl)-1,4-pentadien-3-one (15b). Yel-
1
1
give a yellow solid: mp 167–168 °C; H NMR: d 2.30
low solid: mp 148–149 °C [lit.46 150 °C]; H NMR: d
(s, 6H), 7.00 (d, 2H, J = 15.9 Hz), 7.13 (d, 4H,
J = 8.3 Hz), 7.60 (d, 4H, J = 8.2 Hz), 7.69 (d, 2H,
J = 15.9 Hz); 13C NMR: d 21.1, 122.1, 125.4, 129.4,
132.4, 142.1, 152.2, 168.9, 188.3. Exact mass calcd for
C21H18O5: 350.3646, observed (M+H) 351.1232.
7.11 (d, 2H, J = 16.1 Hz), 7.32 (m, 2H), J = 7.71 (d,
2H, J = 15.9 Hz), 7.90 (d, 2H, J = 6.2 Hz), 8.61 (d, 2H,
J = 4.6 Hz), 8.81 (s, 2H); 13C NMR: d 123.7, 126.7,
130.3, 134.4, 139.9, 149.9, 151.1, 198.6. Hydrochloride
1
salt: yellow solid mp >250 °C; H NMR: d D2O 7.40
(d, 2H, J = 16.3 Hz), 7.78 (d, 2H, J = 16.1 Hz), 8.02 (t,
2H, J = 7.9 Hz), 8.70 (d, 2H, J = 5.6 Hz), 8.79 (d, 2H,
J = 7.9 Hz), 8.98 (s, 2H); 13C NMR: d 130.1, 132.8,
136.9, 139.9, 143.7, 144.3, 147.3, 193.0.
5.1.41. 1,5-Bis(4-carbmethoxyphenyl)-1,4-pentadien-3-one
(9w). Yellow solid: mp 206–210 °C [lit.39 221–223 °C];
1H NMR: d 3.92 (s, 6H), 7.12 (d, 2H, J = 16.1
Hz), 7.65 (d, 4H, J = 8.1 Hz), 7.73 (d, 2H, J = 15.9 Hz),
8.06 (d, 4H, J = 8.0 Hz); 13C NMR :d 52.3, 127.1,
128.1, 130.1, 131.6, 138.8, 142.1, 166.2, 188.0.
5.1.51. 1,3-Diphenylpropenone (17a). Pale yellow solid:
mp 52–54 °C [lit.47 55–58 °C].
5.1.42. 1-(4-Methoxyphenyl)-5-phenyl-1,4-pentadien-3-one
5.1.52. 3-(4-Carboxyphenyl)-1-phenyl-2-propen-1-one (17b).
Yellow solid: mp 229–232 °C [lit.48 227–229 °C]; 13C
NMR: (DMSO) d 124.2, 128.5, 128.7, 128.8, 129.6,
132.1, 133.2, 137.3, 138.7, 142.4, 166.7, 189.0.
1
(9x). Yellow solid: mp 85–89 °C [lit.40 118–119 °C]; H
NMR: d 3.82 (s, 3H), 6.91 (d, 2H, J = 8.5 Hz), 6.94 (d,
1H, J = 15.9 Hz), 7.06 (d, 1H, J = 16.1 Hz), 7.38 (m,

W. M. Weber et al. / Bioorg. Med. Chem. 13 (2005) 3811–3820
3819
5.1.53. 1-(4-Carboxyphenyl)-3-phenyl-2-propen-1-one (17c).
Acknowledgements
Yellow solid: mp 217–220 °C; 13C NMR: (DMSO) d
121.9, 128.5, 128.8, 128.9, 129.4, 130.6, 134.3, 134.4,
140.6, 144.6, 166.4, 188.8.
This work was supported by NIH grant EY13695 from
the National Eye Institute and grant BC043125 from the
US Army/DOD Breast Cancer Program.
5.1.54. 1-(4-Cyanophenyl)-3-phenyl-2-propen-1-one (17d).
Yellow solid: mp 120 °C [lit.49 119–120 °C].
References and notes
5.1.55. 1-(2,4-Dimethylphenyl)-3-phenyl-2-propen-1-one
(17e). Yellow oil [lit.50 68 °C]; 1H NMR: d 2.37 (s,
3H), 2.44 (s, 3H), 7.05 (m, 2H), 7.16 (d, 1H,
J = 16.1 Hz), 7.38 (m, 3H), 7.49 (d, 1H, J = 15.9 Hz),
7.54 (m, 3H); 13C NMR :d 20.4, 21.4, 126.0, 126.6,
128.2, 128.5, 128.8, 130.4, 132.2, 134.7, 136.1, 137.4,
140.8, 145.0, 195.6.
1. Ammon, H. P.; Wahl, M. A. Planta Med. 1991, 57, 1.
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3. Menon, L. G.; Kuttan, R.; Kuttan, G. Cancer Lett. 1999,
41, 159.
4. Zhang, F.; Altorki, N. K.; Mestre, J. R.; Maiah, K.;
Dannenberg, A. J. Carcinogenesis 1999, 20, 445.
5. (a) Shim, J. S.; Kim, J. H.; Cho, H. Y.; Yum, Y. N.; Kim,
S. H.; Park, H.-J.; Shim, B. S.; Choi, S. H.; Kwon, H. J.
Chem. Biol. 2003, 10, 695; (b) Hahm, E.-R.; Gho, Y. S.;
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Biophys. Res. Comm. 2004, 321, 337; (c) Ahn, C. M.; Shin,
W.-S.; Woo, H. B.; Lee, S.; Lee, H.-W. Bioorg. Med.
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Drugs 2005, 16, 263.
5.1.56. 3-(4-Hydroxy-3-methoxyphenyl)-1-phenyl-2-pro-
pen-1-one (17f). Yellow solid: mp 81–84 °C [lit.51 85–
90 °C]; 13C NMR: d 56.1, 110.0, 114.8, 119.8, 123.3,
127.4, 128.4, 128.5, 132.5, 138.5, 145.1, 146.7, 148.2,
190.5.
5.1.57. 1-(4-Hydroxy-3-methoxyphenyl)-3-phenyl-2-pro-
pen-1-one (17g). Yellow solid: mp 61–64 °C [lit.52 63–
6. Barclay, L. R.; Vinqvist, M. R.; Mukai, K.; Goto, H.;
Hashimoto, Y.; Tokunaga, A.; Uno, H. Org. Lett. 2000, 2,
2841.
7. Priyadarsini, K. I.; Maity, D. K.; Naik, G. H.; Kumar, M.
S.; Unnikrishnan, M. K.; Satav, J. G.; Mohan, H. Free
Rad. Biol. Med. 2003, 35, 475.
1
66 °C]; H NMR: d 3.95 (s, 3H), 6.29 (s, 1H), 6.98 (d,
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