Synthesis of 5-aryl-6-cinnamoyl-7-methyl-flavanones as novel antioxidants and antihyperlipidemics

Article abstract of DOI:10.3109/14756366.2011.585134

An economical and efficient one-pot synthesis of a series of novel 5-aryl-6-cinnamoyl-7-methyl-flavanones has been developed by simple refluxing of cinnamoyl chalcones with NaOAc in aqueous ethanol in quantitative yields. These flavanones were screened for their in vitro antioxidant and in vivo antidyslipidemic activities. Among 24 compounds screened, four compounds 28, 29, 30, and 48 showed significant antidyslipidemic activities. However, out of all the compounds, only compound 28 exhibited significant antioxidant activity and other compounds showed moderate antioxidant activities.

Full text of DOI:10.3109/14756366.2011.585134

Journal of Enzyme Inhibition and Medicinal Chemistry, 2012; 27(2): 211–222
© 2012 Informa UK, Ltd.
ISSN 1475-6366 print/ISSN 1475-6374 online
DOI: 10.3109/14756366.2011.585134
RESEARCH ARTICLE
Synthesis of 5-aryl-6-cinnamoyl-7-methyl-flavanones as novel
antioxidants and antihyperlipidemics
Anindra Sharma1, Namrata Anand1, Rahul Sharma1, Upma Chaturvedi2, A. K. Khanna2,
Gitika Bhatia2, and Rama P. Tripathi1
1Medicinal and Process Chemistry Division, Central Drug Research Institute Lucknow, CSIR, India and 2Biochemistry
Division, Central Drug Research Institute Lucknow, CSIR, India
Abstract
An economical and efficient one-pot synthesis of a series of novel 5-aryl-6-cinnamoyl-7-methyl-flavanones has been
developed by simple refluxing of cinnamoyl chalcones with NaOAc in aqueous ethanol in quantitative yields. These
flavanones were screened for their in vitro antioxidant and in vivo antidyslipidemic activities. Among 24 compounds
screened, four compounds 28, 29, 30, and 48 showed significant antidyslipidemic activities. However, out of all the
compounds, only compound 28 exhibited significant antioxidant activity and other compounds showed moderate
antioxidant activities.
Keywords: Cholesterol lowering agents, antidyslipidemic, cinnamoyl chalcones, diacetyl benzene, sodium acetate
Introduction
TNF-α inhibitory and hormone-dependent anticancer
Oxidative stress is intricately involved in the patho-
genesis and development of several diseases and more
particularly atherosclerosis1. It is one of the impor-
tant factors for the development and progression of
CHD (coronary heart disease2). On the other hand,
dyslipidemia is also a threat to serious cardiovascu-
lar problems, including atherosclerosis, stroke, and
cardiac arrest. The most common dyslipidemia treat-
ment, however, is a carefully regulated regimen of diet
and exercise. More serious conditions may require a
combination of exercise, medication, and surgery to
prevent life-threatening complications3. Therefore,
antioxidants and lipid lowering agents play a major role
in prevention of CHD. Flavanones, the cyclic isomer of
chalcones, are naturally occurring antioxidants and
have been investigated in great detail for their antioxi-
dant, hypolipidemic and free radical scavenging activi-
ties4. They are also known to play an important role in
defence mechanism of plants against several toxicants,
microbes and parasites5. They are associated with anti-
activities9–11. Several naturally occurring and synthetic
chalcones also possess most of the pharmacologi-
cal activities of the flavanones12–20. Therefore, it was
envisaged to synthesize hybrid molecules where both
the chalcone and flavanone skeletons are in the same
molecule and screen them for their antioxidant anti-
dyslipidemic activities (Figure 1). There are several
methods to prepare flavanones involving the oxida-
tive cyclization of 2′-hydroxychalcones using different
reagents21–25
.
Herein, we have reported one-pot, economical and
eco-friendly syntheses of 6-cinnamoyl flavanones by
reacting preformed cinnamoyl chalcones26 with NaOAc
in refluxing aqueous ethanol in quantitative yields.
e method of synthesis is quite simple as it does not
involve any sophisticated chemical or apparatus. e
purification of the compounds is either by crystalliza-
tion or by simple filtration of compounds on a short
column of silica gel. e compounds synthesized were
screened for their antioxidant and antihyperlipidemic
activities.
bacterial, antifungal6, estrogen receptor modulatory7,8
,
Address for Correspondence: Prof. R.P. Tripathi, M.Phil, PhD, Medicinal and Process Chemistry Division, Central Drug Research Institute
Lucknow-226001, CSIR, India. Tel.: +91 0522 2612411; Fax: +91 522 2623405/2623938/2629504. E-mail: rpt.cdri@gmail.com
(Received 18 March 2011; revised 27 April 2011; accepted 28 April 2011)
211

212 A. Sharma et al.
In the 1H NMR spectrum of compound 25, the aromatic
protons and one of the olefinic protons of the cinnamoyl
moiety, adjacent to aromatic ring were observed as m in
the range of δ 7.42–6.95. e other olefinic proton of the
cinnamoyl group appeared as a d at δ 6.36 (J= 16.1 Hz).
e benzylic proton (H-2) was visible as dd at δ 5.56 with
J1 = 12.8 Hz and J2 = 3.1 Hz, whereas the two methylene
protons (H-3) were observed as dd at two different field
strengths at δ 3.07 (J1 = 16.5 Hz and J2 = 12.8 Hz), and at
δ 2.81 (J1 = 16.5 Hz and J2 = 3.1 Hz), respectively. e C-7
methyl was visible as singlet at δ 2.30.
Results and discussion
Chemistry
e starting chalcones (1–24) were prepared in a straight-
forward manner by reaction of diacetyl benzenes27 and
different aromatic aldehydes as reported earlier by us26.
e compounds were identical in all respects to those
reported earlier. e reaction of the above chalcones
(1–24) separately with sodium acetate in ethanol and
water (1:1) at 70–80°C for different time intervals gave the
hybrid molecules of 5-aryl-6-cinnamoyl-7-methyl-fla-
vanones (25–48) in almost quantitative yields (Scheme 1
and Table 1).
Structures of these compounds were established on
the basis of their spectroscopic data and microanalyses.
e IR spectra of all the flavanones exhibited the absorp-
tion bands around 1670 and 3060 cm−1 for their carbonyl
group and alkene CH stretching vibrations. e ESMS
(mass spectra) of the compounds showed [M+H]+ peaks
corresponding to their molecular formulae. e NMR
spectra (1H and 13C) were consistent with the proposed
structures.
In the 13C NMR spectrum, the two carbonyl carbons
appeared at δ 197.1 and 190.0, whereas the quaternary
aromatic carbon C-9 was visible at δ 162.5 ppm and C-7
at δ 143.9 ppm. e other aromatic quaternary carbons
(ArC) were observed at their usual chemical shifts of δ
141.5, 138.6, 137.4, 136.9, 136.3, 135.1, 133.2, 129.7, and
116.9 ppm. e C-2 carbon appeared at δ 78.8 ppm,
whereas the other tertiary aromatic carbons (ArCH)
appeared at δ 143.2, 129.6, 129.5, 129.4, 129.3, 128.5,
128.2, 128.0, 127.8, and 119.6 ppm. e C-3 carbon was
visible at δ 46.1 ppm, whereas the methyl carbon was vis-
ible at δ 20.8 ppm. Almost similar patterns were observed
As a prototype, the detailed NMR spectra of (E)-2-
(4-chlorophenyl)-6-(3-(4-chlorophenyl)
methyl-5-phenylchroman-4-one (25, Figure 2) has been
described herein.
acryloyl)-7-
1
in H NMR and 13C NMR spectra of other compounds
26–48 of the series.
Figure 1. Hybridization of chalcone and flavanone to Cinamoyl flavanone.
Scheme 1. Synthesis of 5-phenyl-6-cinnamoyl-7-methyl-flavanones (25–48).
Journal of Enzyme Inhibition and Medicinal Chemistry

Synthesis of 5-aryl-6-cinnamoyl-7-methyl-flavanones 213
Table 1. Synthesis of 5-aryl-6-cinnamoyl-7-methyl-flavanone derivatives (25–48) by cyclization of different cinnamoyl chalcones.
Entry
1
Ring A
Ring B
Product
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
Time (h)
40
Isolated yield (%)
cLogPa
8.15
6.92
7.04
8.32
9.45
8.15
6.51
9.29
9.29
7.62
9.02
7.74
8.85
10.15
7.41
8.19
9.58
9.41
10.72
7.98
7.77
8.79
9.90
9.90
Phenyl
4-chloro phenyl
Phenyl
94
92
90
93
94
93
92
90
94
89
90
92
92
88
91
90
93
89
92
91
93
93
90
94
2
Phenyl
40
3
Phenyl
4-fluoro phenyl
4-bromo phenyl
4-benzloxy phenyl
3-chloro phenyl
3,4-dimethoxy phenyl
1-naphthyl
41
4
Phenyl
40
5
Phenyl
40
6
Phenyl
42
7
Phenyl
41
8
Phenyl
40
9
Phenyl
2-naphthyl
41
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
4-bromo phenyl
4-bromo phenyl
4-bromo phenyl
4-bromo phenyl
4-bromo phenyl
4-bromo phenyl
4-Benzloxy phenyl
4-benzloxy phenyl
4-benzloxy phenyl
4-Benzloxy phenyl
4-Benzloxy phenyl
4-benzloxy phenyl
4-chloro phenyl
4-chloro phenyl
4-chloro phenyl
Phenyl
42
4-bromo phenyl
4-fluoro phenyl
4-chloro phenyl
4-benzloxy phenyl
4-methoxy phenyl
Phenyl
43
43
42
41
40
44
4-bromo phenyl
4-chloro phenyl
4-benzloxy phenyl
4-methoxy phenyl
3,4-dimethoxy phenyl
2-chloro phenyl
1-naphthyl
41
41
42
41
43
42
40
2-naphthyl
41
acLogP was determined by OSIRIS Property Explorer Programme, available at htpp://www.organic-chemistry.org/prog/peo/.
Biology
Antioxidant activities of 5-aryl-6-cinnamoyl-7-methyl-
flavanones
e antioxidant activities of compounds 25–48 were
evaluated by generating free radicals (superoxide ions
−
(O2 ), hydroxyl radicals (OH·), microsomal lipid peroxi-
dation) in vitro in the presence of 200 µg/mL compounds
dissolved in DMSO and compared with the control
where no compound was added. Superoxide anions were
generated enzymatically28 from xanthine (160 mM) using
xanthine oxidase (0.04 U) and nitroblue tetrazolium
(320 μM). Hydroxyl radicals (OH·) were generated in a
Figure 2. Structure of the compound no. 25.
antioxidant activities. Compounds 25–48 inhibit super-
oxide ions by 7, 4, 8, 13, 3, 11, 5, 14, 5, 5, 6, 5, 6, 6, 13,
7, 7, 8, 11, 8, 4, 10, 7, and 7%, respectively. ey inhibit
hydroxyl radicals by 13, 8, 10, 18, 9, 7, 11, 8, 8, 11, 6, 7,
9, 9, 10, 11, 5, 12, 8, 7, 11, 10, 10, and 8%, respectively,
whereas inhibition of microsomal lipid peroxidation is
6, 1, 8, 17, 6, 7, 5, 9, 13, 13, 4, 9, 12, 6, 9, 8, 16, 5, 11, 7, 7,
13, 6, and 6%, respectively. e compound 28 having Br
group in ring B was found to be the most active com-
pound of the series. It showed significant inhibition of
superoxide anions (24%), hydroxyl radicals (19%) and
microsomal lipid peroxidation (21%), respectively. e
properties of these cinnamoyl flavanones as antioxidant
and free radical scavenger appear to be due to extended
conjugation in the molecule which facilitates the elec-
tron transfer and the resonance stabilization through
keto-enol tautomerism of propenone moiety. e lat-
ter has the ability to delocalize unpaired electrons of
nonenzymatic system comprising deoxyribose (2.8 mM),
FeSO4.7H2O (2.0 mM), sodium ascorbate (2.0 mM) and
H2O2 (2.8 mM) in 50 mM KH2 PO4 buffer (pH 7.4) to a
final volume of 2.5 mL. e test compounds were also
studied for their inhibitory action against microsomal
lipid peroxidation in vitro by nonenzymatic inducer. e
−
scavenging potential of the compounds for O2 , OH·, and
microsomal lipid peroxidation is depicted in Figure 3.
Alloprinol, mannitol and α-tocopherol were used as stan-
−
dard scavengers for the superoxide ions (O2 ), hydroxyl
free radicals (OH·) and microsomal lipid peroxidation,
respectively.
Alloprinol showed 77% superoxide ions scavenging
activity at 200 µg/mL, whereas mannitol showed 44%
hydroxyl radical scavenging activity at the same con-
centration. α-tocopherol showed 52% inhibition of lipid
peroxidation at 200 µg/mL concentrations. e com-
pounds of the series showed moderate to significant
© 2012 Informa UK, Ltd.

214 A. Sharma et al.
free radicals29–36. No definite structure activity relation-
ship could be established in the series for antioxidant
activity.
triton WR-1339 in rats induced marked hyperlipidemia
as evidenced by 3.87-fold increase in the plasma levels
of TC (329.04 15.00). e standard drug gemfibrozil
decreased the TC level by 35% as compared to triton
only group. e compounds 25–48 exhibited their TC
lowering activity in 2–25% range. Five compounds
of the series, compounds 28, 29, 30, 32, and 48, were
found to have significant TC inhibitory activities as
Effect of 5-aryl-6-cinnamoyl-7-methyl-flavanones on
hyperlipidemia
etotalcholesterol(TC)ofcontrolgroupswasestimated
to be 85.40 4.00 mg/dl (Figure 4). Administration of
Figure 3. Showing the effect of compounds 25–48 at 200 µg/mL on superoxide ion (n mole formazone formed/min), hydroxyl radicals (n
mole MDA formed/h) and lipid peroxidation in microsomes (n mole MDA formed/mg protein).
Figure 4. Total cholesterol lowering activity of compounds 25–48 and the standard drug gemfibrozil.
Journal of Enzyme Inhibition and Medicinal Chemistry

Synthesis of 5-aryl-6-cinnamoyl-7-methyl-flavanones 215
they decreased the TC level by 22, 25, 21, 21 and 25%,
respectively.
compounds both were compared. e compounds
showed their Tg lowering activities in a range of 4–24%.
Five compounds 28, 29, 30, 32, and 48 of the series
were found to decrease the Tg level by 19, 25, 23, 18
and 24%, respectively. us compound 29 with 25% Tg
lowering was the most active compound of the series as
compared to the drug gemfibrozil with 32% Tg lowering
activity.
Administration of triton in rats elevated their protein
levels by 2.08-fold (Figure 7). Triton WR-1339 acts as
surfactant, suppresses the action of lipase and blocks
the uptake of lipoproteins from the circulation of extra
hepatic tissues resulting in an increased level of circu-
latory lipids37,38. Treatment of hyperlipidemic rats with
compounds 25–48 reversed the plasma level of protein
with varying extents. Compounds 28, 29, 30, 46 and 48
exhibited 16, 23, 22, 22 and 20% protein lowering activity,
respectively, whereas other compounds exhibited mild
Treatment of rats with triton WR-1339 increased their
plasma phospholipids (PL) by 3.75-folds (Figure 5).
e animal group treated with triton only were com-
pared with the animal group treated with triton and
compounds both. e compounds 25–28 showed their
PL-lowering activities in a range of 4–26%. Five com-
pounds of the series 28, 29, 30, 32, and 48 decreased
the PL level by 21, 26, 24, 20 and 24%, respectively.
us compound 29 with 26% PL-lowering activity was
the most active compound of the series as compared
to the standard drug gemfibrozil, which displayed 33%
PL-lowering activity.
Treatment of rats with triton WR-1339 increased
their triglyceride (Tg) level by 3.92-folds (Figure 6). e
Tg levels in the two animal groups, one group treated
with triton only and the other group with triton and
Figure 5. Phospholipid lowering activity of compounds 25–48 and the standard drug gemfibrozil.
Figure 6. Triglyceride lowering activity of compounds 25–48 and the standard drug gemfibrozil.
© 2012 Informa UK, Ltd.

216 A. Sharma et al.
Figure 7. Protein lowering activity of compounds 25–48 and the standard drug gemfibrozil.
lowering of protein levels as compared to triton. ese
data were compared with gemfibrozil, which showed a
decrease of 36% in protein levels.
E. Merck Kieselgel 60 F254, with detection by UV light,
spraying a 20% KMnO4 aq solution. Column chroma-
tography was performed on silica gel (100–200 mesh
E. Merck). IR spectra were recorded as thin films or
in KBr solution with a Perkin-Elmer Spectrum RX-1
(4000–450 cm−1) spectrophotometer. 1H and 13C NMR
spectra were recorded on a Brucker DRX-200 in CDCl3
and CDCl3+CCl4. Chemical shift values are reported
in ppm relative to TMS (tetramethylsilane) as inter-
nal reference, unless otherwise stated; s (singlet), d
(doublet), dd (doublet of doublet), m (multiplet); J in
hertz. ESI mass spectra were performed using Quattro
II (Micromass). Elemental analyses were performed on
a Perkin-Elmer 2400 II elemental analyzer.
With this sizable number of compounds, although no
definite SAR could be established on protein lowering
activity, yet a closure look into the structure activity rela-
tionship revealed that in general, compounds (32) B ring
as naphthyl substituent are more active than those with
phenyl ring substituent. e effect of halo substituents in
the aryl ring B, in general, results in the increased activity
with Br > F > Cl trend with the exception of compound
35. Further, positional substitution of halo substituents
follows the pattern m > p > o. It is also observed that
substitution of phenyl ring of the cinnamoyl group with
4-OCH2Phresultsinbetteractivityascomparedto4-OCH3
or halogen. In general, the compounds having phenyl or
chlorophenyl as ring A are more active than compounds
with benzyloxy or bromophenyl substituents.
General procedure for the synthesis of cinnamoyl flavanones
To a stirring solution of (2E,2′E)-1,1′-(3-hydroxy-5-
methylbiphenyl-2,6-diyl)-bis(3-pheylprop-2-ene-1-ones
derivatives (1 equiv.) in minimum amount of a mixture
of EtOH: H2O (1:1) and NaOAc (4 equiv.) was added. e
reaction mixture was heated to reflux till the disappear-
ance of the starting materials. After completion of reac-
tion (TLC), the reaction mixture was allowed to cool to
roomtemperature. emixturewasthendilutedwithH2O
and extracted with Et2O. e combined organic phases
were washed with brine, dried over anhydrous sodium
sulphate, and concentrated under reduced pressure. e
crude product was purified either by crystallization or by
filtration through a short column of SiO2 (60–120 mesh)
using appropriate eluent to give the desired flavanone.
Conclusion
In conclusions, a series of novel 5-aryl-6-cinnamoyl-
7-methyl-flavanones has been synthesized from
(2E,2′E)-1,1′-(3-hydroxy-5-methylbiphenyl-2,6-
diyl)bis(3-phenylprop-2-en-1-one) derivatives in very
good yields. e compounds were evaluated for their
antidyslipidemic and antioxidant activities. A number
of compounds showed significant to moderate activities.
Furtherworkwiththesemoleculesisunderwaytoprepare
more potent compounds having drug like properties.
(E)-2-(4-chlorophenyl)-6-[3-(4-chlorophenyl)acryloyl]-7-
methyl-5-phenylchroman-4-one (25)
Experimental
Chemistry
It was obtained as light yellow solid, mp 190–192°C, in
94% yield; Rf = 0.6 (8:2 hexane:ethylacetate); IR (KBr): υmax
in cm−1 3360, 3060, 1691, 1670, 1597, 1489, 1425, 1319,
Commercially available reagent grade chemicals were
used as received. All reactions were followed by TLC on
Journal of Enzyme Inhibition and Medicinal Chemistry

Synthesis of 5-aryl-6-cinnamoyl-7-methyl-flavanones 217
1
1159, 1088, 818, 700; H NMR (200 MHz, CDCl3+CCl4):
128.6, 128.2, 128.1, 125.3, 123.2, 119.6, 116.9, 78.8, 46.1,
20.8; MS (ESI+): m/z: 601[M+H]+. Elemental analysis for
C31H22O3Br2: Calcd. C, 61.82; H, 3.68. Found: C, 61.81; H,
3.65.
δ= 7.42 (s, 4H, 3 × ArH & = CH), 7.31–7.14 (m, 8H, ArH),
7.06–6.95 (m, 3H, ArH), 6.36 (d, J= 16.1 Hz, 1H, = CH),
5.56 (dd, J1 = 12.8 Hz, J2 = 3.1 Hz, 1H, CH), 3.07 (dd, J1 = 16.5
Hz, J2 = 12.8 Hz, 1H, Ha, CH2), 2.81 (dd, J1 = 16.5 Hz, J2 = 3.1
Hz, 1H, Hb, CH2), 2.30 (s, 3H, CH3); 13C NMR (50 MHz,
CDCl3+CCl4): δ= 197.1, 190.0 (2 × CO), 162.5, 143.9, 141.5,
138.6, 137.4, 136.9, 135.1, 133.2, 129.7, 129.6, 129.5, 129.4,
129.3, 128.5, 128.2, 128.0, 127.8, 119.6, 116.9, 78.8, 46.1,
20.8; MS (ESI+): m/z: 513[M+H]+. Elemental analysis for
C31H22O3Cl2: Calcd. C, 72.52; H, 4.32. Found: C, 72.50; H,
4.28.
(E)-2-[4-(benzyloxy)phenyl]-6-[3-{4-(benzyloxy)phenyl}
acryloyl]-7-methyl-5-phenylchroman-4-one (29)
It was obtained as light yellow solid, mp 163–165°C, in
94% yield; Rf = 0.4 (8:2 hexane:ethylacetate); IR (KBr):
υmax in cm−1 3449, 3055, 2368, 1692, 1597, 1510, 1240,
1
1170, 1002, 743, 697; H NMR (200 MHz, CDCl3+CCl4):
δ = 7.41–7.23 (m, 18H, 17 ArH & = CH), 7.04–6.88 (m,
7H, ArH), 6.33 (d, J = 16.4 Hz, 1H, = CH), 5.51 (d, J = 12.5
Hz, 1H, CH), 5.10 (s, 2H, OCH2), 5.07 (s, 2H, OCH2),
3.13 (dd, J1 = 15.5 Hz, J2 = 13.8 Hz, 1H, Ha, CH2), 2.78 (d,
J = 16.1 Hz, 1H, Hb, CH2), 2.29 (s, 3H, CH3); 13C NMR
(50 MHz, CDCl3+CCl4): δ = 197.3, 190.2 (2 × CO), 162.6,
143.8, 143.6, 141.4, 138.6, 136.3, 134.8, 134.7, 131.0,
130.9, 130.5, 130.3, 129.7, 129.3, 128.4, 128.2, 128.1,
127.9, 119.6, 116.9, 116.6, 116.4, 116.2, 116.0, 78.9,
70.4, 46.2, 20.8; MS (ESI+): m/z: 657[M+H]+. Elemental
analysis for C45H36O5: Calcd. C, 82.29; H, 5.52. Found: C,
82.10; H, 5.50.
6-cinnamoyl-7-methyl-2,5-diphenylchroman-4-one (26)
It was obtained as light yellow solid, mp 148–150°C, in
93% yield; Rf = 0.6 (8:2 hexane:ethylacetate); IR (KBr): υmax
in cm−1 3410, 3021, 2359, 1636, 1596, 1217, 769; H NMR
1
(200 MHz, CDCl3+CCl4): δ= 7.47–7.41 (m, 5H, 4 × ArH
& = CH), 7.32–7.24 (m, 9H, ArH), 7.11–7.02 (m, 3H, ArH),
6.44 (d, J= 16.1 Hz, 1H, = CH), 5.59 (d, J= 12.6 Hz, 1H,
CH), 3.13 (dd, J1 = 16.3 Hz, J2 = 13.3 Hz, 1H, Ha, CH2), 2.82
(d, J= 16.3 Hz, 1H, Hb, CH2), 2.31 (s, 3H, CH3); 13C NMR
(50 MHz, CDCl3+CCl4): δ= 197.6, 190.5 (2 × CO), 162.7,
145.1, 143.6, 141.5, 139.0, 138.7, 136.2, 134.8, 130.8, 129.8,
128.6, 128.4, 128.1, 127.8, 126.4, 119.6, 117.0, 79.6, 46.3,
20.8; MS (ESI+): m/z: 445[M+H]+. Elemental analysis for
C31H24O3: Calcd. C, 83.76; H, 5.44, Found: C, 83.69; H,
5.40.
(E)-2-(3-chlorophenyl)-6-[3-(3-chlorophenyl)acryloyl]-7-
methyl-5-phenylchroman-4-one (30)
It was obtained as light yellow solid, mp 190–192°C, in
94% yield; Rf = 0.6 (8:2 hexane:eyhylacetate); IR (KBr):
υmax in cm−1 3434, 3020, 2365, 1690, 1595, 1218, 768;
1H NMR (200 MHz, CDCl3+CCl4): δ = 7.51 (s, 1H, ArH),
7.39–7.15 (m, 11H, 10 ArH & = CH), 7.07–7.02 (m, 2H,
ArH), 6.94 (s, 1H, ArH), 6.39 (d, J = 16.0 Hz, 1H, = CH),
5.56 (dd, J1 = 12.9 Hz, J2 = 3.1 Hz, 1H, CH), 3.08 (dd,
J1 = 16.5 Hz, J2 = 12.9 Hz, 1H, Ha, CH2), 2.83 (dd, J1 = 16.5
Hz, J2 = 3.2 Hz, 1H, Hb, CH2), 2.31 (s, 3H, CH3); 13C NMR
(50 MHz, CDCl3+CCl4): δ = 197.1, 189.8 (2 × CO), 162.5,
143.9, 143.0, 141.6, 141.0, 138.5, 136.6, 136.2, 135.3,
130.6, 130.5, 130.4, 129.8, 129.4, 129.3, 128.4, 128.2,
128.0, 126.7, 126.5, 124.4, 119.6, 116.9, 78.8, 46.2, 20.8;
MS (ESI+): m/z: 513[M+H]+. Elemental analysis for
C31H22O3Cl2: Calcd. C, 72.52; H, 4.32. Found: C, 72.50;
H, 4.28.
(E)-2-(4-fluorophenyl)-6-[3-(4-fluorophenyl)acryloyl]-7-
methyl-5-phenylchroman-4-one (27)
It was obtained as yellow solid, mp 152–154°C, in 93%
yield; Rf = 0.6 (8:2 hexane:ethylacetate); IR (KBr): υmax in
cm−1 3862, 3429, 3021, 2359, 1639, 1515, 1216, 1043, 766,
1
671; H NMR (200 MHz, CDCl3+CCl4): δ= 7.49–7.00 (m,
15H, 14 ArH & = CH), 6.34 (d, J= 16.1 Hz, 1H, = CH), 5.55
(d, J= 12.6 Hz, 1H, CH), 3.09 (dd, J1 = 16.2 Hz, J2 = 13.3 Hz,
1H, Ha, CH2), 2.80 (d, J= 16.3 Hz, 1H, Hb, CH2), 2.30 (s, 3H,
CH3); 13C NMR (50 MHz, CDCl3+CCl4): δ= 197.3, 190.2
(2 × CO), 162.6, 143.8, 143.6, 141.5, 138.6, 136.3, 134.8,
134.7, 131.0 130.9, 130.5, 130.3, 129.7, 129.3, 128.4, 128.2,
128.1, 128.0, 127.9, 119.6, 116.9, 116.6, 116.4, 116.2, 116.0,
78.9, 46.2, 20.8; MS (ESI+): m/z: 481[M+H]+. Elemental
analysis for C31H22O3F2: Calcd. C, 77.49; H, 4.61. Found:
C, 77.38; H, 4.57.
(E)-2-(3,4-dimethoxyphenyl)-6-[3-(3,4-dimethoxyphenyl)
acryloyl]-7-methyl-5-phenylchroman-4-one (31)
It was obtained as light yellow solid, mp 90–92°C, in 92%
yield; Rf = 0.4 (7:3 hexane:ethylacetate); IR (KBr): υmax
in cm−1 3445, 2960, 2370, 1691, 1637, 1596, 1514, 1428,
(E)-2-(4-bromophenyl)-6-[3-(4-bromophenyl)acryloyl]-7-
methyl-5-phenylchroman-4-one (28)
1
It was obtained as light yellow solid, mp 188–190°C, in
93% yield; Rf = 0.6 (8:2 hexane:ethylacetate); IR (KBr): υmax
in cm−1 3779, 3459, 2366, 1670, 1596, 1318, 1159, 1008,
1261, 1024, 859, 555; H NMR (200 MHz, CDCl3+CCl4):
δ= 7.26–7.13 (m, 4H, 3 ArH & = CH), 7.04–6.75 (m, 9H,
ArH), 6.31 (d, J= 16.0 Hz, 1H, = CH), 5.50 (dd, J1 = 2.6 Hz
and J2 = 12.9 Hz, 1H, CH), 3.92–3.84 (m, 12H, 4 × OCH3),
3.12 (dd, J1 = 13.1 Hz and J2 = 16.4 Hz, 1H, Ha, CH2), 2.78
(dd, J1 = 16.5 Hz, J2 = 2.8 Hz, 1H, Hb, CH2), 2.29 (s, 3H, CH3);
13C NMR (50 MHz, CDCl3+CCl4): δ= 197.6, 190.7 (2 × CO),
162.6, 151.9, 149.9, 149.8, 149.6, 145.6, 143.6, 141.3, 138.8,
136.3, 131.4, 129.7, 129.3, 128.0, 127.8, 127.7, 126.6,
123.4, 119.6, 119.2, 117.1, 111.6, 111.4, 110.1, 109.9, 79.5,
1
815; H NMR (200 MHz, CDCl3+CCl4): δ= 7.59–6.93 (m,
15H, 14 ArH & = CH), 6.37 (d, J= 16.0 Hz, 1H, = CH), 5.55
(dd, J1 = 12.7 Hz, J2 = 2.8 Hz, 1H, CH), 3.06 (dd, J1 = 16.5
Hz, J2 = 13.1 Hz, 1H, Ha, CH2), 2.81 (dd, J1 = 16.5 Hz, J2 = 2.9
Hz, 1H, Hb, CH2), 2.30 (s, 3H, CH3); 13C NMR (50 MHz,
CDCl3+CCl4): δ= 197.2, 189.9 (2 × CO), 162.5, 143.9,
143.3, 138.5, 137.9, 133.6, 132.5, 132.4, 129.8, 129.7, 129.3,
© 2012 Informa UK, Ltd.

218 A. Sharma et al.
56.3, 56.2, 56.1, 46.2, 20.8; MS (ESI+): m/z: 565[M+H]+.
Elemental analysis for C35H32O7: Calcd. C, 74.45; H, 5.71.
Found: C, 74.39; H, 5.67.
(E)-2,5-bis(4-bromophenyl)-6-[3-(4-bromophenyl)acryloyl]-7-
methylchroman-4-one (35)
It was obtained as yellow solid, mp 221–223°C in 94%
yield; Rf = 0.5 (8:2 hexane:ethylacetate); IR (KBr): υmax
1
in cm−1 3426, 3021, 2363, 1633, 1584, 1216, 761, 671; H
(E)-7-Methyl-2-(naphthalen-1-yl)-6-[3-(naphthalen-1-yl)
acryloyl]-5-phenylchroman-4-one (32)
NMR (200 MHz, CDCl3+DMSO): δ= 7.59–7.30 (m, 10H, 9
ArH & = CH), 7.05–6.89 (m, 4H, ArH), 6.54 (d, J= 16.0 Hz,
1H, = CH), 5.67 (d, J= 11.9 Hz, 1H, CH), 3.08 (dd, J1 = 16.4
Hz, J2 = 13.0 Hz, 1H, Ha, CH2), 2.79 (d, J= 16.3 Hz, 1H, Hb,
CH2), 2.23 (s, 3H, CH3); 13C NMR (50 MHz, CDCl3+CCl4):
δ= 197.4, 190.2 (2 × CO), 162.5, 144.9, 143.3, 139.6, 138.6,
138.4, 135.9, 133.8, 132.6, 132.3, 132.1, 131.5, 130.9, 130.7,
129.1, 128.9, 125.3, 122.8, 121.5, 120.1, 117.2, 78.7, 45.9,
20.7; MS (ESI+): m/z: 679[M+H]+. Elemental analysis for
C31H21Br3O3: Calcd. C, 54.66; H, 3.11. Found: C, 54.50; H,
3.09.
It was obtained as light yellow solid, mp 180–181°C, in
92% yield; Rf = 0.4 (7:3 hexane:ethylacetate); IR (KBr):
υmax in cm−1 3428, 3056, 2367, 1695, 1635, 1596, 1342,
1178, 980, 775, 698; 1H NMR (200 MHz, CDCl3+CCl4):
δ= 8.10 (d, J = 7.5 Hz, 1H, ArH), 7.99–7.77 (m, 7H, 6 ArH
& = CH), 7.55–7.09 (m, 12H, ArH), 6.54 (d, J = 15.8 Hz,
1H, = CH), 6.35 (d, J = 12.7 Hz, 1H, CH), 3.31 (dd, J1 = 16.4
Hz, J2 = 13.3 Hz, 1H, Ha, CH2), 3.05 (d, J = 16.2 Hz, 1H, Hb,
CH2), 2.40 (s, 3H, CH3); 13C NMR (50 MHz, CDCl3+CCl4):
δ= 197.5, 190.8 (2 × CO), 163.0, 143.8, 141.8, 141.6, 138.8,
136.6, 134.4, 134.3, 134.0, 132.3, 131.8, 131.0, 130.6, 130.1,
129.8, 129.6, 129.5, 129.1, 128.3, 128.0, 127.2, 127.1, 126.6,
126.3, 125.7, 124.1, 123.7, 123.2, 119.8, 117.1, 78.0, 45.6,
20.9; MS (ESI+): m/z: 545[M+H]+. Elemental analysis for
C39H28O3: Calcd. C, 86.01; H, 5.18. Found: C, 85.91; H,
5.15.
(E)-5-(4-bromophenyl)-2-(4-fluorophenyl)-6-[3-(4-
fluorophenyl)acryloyl]-7-methylchroman-4-one (36)
It was obtained as light yellow solid, mp 168–170°C in 92%
yield; Rf = 0.5 (8:2 hexane:ethylacetate); IR (KBr): υmax in
cm−1 3426, 2927, 2365, 1636, 1595, 1509, 1230, 1160, 836,
1
755, 514; H NMR (200 MHz, CDCl3+CCl4): δ= 7.49–7.26
(E)-7-methyl-2-(naphthalen-2-yl)-6-[3-(naphthalen-2-yl)
acryloyl]-5-phenylchroman-4-one (33)
(m, 6H, 5 ArH & = CH), 7.18–6.80 (m, 8H, ArH), 6.38 (d,
J= 16.1 Hz, 1H, = CH), 5.55 (dd, J1 = 13.0 Hz, J2 = 2.9 Hz, 1H,
CH), 3.09 (dd, J1 = 16.5 Hz, J2 = 13.0 Hz, 1H, Ha, CH2), 2.80
(dd, J1 = 16.5 Hz, J2 = 3.0 Hz, 1H, Hb, CH2), 2.29 (s, 3H, CH3);
13C NMR (50 MHz, CDCl3+CCl4): δ= 197.1, 190.1 (2 × CO),
162.5, 144.3, 143.8, 140.0, 137.5, 136.1, 134.6, 131.4, 131.3,
131.1, 130.9, 130.7, 130.6, 130.4, 128.4, 128.2, 119.9,
116.8, 116.4, 116.3, 116.0, 78.9, 46.1, 20.7; MS (ESI+): m/z:
559[M+H]+. Elemental analysis for C31H21BrF2O3: Calcd.
C, 66.56; H, 3.78. Found: C, 66.50; H, 3.71.
It was obtained as light yellow solid, mp 184–185°C, in
94% yield; Rf = 0.4 (8:2 hexane:ethylacetate); IR (KBr): υmax
in cm−1 3465, 3050, 2369, 1690, 1597, 1429, 1263, 1187, 984,
1
747, 473; H NMR (200 MHz, CDCl3+CCl4): δ= 7.95–7.73
(m, 8H, 7 ArH & = CH), 7.62–7.40 (m, 7H, ArH), 7.27–7.19
(m, 4H, ArH), 7.12–7.07 (m, 2H, ArH), 6.55 (d, J= 16.0 Hz,
1H, = CH), 5.77 (dd, J1 = 13.6 Hz, J2 = 2.9 Hz, 1H, CH), 3.24
(dd, J1 = 16.5 Hz, J2 = 13.0 Hz, 1H, Ha, CH2), 2.93 (dd, J1 = 16.5
Hz, J2 = 3.0 Hz, 1H, Hb, CH2), 2.35 (s, 3H, CH3); 13C NMR
(50 MHz, CDCl3+CCl4): δ= 197.7, 190.5 (2 × CO), 162.7,
145.3, 143.8, 141.5, 138.8, 136.3, 134.7, 133.8, 133.6, 132.3,
130.7, 129.8, 129.4, 129.2, 129.0, 128.9, 128.5, 128.2, 127.9,
127.8, 127.7, 127.1, 126.9, 125.7, 123.9, 123.8, 119.7, 117.1,
79.7, 46.3, 20.8; MS (ESI+): m/z: 545[M+H]+. Elemental
analysis for C39H28O3: Calcd. C, 86.01; H, 5.18. Found: C,
85.89; H, 5.15.
(E)-5-(4-bromophenyl)-2-(4-chlorophenyl)-6-[3-(4-
chlorophenyl)acryloyl]-7-methylchroman-4-one (37)
It was obtained as light yellow solid, mp 174–176°C in
94% yield; Rf = 0.5 (8:2 hexane:ethylacetate); IR (KBr): υmax
in cm−1 3458, 3020, 2365, 1691, 1594, 1216, 1089, 765, 501;
1H NMR (200 MHz, CDCl3+CCl4): δ= 7.41–7.23 (m, 10H, 9
ArH & = CH), 7.01–6.88 (m, 4H, ArH), 6.41 (d, J= 16.1 Hz,
1H, = CH), 5.55 (d, J= 11.0 Hz, 1H, CH), 3.07 (dd, J1 = 16.3
Hz, J2 = 12.9 Hz, 1H, Ha, CH2), 2.80 (d, J= 15.7 Hz, 1H, Hb,
CH2), 2.29 (s, 3H, CH3); 13C NMR (50 MHz, CDCl3+CCl4):
δ= 197.1, 190.0 (2 × CO), 162.5, 144.1, 143.8, 140.1, 137.4,
137.2, 136.1, 135.2, 133.0, 131.3, 131.1, 131.0, 129.7,
129.6, 129.5, 128.7, 127.7, 122.3, 119.9, 116.8, 78.8, 46.0,
20.7; MS (ESI+): m/z: 591[M+H]+. Elemental analysis for
C31H21BrCl2O3: Calcd. C, 62.86; H, 3.57. Found: C, 62.80;
H, 3.43.
5-(4-bromophenyl)-6-cinnamoyl-7-methyl-2-phenylchroman-
4-one (34)
It was obtained as light yellow solid, mp 168–170°C in
92% yield; Rf = 0.6 (8:2 hexane:ethylacetate); IR (KBr):
υmax in cm−1 3434, 3022, 2364, 1639, 1216, 767, 671; H
1
NMR (200 MHz, CDCl3+CCl4): δ = 7.46–7.26 (m, 12H, 11
ArH & = CH), 7.03–6.91 (m, 4H, ArH), 6.49 (d, J = 16.1 Hz,
1H, = CH), 5.58 (d, J = 12.1 Hz, 1H, CH), 3.13 (dd, J1 = 16.3
Hz, J2 = 13.7 Hz, 1H, Ha, CH2), 2.82 (d, J = 16.1 Hz, 1H, Hb,
CH2), 2.30 (s, 3H, CH3); 13C NMR (50 MHz, CDCl3+CCl4):
δ = 197.7, 190.6 (2 × CO), 162.7, 146.1, 143.7, 140.0,
138.8, 137.6, 136.0, 134.6, 131.4, 131.3, 131.1, 130.9,
129.3, 129.2, 128.7, 128.6, 126.4, 122.1, 119.9, 116.9,
79.6, 46.2, 20.7; MS (ESI+): m/z: 523[M+H]+. Elemental
analysis for C31H23BrO3: Calcd. C, 71.13; H, 4.43. Found:
C, 71.06; H, 4.40.
(E)-2-(4-(benzyloxy)phenyl)-6-[3-{4-(benzyloxy)phenyl}
acryloyl]-5-(4-bromophenyl)-7-methylchroman-4-one (38)
It was obtained as light yellow solid, mp 192–195°C in
92% yield; Rf = 0.5 (7:3 hexane:ethylacetate); IR (KBr):
υ
max in cm−1 3752, 3454, 3021, 2364, 1563, 1216, 1017, 761;
1H NMR (200 MHz, CDCl3+CCl4): δ= 7.43–7.26 (m, 16H,
15 ArH & = CH), 7.06–6.92 (m, 8H, ArH), 6.42 (d, J= 16.1
Journal of Enzyme Inhibition and Medicinal Chemistry

Synthesis of 5-aryl-6-cinnamoyl-7-methyl-flavanones 219
Hz, 1H, = CH), 5.53 (dd, J1 = 13.1 Hz, J2 = 2.6 Hz, 1H, CH),
5.11–5.09 (m, 4H, 2 × OCH2), 3.15 (dd, J1 = 16.6 Hz, J2 = 13.2
Hz, 1H, Ha, CH2), 2.79 (dd, J1 = 16.6 Hz, J2 = 2.8 Hz, 1H, Hb,
CH2), 2.27 (s, 3H, CH3); 13C NMR (50 MHz, CDCl3+CCl4):
δ= 198.2, 190.4 (2 × CO), 162.7, 161.5, 159.6, 146.6, 143.7,
139.8, 137.8, 137.1, 136.7, 136.0, 131.3, 131.2, 131.1, 130.8,
130.6, 129.1, 128.6, 128.5, 128.1, 127.8, 127.4, 126.6, 122.0,
119.9, 116.9, 115.7, 115.6, 79.4, 70.5, 45.9, 20.7; MS (ESI+):
m/z: 735[M+H]+. Elemental analysis for C45H35O5Br:
Calcd. C, 73.47; H, 4.80. Found: C, 73.41; H, 4.75.
(2 × CO), 162.7, 158.6, 151.9, 149.9, 149.6, 145.3, 143.7,
137.3, 131.4, 130.6, 128.8, 128.2, 127.8, 126.6, 123.4, 119.2,
109.9, 70.5, 20.9; MS (ESI+): m/z: 707[M+H]+. Elemental
analysis for C38H28O4Br2: Calcd. C, 64.42; H, 3.98. Found:
C, 64.39; H, 3.88.
(E)-5-(4-(benzyloxy)phenyl)-2-(4-chlorophenyl)-6-[3-(4-
chlorophenyl)acryloyl]-7-methylchroman-4-one (42)
It was obtained as light yellow solid, mp 164–165°C in 93%
yield; Rf = 0.4 (7:3 hexane:ethylacetate); IR (KBr): υmax in
cm−1 3420, 2368, 1687, 1598, 1511, 1244, 1173, 1029, 838,
1
(E)-5-(4-bromophenyl)-2-(4-methoxyphenyl)-6-[3-(4-
methoxyphenyl)acryloyl]-7-methylchroman-4-one (39)
It was obtained as light yellow solid, mp 178–180°C in
91% yield; Rf = 0.4 (7:3 hexane:ethylacetate); IR (KBr):
760, 522; H NMR (200 MHz, CDCl3+CCl4): δ= 7.42–7.24
(m, 13H, 12 ArH & = CH), 7.20–6.95 (m, 4H, ArH), 6.86–
6.83 (m, 2H, ArH), 6.36 (d, J= 16.0 Hz, 1H, = CH), 5.56
(dd, J1 = 12.7 Hz, J2 = 3.2 Hz, 1H, CH), 4.95 (s, 2H, OCH2),
3.07 (dd, J1 = 16.5 Hz, J2 = 12.7 Hz, 1H, Ha, CH2), 2.82 (dd,
υ
max in cm−1 3756, 3019, 2364, 1598, 1216, 1168, 1030, 763;
1H NMR (200 MHz, CDCl3+CCl4): δ= 7.41–7.26 (m, 6H,
5 ArH & = CH), 7.04–6.83 (m, 8H, ArH), 6.38 (d, J= 16.1
Hz, 1H, = CH), 5.52 (dd, J1 = 13.1 Hz, J2 = 2.7 Hz, 1H, CH),
3.84–3.80 (m, 6H, 2 × OCH3), 3.13 (dd, J1 = 16.5 Hz, J2 = 13.2
Hz, 1H, Ha, CH2), 2.78 (dd, J1 = 16.5 Hz, J2 = 2.8 Hz, 1H, Hb,
CH2), 2.28 (s, 3H, CH3); 13C NMR (50 MHz, CDCl3+CCl4):
δ= 197.7, 190.9 (2 × CO), 162.7, 162.3, 160.4, 146.2, 143.6,
139.9, 137.8, 136.1, 131.4, 131.2, 131.0, 130.8, 130.5, 128.0,
127.2, 126.5, 122.0, 119.8, 116.8, 114.8, 114.6, 79.3, 55.7,
55.6, 46.0, 20.7; MS (ESI+): m/z: 583[M+H]+. Elemental
analysis for C33H27O5Br: Calcd. C, 67.93; H, 4.66. Found:
C, 67.80; H, 4.55.
J1 = 16.5 Hz, J2 = 3.2 Hz, 1H, Hb, CH2), 2.30 (s, 3H, CH3); 13
C
NMR (50 MHz, CDCl3+CCl4): δ= 197.1, 190.0 (2 × CO),
162.6, 158.8, 143.9, 142.6, 141.4, 137.4, 137.2, 136.8, 136.6,
135.1, 133.4, 130.9, 129.6, 129.5, 129.4, 128.8, 128.6, 128.2,
127.7, 119.5, 117.0, 78.7, 70.2, 46.2, 20.8; MS (ESI+): m/z:
619[M+H]+. Elemental analysis for C38H28O4Cl2: Calcd. C,
73.67; H, 4.56. Found: C, 73.60; H, 4.52.
(E)-2,5-bis(4-(benzyloxy)phenyl)-6-[3-{4-(benzyloxy)phenyl}
acryloyl]-7-methylchroman-4-one (43)
It was obtained as light yellow solid, mp 64–65°C in 92%
yield; Rf = 0.4 (7:3 hexane:ethylacetate); IR (KBr): υmax in
cm− 3781, 3324, 3036, 2362, 1602, 1505, 1247, 1016, 829,
1
5-(4-(benzyloxy)phenyl)-6-cinnamoyl-7-methyl-2-
731, 607; H NMR (200 MHz, CDCl3+CCl4): 7.43–7.26 (m,
phenylchroman-4-one (40)
19H, 18 ArH & = CH), 7.19–6.30 (m, 10H, ArH), 6.38 (d,
J= 16.0 Hz, 1H, = CH), 5.53 (dd, J1 = 13.0 Hz, J2 = 2.4 Hz,
1H, CH), 5.11–4.96 (m, 6H, 3 × OCH2), 3.15 (dd, J1 = 16.5
Hz, J2 = 13.4 Hz, 1H, Ha, CH2), 2.80 (dd, J1 = 16.5 Hz, J2 = 2.7
Hz, 1H, Hb, CH2), 2.28 (s, 3H, CH3); 13C NMR (50 MHz,
CDCl3+CCl4): δ= 198.5, 191.4 (2 × CO), 162.8, 161.2, 159.6,
158.6, 145.4, 143.7, 137.4, 137.1, 136.7, 131.4, 131.2, 131.0,
130.5, 129.1, 128.9, 128.6, 128.5, 128.3, 128.1, 128.0, 127.8,
127.7, 126.5, 119.5, 115.6, 115.5, 114.6, 114.2, 79.3, 70.2,
46.1, 20.8; MS (ESI+): m/z: 763[M+H]+. Elemental analysis
for C52H42O6: Calcd. C, 81.87; H, 5.55. Found: C, 81.80; H,
5.53.
It was obtained as light yellow solid, mp 168–169°C in 90%
yield; Rf = 0.4 (7:3 hexane:ethylacetate); IR (KBr): υmax in
cm−1 3779, 3380, 3021, 2359, 1596, 1216, 762, 671; 1H NMR
(200 MHz, CDCl3+CCl4): δ= 7.47–7.26 (m, 15H, 14 ArH
& = CH), 7.14–7.11 (m, 2H, ArH), 7.03–6.89 (m, 2H, ArH),
6.88–6.84 (m, 2H, ArH), 6.44 (d, J= 16.1 Hz, 1H, = CH), 5.59
(dd, J1 = 13.1 Hz, J2 = 3.0 Hz, 1H, CH), 4.95 (s, 2H, OCH2),
3.13 (dd, J1 = 16.5 Hz, J2 = 13.1 Hz, 1H, Ha, CH2), 2.84 (dd,
J1 = 16.5 Hz, J2 = 3.0 Hz, 1H, Hb, CH2), 2.31 (s, 3H, CH3); 13
C
NMR (50 MHz, CDCl3+CCl4): δ= 197.8, 190.6 (2 × CO),
162.8, 158.7, 144.7, 143.7, 141.3, 139.0, 137.3, 136.5, 134.9,
131.1, 130.8, 130.7, 129.2, 128.8, 128.6, 128.4, 128.2, 127.8,
126.4, 119.5, 114.3, 79.5, 70.2, 46.4, 20.8; MS (ESI+): m/z:
551[M+H]+. Elemental analysis for C38H30O4: Calcd. C,
82.89; H, 5.49. Found: C, 82.70; H, 5.45.
(E)-5-(4-(benzyloxy)phenyl)-2-(4-methoxyphenyl)-6-[3-(4-
methoxyphenyl)acryloyl]-7-methylchroman-4-one (44)
It was obtained as yellow solid, mp 69–70°C in 91% yield;
Rf = 0.4 (7:3 hexane:ethylacetate); IR (KBr): υmax in cm−1
3783, 2838, 2362, 1628, 1604, 1509, 1248, 1169, 1027, 830,
728, 561; 1H NMR (200 MHz, CDCl3+CCl4): 7.42–7.20
(m, 9H, 8 ArH & = CH), 7.12–6.80 (m, 10H, ArH), 6.34 (d,
J= 16.0 Hz, 1H, = CH), 5.52 (dd, J1 = 13.1 Hz, J2 = 2.7 Hz, 1H,
CH), 4.95 (m, 2H, OCH2), 3.84–3.81 (m, 6H, 2 × OCH3),
3.13 (dd, J1 = 16.5 Hz, J2 = 13.2 Hz, 1H, Ha, CH2), 2.79 (dd,
(E)-5-(4-(benzyloxy)phenyl)-2-(4-bromophenyl)-6-[3-(4-
bromophenyl)acryloyl]-7-methylchroman-4-one (41)
It was obtained as light yellow solid, mp 170–171°C in 93%
yield; Rf = 0.4 (7:3 hexane:ethylacetate); IR (KBr): υmax in
cm−1 3762, 3427, 3022, 2368, 1635, 1217, 767, 671; 1H NMR
(200 MHz, CDCl3+CCl4): δ= 7.59–7.26 (m, 11H, 10 ArH
& = CH), 7.17–7.07 (m, 3H, ArH), 7.01–6.83 (m, 5H, ArH),
6.37 (d, J= 16.0 Hz, 1H, = CH), 5.54 (d, J= 12.6 Hz, 1H, CH),
4.95 (m, 2H, OCH2), 3.06 (dd, J1 = 16.1 Hz, J2 = 12.9 Hz, 1H,
Ha, CH2), 2.81 (d, J= 16.4 Hz, 1H, Hb, CH2), 2.30 (s, 3H,
CH3); 13C NMR (50 MHz, CDCl3+CCl4): δ= 197.8, 191.0
J1 = 16.5 Hz, J2 = 2.8 Hz, 1H, Hb, CH2), 2.29 (s, 3H, CH3); 13
C
NMR (50 MHz, CDCl3+CCl4): δ= 197.7, 190.9 (2 × CO),
162.8, 162.0, 160.4, 158.6, 144.8, 143.5, 141.2, 137.4, 136.6,
131.3, 131.1, 130.6, 130.3, 128.8, 128.1, 128.0, 127.8, 127.5,
126.4, 119.4, 117.1, 114.7, 114.2, 79.2, 70.1, 55.6, 46.2,
© 2012 Informa UK, Ltd.

220 A. Sharma et al.
20.8; MS (ESI+): m/z: 611[M+H]+. Elemental analysis for
C40H34O6: Calcd. C, 78.67; H, 5.61. Found: C, 78.65; H,
5.58.
(E)-5-(4-chlorophenyl)-7-methyl-2-(naphthalen-2-yl)-6-[3-
(naphthalen-1-yl)acryloyl]chroman-4-one (48)
It was obtained as light yellow solid, mp 184–185°C in 923%
yield; Rf =0.4 (7:3 hexane:ethylacetate); IR (KBr): υmax in
cm−1 3765, 3412, 2922, 2364, 1636, 1596, 1429, 1183, 1088,
814, 473; 1H NMR (200MHz, CDCl3+CCl4): δ=7.94–7.78(m,
8H, 7 ArH &=CH), 7.62–7.45 (m, 6H, ArH), 7.26–7.01 (m,
6H, ArH), 6.60 (d, J=16.0 Hz, 1H, =CH), 5.77 (dd, J1 =12.9
Hz, J2 =2.6 Hz, 1H, CH), 3. 24 (dd, J1 =16.5 Hz, J2 =13.0
Hz, 1H, Ha, CH2), 2.93 (dd, J1 =16.5 Hz, J2 =2.8 Hz, 1H, Hb,
CH2), 2.34 (s, 3H, CH3); 13C NMR (50MHz, CDCl3+CCl4):
δ=197.7, 190.5 (2×CO), 162.7, 146.2, 143.7, 140.1, 137.1,
136.1, 134.9, 133.9, 133.8, 133.6, 132.1, 131.1, 130.9, 130.7,
129.2, 128.9, 128.7, 128.5, 128.3, 128.2, 127.9, 127.2, 127.0,
125.7, 123.9, 123.7, 120.0, 117.0, 79.75, 46.20, 30.1, 20.8; MS
(ESI+): m/z: 579 [M+H]+. Elemental analysis for C39H27O3Cl:
Calcd. C, 80.89; H, 4.70. Found: C, 80.81; H, 4.67.
(E)-5-(4-(benzyloxy)phenyl)-2-(3,4-dimethoxyphenyl)-6-[3-
(3,4-dimethoxyphenyl)acryloyl]-7-methylchroman-4-one (45)
It was obtained as light yellow solid, mp 138–140°C in
93% yield; Rf = 0.4 (7:3 hexane:ethylacetate); IR (KBr):
υmax in cm−1 3767, 3427, 2932, 2363, 1594, 1510, 1261,
1150, 1021, 770; 1H NMR (200 MHz, CDCl3+CCl4):
δ= 7.32–7.26 (m, 5H, 4 ArH & = CH), 7.11–6.75 (m, 12H,
ArH), 6.32 (d, J = 16.0 Hz, 1H, = CH), 5.51 (dd, J1 = 12.8 Hz,
J2 = 2.6 Hz, 1H, CH), 4.95 (m, 2H, OCH2), 3.93–3.85 (m,
12H, 4 × OCH3), 3.13 (dd, J1 = 16.5 Hz, J2 = 13.2 Hz, 1H, Ha,
CH2), 2.80 (dd, J1 = 16.5 Hz, J2 = 2.8 Hz, 1H, Hb, CH2), 2.29
(s, 3H, CH3); 13C NMR (50 MHz, CDCl3+CCl4): δ= 197.8,
191.0 (2 × CO), 162.7, 158.6, 151.9, 149.9, 149.6, 145.3,
143.7, 137.3, 131.4, 130.6, 128.8, 128.2, 127.8, 126.6,
123.4, 119.2, 114.5, 111.6, 111.4, 110.1, 109.9, 79.5, 70.2,
56.3, 46.3, 20.8. MS (ESI+): m/z: 671[M+H]+. Elemental
analysis for C42H38O8: Calcd. C, 75.21; H, 5.71. Found: C,
75.12; H, 5.69.
Biology
Animal used
Rats (Charles Foster strain, male, adult, body weight
200–225 g) were kept in a room with controlled tempera-
ture (25–26°C), humidity (60–80%) and 12/12-h light/
dark cycle (light on from 8.00 a.m. to 8.00 p.m.) under
hygienic conditions. Animals, which were acclimatized
for 1 week before starting the experiment, had free access
to the normal diet and water.
(E)-2-(2-chlorophenyl)-5-(4-chlorophenyl)-6-[3-(2-
chlorophenyl)acryloyl]-7-methylchroman-4-one (46)
It was obtained as light yellow solid, mp 190–192°C in 91%
yield; Rf = 0.4 (7:3 hexane:ethylacetate); IR (KBr): υmax in
cm−1 3757, 3065, 2364, 1696, 1591, 1436, 1316, 1161, 1041,
1
861, 746; H NMR (200 MHz, CDCl3+CCl4): δ= 7.76–7.72
Antidyslipidemic activity
(m, 1H, ArH), 7.50–7.23 (m, 11H, 10 ArH &= CH), 7.19–
6.98 (m, 2H, ArH), 6.42 (d, J= 16.2 Hz, 1H, = CH), 5.98
(dd, J1 = 11.7Hz, J2 = 4.4 Hz, 1H, CH), 2.91–2.84 (m, 2H,
CH2), 2.32 (s, 3H, CH3); 13C NMR (50 MHz, CDCl3+CCl4):
δ= 197.7, 190.0 (2 × CO), 162.8, 143.8, 141.9, 140.3, 136.9,
135.9, 135.3, 134.0, 133.0, 132.1, 131.7, 131.5, 130.8, 130.5,
130.1, 130.0, 128.3, 128.1, 127.8, 127.5, 119.9, 116.9, 76.5,
44.9, 20.8; MS (ESI+): m/z: 547[M+H]+. Elemental analysis
for C31H21O3Cl3: Calcd. C, 67.94; H, 3.86. Found: C, 67.88;
H, 3.85.
e antidyslipidemic activities of all compounds were
evaluated in a triton model39. Rats were divided in control,
triton induced, triton plus compounds and gemfibrozil
(standard drug, 100 mg/kg) treated groups containing
six rats in each group. Hyperlipidemia was developed
by administration of triton WR-1339 (sigma chemical
company, St Louis, MO) at a dose of 400 mg/kg body wt.
intraperitoneally to animals of all groups except the con-
trol. All the compounds were macerated with gum aca-
cia suspension (vehicle). After 18 h of treatment 3.0 mL,
blood was withdrawn from retro-orbital sinus using
glass capillary in EDTA coated eppendorf tube (3.0mg/
mL) and plasma was separated. Plasma was diluted with
normal saline (ratio 1:3) and used for the analysis of TC,
PL, Tg, and protein by standard enzymatic procedures
using spectrometer and standard kits purchased from
Beckmann Coulter International (USA).
(E)-5-(4-chlorophenyl)-7-methyl-2-(naphthalen-1-yl)-6-[3-
(naphthalen-1-yl)acryloyl]chroman-4-one (47)
Itwasobtainedaslightyellowsolid,mp184–185°Cin923%
yield; Rf = 0.4 (7:3 hexane:ethylacetate); IR (KBr): υmax in
cm−1 3778, 3362, 3060, 2920, 2365, 1691, 1639, 1594, 1340,
1
1180, 1085, 775, 528; H NMR (200 MHz, CDCl3+CCl4):
δ= 8.10–7.76 (m, 8H, 7 ArH & = CH), 7.59–7.11 (m, 12H,
ArH), 6.57 (d, J= 15.8 Hz, 1H, = CH), 6.35 (dd, J1 = 12.8
Hz, J2 = 2.7 Hz, 1H, CH), 3. 31 (dd, J1 = 16.7 Hz, J2 = 12.9
Hz, 1H, Ha, CH2), 3.06 (dd, J1 = 16.7 Hz, J2 = 2.9 Hz, 1H, Hb,
CH2), 2.39 (s, 3H, CH3); 13C NMR (50 MHz, CDCl3+CCl4):
δ= 197.4, 190.8 (2 × CO), 163.0, 143.8, 142.7, 140.2, 137.2,
136.5, 134.3, 134.2, 134.1, 132.1, 131.7, 131.4, 131.3, 131.1,
130.9, 130.6, 129.8, 129.5, 129.2, 128.5, 128.3, 127.4, 126.6,
126.4, 125.9, 125.8, 125.7, 124.1, 123.5, 123.1, 120.1, 117.0,
76.90, 45.51, 20.8; MS (ESI+): m/z: 579 [M+H]+. Elemental
analysis for C39H27O3Cl: Calcd. C, 80.89; H, 4.70. Found:
C, 80.81; H, 4.67.
Antioxidant activity determination
Superoxides anions were generated enzymatically28 from
xanthine (160 mM) using xanthine oxidase (0.04 U) and
nitrobluetetrazolium(320μM)intheabsenceorpresence
of compounds 25–48 (200 μg/mL) in 100 mM phosphate
buffer (pH-8.2). Fractions were sonicated well in phos-
phate buffer before use. e reaction mixtures were incu-
bated at 37°C, and after 30 min, the reaction was stopped
by adding 0.5 mL glacial acetic acid. e amount of for-
mazone formed was calculated spectrophotometrically.
In another set of experiment, an effect of compounds on
Journal of Enzyme Inhibition and Medicinal Chemistry

Synthesis of 5-aryl-6-cinnamoyl-7-methyl-flavanones 221
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generation of hydroxyl radicals (OH·) was also studied by
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were generated in a nonenzymatic system comprising
deoxyribose (2.8 mM), FeSO4·7H2O (2.0 mM), sodium
ascorbate (2.0 mM) and H2O2 (2.8 mM) in 50 mM KH2
PO4 buffer, pH 7.4 to a final volume of 2.5 mL. e above
reaction mixtures in the absence or presence of test com-
pounds (200 μg/mL) were incubated at 37°C for 90 min.
e test compounds were also studied for their inhibitory
action against microsomal lipid peroxidation in vitro by
non enzymatic inducer. Reference samples and reagent
blanks were also run simultaneously. Malondialdehyde
content in both experimental and reference samples were
estimated spectrophotometriclly by thiobarbituric acid
method as mentioned earlier40. Alloprinol, mannitol, and
α-tocopherol were used as standard drugs for superox-
ide, hydroxylations and microsomal lipid peroxidations.
Biochemical analysis of plasma/serum
Serum lipids TC41, Pl42, Tg43 and protein44 were estimated
by the standard procedures reported in literature.
Statistical evaluation
Data were analysed using Student’s t-test. e hyper-
lipedemic groups were compared with control drug
treated groups. Similarly, the generation of oxygen free
radicals with different 6-cinnamoyl-7-methyl-5-phenyl-
flavanones derivatives were compared with that of their
formation without compounds. P< 0.05 was considered
to be significant.
Supplementary data
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Supplementary data associated with this article can be
found, in the online version, at doi:10.3109/14756366.2
011.585134.
Declaration of interest
is is CDRI Communication No 8052. e authors thank
CSIR and DRDO New Delhi for the SRF and PA to Anindra,
Namrata and Rahul, respectively. We are also thankful to
the SAIF Division of C.D.R.I. for providing all the spectral
data. We sincerely acknowledge the financial assistance
from DRDO New Delhi.
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of2′-hydroxychalconestoflavanonesusingphasetransfercatalysis.
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RP. Synthesis and anti breast cancer activity of biphenyl based
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