Effects of structural and electronic characteristics of chalcones on the activation of peroxisome proliferator-activated receptor gamma

Article abstract of DOI:10.1248/cpb.c12-00749

Chalcones share some structural similarities with GW-1929, a highly-selective and potent agonist for peroxisome proliferator-activated receptor-gamma (PPARγ). In this study, we tested 53 structurally diverse chalcones to identify characteristics essential for PPARγ activation in a GAL4-based transactivation assay. This screen identified several novel chalcone agonists of PPARγ. Our results indicate that chalcones with an electron rich group or sterically large groups such as naphthyl on the carbonyl side tend to activate PPARγ. The absence of any strict structural or electronic requirements suggests that the flexibility of the PPARγ ligand binding pocket may allow binding of diverse chalcones with some preference for a slightly larger electron-rich group on the carbonyl side. We predict that further structure-activity relationship studies on chalcones with naphthalene or electron-rich groups near the carbonyl moiety will lead to the development of more potent PPARγ agonists.

Full text of DOI:10.1248/cpb.c12-00749

February 2013
Note
Chem. Pharm. Bull. 61(2) 229–236 (2013)
229
Effects of Structural and Electronic Characteristics of Chalcones on the
Activation of Peroxisome Proliferator-Activated Receptor Gamma
Jason Taylor Schott,a Charles Edward Mordaunt,a Anthony Joseph Vargas,a
Martin Antonio Leon,b Kevin Hsinwen Chen,c Mandeep Singh,b Mikiko Satoh,c
,a,d
Emilio Leal Cardenas,b Santanu Maitra,b Nilay Vinod Patel,* and
,c
Hubrecht Johan Peter de Lijser*
c
a Department of Biological Science, California State University; Department of Chemistry and Biochemistry,
d
California State University; Center for Applied Biotechnology Studies, California State University; Fullerton, CA
b
92831, U.S.A. and Department of Chemistry, California State University; Fresno, CA 93740, U.S.A.
Received August 24, 2012; accepted November 6, 2012; advance publication released online November 27, 2012
Chalcones share some structural similarities with GW-1929, a highly-selective and potent agonist for
peroxisome proliferator-activated receptor-gamma (PPARγ). In this study, we tested 53 structurally diverse
chalcones to identify characteristics essential for PPARγ activation in a GAL4-based transactivation assay.
This screen identified several novel chalcone agonists of PPARγ. Our results indicate that chalcones with an
electron rich group or sterically large groups such as naphthyl on the carbonyl side tend to activate PPARγ.
The absence of any strict structural or electronic requirements suggests that the flexibility of the PPARγ
ligand binding pocket may allow binding of diverse chalcones with some preference for a slightly larger
electron-rich group on the carbonyl side. We predict that further structure–activity relationship studies on
chalcones with naphthalene or electron-rich groups near the carbonyl moiety will lead to the development of
more potent PPARγ agonists.
Key words naphthyl-chalcone; peroxisome proliferator-activated receptor gamma; GAL4 assay
Peroxisome proliferator-activated receptor-gamma (PPARγ) studies have found that chalcones with hydroxyl and methoxy
is an important pharmacological target for treatment of hy- groups present in certain positions had more potent or similar
perglycemia, dyslipidemia, inflammation, atherosclerosis, and PPARγ agonistic activity compared with the reference dose
several other conditions.1) Thiazolidinediones are among the of troglitazone and 15-deoxy-Δ12,14-prostaglandin J2 (PGJ2).9)
best-known PPARγ specific ligands and are often prescribed However, the chosen chalcone library consisted mostly of
for management of hyperglycemia in type 2 diabetes mellitus. small molecules, and the vast majority contained electron-rich
One of the underlying causes of hyperglycemia is increased groups. Because of those limitations we have chosen to fur-
gluconeogenesis resulting from accumulation of triglycer- ther investigate chalcones as potential PPARγ agonists. Chal-
ides in liver (steatosis). Thiazolidinediones attenuate liver cones are relatively easy to synthesize in the laboratory from a
steatosis by promoting differentiation of pre-adipocytes into wide variety of commercially available and affordable starting
adipocytes, which improves vascular lipid profile. Activation materials, which makes them advantageous when preparing
of PPARγ in adipocytes also leads to increased expression of a diverse library of potential PPARγ ligands. Here we report
adiponectin and attenuated expression of pro-inflammatory on the observed effects of using a varied set of chalcones to
genes.1,2) All of these events increase insulin sensitivity, im- probe for additional steric and electronic requirements for
prove dyslipidemia, and could attenuate inflammation and ligand-dependent activation of PPARγ.
atherosclerosis.2) These drugs are also beneficial in manage-
ment of non-alcoholic steatohepatitis and possibly Metabolic
Results and Discussion
To monitor the activation of PPARγ by chalcones, the
Syndrome (Syndrome X).3) Nevertheless, thiazolidinediones
are also known to increase the risk of bone fracture, myo- PPARγ ligand binding domain (LBD) was fused with the
cardial infarction, and cancer.4–6) One possible solution is to yeast GAL4 DNA binding domain (DBD) and expressed in
develop partial PPARγ agonists, selective PPARγ modulators, HEK293 cells along with a GAL4 responsive Firefly luciferase
or less potent agonists that are selective for PPAR isoforms.2) reporter. Transfected cells were treated in quadruplicate with
For example, GQ-16 has a maximal activation that is lower a 10µm dose of test compound, and luciferase expression was
than rosiglitazone’s EC50 for PPARγ, yet it promotes insulin quantified 24h later using a luminometer. The chalcones were
sensitization.7) However, GQ-16 and several other selective classified into three categories based on the substituents at
PPARγ modulators have not progressed further than preclini- the carbonyl and alkene ends. Series A (Table 1) consists of
cal or phase II trials.2) This necessitates the development of molecules containing the basic chalcone skeleton with simple
additional pharmacophores that activate PPARγ.
electron-rich or electron-poor substituents on one or both
One of the most potent and selective PPARγ agonists is benzene rings; series B (Table 2) contains the naphthyl moiety
GW-1929 (1), which has an EC50 of approximately 0.01µm.8) at the carbonyl end; and series C (Table 3) is comprised of
A structural analysis of GW-1929 reveals a benzophenone chalcone-like compounds with heteroatom-containing groups
core with some structural similarities to chalcones. Previous (furan, thiophene, pyrrole, pyridine) at one end. Two of the
compounds listed as part of series C have different structural
features. Compound 52 contained an additional double bond
The authors declare no conflict of interest.
© 2013 The Pharmaceutical Society of Japan
*To whom correspondence should be addressed. e-mail: npatel@fullerton.edu; pdelijser@fullerton.edu

230
Vol. 61, No. 2
Table 2. Structures of Naphthylchalcones (Series B)
Compound
Z
41
42
43
44
45
4-CH3
4-Cl
2-NO2
4-NO2
3-Br
Fig. 1. Compound 54
Table 1. Structures of Simple Chalcone Derivatives with Electron-Rich
and Electron-Poor Substituents (Series A)
Table 3. Structures of Chalcone-Like Compounds (Series C)
Compound
X
Y
2
3
H
H
H
2-OCH3
4
5
6
7
8
9
4-OCH3
4-F
4-F
4-F
4-CH3
4-F
3-CH3
Compound
R1
R2
4-CH2CH2CH2CH3
4-OCH2CH2CH2CH3
4-CH(CH3)2
4-OCH2CH2CH2CH3
3-F
3-NO2
4-Cl
4-Cl
3-NO2
4-Cl
4-F
4-F
4-NO2
4-NO2
4-NO2
4-Cl
3-CF3
4-OC(CH3)3
4-OCH2CH2CH2CH3
4-C(CH3)3
4-OC(CH3)3
4-CH(CH3)2
4-OCH2CH2CH2CH3
4-OCH2CH2CH2CH3
4-OC(CH3)3
4-OCH2CH2CH2CH3
4-CH2CH2CH2CH3
H
46
47
48
49
50
51
52
53
2-Thiophene
2-Thiophene
4-CH3OC6H4
2-Pyridine
2-Pyridine
2-Furan
4-CH3OC6H4
H
2-Furan
4-CH3OC6H4
4-(CH3)2CHC6H4
4-CH3CH2CH2CH2OC6H4
Styrene
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
4-F
4-Cl
C6H5
C6H5
3-OCH3
4-NO2
3-NO2
3-NO2
4-Cl
2-Pyrrole
pounds synthesized and tested in the GAL4-PPARγ transac-
tivation assay are presented in Fig. 2. Here, we have included
GW-1929 (1), which has an EC50 of approximately 0.01µm
in GAL4-transactivation assays, as the positive control at a
0.1 µm dose in our GAL4-PPARγ assay.8) The parent chalcone
(2), which failed to activate PPARγ, served as the “base-
line.” Chalcones which activated PPARγ by a fold-change
greater than 3 standard deviations (3σ) over dimethylsulfoxide
(DMSO) (vehicle control) were classified as activators. Ac-
cording to this criterion, 23 of the 52 compounds tested (not
including 1, 2) can be considered activators. We further dif-
ferentiated (arbitrarily) between weak (1.51–1.70), moderate
(1.71–2.00), and strong (2.01–3.2) activators. Eight compounds
can be classified as strong activators and of these, five com-
pounds (3, 41, 42, 21, 53; in order of activation) were found to
give better results than 0.1µm GW-1929 (1). It is possible that
these moderate–strong chalcone activators can yield beneficial
effects similar to those observed for other partial agonists of
PPARγ such as GQ-16.7)
4-Cl
4-CH3
4-OCH3
4-CH3
4-CH3
4-CH3
4-Cl
4-Cl
4-Cl
4-Cl
3-OCH3
4-NO2
4-NO2
4-OCH3
4-Cl
4-OCH3
4-CH3
4-OCH3
4-OCH3
H
3-OCH3
4-OCH3
3-NO2
4-OCH3
Analysis of the three individual series shows that 16 out
of the 39 compounds from series A are activators (>1.5-fold
activation compared to the DMSO vehicle control). Two of
these compounds (3, 21) showed higher PPARγ activation than
0.1 µm GW-1929 (1). In fact, chalcone 3 showed the best re-
sponse of all the compounds that we tested. All but one of the
4-CH3
4-OCH3
H
H
3-OCH3
4-Cl
3-CH3
4-Cl
(from cinnamaldehyde) and compound 54 (Fig. 1) was the un- compounds from series B were activators (>1.5-fold activa-
expected result of a double Claisen–Schmidt condensation re- tion) and 2 compounds (41, 42) showed better activation than
action. This wide variety of steric and electronic components 0.1 µm GW-1929 (1). Three out of the nine compounds from
has allowed for a detailed structure–activity study.
series C were activators but only 53 was a better activator
The results for all the chalcones and chalcone-like com- than 0.1µm GW-1929 (1).

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231
Fig. 2. Identification of a Variety of Chalcones as PPARγ Activators
GAL4-PPARγ fusion construct or empty GAL4-DBD control vector were co-electroporated with the GAL4 9xUAS luciferase reporter into HEK293 cells. The cells
were treated in quadruplicate for 24h with vehicle (0.1% DMSO), 0.1µm GW-1929 (a highly-selective and potent PPARγ agonist with an EC50 of 0.01µm),8) or 10µm of the
indicated chalcone. Luciferase measurements were normalized to DMSO controls, and then fold-activities for GAL4-PPARγ samples were normalized to the average fold-
activities for GAL4-DBD samples for each treatment. Data shown are the mean of 2 or more quadruplicate measurements S.E.M.
Our initial analysis did not reveal any obvious structural
Next, we did an analysis of individual groups to see if using
trends in chalcone-mediated PPARγ activation, but we none- any specific activating group would give a significant advan-
theless made a number of interesting observations. When the tage. No such requirement was observed. The compounds
moiety on the carbonyl side of the molecule is an electron-rich that yielded greater than two-fold activation included neutral
group (aromatic ring with electron-rich substituent attached or or electron-rich groups on the carbonyl side of the molecule:
naphthalene), the molecule is typically an activator. About half hydrogen (3, 36, 53), naphthalene (41, 42), methyl (8, 21), or
of the compounds (14 out of 27) with electron-rich substitu- methoxy (27, 32, 35) groups. Interestingly, almost every one
ents were activators and the three best compounds (21, 42, 43) of these ten compounds had a different group on the alkene
in this particular set were all better than 0.1µm GW-1929 (1). side: methoxy (3, 36), n-butoxy (8, 27), trifluoromethyl (21),
Interestingly, four of the five naphthalene compounds (series hydrogen (32), nitro (35), methyl (41), chloro (42), and pyrrole
B) were part of this group suggesting a special feature inher- (53). This observation again suggests that the nature of the
ent to this functionality. It is also noteworthy that compounds alkene side of the molecule is less important than the group or
containing the thiophene, furan, or pyridine moiety (series C) substituent present on the carbonyl side.
failed to activate the PPARγ LBD. Comparing this set of com-
Conceptually, our observation that compounds with a va-
pounds to those that have an electron-poor group (aromatic riety of steric and electronic features can activate PPARγ is
ring with electron-withdrawing substituent) attached to the supported by the evidence that the LBDs of PPARγ and other
carbonyl side demonstrated the importance of the electron-rich nuclear receptors are highly flexible and often change their
character of this particular group. Of the 19 compounds with structure to bind to their ligand.10–12) For example, rosigli-
electron-poor groups, only five were considered activators and tazone stabilizes the PPARγ LBD into a single conformation,
none were strong activators.
whereas partial agonists may alter the conformational dynam-
A similar analysis of the group attached to the alkene moi- ics of the receptor by binding in multiple orientations.12) Fur-
ety suggests that the activity of the chalcones and chalcone- thermore, a recent study by Kumari and co-workers in which
like compounds is not influenced as much by this side of the computer-aided virtual screening was used to identify novel
molecule. The set of compounds with an electron-rich group chalcones as candidate PPARγ agonists also lends support to
(30 compounds total; 12 activators; three compounds (3, 41, our observations.13) Several of the top hits in that study were
53) in the overall top five) is similar to the set of compounds chalcones with high molecular weight, including some with
with an electron-poor group (19 compounds total; nine activa- naphthalene-like moieties. According to our data, a wide vari-
tors; two compounds (21, 42) in the overall top five).
ety of chalcones are PPARγ agonists but not all of them have
To see the effect of both groups (carbonyl and alkene sides) high molecular weights. The active site of PPARγ exhibits a
we compared (i) compounds that had electron-rich groups fairly large cavity that could easily house our chalcones with
on both sides, (ii) compounds with electron-poor groups the carbonyl group lined up to hydrogen bond with Ser 289.14)
on both sides, and (iii) compounds with mixed groups. The The fact that most of the naphthalene-containing chalcones are
best results are obtained when compounds have at least one among the top activators suggests that the cavity is well-suited
electron-rich group on either the carbonyl or the alkene side. to accommodate that type of functionality.14) Furthermore,
The compounds that have electron-rich groups on both sides identification of PPARγ agonists in all three series raises the
(22 compounds total) contained 11 activators, three of which possibility that the mixed chalcones with electron poor groups
(3, 41, 53) were better than 0.1µm GW-1929 (1). The set of on the carbonyl side bind less stably to the PPARγ LBD in a
compounds with mixed groups (22 compounds total) had ten “flipped” orientation such that the electron-rich and carbonyl
activators with two (21, 42) better than the positive control moieties still interact with the functionally important residues
(1). The best performers in the mixed set were the compounds but over longer distances, and the alkene side is positioned in
with electron-rich groups attached to the carbonyl side.
the fairly large space towards Glu 343 and Phe 264.

232
Vol. 61, No. 2
All of the chalcones tested in this study are much smaller
(2E)-1-(4-Ethoxyphenyl)-3-(3-methylphenyl)lprop-2-en-1-
than the known PPARγ agonists such as thiazolidinediones, one (4): Recrystallized from ethanol. Yellow crystals, 54%
1
GQ-16 and GW-1929. Thus, we conclude that the flexibility yield, mp 83.0–84.0°C. H-NMR (400MHz, CDCl3) δ: 8.10
of the LBD allows binding of a fairly diverse group of chal- (d, J=15.5Hz, 1H), 8.07–8.01 (m, 2H), 7.69 (dd, J=7.8, 1.5Hz,
cones.12) The size of the tested chalcones also allows this 1H), 7.47 (d, J=15.5Hz, 1H), 7.35–7.27 (m, 1H), 7.23 (dd,
study to be considered as an optimization of a “fragment” J=7.9, 1.8Hz, 2H), 7.01–6.93 (m, 2H), 4.13 (q, J=7.0Hz, 2H),
that binds to a small portion of the PPARγ LBD.13) There is a 1.46 (t, J=7.0Hz, 3H). 13C-NMR (101MHz, CDCl3) δ: 188.70,
growing body of literature that supports the notion that these 162.87, 141.56, 138.24, 134.18, 130.95, 130.87, 130.84, 130.02,
types of fragment hits can be successfully assembled with 126.37, 126.29, 123.07, 114.29, 63.78, 19.90, 14.70. EI-MS m/z:
other fragment hits to generate a lead compound.15)
266.0 (M+); Calcd for C18H18O2, 266.1307.
In summary, a wide variety of chalcones can activate
(2E)-3-(4-Butylphenyl)-1-(4-fluorophenyl)prop-2-en-1-one
PPARγ to varying levels. Our analysis revealed two trends. (5): Recrystallized from aq. ethanol. White crystals, 84%
First, several of the more potent PPARγ activators possessed yield, mp 73.0–74.6°C. 1H-NMR (400MHz, CDCl3) δ:
an electron-rich group on the carbonyl side. Second, naphtha- 8.14–8.02 (m, 2H), 7.83 (d, J=15.7Hz, 1H), 7.58 (d, J=8.1Hz,
lene and the anisyl (methoxybenzene) groups appeared several 2H), 7.49 (d, J=15.6Hz, 1H), 7.26 (d, J=8.1Hz, 2H), 7.23–7.14
times among the top activators. However, our screen of 53 (m, 2H), 2.67 (t, J=7.7Hz, 2H), 1.65 (tt, J=9.1, 6.8Hz, 2H),
varied chalcones failed to identify any strict requirements for 1.39 (dq, J=14.6, 7.3Hz, 2H), 0.96 (t, J=7.3Hz, 3H). 13C-NMR
1
ligand binding, presumably due to the highly flexible PPARγ (101MHz, CDCl3) δ: 188.94, 165.54 (d, JCF=254Hz), 146.26,
3
LBD.12) This poses a significant challenge to the development 145.21, 134.71, 134.68, 132.25, 131.04 (d, JCF=9.2Hz), 129.10,
2
of simple chalcones as novel PPARγ ligands. Nonetheless, our 128.53, 120.62, 115.69 (d, JCF=21.9Hz), 35.64, 33.37, 22.34,
observations suggest that development of larger, complex chal- 13.92. EI-MS m/z: 282.1 (M+); Calcd for C19H19FO, 282.3519.
cones or chalcone-like compounds with an electron rich group
(2E)-3-(4-Butoxyphenyl)-1-(4-fluorophenyl)prop-2-en-1-one
or sterically large groups such as napthyl on the carbonyl side (6): Recrystallized from aq. ethanol. Yellow crystals, 70%
should yield better PPARγ partial agonists.
yield, mp 79.5–80.2°C. 1H-NMR (400MHz, CDCl3) δ:
8.12–7.99 (m, 2H), 7.78 (d, J=15.6Hz, 1H), 7.62–7.54 (m, 2H),
7.37 (d, J=15.6Hz, 1H), 7.20–7.11 (m, 2H), 6.96–6.87 (m,
Experimental
Chemistry GW1929 (1) was obtained from Sigma-Aldrich 2H), 4.00 (t, J=6.5Hz, 2H), 1.78 (ddt, J=8.9, 7.9, 6.4Hz, 2H),
and dissolved in DMSO to a stock concentration of 10mm. 1.60–1.43 (m, 2H), 0.98 (t, J=7.4Hz, 3H). 13C-NMR (101MHz,
1
(E)-Chalcone (2) was obtained from Alfa Aesar and used CDCl3) δ: 188.88, 165.46 (d, JCF=254Hz), 161.43, 145.03,
3
as received. The remaining chalcones were prepared via a 134.88, 134.85, 130.95 (d, JCF=9.2Hz), 130.27, 127.26, 119.07,
2
Claisen-Schmidt condensation using commercially available 115.64 (d, JCF=21.7Hz), 114.97, 67.90, 31.20, 19.21, 13.81.
substituted aldehydes and ketones.16) Analysis of the purified EI-MS m/z: 298.0 (M+); Calcd for C19H19FO2, 298.3513.
1
materials by H-NMR clearly suggested the formation of the
(2E)-1-(4-Fluorophenyl)-3-(4-isopropylphenyl)prop-2-en-1-
(E)-chalcone as shown by the coupling constant (3J=15Hz) one (7): Recrystallized from aq. ethanol. Off-white crystals,
1
1
for the 2 doublets representing the double bond. H (400MHz) 91% yield, mp 73.6–74.5°C. H-NMR (400MHz, CDCl3) δ:
and 13C (101MHz) NMR spectra were obtained with a Bruker 8.10–8.01 (m, 2H), 7.81 (d, J=15.7Hz, 1H), 7.63–7.54 (m, 2H),
Avance 400 spectrometer. Chemical shifts (δ) are reported in 7.46 (d, J=15.6Hz, 1H), 7.31–7.26 (m, 2H), 7.21–7.12 (m, 2H),
ppm relative to tetramethylsilane (TMS) as the internal stan- 2.95 (hept, J=6.9Hz, 1H), 1.27 (d, J=6.9Hz, 6H). 13C-NMR
dard. The mass of the compounds was determined by electron (101MHz, CDCl3) δ: 189.10, 165.68 (d, JCF=254Hz), 152.27,
impact (EI) mass spectrometry using a Hewlett Packard 5917 145.31, 134.85, 134.82, 132.56, 131.18 (d, JCF=9.4Hz), 128.77,
1
3
2
quadrupole mass analyzer connected to a Hewlett Packard 127.27, 120.83, 115.84 (d, JCF=21.7Hz), 34.30, 23.90. EI-MS
5890 Series II gas chromatograph.
m/z: 268.0 (M+); Calcd for C18H17FO, 268.3253.
General Procedure for Preparation of Chalcones
A
(2E)-3-(4-Butoxyphenyl)-1-(4-methylphenyl)prop-2-en-1-
100-mL round bottom flask was charged with the appropriate one (8): Recrystallized from aq. ethanol. Off-white crystals,
1
aldehyde (5.0mmol) and ketone (5.3mmol). The contents were 59% yield, mp 97.8–99.3°C. H-NMR (400MHz, CDCl3) δ:
stirred and 6mL of 95% ethanol was added to the flask. Slow- 7.96–7.89 (m, 2H), 7.78 (d, J=15.6Hz, 1H), 7.62–7.55 (m, 2H),
ly, sodium hydroxide (15m, 0.7mL) was added drop-wise and 7.41 (d, J=15.6Hz, 1H), 7.32–7.26 (m, 2H), 6.95–6.89 (m,
the reaction was continued until the reaction mixture solidi- 2H), 4.00 (t, J=6.5Hz, 2H), 2.43 (s, 3H), 1.78 (ddt, J=8.9,
fied. Afterwards, 20mL of ice water was added and the mix- 7.9, 6.4Hz, 2H), 1.57–1.44 (m, 2H), 0.98 (t, J=7.4Hz, 3H).
ture was stirred until a suspension formed. The crude product 13C-NMR (101MHz, CDCl3) δ: 190.22, 161.37, 144.50, 143.45,
was washed, collected by suction filtration and then recrystal- 136.10, 130.30, 129.39, 128.70, 127.64, 119.77, 115.03, 68.01,
lized from an appropriate solvent. Characterization of known 31.35, 21.80, 19.36, 13.97. EI-MS m/z: 294.1 (M+); Calcd for
1
compounds was done by H-NMR and the data was compared C20H22O2, 294.3875.
to literature values; new compounds were characterized by
(2E)-3-(3-Fluorophenyl)-1-(4-fluorophenyl)prop-2-en-1-one
1
1H- and 13C-NMR, EI-MS, and melting point (uncorrected).
(9)18): H-NMR (400MHz, CDCl3) δ: 8.13–8.01 (m, 2H), 7.76
(2E)-3-(2-Methoxyphenyl)-1-phenylprop-2-en-1-one
(3)17): (d, J=15.4Hz, 1H), 7.49 (d, J=15.7Hz, 1H), 7.45–7.37 (m, 2H),
1H-NMR (400MHz, CDCl3) δ: 8.10 (d, J=15.6Hz, 1H), 7.37–7.31 (m, 1H), 7.24–7.15 (m, 2H), 7.12 (ddt, J=8.3, 6.8,
8.00 (d, J=6.8Hz, 2H), 7.62 (dd, J=7.6, 1.2Hz, 1H), 7.61 (d, 2.6Hz, 1H).
J=16.0Hz, 1H), 7.55 (t, J=7.2Hz, 1H), 7.48 (dd, J=7.2, 6.8Hz,
2H), 7.37 (ddd, J=8.8, 7.8, 2.0Hz, 1H), 6.98 (dd, J=7.6, (10)19): 1H-NMR (400MHz, CDCl3) δ: 8.52 (t, J=2.0Hz,
7.4Hz, 1H), 6.93 (d, J=8.4Hz, 1H) 3.90 (s, 3H). 1H), 8.27 (ddd, J=8.3, 2.3, 1.0Hz, 1H), 8.14–8.05 (m, 2H),
(2E)-1-(4-Fluorophenyl)-3-(3-nitrophenyl)prop-2-en-1-one

February 2013
233
7.95–7.89 (m, 1H), 7.85 (d, J=15.7Hz, 1H), 7.63 (d, J=15.7Hz, 2H), 7.44 (d, J=15.7Hz, 1H), 7.30 (dd, J=8.5, 0.7Hz, 2H),
1H), 7.63 (d, 1H, J=8.3Hz), 7.25–7.17 (m, 2H).
7.06–6.97 (m, 2H), 2.43 (s, 3H), 1.40 (s, 9H). 13C-NMR
(2E)-1,3-Bis(4-chlorophenyl)prop-2-en-1-one (11)20)
:
1H- (101MHz, CDCl3) δ: 190.21, 158.14, 144.29, 143.58, 136.00,
NMR (400MHz, CDCl3) δ: 7.99–7.94 (m, 2H), 7.76 (d, J= 129.91, 129.54, 129.43, 128.74, 123.89, 120.81, 79.53, 29.07,
15.6Hz, 1H), 7.61–7.55 (m, 2H), 7.51–7.43 (m, 3H), 7.43–7.37 21.82. EI-MS m/z: 294.0 (M+); Calcd for C20H22O2, 294.3875.
(m, 2H).
(2E)-3-(4-Butoxyphenyl)-1-(4-chlorophenyl)prop-2-en-1-one
(2E)-3-(4-Chlorophenyl)-1-(3-methoxyphenyl)prop-2-en-1- (23): Recrystallized from ethanol. Yellow crystals, 36% yield,
1
one (12)21): H-NMR (400MHz, CDCl3) δ: 7.74 (d, J=15.7Hz, mp 96.0–99.3°C. 1H-NMR (400MHz, CDCl3) δ: 8.03–7.90
1H), 7.63–7.50 (m, 4H), 7.47 (dd, J=15.7, 0.7Hz, 1H), (m, 2H), 7.79 (d, J=15.6Hz, 1H), 7.64–7.53 (m, 2H), 7.52–7.42
7.44–7.34 (m, 3H), 7.16–7.10 (m, 2H), 3.87 (s, 3H).
(m, 2H), 7.35 (d, J=15.6Hz, 1H), 6.99–6.88 (m, 2H), 4.01 (t,
(2E)-3-(3-Nitrophenyl)-1-(4-nitrophenyl)prop-2-en-1-one J=6.5Hz, 2H), 1.86–1.73 (m, 2H), 1.50 (dq, J=14.8, 7.4Hz,
1
(13)22): H-NMR (400MHz, CDCl3) δ: 8.54 (dd, J=2.3, 1.7Hz, 2H), 0.99 (t, J=7.4Hz, 3H). 13C-NMR (101MHz, CDCl3) δ:
1H), 8.43–8.36 (m, 2H), 8.31 (ddd, J=8.2, 2.3, 1.0Hz, 1H), 189.39, 161.65, 145.50, 139.05, 137.00, 130.48, 129.96, 129.00,
8.23–8.16 (m, 2H), 7.98–7.93 (m, 1H), 7.90 (d, J=15.7Hz, 1H), 127.33, 119.14, 115.11, 68.06, 31.33, 19.35, 13.97. EI-MS m/z:
7.70–7.58 (m, 2H).
315.0 (M+); Calcd for C19H19ClO2, 314.8059.
(2E)-3-(4-Chlorophenyl)-1-(3-nitrophenyl)prop-2-en-1-one
(2E)-3-(4-tert-Butylphenyl)-1-(4-chlorophenyl)prop-2-en-1-
1
(14)23): H-NMR (400MHz, CDCl3) δ: 8.84 (ddd, J=2.2, 1.7, one (24): Recrystallized from ethanol. White crystals, 45%
0.5Hz, 1H), 8.46 (ddd, J=8.2, 2.3, 1.1Hz, 1H), 8.35 (ddd, yield, mp 107.9–110.0°C. 1H-NMR (400MHz, DMSO-d6)
J=7.8, 1.7, 1.1Hz, 1H), 7.85 (d, J=15.6Hz, 1H), 7.73 (t, δ: 8.21–8.13 (m, 2H), 7.87 (d, J=15.6Hz, 1H), 7.84–7.78 (m,
J=8.0Hz, 1H), 7.66–7.58 (m, 2H), 7.51 (d, J=15.7Hz, 1H), 2H), 7.74 (d, J=15.6Hz, 1H), 7.68–7.61 (m, 2H), 7.52–7.45
7.47–7.40 (m, 2H).
(m, 2H), 1.31 (s, 9H). 13C-NMR (101MHz, CDCl3) δ: 189.48,
(2E)-3-(4-Fluorophenyl)-1-(3-nitrophenyl)prop-2-en-1-one 154.62, 145.51, 139.22, 136.82, 132.10, 130.03, 129.06, 128.55,
(15): Recrystallized from chloroform. Brown crystals, 66% 126.14, 120.88, 35.13, 31.30. EI-MS m/z: 299.0 (M+); Calcd for
yield, mp 165.0–167.5°C. 1H-NMR (400MHz, CDCl3) δ: C19H19ClO, 298.8066.
8.84 (dd, J=2.3, 1.7Hz, 1H), 8.45 (ddd, J=8.2, 2.3, 1.1Hz,
(2E)-3-(4-tert-Butoxyphenyl)-1-(4-chlorophenyl)prop-2-
1H), 8.35 (ddd, J=7.7, 1.7, 1.1Hz, 1H), 7.87 (d, J=15.6Hz, en-1-one (25): Recrystallized from ethanol. Yellow crystals,
1
1H), 7.77–7.63 (m, 3H), 7.47 (d, J=15.7Hz, 1H), 7.20–7.10 42% yield, mp 76.0–79.0°C. H-NMR (400MHz, CDCl3) δ:
(m, 2H). 13C-NMR (101MHz, CDCl3) δ: 187.94, 164.61 (d, 8.00–7.91 (m, 2H), 7.79 (d, J=15.6Hz, 1H), 7.61–7.52 (m,
3
1JCF=253Hz), 145.59, 139.59, 134.22, 130.89 (d, JCF=8.7Hz), 2H), 7.51–7.44 (m, 2H), 7.38 (d, J=15.6Hz, 1H), 7.07–6.99
130.77 (d, JCF=3.3Hz), 130.11, 127.27, 123.39, 120.50 (d, (m, 2H), 1.40 (s, 9H). 13C-NMR (101MHz, CDCl3) δ: 189.38,
2
JCF=2.2Hz), 116.51 (d, JCF=22.1Hz). EI-MS m/z: 271.0 (M+); 158.49, 145.28, 139.17, 135.84, 130.00, 129.71, 129.53, 129.04,
Calcd for C15H10FNO3, 271.2431.
(2E)-1-(4-Chlorophenyl)-3-(4-fluorophenyl)prop-2-en-1-one C19H19ClO2, 314.8059.
123.82, 120.16, 79.65, 29.07. EI-MS m/z: 314.9 (M+); Calcd for
1
(16)24): H-NMR (400MHz, CDCl3) δ: 7.99–7.93 (m, 2H), 7.78
(d, J=15.6Hz, 1H), 7.68–7.60 (m, 2H), 7.51–7.45 (m, 2H), 7.41 one (26)28): H-NMR (400MHz, CDCl3) δ: 8.00–7.92 (m, 2H),
(d, J=15.7Hz, 1H), 7.16–7.08 (m, 2H). 7.81 (d, J=15.7Hz, 1H), 7.62–7.55 (m, 2H), 7.51–7.40 (m, 3H),
(2E)-1-(4-Chlorophenyl)-3-(4-nitrophenyl)prop-2-en-1-one 7.32–7.27 (m, 2H), 2.95 (p, J=6.9Hz, 1H), 1.28 (d, J=6.9Hz,
(17)25) 1H-NMR (400MHz, CDCl3) δ: 8.33–8.26 (m, 2H), 6H).
(2E)-1-(4-Chlorophenyl)-3-(4-isopropylphenyl)prop-2-en-1-
1
:
8.02–7.96 (m, 2H), 7.83 (d, J=15.8Hz, 1H), 7.82–7.77 (m, 2H),
7.60 (d, J=15.7Hz, 1H), 7.54–7.48 (m, 2H).
(2E)-3-(4-Butoxyphenyl)-1-(3-methoxyphenyl)prop-2-en-1-
one (27): Recrystallized from ethanol. Yellow crystals, 51%
1
(2E)-3-(4-Nitrophenyl)-1-(4-methylphenyl)prop-2-en-1-one yield, mp 114.0–116.0°C. H-NMR (400MHz, CDCl3) δ: 7.79
1
(18)25): H-NMR (400MHz, CDCl3) δ: 8.32–8.25 (m, 2H), 7.95 (d, J=15.6Hz, 1H), 7.63–7.56 (m, 3H), 7.54 (dd, J=2.6, 1.5Hz,
(d, J=8.2Hz, 2H), 7.86–7.75 (m, 3H), 7.65 (d, J=15.8Hz, 1H), 1H), 7.44–7.35 (m, 2H), 7.12 (ddd, J=8.2, 2.7, 0.9Hz, 1H),
7.33 (d, J=8.1Hz, 2H), 2.46 (s, 1H).
(2E)-1-(4-Methoxyphenyl)-3-(4-nitrophenyl)prop-2-en-1-one (ddt, J=9.0, 7.9, 6.3Hz, 2H), 1.59–1.42 (m, 2H), 0.99 (t, J=
(19)25) 1H-NMR (400MHz, CDCl3) δ: 8.31–8.25 (m, 2H), 7.4Hz, 3H). 13C-NMR (101MHz, CDCl3) δ: 190.47, 161.50,
8.09–8.02 (m, 2H), 7.86–7.75 (m, 3H), 7.65 (d, J=15.7Hz, 1H), 160.02, 145.00, 140.12, 130.39, 129.64, 127.53, 121.10, 119.81,
6.96–6.88 (m, 2H), 4.01 (t, J=6.5Hz, 2H), 3.88 (s, 3H), 1.79
:
7.05–6.97 (m, 2H), 3.91 (s, 3H).
119.19, 115.08, 112.97, 68.04, 55.64, 31.35, 19.37, 13.98. EI-MS
(2E)-3-(4-Chlorophenyl)-1-(4-methylphenyl)prop-2-en-1-one m/z: 310.0 (M+); Calcd for C20H22O3, 310.3869.
1
(20)26): H-NMR (400MHz, CDCl3) δ: 7.97–7.90 (m, 2H), 7.75
(2E)-3-(4-Butoxyphenyl)-1-(4-nitrophenyl)prop-2-en-1-one
(d, J=15.7Hz, 1H), 7.61–7.55 (m, 2H), 7.51 (d, J=15.7Hz, 1H), (28)29)
:
1H-NMR (400MHz, CDCl3) δ: 8.39–8.31 (m, 2H),
7.43–7.36 (m, 2H), 7.35–7.28 (m, 2H), 2.44 (s, 3H).
(2E)-1-(4-Methylphenyl)-3-(3-(trifluoromethyl)phenyl)- 7.35 (d, J=15.6Hz, 1H), 6.99–6.90 (m, 2H), 4.02 (t, J=6.5Hz,
prop-2-en-1-one (21)27) 1H-NMR (400MHz, CDCl3) δ: 2H), 1.87–1.72 (m, 2H), 1.56–1.44 (m, 2H), 0.99 (t, J=7.4Hz,
8.17–8.08 (m, 2H), 7.82 (d, J=15.6Hz, 1H), 7.65–7.56 (m, 2H),
:
7.99–7.92 (m, 2H), 7.89 (s, 1H), 7.81 (d, J=15.7Hz, 2H), 7.66 3H).
(d, J=7.8Hz, 1H), 7.59 (d, J=15.7Hz, 1H), 7.55 (d, J=7.8Hz,
(2E)-3-(4-tert-Butoxyphenyl)-1-(4-nitrophenyl)prop-2-en-1-
one (29): Recrystallized from ethanol. Orange crystals,
(2E)-3-(4-tert-Butoxyphenyl)-1-(4-methylphenyl)prop-2- 12% yield, mp 59.6–60.7°C. H-NMR (400MHz, CDCl3) δ:
en-1-one (22): Recrystallized from ethanol. White crystals, 8.40–8.31 (m, 2H), 8.18–8.09 (m, 2H), 7.82 (d, J=15.6Hz,
35% yield, mp 90.0–93.5°C. 1H-NMR (400MHz, CDCl3) 1H), 7.63–7.55 (m, 2H), 7.38 (d, J=15.6Hz, 1H), 7.09–7.01
δ: 7.97–7.87 (m, 2H), 7.78 (d, J=15.7Hz, 1H), 7.61–7.51 (m, (m, 2H), 1.42 (s, 9H). 13C-NMR (101MHz, CDCl3) δ: 189.17,
1H), 7.33 (ddd, J=7.5, 1.3, 0.7Hz, 2H), 2.45 (s, 3H).
1

234
Vol. 61, No. 2
159.03, 150.12, 146.77, 143.51, 130.01, 129.48, 129.00, 123.97, 256.7268.
123.70, 119.88, 79.80, 29.08. EI-MS m/z: 324.9 (M+); Calcd for
C19H19NO4, 325.5284.
(2E)-1-Naphthalen-2-yl-3-(4-methylphenyl)prop-2-en-1-one
1
(41)32): H-NMR (400MHz, CDCl3) δ: 8.52 (s, 1H), 8.08 (dd,
(2E)-3-(4-Butoxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1- J=8.8, 0.8Hz, 1H), 7.98 (d, J=8.4Hz, 1H), 7.92 (d, J=8.8Hz,
1
one (30)29): H-NMR (400MHz, DMSO-d6) δ: 8.19–8.12 (m, 1H), 7.88 (d, J=8.0Hz, 1H), 7.84 (d, J=16.0Hz, 1H), 7.63 (d,
2H), 7.87–7.75 (m, 3H), 7.67 (d, J=15.5Hz, 1H), 7.12–7.05 (m, J=16.0Hz, 1H), 7.60–7.53 (m, 4H), 7.23 (d, J=6.4Hz, 2H),
2H), 7.04–6.97 (m, 2H), 4.04 (t, J=6.5Hz, 2H), 3.87 (s, 3H), 2.39 (s, 3H).
1.78–1.65 (m, 2H), 1.52–1.37 (m, 2H), 0.94 (t, J=7.4Hz, 3H).
(2E)-3-(4-Chlorophenyl)-1-naphthalen-2-yl-prop-2-en-1-one
(2E)-3-(4-Butylphenyl)-1-(4-chlorophenyl)prop-2-en-1-one (42)32): H-NMR (400MHz, CDCl3) δ: 8.54 (s, 1H), 8.07 (dd,
(31): Recrystallized from aq. ethanol. White crystals, 42% J=8.8, 1.6Hz, 1H), 8.01 (d, J=8.0Hz, 1H), 7.95 (d, J=8.0Hz,
yield, mp 93.3–94.0°C. 1H-NMR (400MHz, CDCl3) δ: 1H), 7.91 (d, J=8.0Hz, 1H), 7.83 (d, J=16.0Hz, 1H), 7.67 (d,
8.00–7.93 (m, 2H), 7.81 (d, J=15.7Hz, 1H), 7.60–7.53 (m, J=16.0Hz, 1H), 7.63 (d, J=8.0Hz, 2H), 7.61–7.56 (m, 2H),
2H), 7.51–7.40 (m, 3H), 7.24 (d, J=8.1Hz, 2H), 2.70–2.60 (m, 7.42 (d, J=8.0Hz, 2H).
1
2H), 1.68–1.57 (m, 2H), 1.44–1.30 (m, 2H), 0.94 (t, J=7.3Hz,
(2E)-1-Naphthalen-2-yl-3-(2-nitrophenyl)-prop-2-en-1-one
3H). 13C-NMR (101MHz, CDCl3) δ: 189.45, 146.52, 145.66, (43)32): 1H-NMR (400MHz, CDCl3) δ: 8.57 (s, 1H), 8.20
139.21, 136.83, 132.33, 130.02, 129.26, 129.05, 128.72, 120.70, (d, J=16.0Hz, 1H), 8.11–8.09 (m, 2H), 8.03 (d, J=8.0Hz,
35.79, 33.51, 22.49, 14.07. EI-MS m/z: 299.0 (M+); Calcd for 1H), 7.97 (d, J=8.0Hz, 1H), 7.91 (d, J=8.0Hz, 1H), 7.80 (d,
C19H19ClO, 298.8065.
J=8.0Hz, 1H), 7.72 (dd, J=8.0, 8.0Hz, 1H), 7.65–7.52 (m, 3H),
7.45 (d, J=16.0Hz, 1H).
(2E)-1-Naphthalen-2-yl-3-(4-nitrophenyl)-prop-2-en-1-one
(2E)-1-(4-Methoxyphenyl)-3-phenylprop-2-en-1-one (32)30)
:
1H-NMR (400MHz, CDCl3) δ: 8.10–8.00 (m, 2H), 7.81 (d,
J=15.6Hz, 1H), 7.69–7.61 (m, 2H), 7.55 (d, J=15.7Hz, 1H), (44)32): 1H-NMR (400MHz, CDCl3) δ: 8.56 (s, 1H), 8.31
7.42 (dd, J=5.1, 2.0Hz, 2H), 7.03–6.96 (m, 2H), 3.90 (s, 3H).
(2E)-3-(3-Methoxyphenyl)-1-(4-methylphenyl)prop-2-en-1- J=8.0Hz, 1H), 7.98–7.79 (m, 6H), 7.66–7.58 (m, 2H).
(d, J=8.0Hz, 2H), 8.12 (dd, J=12.0, 0.8Hz, 1H), 8.02 (d,
1
one (33)31): H-NMR (400MHz, CDCl3) δ: 7.97–7.90 (m, 2H),
(2E)-3-(3-Bromophenyl)-1-naphthalen-2-yl-prop-2-en-1-one
7.77 (d, J=15.7Hz, 1H), 7.51 (d, J=15.7Hz, 1H), 7.37–7.28 (45)32): H-NMR (400MHz, CDCl3) δ: 8.55 (s, 1H), 8.11 (dd,
1
(m, 3H), 7.26–7.22 (m, 1H), 7.16 (dd, J=2.5, 1.7Hz, 1H), 6.97 J=8.0, 0.1Hz, 1H), 8.02 (d, J=8.0Hz, 1H), 7.97–7.90 (m, 2H),
(ddd, J=8.2, 2.6, 1.0Hz, 1H), 3.86 (s, 3H), 2.44 (s, 3H).
(2E)-1,3-Bis(4-methoxyphenyl)prop-2-en-1-one (34)24)
NMR (400MHz, CDCl3) δ: 8.08–8.00 (m, 2H), 7.78 (d, J=
15.6Hz, 1H), 7.65–7.56 (m, 2H), 7.43 (d, J=15.6Hz, 1H), (46)33): H-NMR (400MHz, CDCl3) δ: 7.835 (d, J=4.0Hz, 1H),
7.02–6.90 (m, 4H), 3.89 (s, 3H), 3.86 (s, 3H). 7.82 (d, J=15.2Hz, 1H), 7.65 (dd, J=4.8, 0.8Hz, 1H), 7.59
7.86 (brs, 1H), 7.80 (d, J=16.0Hz, 1H), 7.69 (d, J=16.0Hz,
1H- 1H), 7.65–7.55 (m, 4H), 7.33 (dd, J=8.0, 6.0Hz, 1H).
:
(2E)-3-(4-Methoxyphenyl)-1-thiophen-2-yl-prop-2-en-1-one
1
(2E)-1-(4-Methoxyphenyl)-3-(3-nitrophenyl)prop-2-en-1-one (d, J=8.8Hz, 2H), 7.29 (d, J=15.2Hz, 1H), 7.162 (dd, J=5.2,
1
(35)30): H-NMR (400MHz, CDCl3) δ: 8.52 (dd, J=2.3, 1.7Hz, 0.8Hz, 1H), 6.93 (d, J=8.8Hz, 2H), 3.84 (s, 3H).
1H), 8.25 (ddd, J=8.2, 2.2, 1.0Hz, 1H), 8.12–8.03 (m, 2H),
7.94–7.88 (m, 1H), 7.83 (d, J=15.6Hz, 1H), 7.67 (d, J=15.6Hz, NMR (400MHz, CDCl3) δ: 7.87 (d, J=3.60Hz, 1H), 7.86 (d,
(2E)-3-Phenyl-1-thiophen-2-yl-prop-2-en-1-one (47)34) 1H-
:
1H), 7.61 (t, J=8.0Hz, 1H), 7.06–6.98 (m, 2H), 3.91 (s, 3H).
J=16.0Hz, 1H), 7.69 (dd, J=4.8, 0.80Hz, 1H), 7.66–7.64 (m,
2H), 7.45–7.41 (m, 4H), 7.43 (d, J=16.0Hz), 7.19 (dd, J=4.8,
(2E)-3-(4-Methoxyphenyl)-1-phenylprop-2-en-1-one (36)20)
:
1H-NMR (400MHz, CDCl3) δ: 8.07–7.97 (m, 2H), 7.79 (d, 4.8Hz, 1H).
J=15.7Hz, 1H), 7.66–7.54 (m, 3H), 7.54–7.47 (m, 2H), 7.42 (d,
J=15.7Hz, 1H), 6.99–6.90 (m, 2H), 3.86 (s, 3H).
(2E)-3-Furan-2-yl-1-(4-methoxyphenyl)-prop-2-en-1-one
1
(48)35): H-NMR (400MHz, CDCl3) δ: 8.03 (d, J=8.8Hz, 2H),
(2E)-1-(4-Methylphenyl)-3-phenylprop-2-en-1-one
(37)26)
:
7.56 (d, J=16.0Hz, 1H), 7.53–7.48 (m, 1H), 7.45 (d, J=16.0Hz,
1H-NMR (400MHz, CDCl3) δ: 7.98–7.91 (m, 2H), 7.81 (d, 1H), 6.96 (d, J=8.8Hz, 2H), 6.68 (d, J=4.0Hz, 1H), 6.51–6.47
J=15.7Hz, 1H), 7.69–7.61 (m, 2H), 7.54 (d, J=15.7Hz, 1H), (m, 1H), 3.87 (s, 3H).
7.42 (dd, J=5.0, 2.0Hz, 3H), 7.34–7.28 (m, 2H), 2.44 (s, 3H).
(2E)-3-(4-Ethoxyphenyl)-1-(pyridin-2-yl)prop-2-en-1-one
(2E)-3-(3-Methoxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1- (49): Recrystallized from ethanol. Dark green crystals, 39%
one (38)31): 1H-NMR (400MHz, CDCl3) δ: 8.09–8.00 (m, yield, mp 81.0–83.0°C. 1H-NMR (400MHz, CDCl3) δ: 8.74
2H), 7.77 (d, J=15.6Hz, 1H), 7.52 (d, J=15.7Hz, 1H), 7.34 (ddd, J=4.8, 1.7, 0.9Hz, 1H), 8.22–8.12 (m, 2H), 7.92 (d,
(dd, J=8.2, 7.6Hz, 1H), 7.26–7.21 (m, 1H), 7.18–7.13 (m, 1H), J=16.0Hz, 1H), 7.87 (td, J=7.7, 1.7Hz, 1H), 7.72–7.63 (m, 2H),
7.05–6.93 (m, 3H), 3.90 (s, 3H), 3.86 (s, 3H).
(2E)-3-(4-Chlorophenyl)-1-phenylprop-2-en-1-one
7.48 (ddd, J=7.5, 4.7, 1.3Hz, 1H), 6.97–6.88 (m, 2H), 4.09 (q,
(39)20)
:
J=7.0Hz, 2H), 1.44 (t, J=7.0Hz, 3H). 13C-NMR (101MHz,
1H-NMR (400MHz, CDCl3) δ: 8.05–7.98 (m, 2H), 7.76 CDCl3) δ: 189.55, 161.32, 154.69, 148.93, 144.94, 137.11,
(d, J=15.7Hz, 1H), 7.64–7.55 (m, 3H), 7.55–7.47 (m, 3H), 130.82, 127.96, 126.83, 123.01, 118.55, 114.95, 63.79, 14.89.
7.44–7.37 (m, 2H).
(2E)-1-(4-Chlorophenyl)-3-(3-methylphenyl)prop-2-en-1-one
EI-MS m/z: 253.0 (M+); Calcd for C16H15NO2, 253.1103.
(2E)-3-(4-Butoxyphenyl)-1-(pyridin-2-yl)prop-2-en-1-one
(40): Recrystallized from ethanol. Yellow crystals, 32% yield, (50): Recrystallized from aq. ethanol. Yellow crystals, 36%
1
1
mp 116.0–118.3°C. H-NMR (400MHz, CDCl3) δ: 8.00–7.94 yield, mp 64.0–66.1°C. H-NMR (400MHz, CDCl3) δ: 8.73
(m, 2H), 7.79 (d, J=15.7Hz, 1H), 7.51–7.42 (m, 5H), 7.32 (dd, (ddt, J=4.8, 1.5, 0.8Hz, 1H), 8.23–8.12 (m, 2H), 7.92 (d,
J=8.8, 7.1Hz, 1H), 7.26–7.21 (m, 1H), 2.41 (s, 3H). 13C-NMR J=16.0Hz, 1H), 7.86 (ddd, J=7.8, 7.3, 1.7Hz, 1H), 7.71–7.65
(101MHz, CDCl3) δ: 189.37, 145.73, 139.31, 138.84, 136.72, (m, 2H), 7.47 (ddd, J=7.5, 4.7, 1.3Hz, 1H), 6.97–6.88 (m, 2H),
134.80, 131.76, 130.07, 129.24, 129.07, 129.04, 125.92, 121.46, 4.01 (t, J=6.5Hz, 2H), 1.86–1.74 (m, 2H), 1.59–1.44 (m, 2H),
100.13, 21.49. EI-MS m/z: 257.0 (M+); Calcd for C16H13ClO, 0.98 (t, J=7.4Hz, 3H). 13C-NMR (101MHz, CDCl3) δ: 189.56,

February 2013
235
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123.01, 118.47, 114.97, 68.01, 31.36, 19.36, 13.97. EI-MS m/z:
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(2E)-3-(4-Butoxyphenyl)-1-(furan-2-yl)prop-2-en-1-one (51):
Recrystallized from aq. ethanol. White crystals, 50% yield,
mp 84.0–85.4°C. 1H-NMR (400MHz, CDCl3) δ: 7.85 (d,
J=15.7Hz, 1H), 7.67–7.55 (m, 3H), 7.37–7.28 (m, 2H),
6.96–6.88 (m, 2H), 6.58 (dd, J=3.6, 1.7Hz, 1H), 4.01 (t,
J=6.5Hz, 2H), 1.85–1.73 (m, 2H), 1.56–1.42 (m, 2H), 0.98 (t,
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Calcd for C17H18O3, 270.3230.
(2E,4E)-1,5-Diphenylpenta-2,4-dien-1-one (52)19): 1H-NMR
(400MHz, CDCl3) δ: 8.01–7.94 (m, 2H), 7.66–7.54 (m, 2H),
7.54–7.45 (m, 4H), 7.43–7.29 (m, 3H), 7.10 (d, J=14.9Hz, 1H),
7.06–7.00 (m, 2H).
(2E)-1-Phenyl-3-(1H-pyrrol-2-yl)prop-2-en-1-one
(53)36)
:
1H-NMR (400MHz, CDCl3) δ: 9.22 (s, 1H), 8.02–7.96 (m,
2H), 7.78 (d, J=15.6Hz, 1H), 7.61–7.51 (m, 1H), 7.51–7.42 (m,
2H), 7.19 (d, J=15.5Hz, 1H), 7.00 (td, J=2.7, 1.4Hz, 1H), 6.72
(ddd, J=3.8, 2.6, 1.3Hz, 1H), 6.34 (dt, J=3.7, 2.5Hz, 1H).
1,5-Diphenyl-3-(pyridine-2-yl)pentane-1,5-dione
(54)37)
:
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3.66 (dd, J=17.3, 7.7Hz, 2H), 3.45 (dd, J=17.3, 6.0Hz, 2H).
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Acknowledgements This research was supported by
CSUPERB, the State of California, and in part by a Grant
to California State University, Fullerton from the Howard
Hughes Medical Institute through the Student Research and
Broadening Access to Science program (Grant #52006284).
We thank Brenda Hinh and Kavita Amin for assistance with
the preparation of some of the chalcone derivatives.
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