Synthesis, in vitro and in silico evaluation of diaryl heptanones as potential 5LOX enzyme inhibitors

Article abstract of DOI:10.1016/j.bioorg.2018.06.015

A new series of diaryl heptanones (12a-q) were synthesized and their structures were confirmed by its ¹H, ¹³C NMR and Mass spectral data. These analogs were evaluated for their anti-oxidant activity and potential to inhibit 5-lipoxygenase. Compounds 12k and 12o showed potent in vitro 5-lipoxygenase enzyme inhibitory activity with IC₅₀ values of 22.2, 21.5 μM, which are comparable to curcumin (24.4 μM). Further they also have shown significant antioxidant activity. Molecular docking studies clearly showed correlation between binding energy and potency of these compounds.

Full text of DOI:10.1016/j.bioorg.2018.06.015

Accepted Manuscript
Synthesis, in vitro and in silico Evaluation of Diaryl Heptanones as Potential
5LOX Enzyme Inhibitors
Bharani Meka, Suryachandra Rao Ravada, Muthyala Murali Krishna Kumar,
Kurre Purna Nagasree, Trimurtulu Golakoti
PII:
S0045-2068(18)30324-9
DOI:
https://doi.org/10.1016/j.bioorg.2018.06.015
YBIOO 2395
Reference:
Bioorganic Chemistry
To appear in:
Received Date:
Revised Date:
Accepted Date:
5 April 2018
6 June 2018
7 June 2018
Please cite this article as: B. Meka, S.R. Ravada, M.M. Krishna Kumar, K.P. Nagasree, T. Golakoti, Synthesis, in
vitro and in silico Evaluation of Diaryl Heptanones as Potential 5LOX Enzyme Inhibitors, Bioorganic Chemistry
(2018), doi: https://doi.org/10.1016/j.bioorg.2018.06.015
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Synthesis, in vitro and in silico Evaluation of Diaryl Heptanones as
Potential 5LOX Enzyme Inhibitors
Bharani Mekaa, Suryachandra Rao Ravadaa, Muthyala Murali Krishna Kumarb, Kurre Purna
Nagasreeb, Trimurtulu Golakotia*
aLailaImpex R&D Center, Unit-I, Phase-III, Jawahar Auto Nagar, Vijayawada-520 007, Andhra
Pradesh, India.
bDepartment of Pharmaceutical Chemistry, AU College of Pharmaceutical Sciences, Andhra
University, Visakhapatnam -530 00, Andhra Pradesh, India.
Abstract: A new series of diaryl heptanones (12a-q) were synthesized and their structures were
1
13
confirmed by its H, C NMR and Mass spectral data. These analogs were evaluated for their
anti-oxidant activity and potential to inhibit 5-lipoxygenase. Compounds 12k and 12o showed
potent in vitro 5-lipoxygenase enzyme inhibitory activity with IC50 values of 22.2, 21.5 μM,
which are comparable to curcumin (24.4 μM). Further they also have shown significant
antioxidant activity. Molecular docking studies clearly showed correlation between binding
energy and potency of these compounds.
Key words: Diarylheptanones, 5-lipoxygenase, anti-inflammatory, anti-oxidant, molecular
docking.
Abbreviations: 5-LOX, 5-lipoxygenase; IBX, iodoxy benzoic acid; DCM, dichloromethane;
LaH, lithium aluminum hydride.
Introduction:
Inflammation is a complex biological response in vascular tissues against the harmful
stimuli, such as pathogens, damaged cells, or irritants [1]. It is a protective mechanism adopted
by the organisms to remove the injurious stimuli and to initiate the healing process. Hence,
inflammation is considered as an essential survival strategy adopted by the body to ward off
major damage. However, inflammation can also lead to a host of diseases, such as hay fever,
atherosclerosis, rheumatoid arthritis and even cancer [2].

In acute inflammation, the cellular phospholipases are activated to break down membrane
phospholipids into arachidonic acid, which in turn is metabolized to inflammatory prostaglandins
and leucotrienes respectively by the enzymes cyclooxygenase (COX) and lipoxygenase (LOX).
The search for inhibitors of these enzymes thus forms the basis for development of new anti-
inflammatory agents. In the enzyme family of cyclooxygenases, inhibition of cyclooxygenase-2
(COX-2) is more desirable. However, recent studies revealed that selective inhibition of COX-2
does reduce inflammation, but causes side effects, particularly those leading to cardiovascular
complications [3]. On the contrary, the inhibition of the 5-lipoxygenase (5-LOX) enzyme of the
alternative pathway of inflammation not only reduces inflammation but also improves cardiac
health by reducing risk of atherosclerosis [4]. The alternative pathway mediated by 5-LOX has
thus become an important target for the development of new anti-inflammatory drugs.
Diarylheptanoids are a class of plant secondary metabolites, which are structurally made
up of two aromatic rings connected by a seven carbon aliphatic chain. There are two major
categories of diarylheptanoids, linear diarylheptanoids and cyclic diarylheptanoids [5-14] were
depicted in figure 1. Several natural and synthetic diarylheptanoid derivatives are known to
possess a broad spectrum of biological activities. Some of them are well known for their anti-
inflammatory, anti-oxidant and anti-cancer potentials [15-22]. Few synthetic methodologies are
reported for diarylheptanoids and structurally related diarylnonanones, which are also reported to
be effective cytotoxic and anti-inflammatory agents [16, 18, 23]. In view of the biological
potential of diarylheptanoids and diarylnonanones, we report herein the synthesis, anti-oxidant
and anti-inflammatory activities of several new diarylheptanoids. The anti-inflammatory activity
of the synthesized compounds was also evaluated in silico using molecular docking studies.

O
O
H3CO
H3CO
H3CO
HO
OCH3
OH
O
O
Curcumin (13)
HO
O
Juglanin A (14)
H3CO
HO
OCH3
OH
HO
HO
O
O
Cyclocurcumin (16)
Acerogenin E (15)
Figure 1: Some of the natural heptanones.
Result and discussion: The synthetic approach for diaryl heptanones summarized in Scheme 2
and Scheme 3 were comprehended based on the disconnection approach as depicted in Scheme
1. Here, the enone intermediate moiety (11) could be the precursor for substituted
diarylheptanone compounds. The disconnection of this precursor between the olefinic carbons 
and  to the keto group leads to 5-(substituted phenyl)-pentanal (9) and commercially available
substituted acetophenone as the most advanced precursors. Further disconnection analysis as
described in Scheme 1 manifested that 5-(substituted phenyl)-pentanal (9) can be produced from
substituted cinnamic acid.
Based on the disconnection approach summarized in Scheme 1 the key intermediate 11a-q of
diarylheptanones synthesis was achieved by adopting the Scheme 2. The intermediates 3-
(substituted-phenyl)-propanoic acid (2a-e) was obtained by the reduction of substituted cinnamic
acid with Zn-Hg amalgam, which were methylated with MeOH/HCl to get 3(substituted-phenyl)-
propnoic acid methyl ester (3a-e). These methyl esters upon reduction with lithium aluminum
hydride followed by mild oxidation with IBX yielded the aldehyde compounds 3-(substituted
phenyl) propan-1-al (5a-e, 72-81 %). The aldehyde compounds 5a-e were treated with
triphenylcarbethoxymethylene phosphorane [24] under modified Wittig reaction conditions to
obtain compounds 5-(substituted-phenyl)-pent-2-en-oic acid ethyl esters 6a-e in good yields (60-
66 %).

O
R5
R1
R2
R3
R6
12a-q
11a-q
R7
R5
R4
R1
O
R2
R3
R6
R4
R7
R1
R4
O
R5
R2
CH2OH
9 a-e
R3
R6
R7
R1
R4
R2
R3
COOH
1a-e
Scheme 1: Retro-synthetic analysis of diarylheptanones (12a-12q)
R4
R3
COOH
Zn-Hg, HCl, THF
R1 2.5h, 79-86%
R4
R3
COOH
SOCl2, MeOH,
3h, 87-90%
R4
R3
COOCH3
R1
R1
R2
R2
2a-e
R2
3a-e
1a-e
1a). R1 = R2 = R3 = R4 = H
LAH, THF,
2.5h, 73-77%
1b). R1 = R2 = R4 = H; R3 = OCH3
1c). R2 = R3 = R4 = H; R1 = OCH3
1d). R1 = R4 = H; R2 = R3 = OCH3
1e). R1 = H; R2 = R3 = R4 = OCH3
R4
CH2OH
R4
R3
CHO
IBX, DMSO
R3
R1
R1
2.5h, 72-81%
R2
4a-e
R2
5a-e
Scheme 2: Synthesis of phenyl propanaldehyde precursors 5a-e.

O
R4
R3
CHO
O
R4
2
OCH2CH3
R4
R3
R1(Ph) P=CH-COOCH CH
3
3
OCH2CH3
Pd/CaCO3, EtOAc
R3
R1
THF, 65°C,
R2
5a-e
R1
7a-e
4-5h, 60-66%
R2
6a-e
2h, RT, 89-91%
R2
LAH, THF, 2h,
RT, 82-88%
R4
R3
CHO
R4
R3
CH2OH
IBX, DMSO, RT
3h, 83-85%
R1
9a-e
R1
R2
R2
8a-e
THF, 10a-d,
65°C, 4h, 46-60%
R4
R2
O
R4
O
R8
R8
R7
Pd/CaCO3, EtOAc
R7
R5
R1
R3
2h, RT, 73-84%
R5
R1
R3
R6
R6
R2
12a-q
11a-q
12a). R1 = R4 = R5 = R6 = R7 = R8 = H; R2 = R3 = OCH3
12b). R1 = R3 = R5 = R6 = R7 = R8 = H; R2 = R4 = OCH3
12c). R1 = R2 = R3 = R4 = R5 = R6 = R8 = H; R7 = OCH3
12d). R2 = R4 = R5 = R6 = R8 = H; R1 = R3 = R7 = OCH3
12e). R2 = R3 = R6 = R7 = R8 = H; R1 = R4 = R5 = OCH3
12f). R1 = R2 = R3 = R4 = R6 = R7 = R8 = H; R5 = OCH3
12g). R1 = R4 = R6 = R7 = R8 = H; R1 = R3 = R5 = OCH3
12h). R1 = R4 = R6 = R7 =R8 = H; R2 = R3 = R5 = OCH3
12i). R2 = R3= R6 = R7 =R8 = H; R1 = R4 = R5 = OCH3
12j). R1 = R2 = R3 = R4 =R5 = R8 = H; R6 = R7 =OCH3
12k). R1 = OH; R2 = R4 = R5 = R8 = H; R3 = R6 = R7 = OCH3
12l). R1 = R4 = R5 = R8 = H; R2 = R3 = R6 = R7 = OCH3
12m). R2= R3 = R5 = R8 = H; R1 = R4 = R6 = R7 = OCH3
12n). R1 = R2 = R3 = R4 = R5 = H; R6 = R7 = R8 = OCH3
12o). R1 = OH; R2 = R4 = R5 = H; R3 = R6 = R7 = R8 = OCH3
12p). R1 = R4 = R5 = H; R2 = R3 = R6 = R7 = R8 = OCH3
12q). R2 = R3 = R5 = H; R1 = R4 = R6 = R7 = R8 = OCH3
R4
O
P(Ph)3
R3
R1
R2
10a-d
10a). R1 = R2 = R3 = R4 = H
10b). R1 = R3 = OCH3; R2 = R4 = H
10c). R2 = R3 = OCH3; R1 = R4= H
10d). R2 = R4 =OCH3; R1 = R3 = H
Scheme 3: Synthesis of diarylheptanones 12a-q.

The compounds 5-(substituted-phenyl)-pent-2-enoic acid ethyl esters (6a-e) were
subjected to catalytic reduction under hydrogen atmosphere with 5% Pd/CaCO3 to obtain ethyl
5-(substituted phenyl)-pentanoates (7a-e) with yields in the range of 89-91%, which upon
reduction with LAH yielded 5-(substituted phenyl)-pentan-1-ol compounds (8a-e) in 82-88%
yield. The compounds 8a-e were treated with IBX in DMSO to obtain 5-(substituted-phenyl)
pentan-1-al compounds (9a-e) in good yields (83 - 85%).
In final condensation, the 5-(substituted-phenyl)-pentan-1-al compounds (9a-e) were
treated with substituted acetophenone phosphoranes 10a-d via modified Wittig reaction to obtain
7-(substituted-phenyl)-1-(substituted-phenyl)-hept-2-ene-1-ones (11a-q) with yields in the range
of 46-60%, which on catalytic hydrogenation with 5% Pd/CaCO3 yielded the corresponding 7-
(substituted-phenyl)-1-(substituted-phenyl)-heptan-1-one compounds (12a-q) in 73-84 % yields.
Biological activities of diarylheptanones:
The synthesized compounds 12a-q were evaluated for their efficacy in inhibiting 5-
lipoxygenase, an enzyme known to be involved in the mediation of inflammation. The analogs
12k and 12o showed potent 5-lipoxygenase inhibition with IC50 values of 22.2 and 21.5 μM
respectively and are comparable with the positive control curcumin (IC50 24.4 μM). Except 12D,
the remaining compounds showed moderate inhibitory activity (IC50) in the range 75-150 μM.
These results clearly showed that 2-hydroxy group on the benzoyl ring is essential for
bioactivity. Further 12k also has shown appreciable anti-oxidant activity (IC50 16.7 μM), when
compared with gallic acid (IC50 13.7 μM). Substitution of either of the benzene rings present in
the heptanone pharmacophore with –OCH3 groups failed to show any influence on bioactivity
profile of these compounds. To have better insight on the inhibitory profile of these compounds,
docking simulations were conducted.

Table 1: In-vitro activities of diarylheptanone analogs 12a-q
5-LOX
Anti-oxidant
S.No Compound inhibition
NBT (IC50µM)
(IC50µM)
1
2
139.9
118.1
145.1
>300
104.2
148.5
115.8
117.3
104.2
134.9
22.22
106.8
96.1
83.3
33.1
12a
12b
3
>300
>300
>300
>300
>300
>300
>300
43.4
12c
4
12d
5
12e
6
12f
7
12g
8
12h
9
12i
10
11
12
13
14
15
16
17
18
19
12j
16.7
12k
>300
36.4
12l
12m
12n
95.4
28.5
21.5
26.1
12o
75.2
>300
>300
13.7
12p
108.4
------
24.4
12q
Gallic acid
Curcumin
------
Docking studies:
Here, the docking simulations were initiated by defining the region containing active site
residues as the receptor site. Partial flexibility was allowed for the amino acids present close to
the active site. The docking simulations were performed with the help of AutoDockVina. In our
computational study, curcumin scored exceptionally well with a score of -11.7 Kcal/mol and it
also showed highest in vitro 5-LOX inhibitory activity (24.4 μM). This compound showed
several interactions with the active site residues His551, Asn555 and nearby lipophilic amino

acids Ala672, Val673. The diketo (or keto-enol) group showed very strong salt-bridge
interactions with Asn426, another important amino acid essential for ligand recognition and its
transit to catalytic site. Docking simulations were also performed with zileuton®, an approved 5-
lox inhibitor. The hydroxyurea moiety showed several interactions with the catalytic site amino
acids Asn555, His551, His373 and the benzothiofuran ring filled the lipophilic pocket of 5-lox
enzyme with a score of -8.9 Kcal/mol. The synthesized compounds were also found to fit very
well into the active site with benzoyl “head” first pose. The tail containing the lipophilic chain
tipped with substituted benzene ring was found to make several lipid-lipid interactions with the
receptor site residues, aiding in further stabilizing the ligand inside the receptor pocket. All the
active compounds are found to interact with at least one histidine present in the catalytic site,
Gln558 and Asn555. Among the synthesized compounds, 12k showed best docking score (-10.8
Kcal) and has shown highest in vitro 5-LOX inhibitory activity followed by 12o (-10.5 Kcal).
The 2-hydroxy group and benzoyl carbonyl showed several interactions with the histidine
residues present in the active site, supporting the bioactivity profile observed for these
compounds. The docking scores for the synthesized compounds and along with their
corresponding 5-LOX inhibition activities are summarized in Table 2. Curcumin as well as the
heptanones did not fit well in the receptor pocket of either COX-I or COX-II (docking scores <8
Kcal/mol) and were often found to dock away from the catalytic site.
One of the reasons for 5-LOX selectivity could be the shape and flexibility of receptor
pocket. In case of 5-LOX, the receptor pocket is relatively large and flexible. The catalytic Fe in
this enzyme is held into place by coordination with side chains of three conserved His residues
(numbered 368, 373 and 551) and the main chain carboxyl group of the C-terminal Ile674 [25]. It
may be also aided in this by the residue Asn 555, which is not close enough to be present in the
actual coordination sphere. Whereas COX-I and COX-II are cytochrome oxidase enzymes with
catalytic iron present in rigid heme ring and the receptor pocket is relatively rigid [26]. This
could be the reason for absence of COX inhibitory activity for curcumin and also heptanones in
this present study.

Figure 02: Docking poses of the compound 12k, Curcumin and zileuton® at the receptor pocket.
Ligand (salmon red), Fe (magenta) and active site residues making polar contacts (light yellow
orange)
Computational studies: The protein X-ray crystal structureof the enzyme 5-LOX (3V99.pdb),
COX-I (3KK6) and COX-II (5KIR.pdb) were obtained from www.rcsb.org. The protein
structures was thoroughly analysed for misalignments, atom clashes and protein breaks. 5-LOX
protein lacked a major loop near the active site. It was repaired by HOMOLOGY modelling
using expasy server (https://swissmodel.expasy.org/) [27] molecular dynamics simulation was
performed
on
the
modelled
protein
by
MDWeb
server
(http://mmb.irbbarcelona.org/MDWeb/index.php) using AMBER forcefield [28]. 3D Ligand
database was prepared using Chemoffice and AutoDock software tools. Protein preparation was
also done using AutoDock tools using default protocol. Docking simulations were performed
with the help of Autodock Vina [29]. The amino acids near the active site were defined as
flexible for optimal interactions. Receptor-ligand interactions were analyzed by PyMol software
[30].
LIGPLOT
interactions
were
plotted
by
using
LigPlot+
software
(http://www.ebi.ac.uk/thornton-srv/software/LIGPLOT/).

Table 2: Results of the docking simulations of synthesized compounds and curcumin
5-LOX
IC50 µM
Compound
Code
Docking score
Kcal/mol
Amino acid interactions
-9.8
139.9
12a
Asn426, Gln364, Leu608, His373
Gln364, His368, Asn555, Leu608,
Ala673
-9.2
118.1
12b
Gln364, Gln558, Lys424, Asn426,
Leu421
-8.7
145.1
12c
-8.9
-7.9
>300
104.2
12d
12e
Asn426, Gln364, His368, Ala673
Glu615, Ala673, Lys174
Gln364, His368, Asn555, Leu608,
Ala673
-9.2
148.5
12f
-8.9
-7.9
-7.9
-8.5
115.8
117.3
104.2
134.9
12g
12h
12i
Asn426, Gln364, His368, Ala673
Glu615, Ala673, Lys174
Glu615, Ala673, Lys174
12j
Glu613, Ala673, His373, Asn555
Ile407, Val176, Val672, His368,
His551, Asn555, Gln558
Ala673, Asn555, Gln558, His368,
Gln364, Lys424, Asn426
Gln364, Gln558, sn426, Asp423,
Leu421
Val672, His551, Asn555, Gln364,
Asn426
Ile407, Val176, Val672, His368,
His551, Asn555, Gln558
Ala673, Gln558, Leu608, His368,
Gln364,
22.2
106.8
96.1
12k
12l
-10.8
-8.5
12m
12n
12o
12p
12q
-8.7
95.4
-8.7
-10.5
21.5
75.2
-9.5
-8.7
Gln364, Gln558, Lys424, Asn426,
Leu421
108.4
Leu421, Trp600, His551, His368,
Asn555, Ala673, Val672, Lys424,
Asn426, Cys419
His551, His373, Asn555, Val176,
Ala673
Curcumin
-11.7
-8.9
24.4
Zileuton®
Not tested

Conclusions
The diarylheptanone analogs were prepared with a view to obtain potent anti-inflammatory
compounds with 5-LOX inhibitory activity and to probe structure activity relationships of diaryl
heptanoids. A total of 17 new compounds were synthesized and screened for in vitro 5-LOX
enzyme inhibition. An attempt was made to investigate selective inhibitory profile of diaryl
heptanoids towards 5-LOX using docking simulations. The studies showed that, diaryl
heptanoids snugly fits the active site of 5-LOX and showed no-fitment at all in the active pockets
of COX-1 and COX-2. Compounds 12k and 12o showed potent in vitro 5-lipoxygenase enzyme
inhibitory activity with IC50 values of 22.2, 21.5 μM, which are comparable to curcumin (24.4
μM). Further they also have shown significant anti-oxidant activity. Molecular docking studies
clearly showed correlation between binding energy and potency of these compounds.
The
compounds containing hydroxyl group adjacent to the keto functional group and also compounds
with few number of methoxy groups exhibited reasonable anti-inflammatory activity.
Experimental:
General experimental procedures: The 1H NMR spectra were recorded on Bruker Avance AV
400 MHz NMR spectrometer and 13C NMR spectra were recorded on Bruker Avance AV 100
MHz NMR spectrometer. Mass studies were performed on LC-MS system equipped with
Agilent 1100 series LC/ MSD detector and 1100 series Agilent HPLC pump. Exact mass was
measured on Water’s Q-Tof instrument. Normal phase silica gel (ACME, 100-200 mesh) was
used for column chromatography. Silica gel pre-coated plates (AlugramSil G/UV254) were used
for thin layer chromatography. The plates were eluted with a solvent system containing
hexane/ethyl acetate (9:1) and visualized by immersing the plate in sulfuric acid/methanol
reagent followed by heating at 110°C. Nitro blue tetrazolium (NBT) was obtained from Sigma
Chemicals (USA). The solvents and other chemicals used were of AR grade and were procured
from Qualigens Fine Chemicals, Mumbai (India).
General procedure for preparation of 3-(substituted phenyl)-propionic acid (2a-e):
A mixture of zinc powder (25 g, 0.384 mol) and mercuric chloride (3.1 g, 0.0114 mol) was
suspended in 100 ml of water in a 250 ml beaker. The mixture was treated with 50 ml of con.
HCl slowly drop wise and after completion of addition, the stirring was continued for 15 min.

The mixture was decanted to separate the solution and the remaining Zn-Hg amalgam was used
for reduction.
To a mixture of substituted cinnamic acid (1a-e, 0.134 mol), THF (150 mL) and 5N HCl (100
mL) was added above freshly prepared Zn-Hg amalgam slowly portion wise. An additional 5N
HCl (50 mL) added and the stirring continued for 2 h. After completion of reaction, as monitored
by TLC hexane/ethyl acetate (8:2), the reaction mixture was poured into water (200 mL) and
extracted with chloroform (2 × 400 mL), The organic layer was washed with brine solution,
dried over Na2SO4 and concentrated. The crude residue was subjected to column
chromatography on silica gel using hexane/ethyl acetate mixtures as eluents. The fractions were
monitored using TLC and pure compound was obtained from the fractions eluted with ethyl
acetate in hexane, 5 % / 95 % (v/v). These fractions were combined and concentrated to obtained
3-(substituted-phenyl)-propionic acids (2a-e) as oily compounds with yields of 79 %-86 %.
3-(Phenyl)-propionic acid (2a): Weight: 16.1 g; % yield: 79.4 %; 1H NMR (CDCl3, 400 MHz): δ
12.2 (1H, s, COOH), 7.34 (2H, t, J = 7.6 Hz, H-3′, 5′), 7.18 (2H, d, J = 7.2 Hz, H-2′, 6′), 7.11
(1H, d, J = 7.2 Hz, H-4′), 2.88 (2H, t, J = 7.2 Hz, H-3), 2.54 (2H, t, J = 7.6 Hz, H-2); 13C NMR
(CDCl3, 100 MHz): δ 178.4 (C=O), 146.2 (C-1′), 132.8 (C-3′, 5′), 132.6 (C-2′, 6′), 122.4 (C-4′),
38.4 (C-2), 32.6 (C-3); LC-MS: m/z 149.3 (M-H)-.
1
3-(4-Methoxy-phenyl)-propionic acid (2b): Weight: 17.4 g; % yield: 86.1 %; H NMR (CDCl3,
400 MHz): δ 12.1 (1H, s, COOH), 7.24 (2H, d, J = 7.6 Hz, H-2′, 6′), 6.88 (2H, d, J = 7.2 Hz, H-
3′, 5′), 3.82 (3H, s, OCH3), 2.89 (2H, t, J = 8.0 Hz, H-3), 2.52 (2H, t, J = 8.0 Hz, H-2); 13C NMR
(CDCl3, 100 MHz): δ 178.8 (C=O), 168.4 (C-4′), 136.3 (C-1′), 132.6 (C-2′, 6′), 118.4 (C-3′, 5′),
55.2 (OCH3), 38.6 (C-2), 33.2 (C-3); LC-MS: m/z 179.2 (M-H)-.
1
3-(2-Methoxy-phenyl)-propionic acid (2c): Weight: 17.2 g; % yield: 85.1 %; H NMR (CDCl3,
400 MHz): δ 11.8 (1H, s, COOH), 7.21 (1H, dd, J = 7.6, 2.4 Hz, H-6′), 7.08 (1H, td, J = 8.0, 3.2
Hz, H-4′), 6.92 (1H, td, J = 8.0, 3.2 Hz, H-5′), 6.86 (1H, dd, J = 7.6, 2.4 Hz, H-3′), 3.78 (3H, s,
13
OCH3), 2.92 (2H, t, J = 7.2 Hz, H-3), 2.62 (2H, t, J = 8.0 Hz, H-2); C NMR (CDCl3, 100
MHz): δ 178.6 (C=O), 166.4 (C-2′), 132.8 (C-6′), 130.8 (C-4′), 128.4 (C-1′), 122.8 (C-5′), 118.6
(C-3′), 55.8 (OCH3), 38.6 (C-2), 24.8 (C-3); LC-MS: m/z 203.5 (M+Na)+.
1
3-(3,4-Dimethoxy-phenyl)-propionic acid (2d): Weight: 16.8 g; % yield: 83.3 %; H NMR
(CDCl3, 400 MHz): δ 11.8 (1H, s, COOH), 6.78 (1H, d, J = 7.6 Hz, H-5′), 6.72 (1H, dd, J = 7.6,
3.2 Hz, H-6′), 6.58 (1H, d, J = 3.2 Hz, H-2′), 3.78 (3H, s, OCH3), 3.72 (3H, s, OCH3), 2.88 (2H,

t, J = 7.6 Hz, H-3), 2.66 (2H, t, J = 7.6 Hz, H-2); 13C NMR (CDCl3, 100 MHz): δ 178.2 (C=O),
156.4 (C-3′), 154.2 (C-4′), 138.4 (C-1′), 128.6 (C-6′), 118.6 (C-5′), 116.8 (C-2′), 55.8 (OCH3),
55.6 (OCH3), 38.9 (C-2), 30.9 (C-3); LC-MS: m/z 233.3 (M+Na)+.
1
3-(3, 4, 5-Tri methoxy-phenyl)-propionic acid (2e): Weight: 16.5 g; % yield: 81.8 %; H NMR
(CDCl3, 400 MHz): δ 11.8 (1H, s, COOH), 6.12 (2H, s, H-2′, 6′), 3.73 (9H, s, OCH3), 2.98 (2H,
t, J = 7.6 Hz, H-3), 2.54 (2H, t, J = 7.6 Hz, H-2); 13C NMR (CDCl3, 100 MHz): δ 178.2 (C=O),
156.4 (C-3′, 5′), 138.9 (C-4′), 134.8 (C-1′), 108.8 (C-2′, 6′), 55.8 (OCH3), 55.6 (OCH3), 55.4
(OCH3), 38.4 (C-2), 31.8 (C-3); LC-MS: m/z 263.2(M+Na)+.
General procedure for preparation of 3-(substituted-phenyl)-propionic acid methyl ester (3a-e):
A mixture of substituted dihydrocinnamic acid (2a-e, 0.133 mol) in methanol (350 mL) was
treated slowly with thionyl chloride (20 mL, 0.275 mol) drop wise during 1 h. After completion
of addition, the reaction mixture was stirred for another 2 h at rt. After completion of reaction,
which was monitored by TLC hexane/ethyl acetate (8:2), the reaction mixture was poured into
water (200 mL), extract with ethyl acetate (2 × 400 mL). The extract was washed with water,
brine solution, dried over Na2SO4 and concentrated. The crude compound was subjected to
column chromatography on silica gel using hexane/ethyl acetate mixtures. The fractions were
monitored and the fractions eluted with ethyl acetate in hexane, 3 % / 97 % (v/v) were combined
and concentrated to obtained 3-(substituted phenyl)-propionic acid methyl esters (3a-e) as oily
compounds with yields in the range of 87 %-90 %.
3-(Phenyl)-propionic acid methyl ester (3a): Weight: 15.6 g; % yield: 89.6 %; 1H NMR (CDCl3,
400 MHz): δ 7.34 (2H, d, J = 8.0 Hz, H-3′, 5′), 7.21 (2H, d, J = 7.6 Hz, H-2′, 6′), 7.11 (1H, d, J =
7.2 Hz, H-4′), 3.68 (3H, s, OCH3), 2.98 (2H, t, J = 7.6 Hz, H-3), 2.62 (2H, t, J = 7.6 Hz, H-2);
13C NMR (CDCl3, 100 MHz): δ 176.2 (C=O), 146.2 (C-1′), 132.6 (C-3′, 5′), 130.8 (C-2′, 6′),
128.3 (C-4′), 50.6 (OCH3), 36.8 (C-2), 30.9 (C-3); LC-MS: m/z 165.2 (M+H)+.
1
3-(4-Methoxy-phenyl)-propionic acid methyl ester (3b): Weight: 15.6 g; % yield: 90.7 %; H
NMR (CDCl3, 400 MHz): δ 7.14 (2H, d, J = 8.0 Hz, H-2′, 6′), 6.84 (2H, d, J = 7.6 Hz, H-3′, 5′),
3.78 (3H, s, OCH3), 3.72 (3H, s, OCH3), 2.98 (2H, t, J = 8.0 Hz, H-3), 2.61 (2H, t, J = 7.6 Hz, H-
13
2); C NMR (CDCl3, 100 MHz): δ 176.2 (C=O), 164.2 (C-4′), 138.4 (C-1′), 130.2 (C-2′, 6′),
118.8 (C-3′, 5′), 55.8 (OCH3), 51.2 (OCH3), 36.2 (C-2), 30.9 (C-3); LC-MS: m/z 193.3 (M-H)-.

1
3-(2-Methoxy-phenyl)-propionic acid methyl ester (3c): Weight: 15.1 g; % yield: 87.8 %; H
NMR (CDCl3, 400 MHz): δ 7.12 (1H, dd, J = 8.0, 3.2 Hz, H-6′), 6.98 (1H, td, J = 8.0, 3.2 Hz, H-
4′), 6.86 (1H, td, J = 8.0, 2.4 Hz, H-5′), 6.72 (1H, dd, J = 8.0, 3.2 Hz, H-3′), 3.78 (3H, s, OCH3),
3.66 (3H, s, OCH3), 2.98 (2H, t, J = 7.6 Hz, H-3), 2.61 (2H, t, J = 7.2 Hz, H-2); 13C NMR
(CDCl3, 100 MHz): δ 174.2 (C=O), 168.2 (C-2′), 132.9 (C-6′), 128.6 (C-4′), 126.9 (C-1′), 120.8
(C-5′), 116.4 (C-3′), 55.8 (OCH3), 50.6 (OCH3), 36.9 (C-2), 22.1 (C-3); LC-MS: m/z 193.2 (M-
H)-.
3-(3, 4-Dimethoxy-phenyl)-propionic acid methyl ester (3d): Weight: 15.30 g; % yield: 89.7 %;
1H NMR (CDCl3, 400 MHz): δ 6.72 (1H, d, J = 8.0 Hz, H-5′), 6.64 (1H, dd, J = 8.0, 3.2 Hz, H-
6′), 6.56 (1H, d, J = 3.2 Hz, H-2′), 3.78 (6H, s, OCH3), 3.66 (3H, s, OCH3), 2.98 (2H, t, J = 7.6
Hz, H-3), 2.66 (2H, t, J = 7.6 Hz, H-2); 13C NMR (CDCl3, 100 MHz): δ 174.4 (C=O), 158.4 (C-
3′), 156.3 (C-4′), 138.2 (C-1′), 126.8 (C-6′), 118.4 (C-5′), 116.8 (C-2′), 55.8 (OCH3), 55.6
(OCH3), 50.1 (OCH3), 38.4 (C-2), 31.8 (C-3); LC-MS: m/z 225.5 (M+H)+, 243.3 (M+Na)+.
3-(3, 4, 5-Trimethoxy-phenyl)-propionic acid methyl ester (3e): Weight: 15.10 g; % yield: 89.3
1
%; H NMR (CDCl3, 400 MHz): δ 6.22 (2H, s, H-2′, 6′), 3.86 (6H, s, OCH3), 3.78 (3H, s,
13
OCH3), 3.66 (3H, s, OCH3), 2.96 (2H, t, J = 8.0 Hz, H-3), 2.62 (2H, t, J = 7.6 Hz, H-2); C
NMR (CDCl3, 100 MHz): δ 172.4 (C=O), 156.4 (C-3′, 5′), 142.8 (C-4′), 136.2 (C-1′), 108.6 (C-
2′, 6′), 56.4 (OCH3), 56.3 (OCH3), 55.9 (OCH3), 50.9 (OCH3), 38.2 (C-2), 31.6 (C-3); LC-MS:
m/z 255.2 (M+H)+, 277.5 (M+Na)+.
General procedure for preparation of 3-(substituted-phenyl)-propan-1-ol (4a-e):
A mixture of Lithium aluminum hydride (9.5 g, 0.250 mol), dry THF (250 mL), to it add
substituted dihydrocinnamic acid methyl ester (3a-e, 0.127 mol), in THF (50 mL) was added
slowly drop wise during 30 min. After completion of addition the reaction mixture was stirred
for 2 h at rt, after completion of reaction as monitored by TLC hexane/ethyl acetate (8:2), the
reaction mixture was poured in water (200 mL), acidified with 5N HCl, extract with chloroform
(2 × 400mL), extract was wash with water, brine solution, dried over Na2SO4 and concentrated.
The crude residue was subjected to column chromatography on silica gel, column was eluted
with hexane/ethyl acetate mixtures, pure compound was eluted in ethyl acetate in hexane, 10 % /
90 % (v/v) which was monitored by TLC, pure fractions were combined and concentrated to
obtained 3-(substituted phenyl)- propan-1-ol as oily compounds with yields of 73 %-77 %.

1
3-(Phenyl)-propan-1-ol (4a): Weight: 9.10 g; % yield: 73.2 %; H NMR (CDCl3, 400 MHz): δ
7.32-7.28 (2H, m, H-3′, 5′), 7.14 (2H, d, J = 8.0 Hz, H-2′, 6′), 7.06 (1H, d, J = 7.2 Hz, H-4′), 3.56
(2H, d, J = 8.0 Hz, CH2), 2.56 (2H, t, J = 7.2 Hz, H-3), 2.43 (1H, s, OH), 1.86 (2H, d, J = 7.6 Hz,
13
H-2); C NMR (CDCl3, 100 MHz): δ 146.2 (C-1′), 132.8 (C-3′, 5′), 130.2 (C-2′, 6′), 126.8 (C-
4′), 65.8 (C-1), 38.3 (C-2), 31.9 (C-3); LC-MS: m/z 135.2 (M-H)-.
3-(4-Methoxy-Phenyl)-propan-1-ol (4b): Weight: 9.90 g; % yield: 77.2 %; 1H NMR (CDCl3, 400
MHz): δ 7.11 (2H, d, J = 7.6 Hz, H-2′, 6′), 6.88 (2H, d, J = 8.0 Hz, H-3′, 5′), 3.78 (3H, s, OCH3),
3.56 (2H, s, CH2), 2.61 (2H, t, J = 7.2 Hz, H-3), 2.51 (1H, s, OH), 1.88 (2H, t, J = 7.6 Hz, H-2);
13C NMR (CDCl3, 100 MHz): δ 156.4 (C-4′), 136.5 (C-1′), 130.8 (C-2′, 6′), 118.2 (C-3′, 5′), 64.8
(C-1), 56.2 (OCH3), 38.6 (C-2), 31.8 (C-3); LC-MS: m/z 165.5 (M-H)-.
3-(2-Methoxy-Phenyl)-propan-1-ol (4c): Weight: 9.50 g; % yield: 74.0 %; 1H NMR (CDCl3, 400
MHz): δ 7.12 (1H, dd, J = 8.0, 3.2 Hz, H-6′), 6.98 (1H, td, J = 7.6, 3.2 Hz, H-4′), 6.79 (1H, td, J
= 7.6, 2.4 Hz, H-5′), 6.68 (1H, dd, J = 7.6, 3.2 Hz, H-3′), 3.78 (3H, s, OCH3), 3.56 (2H, s, CH2),
2.84 (2H, t, J = 7.2 Hz, H-3), 2.42 (1H, s, OH), 1.86 (2H, t, J = 7.6 Hz, H-2); 13C NMR (CDCl3,
100 MHz): δ 168.2 (C-2′), 132.8 (C-6′), 128.4 (C-4′), 126.2 (C-1′), 121.9 (C-5′), 16.8 (C-3′), 66.4
(CH2), 55.8 (OCH3), 38.2 (C-2), 23.9 (C-3); LC-MS: m/z 167.2 (M+H)+.
3-(3, 4-Dimethoxy-Phenyl)-propan-1-ol (4d): Weight: 9.80 g; % yield: 74.8 %; 1H NMR (CDCl3,
400 MHz): δ 6.68 (1H, d, J = 7.6 Hz, H-5′), 6.62 (1H, dd, J = 7.6, 3.2 Hz, H-6′), 6.54 (1H, d, J =
3.2 Hz, H-2′), 3.78 (3H, s, OCH3), 3.62 (2H, s, CH2), 2.68 (2H, t, J = 7.6 Hz, H-3), 2.12 (1H, s,
13
OH), 1.88 (2H, t, J = 7.6 Hz, H-2); C NMR (CDCl3, 100 MHz): δ 156.4 (C-3′), 154.2 (C-4′),
138.6 (C-1′), 126.4 (C-6′), 118.6 (C-5′), 116.8 (C-2′), 66.3 (C-1), 55.8 (OCH3), 55.6 (OCH3),
38.2 (C-2), 30.9 (C-3); LC-MS: m/z 217.5 (M+Na)+.
1
3-(3, 4, 5-Trimethoxy-Phenyl)-propan-1-ol (4e): Weight: 10.20 g; % yield: 76.5 %; H NMR
(CDCl3, 400 MHz): δ 6.12 (2H, s, H-2′, 6′), 3.78 (6H, s, OCH3), 3.76 (3H, s, OCH3), 3.56 (2H, s,
13
CH2), 2.68 (2H, t, J = 7.6 Hz, H-3), 2.12 (1H, s, OH), 1.88 (2H, t, J = 7.2 Hz, H-2); C NMR
(CDCl3, 100 MHz): δ 156.8 (C-3′, 5′), 138.6 (C-1′), 133.8 (C-4′), 109.8 (C-2′, 6′), 66.8 (C-1),
55.8 (OCH3), 55.6 (OCH3), 55.5 (OCH3), 38.2 (C-2), 31.8 (C-3); LC-MS: m/z 249.2 (M+Na)+.
General procedure for 3-(substituted-phenyl)-propan-1-al (5a-e): Suitable 3-(substituted-
phenyl)-propan-1-ol (4a-e, 0.02727 mol) compound was dissolved in DMSO (150 mL) and to
the mixture IBX (28 g, 0.02727 mol) was added portion wise during 45 min. After completion of

addition, the reaction mixture was stirred for 2 h. at room temperature. After completion of
reaction which was monitored by TLC hexane/ethyl acetate (8:2), the reaction mixture was
poured into water (200 mL). The mixture was filter off; the filter bed was washed with
chloroform (200 mL). The filtrate was taken in to a separating funnel, separated the organic layer
and the aqueous layer was extracted with chloroform (200 mL). The combined organic layer was
washed with water, brine solution, dried over Na2SO4 and concentrated under vacuum. The crude
residue was subjected to column chromatography on silica gel, using ethyl acetate in hexane, 15
% / 85 % (v/v) eluents as monitored by TLC, pure fractions were combined and concentrated to
obtained 3-(substituted-phenyl)-propan-1-al as oily compounds with yields of (5a-e, 73 -81 %).
3-(Phenyl)-propan-1-al (5a): Weight: 6.50 g; % yield: 73.4 %; 1H NMR (CDCl3, 400 MHz): δ
9.82 (1H, s, CHO), 7.34 (2H, d, J = 7.6 Hz, H-3′, 5′), 7.21 (2H, d, J = 8.0 Hz, H-2′, 6′), 7.09 (1H,
t, J = 7.2 Hz, H-4′), 2.98 (2H, t, J = 7.6 Hz, H-3), 2.79 (2H, t, J = 7.2 Hz, H-2); 13C NMR
(CDCl3, 100 MHz): δ 201.4 (C=O), 148.2 (C-1′), 136.9 (C-3′, 5′), 136.2 (C-2′, 6′), 129.6 (C-4′),
48.6 (C-2), 29.2 (C-3); LC-MS: m/z 157.3 (M+Na)+.
1
3-(4-Methoxy phenyl)-propan-1-al (5b): Weight: 7.20 g; % yield: 81.0 %; H NMR (CDCl3, 400
MHz): δ 9.82 (1H, s, CHO), 7.14 (2H, d, J = 8.0 Hz, H-2′, 6′), 6.82 (2H, d, J = 7.6 Hz, H-3′, 5′),
13
3.72 (3H, s, OCH3), 2.98 (2H, t, J = 7.6 Hz, H-3), 2.72 (2H, t, J = 7.6 HZ, H-2); C NMR
(CDCl3, 100 MHz): δ 201.4 (C=O), 168.2 (C-4′), 136.8 (C-1′), 130.8 (C-2′, 6′), 116.8 (C-3′, 5′),
55.8 (OCH3), 48.6(C-2), 28.9 (C-3); LC-MS: m/z 187.2 (M+Na)+.
3-(2-Methoxy Phenyl)-propan-1-al (5c): Weight: 6.80 g; % yield: 76.5 %; 1H NMR (CDCl3, 400
MHz): δ 9.72 (1H, s, CHO), 7.12 (1H, dd, J = 7.6, 3.2 Hz, H-6′), 6.98 (1H, td, J = 7.6, 3.2 Hz, H-
4′), 6.88 (1H, td, J = 7.6, 2.4 Hz, H-5′), 6.76 (1H, dd, J = 7.6, 3.2 Hz, H-3′), 3.78 (3H, s, OCH3),
13
2.98 (2H, t, J = 7.6 Hz, H-3), 2.76 (2H, t, J = 7.2 Hz, H-2); C NMR (CDCl3, 100 MHz): δ
202.1 (C=O), 168.9 (C-2′), 132.6 (C-6′), 128.2 (C-4′), 126.4 (C-1′), 121.5 (C-5′), 118.4 (C-3′),
56.3 (OCH3), 46.8 (C-2), 19.8 (C-3); LC-MS: m/z 203.3 (M+K)+.
3-(3, 4-Dimethoxy phenyl)-propan-1-al (5d): Weight: 6.90 g; % yield: 77.4 %; 1H NMR (CDCl3,
400 MHz): δ 9.72 (1H, s, CHO), 6.79 (1H, d, J = 8.0 Hz, H-5′), 6.66 (1H, dd, J = 7.6, 3.2 Hz, H-
6′), 6.58 (1H, d, J = 3.2 Hz, H-2′), 3.78 (6H, s, OCH3), 2.98 (2H, t, J = 8.0 Hz, H-3), 2.76 (2H, t,
J = 7.6 Hz, H-2); 13C NMR (CDCl3, 100 MHz): δ 202.1 (C=O), 156.4 (C-3′), 148.6 (C-4′), 138.6
(C-1′), 126.9 (c-6′), 118.6 (C-5′), 116.8 (C-2′), 55.8 (OCH3), 55.6 (OCH3), 48.3 (C-2), 28.9 (C-
3); LC-MS: m/z 195.2 (M+H)+, 217.3 (M+Na)+.

1
3-(3, 4, 5-Trimethoxy phenyl)-propan-1-al (5e): Weight: 7.10 g; % yield: 79.6 %; H NMR
(CDCl3, 400 MHz): δ 9.72 (1H, s, CHO), 6.12 (2H, s, H-2′, 6′), 3.78 (6H, s, OCH3), 3.76 (3H, s,
OCH3), 2.98 (2H, t, J = 7.6 Hz, H-3), 2.7 6(2H, t, J = 7.2 Hz, H-2); 13C NMR (CDCl3, 100
MHz): δ 202.1 (C=O), 152.4 (C-3′, 5′), 144.6 (C-1′),138.6 (C-4′), 106.8 (C-2′, 6′), 55.8 (OCH3),
55.6 (OCH3), 55.5 (OCH3), 48.2 (C-2), 30.1 (C-3); LC-MS: m/z 225.3 (M+H)+.
General procedure for 5-(Substituted-phenyl)-pent-2-enoic acid ethylester (6a-e): A mixture of
suitable 3-(substituted phenyl)-propan-1-al (5a-e, 0.02038 mol), dry THF (50 mL) and ethyl
triphenylphosphorane (7.1 g, 0.02038 mol) was refluxed for 4-5 h. After completion of reaction,
the reaction mixture was concentrated under vacuum. The crude residue was purified by column
chromatography on silica gel (ethyl acetate in hexane, 5 % / 95 % - 10 % / 90 % (v/v)) to yield
the corresponding 5-(substituted phenyl)-pent-2-enoic acid ethyl ester (6a-e, 60-66%).
5-(Phenyl)-pent-2-enoic acid ethyl ester (6a):Weight: 5.54 g; % yield: 60.7 %;1H NMR (CDCl3,
400 MHz): δ 7.26 (2H, d, J = 7.6 Hz, H-3′, 5′), 7.18 (2H, d, J = 8.0 Hz, H-2′, 6′), 7.08 (1H, d, J =
8.0 Hz, H-4′), 6.98 (1H, d, J = 16.4 Hz, H-3), 5.92 (1H, d, J = 16.0 Hz, H-2), 4.28 (2H, q, J = 7.6
Hz, OCH2), 2.68 (2H, t, J = 7.6 Hz, H-5), 2.36 (2H, t, J = 8.0 Hz, H-4), 1.42 (3H, s, CH3); 13C
NMR (CDCl3, 100 MHz): δ 168.2 (C=O), 148.5 (C-3), 142.8 (C-1′), 136.5 (C-3′, 5′), 132.4 (C-2′,
6′), 128.7 (C-4′), 124.6 (C-2), 62.3 (OCH2), 38.4 (C-5), 35.8 (C-4), 14.6 (CH3); LC-MS: m/z
227.2 (M+Na)+.
5-(4-Methoxy-phenyl)-pent-2-enoic acid ethyl ester (6b): Weight: 5.61 g; % yield: 65.5 %;1H
NMR (CDCl3, 400 MHz): δ 7.28 (2H, d, J = 8.0 Hz, H-2′, 6′), 7.04 (1H, d, J = 16.0 Hz, H-3),
6.86 (2H, d, J = 8.0 Hz, H-3′, 5′), 4.52 (2H, q, J = 7.6 Hz, OCH2), 3.78 (3H, s, OCH3), 2.68 (2H,
13
t, J = 7.6 Hz, H-5), 2.36 (2H, t, J = 8.0 Hz, H-4), 1.42 (3H, s, CH3); C NMR (CDCl3, 100
MHz): δ 168.2 (C=O), 161.2 (C-4′), 148.5 (C-3), 138.6 (C-1′), 132.4 (C-2′, 6′), 122.6 (C-2),
116.8 (C-3′, 5′), 62.1 (OCH2), 56.8 (OCH3), 38.3 (C-5), 35.4 (C-4), 14.6 (CH3); LC-MS: m/z
235.5 (M+H)+, 257.2 (M+Na)+.
5-(2-Methoxy-Phenyl)-Pent-2-enoic acid ethyl ester (6c): Weight: 5.42 g; % yield: 63.3 %;1H
NMR (CDCl3, 400 MHz): δ 7.26 (1H, dd, J = 7.6, 2.4 Hz, H-6′), 7.08 (1H, td, J = 8.0, 2.4 Hz, H-
4′), 6.98 (1H, d, J = 16.4 Hz, H-3), 6.86 (1H, td, J = 8.0, 3.2 Hz, H-5′), 6.78(1H, dd, J = 7.6, 2.4
Hz, H-3′), 5.88 (1H, d, J = 16.0 Hz, H-2), 4.32 (2H, t, J = 7.6 Hz, OCH2), 3.78 (3H, s, OCH3),
2.68 (2H, t, J = 7.6 Hz, H-5), 2.36 (2H, t, J = 8.0 Hz, H-4), 1.42 (3H, s, CH3); 13C NMR (CDCl3,

100 MHz): δ 168.2 (C=O), 164.6 (C-2′), 148.6 (C-3), 136.4 (C-6′), 132.8 (C-4′), 132.6 (C-1′),
128.4 (C-5′), 126.4 (C-2), 116.8 (C-3′), 61.6 (OCH2), 55.8 (OCH3), 36.8 (C-4), 28.4 (C-5), 14.3
(CH3); LC-MS: m/z 235.3 (M+H)+.
5-(3, 4-Dimethoxy-phenyl)-pent-2-enoic acid ethyl ester (6d): Weight: 5.1 g; % yield: 62.5 %;
1H NMR (CDCl3, 400 MHz): δ 7.08 (1H, d, J = 16.0 Hz, H-3), 6.84 (1H, d, J = 7.6 Hz, H-5′),
6.72 (1H, dd, J = 3.2, 7.6 Hz, H-6′), 6.68 (1H, d, J = 3.2 Hz, H-2′), 5.92 (1H, d, J = 16.4 Hz, H-
2), 4.34 (2H, q, J = 7.6 Hz, OCH2), 3.78 (6H, s, OCH3), 2.64 (2H, t, J = 8.0 Hz, H-5), 2.32 (2H,
13
t, J = 8.0 Hz, H-4), 1.46 (3H, s, CH3); C NMR (CDCl3, 100 MHz): δ 168.4 (C=O), 158.6 (C-
3′), 156.8 (C-4′), 148.2 (C-3), 138.6 (C-1′), 126.4 (C-6′), 124.3 (C-2), 118.2 (C-5′), 116.5 (C-2′),
61.8 (OCH2), 55.8 (OCH3), 55.7 (OCH3), 38.6 (C-5), 34.8 (C-4), 14.2 (CH3); LC-MS: m/z 265.5
(M+H)+, 287.3 (M+Na)+.
5-(3, 4, 5-Trimethoxy-Phenyl)-Pent-2-enoic acid ethyl ester (6e): Weight: 5.20 g; % yield: 66.1
1
%; H NMR (CDCl3, 400 MHz): δ 7.12 (1H, d, J = 16.4 Hz, H-3), 6.28 (2H, s, H-2′, 6′) , 5.92
(1H, d, J = 16.0 Hz, H-2), 4.36 (2H, q, J = 7.6 Hz, OCH2), 3.86 (9H, s, OCH3), 2.68 (2H, t, J =
13
8.0 Hz, H-5), 2.31 (2H, t, J = 7.6 Hz, H-4), 1.28 (3H, s, CH3); C NMR (CDCl3, 100 MHz): δ
168.2 (C=O), 156.2 (C-3′, 5′), 152.8 (C-3), 136.4 (C-1′), 134.9 (C-4′), 128.4 (C-2), 114.6 (C-2′,
6′), 61.8 (OCH2), 56.8 (OCH3), 56.5 (OCH3), 55.8 (OCH3), 38.1 (C-5), 34.6 (C-4), 14.3 (CH3);
LC-MS: m/z 295.3 (M+Na)+.
General procedure for 5-(substituted-phenyl)-pentanoic acid ethyl ester (7a-e): A mixture of
suitable 5-(substituted phenyl)-pent-2-enoic acid ethyl esters (6a-e, 0.01 mol), ethyl acetate (40
mL) and palladium on CaCO3 (10 mg) was taken in a RB flask and contents were vigorously
stirred under H2 atmosphere for 2 h. After completion of reaction, the reaction mixture was
filtered on celite, washed with ethyl acetate and the filtrate was concentrated under vacuum to
obtain the corresponding 5-(substituted phenyl)-pentanoic acid ethyl ester (7a-e, 89-91%).
5-(Phenyl)-Pentanoic acid ethyl ester (7a): Weight: 4.55 g; % yield: 90.3 %;1H NMR (CDCl3,
400 MHz): δ 7.32 (2H, d, J = 7.2 Hz, H-3′, 5′), 7.16 (2H, s, H-2′, 6′), 7.06 (1H, d, J = 7.6 Hz, H-
4′), 4.31 (2H, q, J = 7.2 Hz, OCH2), 2.68 (2H, t, J = 8.0 Hz, H-5), 2.31 (2H, t, J = 7.6 Hz, H-2),
13
1.78-1.64 (4H, m, H-3, 4), 1.46 (3H, s, CH3); C NMR (CDCl3, 100 MHz): δ 181.6 (C=O),
146.5 (C-1′), 128.9 (C-2′, 6′), 128.3 (C-3′, 5′), 126.8 (C-4′), 63.1 (OCH2), 36.8 (C-5), 33.9 (C-2),
32.1 (C-4), 26.8 (C-3), 14.5 (CH3); LC-MS: m/z 205.4 (M-H)-.

5-(4-Methoxy-phenyl)-pentanoic acid ethyl ester (7b): Weight: 4.58 g; % yield: 90.9 %;1H NMR
(CDCl3, 400 MHz): δ 7.12 (2H, d, J = 7.2 Hz, H-2′, 6′), 6.88 (2H, d, J = 7.6 Hz, H-3′, 5′), 4.37
(2H, q, J = 8.0 Hz, OCH2), 3.78 (3H, s, OCH3), 2.66 (2H, t, J = 7.2 Hz, H-5), 2.31 (2H, t, J = 7.6
Hz, H-2), 1.76-1.74 (2H, m, H-3), 1.62-1.56 (2H, m, H-4), 1.41 (3H, s, CH3); 13C NMR (CDCl3,
100 MHz): δ 184.1 (C=O), 166.2 (C-4′), 136.3 (C-1′), 129.8 (C-2′, 6′), 116.4 (C-3′, 5′), 62.6
(OCH2), 56.8 (OCH3), 39.6 (C-5), 36.8 (C-2), 32.4 (C-4), 28.4 (C-3), 14.5 (CH3); LC-MS: m/z
259.3 (M+H)+.
5-(2-Methoxy-Phenyl)-Pentanoic acid ethyl ester (7c): Weight: 4.52 g; % yield: 89.7 %;1H NMR
(CDCl3, 400 MHz): δ 7.28 (1H, dd, J = 7.2, 2.4 Hz, H-6′), 7.12 (2H, td, J = 7.6, 3.2 Hz, H-4′, 5′),
7.01 (1H, dd, J = 7.2, 2.4 Hz, H-3′), 4.31 (2H, q, J = 8.0 Hz, OCH2), 3.72 (3H, s, OCH3), 2.74
(2H, t, J = 7.2 Hz, H-5), 2.38 (2H, t, J = 7.6 Hz, H-2), 1.72-1.66 (4H, m, H-3, 4), 1.42 (3H, s,
CH3); 13C NMR (CDCl3, 100 MHz): δ 182.4 (C=O), 168.4 (C-2′), 136.8 (C-6′), 132.4 (C-4′),
1245.9 (C-1′), 122.8 (C-5′), 116.4 (C-3′), 62.6 (OCH2), 56.2(OCH3), 36.4 (C-2), 32.8 (C-4), 26.4
(C-5), 25.1 (C-3), 14.2 (CH3); LC-MS: m/z 237.5 (M+H)+.
5-(3, 4-Dimethoxy-Phenyl)-Pentanoic acid ethyl ester (7d): Weight: 4.54 g; % yield: 90.3 %;1H
NMR (CDCl3, 400 MHz): δ 6.86 (1H, d, J = 7.6 Hz, H-5′), 6.72 (1H, dd, J = 7.6, 2.4 Hz, H-6′),
6.58 (1H, d, J = 2.4 Hz, H-2′), 4.38 (2H, q, J = 7.2 Hz, OCH2), 3.82 (6H, s, OCH3), 2.76 (2H, t, J
= 7.6 Hz, H-5), 2.37 (2H, t, J = 8.0 Hz, H-2), 1.76-1.72 (2H, m, H-3), 1.66-1.59 (2H, m, H-4),
13
1.46 (3H, s, OCH3); C NMR (CDCl3, 100 MHz): δ 184.1 (C=O), 154.1 (C-3′), 152.6 (C-4′),
138.6 (C-1′), 130.1 (C-6′), 116.2 (C-5′), 114.8 (C-2′), 62.3 (OCH2), 56.8 (OCH3), 56.6 (OCH3),
38.6 (C-5), 36.4 (C-2), 31.9 (C-4), 28.3 (C-3), 14.2 (CH3); LC-MS: m/z 267.2 (M+H)+, 289.3
(M+Na)+.
5-(3, 4, 5-Trimethoxy-Phenyl)-Pentanoic acid ethyl ester (7e): Weight: 4.60 g; % yield:
91.4%;1H NMR (CDCl3, 400 MHz): δ 6.28 (2H, s, H-2′, 6′), 4.48 (2H, q, J = 7.6 Hz, OCH2),
3.78 (6H, s, OCH3), 3.72 (3H, s, OCH3), 2.68 (2H, t, J = 8.0 Hz, H-5), 2.36 (2H, t, J = 7.6 Hz, H-
13
2), 1.76-1.72 (4H, m, H-3,4), 1.48(3H, s, CH3); C NMR (CDCl3, 100 MHz): δ 182.2 (C=O),
156.8 (C-3′, 5′), 146.2 (C-1′), 138.6 (C-4′), 110.6 (C-2′, 6′), 63.1 (OCH2), 55.8 (OCH3), 55.6
(OCH3), 55.5 (OCH3), 41.4 (C-5), 36.4 (C-2), 32.8 (C-4), 28.1 (C-3), 14.6 (CH3); LC-MS: m/z
297.2 (M+H)+ , 319.4 (M+Na)+.
General procedure for 5-(substituted-phenyl)-pentan-1-ol (8a-e): Lithium aluminum hydride
(1.1 g, 0.02898 mol) was suspended in dry THF (20 mL) and treated with a solution of suitable

5-(substituted phenyl)-pentanoic acid ethyl esters (7a-e, 0.01449 mol) in THF (5 mL) was added
slowly drop wise for 15 min. Then the reaction mixture was stirred for 2 h at r.t. After
completion of reaction, the reaction mixture was poured into water (100 mL), acidified with 2N
HCl and extracted with chloroform (2 × 250 mL). The combined organic layer was washed with
brine solution, dried over Na2SO4 and concentrated under vacuum. The crude residue was
purified by column chromatography on silica gel (ethyl acetate in hexane, 20 % / 80 % (v/v)) to
yield the corresponding 5-(substituted -phenyl)-pentan-1-ol (8a-e, 82-88 %).
1
5-(Phenyl)-Pentan-1-ol (8a): Weight: 3.08 g; % yield: 86.0 %; H NMR (CDCl3, 400 MHz): δ
7.42 (2H, d, J = 7.6 Hz, H-3′, 5′), 7.26 (2H, d, J = 8.0 Hz, H-2′, 6′), 7.08 (1H, s, H-4′), 3.58 (2H,
t, J = 7.2 Hz, H-1), 2.66 (2H, t, J = 7.6 Hz, H-5), 1.78-1.74 (2H, m, H-4), 1.52-1.49 (2H, m, H-
2), 1.29-1.27 (2H, m, H-3); 13C NMR (CDCl3, 100 MHz): δ 142.6 (C-1′), 129.4 (C-2′, 6′), 128.4
(C-3′, 5′), 126.8 (C-4′), 66.4 (C-1), 38.6 (C-5), 34.6 (C-2), 32.7 (C-4), 28.9 (C-3); LC-MS: m/z
165.2 (M+H)+.
5-(4-Methoxy-Phenyl)-Pentan-1-ol (8b): Weight: 3.25 g; % yield: 87.9 %; 1H NMR (CDCl3, 400
MHz): δ 7.12 (2H, d, J = 8.0 Hz, H-2′, 6′), 6.84 (2H, d, J = 7.6 Hz, H-3′, 5′), 3.88 (2H, t, J = 7.2
Hz, H-1), 3.72 (3H, s, OCH3), 2.72 (2H, t, J = 7.6 Hz, H-5), 2.08 (1H, s, OH), 1.74-1.71 (2H, m,
H-4), 1.51-1.48 (2H, m, H-2), 1.33-1.31 (2H, m, H-3); 13C NMR (CDCl3, 100 MHz): δ 162.8 (C-
4′), 134.6 (C-1′), 132.8 (C-2′, 6′), 114.6 (C-3′, 5′), 66.2 (C-1), 56.1 (OCH3), 38.6 (C-5), 33.7 (C-
2), 32.9 (C-4), 26.1 (C-3); LC-MS: m/z 217.3 (M+Na)+.
5-(2-Methoxy-Phenyl)-Pentan-1-ol (8c): Weight: 3.16 g; % yield: 85.4 %;1H NMR (CDCl3, 400
MHz): δ 7.16 (1H, dd, J = 7.2, 2.4 Hz, H-6′), 7.08 (1H, td, J = 7.6, 3.2 Hz, H-4′), 6.88 (1H, td, J
= 8.0, 2.4 Hz, H-5′), 6.72 (1H, dd, J = 7.6, 3.2 Hz, H-3′), 3.72 (3H, s, OCH3), 3.68 (2H, t, J = 7.2
Hz, H-1), 2.74 (2H, t, J = 7.6 Hz, H-5), 2.08 (1H, s, OH), 1.76-1.72 (2H, m, H-4), 1.48-1.46 (2H,
13
m, H-2), 1.34-1.29 (2H, m, H-3); C NMR (CDCl3, 100 MHz): δ 164.9 (C-2′), 136.5 (C-6′),
128.4 (C-4′), 125.8 (C-1′), 122.6 (C-5′), 116.8 (C-3′), 66.2 (C-1), 55.8 (OCH3), 36.4 (C-2), 32.9
(C-4), 26.4 (C-5), 25.9 (C-3); LC-MS: m/z 217.3 (M+Na)+.
5-(3, 4-Dimethoxy-Phenyl)-Pentan-1-ol (8d): Weight: 3.10 g; % yield: 82.0 %;1H NMR (CDCl3,
400 MHz): δ 6.86 (1H, d, J = 7.6 Hz, H-5′), 6.72 (1H, dd, J = 7.2, 3.2 Hz, H-6′), 6.58 (1H, d, J =
3.2 Hz, H-2′), 3.81 (2H, t, J = 7.6 Hz, H-1), 2.76 (2H, t, J = 8.0 Hz, H-5), 2.08 (1H, s, OH), 1.83-
1.79 (2H, m, H-4), 1.56-1.52 (2H, m, H-2), 1.35-1.33 (2H, m, H-3); 13C NMR (CDCl3, 100
MHz): δ 156.3 (C-3′), 154.2 (C-4′), 136.4 (C-1′), 128.6 (C-6′), 116.8 (C-2′), 114.2 (C-5′), 66.8

(C-1), 55.9 (OCH3), 55.8 (OCH3), 38.5 (C-5), 36.8 (C-2), 32.9 (C-4), 26.4 (C-3); LC-MS: m/z
247.6 (M+Na)+.
1
5-(3, 4, 5-Trimethoxy-Phenyl)-Pentan-1-ol (8e): Weight: 3.21 g; % yield: 83.2 %; H NMR
(CDCl3, 400 MHz): δ 6.28 (2H, s, H-2′, 6′), 3.86 (6H, s, OCH3), 3.78 (3H, s, OCH3), 3.62 (2H, t,
J = 7.6 Hz, H-1), 2.68 (2H, t, J = 7.2 Hz, H-5), 2.07 (1H, s, OH), 1.81-1.79 (2H, m, H-4), 1.56-
13
1.53 (2H, m, H-2), 1.32-1.27 (2H, m, H-3); C NMR (CDCl3, 100 MHz): δ 156.3 (C-3′, 5′),
138.6 (C-1′), 132.4 (C-4′), 114.3 (C-2′,6′), 68.2 (C-1), 55.8 (OCH3), 55.7 (OCH3), 55.6 (OCH3),
39.2 (C-5), 36.1 (C-2), 32.7 (C-4), 26.5 (C-3); LC-MS: m/z 255.4 (M+H)+, 277.2 (M+Na)+.
General procedure for 5-(substituted-phenyl)-pentan-1-al (9a-e): To a mixture of 9-(substituted
phenyl)-pentan-1-ol compounds (8a-e, 0.01 mol) in DMSO (20 mL) in a 100 mL R.B flask was
added IBX (0.01 mol) slowly portion wise and the reaction mixture was then stirred for 3 h at r.t
. After completion of reaction, the reaction mixture was poured into water (100 mL) and
chloroform (100 mL).The mixture was kept under stirring for 10 minutes and then filtered, and
the filter bed washed with chloroform (100 mL). The organic layer was separated. The aqueous
layer was extracted with chloroform (100 mL) and the combined the organic layer was washed
with water, brine solution, dried over Na2SO4 and concentrated under vacuum. The crude residue
was purified by column chromatography on silica gel (ethyl acetate in hexane, 15 % / 85 % (v/v)
as eluent) to obtain the corresponding 5-(substituted phenyl)-pentan-1-al (9a-e, 83-85%).
5-(Phenyl)-pentan-1-al (9a): Weight: 2.46 g; % yield: 83.0 %;1H NMR (CDCl3, 400 MHz): δ
9.71 (1H, s, CHO), 7.38 (2H, s, H-3′, 5′), 7.21 (2H, d, J = 7.6 Hz, H-2′, 6′), 7.08 (1H, d, J = 8.0
Hz, H-4′), 2.66 (2H, t, J = 8.0 Hz, H-5), 2.46 (2H, t, J = 7.2 Hz, H-2), 1.711-1.68 (4H, m, H-3,
4); 13C NMR (CDCl3, 100 MHz): δ 202.6 (C=O), 142.3 (C-1′), 129.8 (C-2′, 6′), 128.2 (C-3′, 5′),
126.3 (C-4′), 46.9 (C-2), 36.8 (C-5), 32.6 (C-4), 22.8 (C-3); LC-MS: m/z 161.4 (M-H)-.
5-(4-Methoxy-phenyl)-pentan-1-al (9b): Weight: 2.50 g; % yield: 84.2 %;1H NMR (CDCl3, 400
MHz): δ 9.76 (1H, s, CHO), 7.12 (2H, d, J = 7.6 Hz, H-2′, 6′), 6.88 (2H, d, J = 7.2 Hz, H-3′, 5′),
3.72 (6H, s, OCH3), 2.68(2H, t, J = 8.0 Hz, H-5), 2.52 (2H, t, J = 7.6 Hz, H-2), 1.74-1.69(4H, m,
13
H-3, 4); C NMR (CDCl3, 100 MHz): δ 202.6 (C=O), 166.4 (C-4′), 136.2 (C-1′), 129.8 (C-2′,
6′), 114.8 (C-3′, 5′), 56.3 (OCH3), 46.2 (C-2), 38.3 (C-5), 33.6 (C-4), 22.6 (C-3); LC-MS: m/z
193.2 (M+H)+, 369.3 (M+Na)+.
5-(2-Methoxy-phenyl)-pentan-1-al (9c): Weight: 2.52g; % yield: 84.9 %;1H NMR (CDCl3, 400
MHz): δ 9.72 (1H, s, CHO), 7.12 (1H, dd, J = 7.6, 2.4 Hz, H-6′), 6.99 (1H, td, J = 8.0, 3.2 Hz, H-

4′), 6.78 (1H, td, J = 7.6, 3.2 Hz, H-5′), 6.68 (1H, dd, J = 7.2, 2.4 Hz, H-3′), 3.76 (3H, s, OCH3),
2.68 (2H, t, J = 8.0 Hz, H-5), 2.46 (2H, t, J = 8.0 Hz, H-2), 1.72-1.69 (4H, m, H-3, 4); 13C NMR
(CDCl3, 100 MHz): δ 202.6 (C=O), 166.8 (C-2′), 136.8 (C-6′), 128.6 (C-4′), 126.9 (C-1′), 122.4
(C-5′), 114.8 (C-3′), 56.6 (OCH3), 46.8 (C-2), 33.8 (C-4), 26.4 (C-5), 22.8 (C-3); LC-MS: m/z
215.6(M+Na)+.
5-(3, 4-Dimethoxy-phenyl)-pentan-1-al (9d): Weight: 2.48 g; % yield: 83.6 %;1H NMR (CDCl3,
400 MHz): δ 9.76 (1H, s, CHO), 6.68 (1H, d, J = 8.0 Hz, H-5′), 6.57 (1H, dd, J = 7.2, 2.4 Hz, H-
6′), 6.52 (1H, d, J = 3.2 Hz, H-2′), 3.78 (6H, s, OCH3), 3.72 (3H, s, OCH3), 2.68 (2H, t, J = 7.6
Hz, H-5), 2.46 (2H, t, J = 7.2 Hz, H-2), 1.72-1.68 (4H, m, H-3, 4); 13C NMR (CDCl3, 100 MHz):
δ 202.4 (C=O), 156.8 (C-3′), 152.8 (C-4′), 136.7 (C-1′), 128.6 (C-6′), 116.4 (C-2′), 114.2 (C-5′),
56.3 (OCH3), 55.9 (OCH3), 46.3 (C-2), 36.9 (C-5), 34.6 (C-4), 26.9 (C-3); LC-MS: m/z 223.5
(M+H)+, 245.2 (M+Na)+.
5-(3, 4, 5-Trimethoxy-phenyl)-pentan-1-al (9e): Weight: 2.51 g; % yield: 84.5 %;1H NMR
(CDCl3, 400 MHz): δ 9.74 (1H, s, CHO), 6.26 (2H, s, H-2′, 6′), 3.86 (6H, s, OCH3), 3.72 (9H, s,
OCH3), 2.58 (2H, t, J = 7.2 Hz, H-5), 2.42 (2H, t, J = 8.0 Hz, H-2), 1.74-1.69 (4H, m, H-3, 4);
13C NMR (CDCl3, 100 MHz): δ 202.1 (C-1), 156.8 (C-3′, 5′), 138.4 (C-1′), 132.6 (C-4′), 110.5
(C-2′, 6′), 56.3 (OCH3), 55.8 (OCH3), 55.7 (OCH3), 46.8 (C-2), 38.2 (C-5), 32.8 (C-4), 28.6 (C-
3); LC-MS: m/z 253.6 (M+H)+, 275.4 (M+Na)+.
General procedure for preparation of 7-(substituted-phenyl)-1-(substituted-phenyl)-hept-2-en-1-
one (11a-q): A mixture of any one of 5-(substituted-phenyl)-propan-1-al (9a-e, 0.0016mol), any
one of 1-(substituted-phenyl)-2-(triphenylphosphonyllidiene)-ethanone (10a-d, 0.0016 mol), dry
THF (20 mL), was refluxed for 4 h. After completion of reaction which was monitored by TLC
hexane/ethyl acetate (9:1), the reaction mixture was concentrated under vacuum. The crude
residue was subjected to column chromatography on silica gel, column was eluted with
hexane/ethyl acetate mixtures. Pure compound was eluted in ethyl acetate in hexane, 5 % / 95 %
(v/v) which were monitored by TLC and pure fractions were combined and concentrated under
vacuum obtained 7-(substituted phenyl)-1-(substituted phenyl)-hept-2en-1-one (11a-q) with
yields of 46-60 %.
7-(Phenyl)-1-(3,4-dimethoxy-phenyl)-hept-2-en-1-one (11a): Weight: 472 mg; % yield: 47.2 %;
1H NMR (CDCl3, 400 MHz): δ 7.42 (1H, dd, J = 7.6, 2.4 Hz, H-6′), 7.24 (2H, d, J = 7.2 Hz, H-

3′′, 5′′), 7.21 (1H, d, J = 2.4 Hz, H-2′), 7.14 (2H, d, J = 8.0 Hz, H-2′′, 6′′), 7.08 (1H, d, J = 7.6
Hz, H-4′′), 7.02 (1H, d, J = 17.2 Hz, H-2), 6.99 (2H, d, J = 16.4 Hz, H-3), 6.88 (1H, d, J = 7.6
Hz, H-5′), 3.78 (6H, s, OCH3), 2.66 (2H, t, J = 8.0 Hz, H-7), 2.03 (2H, t, J = 7.6 Hz, H-4), 1.69-
1.66 (2H, m, H-6), 1.33-1.31 (2H, m, H-5); 13C NMR (CDCl3, 100 MHz): δ 187.2 (C=O), 156.8
(C-4′), 149.6 (C-3′), 147.8 (C-3), 139.6 (C-1′′), 132.1 (C-1′), 129.3 (C-2′′, 6′′), 128.1 (C-3′′, 5′′),
126.7 (C-4′′), 126.2 (C-2), 123.7 (C-6′), 118.2 (C-2′), 115.8 (C-5′), 56.3 (OCH3), 56.2 (OCH3),
36.2 (C-7), 32.9 (C-4), 32.6 (C-6), 29.7 (C-5); LC-MS: m/z 325.3 (M+H)+.
7-(Phenyl)-1-(2,5-dimethoxy-phenyl)-hept-2-en-1-one (11b): Weight: 469 mg; % yield: 46.9
%;1H NMR (CDCl3, 400 MHz): δ 7.38 (1H, d, J = 2.4 Hz, H-6′), 7.21 (2H, s, H-3′′, 5′′), 7.14-
7.12 (2H, m, H-2′′, 6′′), 7.06 (1H, s, H-4′′), 7.01 (1H, d, J = 17.2 Hz, H-2), 6.99 (1H, d, J = 16.4
Hz, H-3), 6.92 (1H, dd, J = 7.6, 2.4 Hz, H-4′), 6.86 (1H, d, J = 7.6 Hz, H-3′), 3.78 (3H, s, OCH3),
3.76 (3H, s, OCH3), 2.68 (2H, t, J = 7.6 Hz, H-7), 2.02 (2H, t, J = 8.0 Hz, H-4), 1.68-1.64 (2H,
13
m, H-6), 1.33-1.31 (2H, m, H-5); C NMR (CDCl3, 100 MHz): δ 187.4 (C=O), 158.6 (C-2′),
156.7 (C-5′), 149.6 (C-3), 142.6 (C-1′′), 129.6 (C-2′′, 6′′), 129.5 (C-3′′, 5′′), 126.8 (C-4′′), 125.8
(C-2), 123.7 (C-1′), 121.6 (C-4′), 118.6 (C-6′), 115.4 (C-3′), 56.8 (OCH3), 56.7 (OCH3), 55.9
(OCH3), 36.1 (C-7), 32.8 (C-4), 32.1 (C-6), 29.5 (C-5); LC-MS: m/z 325.3 (M+H)+, 347.4
(M+Na)+.
1
7-(4-Methoxy-phenyl)-1-(phenyl)-hept-2-en-1-one (11c): Weight: 415 mg; % yield: 54.2 %; H
NMR (CDCl3, 400 MHz): δ 7.88 (2H, d, J = 7.2 Hz, H-2′, 6′), 7.62 (1H, d, J = 8.0 Hz, H-4′),
7.46 (2H, d, J = 7.6 Hz, H-3′, 5′), 7.04 (1H, d, J = 17.2 Hz, H-2), 7.01 (2H, d, J = 7.6 Hz, H-2′′,
6′′), 6.99 (1H, d, J = 16.4 Hz, H-3), 6.78 (2H, d, J = 7.6 Hz, H-3′′, 5′′), 3.82 (3H, s, OCH3), 2.68
(2H, t, J = 7.2 Hz, H-7), 2.01 (2H, t, J = 7.6 Hz, H-4), 1.76-1.72 (2H, m, H-6), 1.33-1.29 (2H, m,
H-5); 13C NMR (CDCl3, 100 MHz): δ 187.1 (C=O), 164.2 (C-4′′), 149.5 (C-3), 139.6 (C-1′),
136.4 (C-4′), 132.7 (C-1′′), 130.8 (C-2′, 6′), 129.4 (C-2′′, 6′′), 128.6 (C-3′, 5′), 125.6 (C-2), 114.8
(C-3′′, 5′′), 56.3 (OCH3), 36.1 (C-7), 32.9 (C-4), 32.3 (C-6), 29.8 (C-5); LC-MS: m/z 295.3
(M+H)+, 317.3 (M+Na)+.
7-(4-Methoxy-phenyl)-1-(2,4-dimethoxy-phenyl)-hept-2-en-1-one (11d): Weight: 455 mg; %
1
yield: 49.3 %; H NMR (CDCl3, 400 MHz): δ 7.68 (1H, d, J = 7.2 Hz, H-6′), 7.03 (1H, d, J =
17.2 Hz, H-2), 7.01 (2H, d, J = 7.2 Hz, H-2′′, 6′′), 6.99 (1H, d, J = 16.4 Hz, H-3), 6.78 (2H, d, J =
7.6 Hz, H-3′′, 5′′), 6.56 (1H, dd, J = 7.2, 3.2 Hz, H-5′), 6.46 (1H, d, J = 3.2 Hz, H-3′), 3.88 (6H,
s, OCH3), 3.84 (3H, s, OCH3), 2.66 (2H, t, J = 7.6 Hz, H-7), 2.02 (2H, t, J = 7.6 Hz, H-4), 1.72-

13
1.68 (2H, m, H-6), 1.3-1.31 (2H, m, H-5); C NMR (CDCl3, 100 MHz): δ 187.2 (C=O), 174.3
(C-4′), 168.6 (C-2′), 160.8 (C-4′′), 148.9 (C-3), 136.8 (C-1′′), 132.7 (C-6′), 129.6 (C-2′′, 6′′),
126.5 (C-2), 116.4 (C-1′), 114.8 (C-3′′, 5′′), 108.6 (C-5′), 101.3 (C-3′), 56.6 (OCH3), 56.4
(OCH3), 56.3 (OCH3), 36.8 (C-7), 32.7 (C-4), 32.1 (C-6), 29.7 (C-5); LC-MS: m/z 355.3
(M+H)+, 377.3 (M+Na)+.
7-(4-Methoxy-phenyl)-1-(2,5-dimethoxy-phenyl)-hept-2-en-1-one (11e): Weight: 415 mg; %
1
yield: 54.2 %; H NMR (CDCl3, 400 MHz): δ 7.38 (1H, d, J = 3.2 Hz, H-6′), 7.04 (1H, d, J =
17.2 Hz, H-2), 7.01 (2H, d, J = 7.2 Hz, H-2′′, 6′′), 6.99 (1H, d, J = 16.4 Hz, H-3), 6.92 (1H, dd, J
= 7.6, 3.2 Hz, H-4′), 6.86 (1H, d, J = 7.6 Hz, H-3′), 6.74 (2H, d, J = 7.2 Hz, H-3′′, 5′′), 3.78 (6H,
s, OCH3), 3.72 (3H, s, OCH3), 2.68 (2H, t, J = 8.0 Hz, H-7), 2.01 (2H, t, J = 7.6 Hz, H-4), 1.72-
1.69 (2H, m, H-6), 1.33-1.29 (2H, m, H-5); 13C NMR (CDCl3, 100 MHz): δ 187.2 (C=O), 168.6
(C-4′′), 158.6 (C-2′), 158.1 (C-2′), 148.6 (C-3), 132.7 (C-1′′), 129.6 (C-2′′, 6′′), 126.5 (C-2),
123.7 (C-1′), 121.6 (C-4′), 118.4 (C-6′), 116.3 (C-3′), 114.7 (C-3′′, 5′′), 56.3 (OCH3), 56.2
(OCH3), 55.8 (OCH3), 36.3 (C-7), 32.8 (C-4), 32.1 (C-6), 29.9 (C-5); LC-MS: m/z 355.3
(M+H)+, 377.2 (M+Na)+.
1
7-(2-Methoxy-phenyl)-1-(phenyl)-hept-2-en-1-one (11f): Weight: 425 mg; % yield: 55.5 %; H
NMR (CDCl3, 400 MHz): δ 7.88 (2H, d, J = 8.0 Hz, H-2′, 6′), 7.62 (1H, d, J = 8.0 Hz, H-4′),
7.48 (2H, d, J = 7.2 Hz, H-3′, 5′), 7.06 (1H, d, J = 17.2 Hz, H-2),7.02 (1H, dd, J = 7.6, 3.2 Hz, H-
6′), 6.98 (1H, d, J = 16.4 Hz, H-3), 6.96 (1H, td, J = 8.0, 2.4 Hz, H-4′′), 6.82 (1H, td, J = 7.6, 3.2
Hz, H-5′′), 6.74 (1H, dd, J = 7.6, 3.2 Hz, H-3′′), 3.72 (3H, s, OCH3), 2.66 (2H, t, J = 8.0 Hz, H-
13
7), 2.08 (2H, t, J = 7.6 Hz, H-4), 1.71-1.68 (2H, m, H-6), 1.33-1.31 (2H, m, H-5); C NMR
(CDCl3, 100 MHz): δ 187.2 (C=O), 166.2 (C-2′′), 148.9 (C-3), 138.6 (C-1′), 136.2 (C-4′), 129.9
(C-2′, 6′), 129.7 (C-6′′), 129.3 (C-3′, 5′), 128.4 (C-4′′), 126.5 (C-2), 125.9 (C-1′′), 121.6 (C-5′′),
114.8 (C-3′′), 56.3 (OCH3), 32.9 (C-6), 32.6 (C-4), 29.8 (C-5), 26.2 (C-7); LC-MS: m/z 295.3
(M+H)+, 317.3 (M+Na)+.
7-(2-Methoxy-phenyl)-1-(2,4-dimethoxy-phenyl)-hept-2-en-1-one (11g): Weight: 462 mg; %
1
yield: 50.1 %; H NMR (CDCl3, 400 MHz): δ 7.68 (1H, d, J = 8.0 Hz, H-6′), 7.12 (1H, dd, J =
7.6, 3.2 Hz, H-6′′), 7.02 (1H, d, J = 17.2 Hz, H-2), 6.99 (1H, d, J = 16.4 Hz, H-3), 6.96 (1H, td, J
= 8.0, 3.2 Hz, H-4′′), 6.88 (1H, td, J = 8.0, 3.2 Hz, H-5′′), 6.74 (1H, dd, J = 7.6, 2.4 Hz, H-3′′),
6.58 (1H, dd, J = 7.6, 2.4 Hz, H-5′), 6.46 (1H, d, J = 2.4 Hz, H-3′), 3.82 (3H, s, OCH3), 3.78 (6H,
s, OCH3), 2.66 (2H, t, J = 8.0 Hz, H-7), 2.03 (2H, t, J = 7.2 Hz, H-4), 1.66-1.63 (2H, m, H-6),

1.33-1.31 (2H, m, H-5); 13C NMR (CDCl3, 100 MHz): δ 187.2 (C=O), 172.8 (C-4′), 166.4 (C-2′),
162.8 (C-2′′), 148.7 (C-3), 132.8 (C-6′), 129.4 (C-6′′), 126.8 (C-4′′), 126.3 (C-2), 125.6 (C-1′′),
122.6 (C-5′′), 118.6 (C-1′), 114.3 (C-3′′), 108.3 (C-5′), 101.8 (C-3′), 56.3 (OCH3), 55.8 (OCH3),
55.6 (OCH3), 32.8 (C-4), 32.4 (C-6), 29.8 (C-5), 26.2 (C-7); LC-MS: m/z 355.4 (M+H)+, 377.2
(M+Na)+.
7-(2-Methoxy-phenyl)-1-(3,4-dimethoxy-phenyl)-hept-2-en-1-one (11h): Weight: 465 mg; %
yield: 50.4 %; 1H NMR (CDCl3, 400 MHz): δ 7.38 (1H, dd, J = 7.2, 2.4 Hz, H-6′), 7.26 (1H, d, J
= 2.4 Hz, H-2′), 7.04 (1H, dd, J = 8.0, 3.2 Hz, H-6′′), 7.01 (1H, d, J = 16.4 Hz, H-2), 6.99 (1H, d,
J = 16.4 Hz, H-3), 6.94 (1H, td, J = 7.6, 3.2 Hz, H-4′′), 6.88 (1H, d, J = 7.2 Hz, H-5′), 6.79 (1H,
td, J = 8.0, 3.2 Hz, H-5′′), 6.72 (1H, dd, J = 7.6, 2.4 Hz, H-3′′), 3.82 (3H, s, OCH3), 3.78 (6H, s,
OCH3), 2.67 (2H, t, J = 8.0 Hz, H-7), 2.06 (2H, t, J = 8.0 Hz, H-4), 1.66-1.62 (2H, m, H-6), 1.33-
13
1.31 (2H, m, H-5); C NMR (CDCl3, 100 MHz): δ 187.2 (C=O), 166.2 (C-2′′), 158.3 (C-4′),
150.8 (C-3′), 148.5 (C-3), 132.6 (C-1′), 129.6 (C-6′′), 128.4 (C-4′′), 125.8 (C-2), 125.1 (C-1′′),
123.8 (C-6′), 120.6 (C-5′′), 118.3 (C-2′), 116.8 (C-5′), 114.3 (C-3′′), 56.3 (OCH3), 56.1 (OCH3),
56.0 (OCH3), 32.8 (C-4), 32.6 (C-6), 29.8 (C-5), 26.3 (C-7); LC-MS: m/z 377.4 (M+Na)+.
7-(2-Methoxy-phenyl)-1-(2,5-dimethoxy-phenyl)-hept-2-en-1-one (11i): Weight: 460 mg; %
1
yield: 49.9 %; H NMR (CDCl3, 400 MHz): δ 7.32 (1H, d, J = 3.2 Hz, H-6′), 7.08 (1H, dd, J =
7.6, 3.2 Hz, H-6′′), 7.02 (1H, d, J = 16.4 Hz, H-2), 6.99 (1H, d, J = 16.0 Hz, H-3), 6.96 (1H, td, J
= 8.0, 3.2 Hz, H-4′), 6.94 (1H, dd, J = 7.2, 2.4 Hz, H-4′′), 6.88 (1H, d, J = 7.2 Hz, H-3′), 6.79
(1H, td, J = 8.0, 3.2 Hz, H-5′′), 6.69 (1H, dd, J = 7.6, 2.4 Hz ,H-3′′), 3.82 (6H, s, OCH3), 3.78
(3H, s, OCH3), 2.67 (2H, t, J = 8.0 Hz, H-7), 2.03 (2H, t, J = 7.6 Hz, H-4), 1.73-1.68 (2H, m, H-
13
6), 1.33-1.30 (2H, m, H-5); C NMR (CDCl3, 100 MHz): δ 187.2 (C=O), 168.5 (C-2′′), 158.2
(C-2′), 156.9 (C-5′), 149.5 (C-3), 130.3 (C-6′′), 128.6 (C-4′′), 126.4 (C-2), 126.1 (C-1′′), 123.9
(C-1′), 121.8 (C-4′), 120.8 (C-5′′), 18.4 (C-6′), 116.3 (C-3′),114.8 (C-3′′), 56.5 (OCH3), 56.3
(OCH3), 55.8 (OCH3), 32.9 (C-4), 32.6 (C-6), 29.8 (C-5), 26.3 (C-7); LC-MS: m/z 355.3
(M+H)+, 377.3 (M+Na)+.
7-(3, 4-Dimethoxy-phenyl)-1-(phenyl)-hept-2-en-1-one (11j): Weight: 440 mg; % yield: 60.3
%;1H NMR (CDCl3, 400 MHz): δ 7.88 (2H, d, J = 7.2 Hz, H-2′, 6′), 7.56 (1H, d, J = 8.0 Hz, H-
4′), 7.48 (2H, d, J = 7.6 Hz, H-3′, 5′), 7.08 (1H, d, J = 17.2 Hz, H-2), 6.99 (1H, d, J = 16.4 Hz,
H-3), 6.83 (1H, d, J = 8.0 Hz, H-5′′), 6.68 (1H, dd, J = 7.6, 3.2 Hz, H-6′′), 6.52 (1H, d, J = 2.4
Hz, H-2′′), 3.78 (3H, s, OCH3), 3.76 (3H, s, OCH3), 2.66 (2H, t, J = 7.2 Hz, H-7), 2.08 (2H, t, J =

13
7.6 Hz, H-4), 166-1.62 (2H, m, H-6), 133-1.31 (2H, m, H-5); C NMR (CDCl3, 100 MHz): δ
187.6 (C=O), 151.2 (C-3′′), 148.9 (C-3), 146.8 (C-4′′), 142.8 (C-1′), 138.1 (C-4′), 134.8 (C-1′′),
132.6 (C-2′, 6′), 130.8 (C-3′, 5′), 128.4 (C-2), 126.3 (C-6′′), 116.3 (C-2′′), 116.1 (C-5′′), 56.3
(OCH3), 56.1 (OCH3), 36.8 (C-7), 32.8 (C-4), 32.1 (C-6), 29.6 (C-5); LC-MS: m/z 325.4
(M+H)+, 347.3 (M+Na)+.
7-(3, 4-Dimethoxy-phenyl)-1-(2-hydroxy-4-methoxy-phenyl)-hept-2-en-1-one (11k): Weight: 445
mg; % yield: 53.4 %; 1H NMR (CDCl3, 400 MHz): δ 7.68 (1H, d, J = 7.2 Hz, H-6′), 7.04 (1H, d,
J = 17.2 Hz, H-2), 6.99 (1H, d, J = 16.4 Hz, H-3), 6.81 (1H, d, J = 8.0 Hz, H-5′′), 6.61 (1H, dd, J
= 7.6, 2.4 Hz, H-6′′), 6.56 (1H, d, J = 2.4 Hz, H-2′′), 6.53 (1H, dd, J = 7.6, 3.2 Hz, H-5′), 6.44
(1H, d, J = 8.0 Hz, H-3′), 3.82 (3H, s, OCH3), 3.78 (6H, s, OCH3), 2.68 (2H, t, J = 8.0 Hz, H-7),
2.08 (2H, t, J = 7.6 Hz, H-4), 1.76-1.74 (2H, m, H-6), 133-1.28 (2H, m, H-5); 13C NMR (CDCl3,
100 MHz): δ 187.3 (C=O), 172.4 (C-4′), 166.2 (C-2′), 156.8 (C-3), 156.3 (C-3′′), 148.9 (C-4′′),
136.3 (C-1′′), 134.8 (C-6′), 128.5 (C-2), 126.2 (C-6′′), 118.9 (C-1′), 116.8 (C-2′′), 116.1 (C-5′′),
108.3 (C-5′), 101.8 (C-3′), 55.8 (OCH3), 55.6 (OCH3), 55.3 (OCH3), 36.9 (C-7), 31.9 (C-4), 31.3
(C-6), 29.1 (C-5); LC-MS: m/z 371.2 (M+H)+, 393.3 (M+Na)+.
7-(3, 4-Dimethoxy-phenyl)-1-(3,4-dimethoxy-phenyl)-hept-2-en-1-one (11l): Weight: 445 mg; %
yield: 51.4 %; 1H NMR (CDCl3, 400 MHz): δ 7.26 (1H, dd, J = 8.0, 3.2 Hz, H-6′), 7.21 (1H, d, J
= 3.2 Hz, H-2′), 7.03 (1H, d, J = 17.2 Hz, H-2), 6.98 (1H, d, J = 16.4 Hz, H-3), 6.91 (1H, d, J =
7.6 Hz, H-5′), 6.66 (1H, d, J = 7.6 Hz, H-5′′), 6.59 (1H, dd, J = 7.6, 2.4 Hz, H-6′′), 6.48 (1H, d, J
= 2.4 Hz, H-2′′), 3.78 (6H, s, OCH3), 3.72 (6H, s, OCH3), 2.68 (2H, t, J = 7.6 Hz, H-7), 2.13 (2H,
t, J = 8.0 Hz, H-4), 1.72-1.69 (2H, m, H-6), 1.33-1.31 (2H, m, H-5); 13C NMR (CDCl3, 100
MHz): δ 187.3 (C=O), 156.5 (C-4′), 148.6 (C-3′), 147.9 (C-3′′), 144.9 (C-4′′), 136.5 (C-1′′),
132.3 (C-1′), 128.6 (C-2), 126.1 (C-6′), 121.8 (C-6′′), 118.9 (C-2′), 116.8 (C-5′), 116.2 (C-2′′),
114.9 (C-5′′), 36.8 (C-7), 32.9 (C-4), 32.6 (C-6), 29.7 (C-5); LC-MS: m/z 385.4 (M+H)+, 407.3
(M+Na)+.
7-(3, 4-Dimethoxy-phenyl)-1-(2,5-dimethoxy-phenyl)-hept-2-en-1-one (11m): Weight: 450 mg;
% yield: 52.0 %; 1H NMR (CDCl3, 400 MHz): δ 7.28 (1H, d, J = 3.2 Hz, H-6′), 7.03 (1H, d, J =
17.2 Hz, H-2), 6.99 (1H, d, J = 16.4 Hz, H-3), 6.96 (1H, dd, J = 7.6, 2.4 Hz, H-4′), 6.88 (1H, d, J
= 7.6 Hz, H-3′), 6.63 (1H, d, J = 8.0 Hz, H-5′′), 6.58 (1H, dd, J = 8.0, 3.2 Hz, H-6′′), 6.52 (1H, d,
J = 3.2 Hz, H-2′′), 3.82 (6H, s, OCH3), 3.78 (6H, s, OCH3), 2.68 (2H, t, J = 7.2 Hz, H-7), 2.03
(2H, t, J = 7.6 Hz, H-4), 1.68-1.63 (2H, m, H-6), 1.33-1.31 (2H, m, H-5); 13C NMR (CDCl3, 100

MHz): δ 187.3 (C=O), 168.4 (C-5′), 166.7 (C-2′), 149.4 (C-3), 148.3 (C-3′′), 144.9 (C-4′′), 136.4
(C-1′′), 128.6 (C-2), 126.2( C-1′), 121.9 (C-6′′), 121.3 (C-4′), 118.9 (C-6′), 116.4 (C-3′), 114.9
(C-5′′), 114.8 (C-2′′), 56.3 (OCH3), 56.2 (OCH3), 55.8 (OCH3), 36.9 (C-7), 32.7 (C-4), 32.1 (C-
6), 29.7 (C-5); LC-MS: m/z 385.3 (M+H)+, 407.3 (M+Na)+.
7-(3, 4, 5-Trimethoxy-phenyl)-1-(phenyl)-hept-2-en-1-one (11n): Weight: 410 mg; % yield: 58.4
%;1H NMR (CDCl3, 400 MHz): δ 7.92 (2H, d, J = 7.2 Hz, H-2′, 6′), 7.58 (1H, d, J = 7.6 Hz, H-
4′), 7.46 (2H, d, J = 7.6 Hz, H-3′, 5′), 6.99 (1H, d, J = 16.4 Hz, H-2), 6.94 (1H, d, J = 16.0 Hz,
H-3), 6.18 (2H, s, H-2′′, 6′′), 3.78 (6H, s, OCH3), 3.72 (3H, s, OCH3), 2.68 (2H, t, J = 7.6 Hz, H-
13
7), 2.11 (2H, t, J = 7.2 Hz, H-4), 1.66-1.62 (2H, m, H-6), 1.38-1.33 (2H, m, H-5); C NMR
(CDCl3, 100 MHz): δ 188.2 (C=O), 154.2 (C-3′′, 5′′), 148.6 (C-3), 133.9 (C-1′), 137.5 (C-6′),
136.8 (C-1′′), 132.6 (C-4′′), 129.8 (C-2′, 6′), 129.2 (C-3′, 5′), 126.4 (C-2), 110.7 (C-2′′,6′′), 56.8
(OCH3), 56.6 (OCH3), 55.8(OCH3), 36.9 (C-7), 33.6 (C-4), 32.4 (C-6), 29.8 (C-5); LC-MS: m/z
355.3 (M+H)+, 377.2 (M+Na)+.
7-(3, 4, 5-Trimethoxy-phenyl)-1-(2-hydroxy-4-methoxy-phenyl)-hept-2-en-1-one(11o): Weight:
1
435 mg; % yield: 54.9 %; H NMR (CDCl3, 400 MHz): δ 7.62 (1H, d, J = 7.2 Hz, H-6′), 7.01
(1H, d, J = 16.4 Hz, H-2), 6.98 (1H, d, J = 16.0 Hz, H-3), 6.68 (1H, dd, J = 7.2, 3.2 Hz, H-5′),
6.48 (1H, d, J = 3.2 Hz, H-3′), 6.14 (2H, s, H-2′′, 6′′), 3.78 (6H, s, OCH3), 3.72 (3H, s, OCH3),
2.72 (2H, t, J = 7.6 Hz, H-7), 2.01 (2H, t, J = 7.2 Hz, H-4), 1.68-1.62 (2H, m, H-6), 1.48-1.42
(2H, m, H-5); 13C NMR (CDCl3, 100 MHz): δ 188.2 (C=O), 169.8 (C-4′), 159.6 (C-2′), 152.2 (C-
3′′, 5′′), 148.6 (C-3), 138.2 (C-1′′), 136.3 (C-6′), 132.8 (C-4′′), 128.2 (C-2), 118.5 (C-1′), 110.6
(C-2′′, 6′′), 108.4 (C-5′), 103.6 (C-3′), 56.8 (OCH3), 56.7 (OCH3), 55.9 (OCH3), 38.5(C-7), 33.7
(C-4), 32.8 (C-6), 29.8 (C-5); LC-MS: m/z 401.3 (M+H)+, 423.4 (M+Na)+.
7-(3, 4, 5-Trimethoxy-phenyl)-1-(3, 4-dimethoxy-phenyl)-hept-2-en-1-one (11p): Weight: 440 mg
; % yield: 53.6 %; 1H NMR (CDCl3, 400 MHz): δ 7.38 (1H, dd, J = 8.0, 3.2 Hz, H-6′), 7.21 (1H,
d, J = 3.2 Hz, H-2′), 7.08 (1H, d, J = 16.4 Hz, H-2), 6.99 (1H, d, J = 16.0 Hz, H-3), 6.91 (1H, d,
J = 8.0 Hz, H-5′), 6.14 (2H, s, H-2′′, 6′′), 3.86 (6H, s, OCH3), 3.78 (3H, s, OCH3), 3.72 (6H, s,
OCH3), 2.68 (2H, t, J = 8.0 Hz, H-7), 2.06 (2H, t, J = 7.6 Hz, H-4), 1.68-1.63 (2H, m, H-6), 1.31-
1.33 (2H, m, H-5); 13C NMR (CDCl3, 100 MHz): δ 187.6 (C=O), 159.2 (C-4′), 152.6 (C-3′′, 5′′),
152.8 (C-3′), 149.5 (C-3), 136.1 (C-1′′), 132.8 (C-4′′), 132.1 (C-1′), 128. (C-2), 126.3 (C-6′),
118.6 (C-2′), 115.7 (C-5′), 108.5 (C-2′′, 6′′), 56.8 (OCH3), 56.7 (OCH3), 56.4 (OCH3), 55.6

(OCH3), 55.3 (OCH3), 36.8 (C-7), 32.9 (C-4), 32.6 (C-6), 29.6 (C-5); LC-MS: m/z 415.4
(M+H)+, 437.2 (M+Na)+.
7-(3, 4, 5-trimethoxy-phenyl)-1-(2, 5-dimethoxy-phenyl)-hept-2-en-1-one (11q): Weight: 430 mg;
% yield: 52.2 %; 1H NMR (CDCl3, 400 MHz): δ 7.24 (1H, d, J =3.2 Hz, H-6′), 7.02 (1H, d, J =
17.2 Hz, H-2), 6.99 (1H, d, J = 16.4 Hz, H-3), 6.96 (1H, dd, J = 7.2, 2.4 Hz, H-4′), 6.88 (1H, d, J
= 7.2 Hz, H-3′), 6.09 (2H, s, H-2′′, 6′′), 3.78 (9H, s, OCH3), 3.76 (6H, s, OCH3), 2.68 (2H, t, J =
7.6 Hz, H-7), 2.04 (2H, t, J = 8.0 Hz, H-4), 1.78-1.73 (2H, m, H-6), 1.43-1.38 (2H, m, H-5); 13C
NMR (CDCl3, 100 MHz): δ 187.6 (C=O), 159.4 (C-2′), 156.3 (C-5′), 152.6 (C-3′′, 5′′), 148.9 (C-
3), 136.4 (C-1′′), 132.4 (C-4′′), 128.6 (C-2), 126.5 (C-1′), 122.8 (C-4′), 118.6 (C-6′), 116.5 (C-3′),
108.3 (C-2′′, 6′′), 56.3 (OCH3), 56.2 (OCH3), 56.1 (OCH3), 55.8 (OCH3), 38.6 (C-7), 33.7 (C-4),
32.8 (C-6), 29.8 (C-5); LC-MS: m/z 415.3 (M+H)+, 437.4 (M+Na)+.
General procedure for 7-(substituted-phenyl)-1-(substituted-phenyl)-hept-1-one (12a-q):
A mixture of any one of 7-(substituted-phenyl)-1-(substituted-phenyl)-hept-2-en-1-one (11a-q,
0.0015 mol), ethyl acetate (20 mL), and catalytic amount of palladium on CaCO3 then hydrogen
gas was passed through the reaction mixture for 1h. After completion of reaction which was
monitored by TLC hexane/ethyl acetate (8:2), the reaction mixture was filtered off on celite, and
was wash with ethyl acetate, the filtrate was concentrated. The crude residue was subjected to
column chromatography on silica gel; column was eluted with hexane/ethyl acetate mixtures.
Pure compound was eluted in ethyl acetate in hexane, 10 % / 90 % (v/v), which were monitored
by TLC and pure fractions were combined, concentrated to obtained 7-(substituted-phenyl)-1-
(substituted-phenyl)-hept-1-one (12a-q) with yields of 73 % - 84 % respectively.
7-(Phenyl)-1-(3, 4-dimethoxy-phenyl)-heptan-1-one (12a): Weight: 240 mg; % yield: 79.5 %; 1H
NMR (CDCl3, 400 MHz): δ 7.57 (1H, dd, J = 1.6, 8.0 Hz, H-6′), 7.53 (1H, d, J = 2.0 Hz, H-2′),
7.26 (2H, d, J = 7.2 Hz, H-3′′, 5′′), 7.16 (3H, d, J = 7.6 Hz, H-2′′, 4′′, 6′′), 6.87 (1H, d, J = 8.4 Hz,
H-5′), 3.93 (6H, s, OCH3), 2.91 (2H, t, J = 7.6 Hz, H-7), 2.61 (2H, t, J = 7.6 Hz, H-2), 1.76-1.69
(2H, m, H-6), 1.67-1.59 (2H, m, H-3), 1.41-1.39 (4H, m, H-4, 5); 13C NMR (CDCl3, 100 MHz):
δ 199.1 (C=O), 153.2 (C-4′), 149.1 (C-3′), 142.7 (C-1′′), 130.4 (C-1′), 128.4 (C-2′′), 128.3 (C-
6′′), 128.2 (C-3′′, 5′′), 125.6 (C-4′′), 122.7 (C-6′), 110.3 (C-2′), 110.0 (C-5′), 56.0 (OCH3), 55.9
(OCH3), 38.1 (C-2), 35.9 (C-7), 31.3 (C-6), 29.2 (C-4), 29.1 (C-5), 24.7 (C-3); LC-MS: m/z

327.4 (M+H)+, 349.4 (M+Na)+. Q-Tof: m/z 327.1965 [M+H]+ (Calculated for C21H27O3,
327.1960).
1
7-(Phenyl)-1-(2,5-dimethoxy-phenyl)-heptan-1-one (12b): Weight: 225 mg; % yield: 74.5 %; H
NMR (CDCl3, 400 MHz): δ 7.26 (2H, q, J = 4.0 Hz, H-3′′, 5′′), 7.21 (1H, d, J = 2.8 Hz, H-6′),
7.18 (3H, d, J = 6.0 Hz, H-2′′, 4′′, 6′′), 6.99 (1H, dd, J = 3.2, 8.8 Hz, H-4′), 6.88 (1H, d, J = 9.2
Hz, H-3′), 3.84 (3H, s, OCH3), 3.78 (3H, s, OCH3), 2.95 (2H, t, J = 7.6 Hz, H-7), 2.59 (2H, t, J =
8.0 Hz, H-2), 1.71-1.60 (4H, m, H-3, 6), 1.37-1.36 (4H, m, H-4, 5); 13C NMR (CDCl3, 100
MHz): δ 202.7 (C=O), 153.5 (C-2′), 152.8 (C-5′), 142.8 (C-1′′), 129.1 (C-2′′, 6′′), 128.4 (C-3′′,
5′′), 128.2 (C-4′′), 125.6 (C-1′), 119.5 (C-4′), 114.0 (C-6′), 113.2 (C-3′), 56.1 (OCH3), 55.8
(OCH3), 43.7 (C-2), 35.9 (C-7), 31.3 (C-6), 29.2 (C-4), 29.1 (C-5), 24.3 (C-3); LC-MS: m/z
327.3 (M+H)+, 349.4 (M+Na)+. Q-Tof: m/z 327.1965 [M+H]+ (Calculated for C21H27O3,
327.1960).
1
7-(4-Methoxy-phenyl)-1-(phenyl)-heptan-1-one (12c): Weight: 235 mg; % yield: 77.8 %; H
NMR (CDCl3, 400 MHz): δ 7.85 (2H, d, J = 7.2 Hz, H-2′, 6′), 7.45 (1H, t, J = 7.2 Hz, H-4′), 7.35
(2H, t, J = 7.6 Hz, H-3′, 5′), 6.98 (2H, d, J = 8.4 Hz, H-2′′, 6′′), 6.72 (2H, d, J = 8.8 Hz, H-3′′,5′′),
3.67 (3H, s, OCH3), 2.85 (2H, t, J = 7.2 Hz, H-7), 2.45 (2H, t, J = 8.0 Hz, H-2), 1.68-1.61 (2H,
13
m, H-6), 1.54-1.47 (2H, m, H-3), 1.31-1.25 (4H, m, H-4, 5); C NMR (CDCl3, 100 MHz): δ
200.3 (C=O), 157.6 (C-4′′), 137.1 (C-1′), 134.7 (C-4′), 132.7 (C-1′′), 129.2 (C-2′′, 6′′), 128.5 (C-
2′, 6′), 127.9 (C-3′, 5′), 113.6 (C-3′′, 5′′), 55.2 (OCH3), 38.5 (C-2), 34.9 (C-7), 31.4 (C-6), 29.1
(C-4), 28.9 (C-5), 24.2 (C-3); LC-MS: m/z 297.3 (M+H)+. Q-Tof: m/z 297.1866 [M+H]+
(Calculated for C20H25O2, 297.1855).
7-(4-Methoxy-phenyl)-1-(2, 4-dimethoxy-phenyl)-heptan-1-one (12d): Weight: 240 mg; % yield:
1
79.7 %; H NMR (CDCl3, 400 MHz): δ 7.56 (1H, dd, J = 1.2, 8.0 Hz, H-5′), 7.53 (1H, s, H-3′),
7.07 (2H, d, J = 8.4 Hz, H-2′′, 6′′), 6.87 (1H, d, J = 8.4 Hz, H-6′), 6.81 (2H, d, J = 8.4 Hz, H-3′′,
5′′), 3.94 (6H, s, OCH3), 3.78 (3H, s, OCH3), 2.90 (2H, t, J = 7.2 Hz, H-7), 2.55 (2H, t, J = 7.6
Hz, H-2), 1.76-1.69 (2H, m, H-6), 1.64-1.56 (2H, m, H-3), 1.39-1.36 (4H, m, H-4, 5); 13C NMR
(CDCl3, 100 MHz): δ 199.2 (C=O), 157.6 (C-2′), 153.2 (C-4′), 149.1 (C-4′′), 134.8 (C-1′′), 129.2
(C-6′), 122.6 (C-2′′, 6′′), 113.7 (C-1′), 110.3 (C-3′′, 5′′), 110.0 (C-5′), 101.4 (C-3′), 56.0 (OCH3),
55.9 (OCH3), 55.2 (OCH3), 38.1 (C-2), 34.9 (C-7), 31.5 (C-6), 29.3 (C-4), 29.0 (C-5), 24.6 (C-3);