Syntheses and antibacterial activities of 4 linear nonphenolic diarylheptanoids

Article abstract of DOI:10.3906/KIM-1911-61

Four linear nonphenolic diarylheptanoids were synthesized and their antibacterial activities were studied. (S)-2-Me-CBS-catalysed reduction of alnustone with BH₃.SMe₂gave (R) (-)(4E,6E)-1,7-diphenylhepta-4,6-dien-3-ol, a natural product. Reduction of alnustone with Na in t-BuOH at-15 °C under NH₃atm gave (E)-1,7-diphenylhept-5-en-3-one as a Birch-type reduction product. t-BuOK catalysed condensation of benzalacetone with propionyl chloride gave (4Z ,6E)-5-hydroxy-1,7-diphenylhepta-4,6-dien-3-one, a natural product. (1E,4Z ,6E)-5-Hydroxy-4-phenethyl-1,7-diphenylhepta-1,4,6-trien-3-one, a curcuminoid, was synthesized starting from pentan-2,4-dione in 3 steps. The synthesized chemical compounds were applied against 2 gram-positive bacteria (Bacillus cereus and Arthrobacter agilis), 4 gram-negative bacteria (Pseudomonas aeruginosa, Xanthomonas campestris, Klebsiella oxytoca, and Helicobacter pylori), and 1 yeast (Candida albicans) by the disc diffusion method. All of the synthesized compound exhibited different degrees of antimicrobial activity at concentrations between 20-100 μg/disc against the test organisms.

Full text of DOI:10.3906/KIM-1911-61

Turk J Chem
Turkish Journal of Chemistry
(2020) 44: 589 – 601
© TÜBİTAK
http://journals.tubitak.gov.tr/chem/
doi:10.3906/kim-1911-61
Research Article
Syntheses and antibacterial activities of 4 linear nonphenolic diarylheptanoids
1
2
Şemsi Betül DEMİR , Hatice SEÇİNTİ1,a, Neslihan ÇELEBİOĞLU1,a, Murat ÖZDAL ,
Alev SEZEN , Özlem GÜLMEZ , Ömer Faruk ALGUR2,∗, Hasan SEÇEN1,∗
2
2
1
Department of Chemistry, Faculty of Sciences, Atatürk University, Erzurum, Turkey
2
Department of Biology, Faculty of Sciences, Atatürk University, Erzurum, Turkey
Received: 27.11.2019
•
Accepted/Published Online: 06.03.2020
•
Final Version: 01.06.2020
Abstract: Four linear nonphenolic diarylheptanoids were synthesized and their antibacterial activities were studied.
(S)-2-Me-CBS-catalysed reduction of alnustone with BH3 .SMe2 gave (R)(-)(4E ,6E)-1,7-diphenylhepta-4,6-dien-3-ol,
a natural product. Reduction of alnustone with Na in t-BuOH at –15 °C under NH3 atm gave (E)-1,7-diphenylhept-5-
en-3-one as a Birch-type reduction product. t-BuOK catalysed condensation of benzalacetone with propionyl chloride
gave (4Z ,6E)-5-hydroxy-1,7-diphenylhepta-4,6-dien-3-one, a natural product. (1E ,4Z ,6E)-5-Hydroxy-4-phenethyl-
1,7-diphenylhepta-1,4,6-trien-3-one, a curcuminoid, was synthesized starting from pentan-2,4-dione in 3 steps. The
synthesized chemical compounds were applied against 2 gram-positive bacteria (Bacillus cereus and Arthrobacter agilis), 4
gram-negative bacteria (Pseudomonas aeruginosa, Xanthomonas campestris, Klebsiella oxytoca, and Helicobacter pylori),
and 1 yeast (Candida albicans) by the disc diffusion method. All of the synthesized compound exhibited different degrees
of antimicrobial activity at concentrations between 20–100 µg/disc against the test organisms.
Key words: Linear diarylheptanoid, curcuminoid, alnustone, natural product, synthesis, antimicrobial activity
1. Introduction
Diarylheptanoids, a special class of natural products, are compounds with the structure of Ar-C7 -Ar. Diaryl-
heptanoids are classified into 4 categories: i) phenolic or nonphenolic linear diarylheptanoids, ii) macrocyclic
diarylheptanoids, iii) macrocyclic diaryl ether heptanoids, and iv) C7 chain-cyclized diarylheptanoids [1]. Non-
phenolic diarylheptanoids constitute a special group of linear diarylheptanoids. Alnustone (1) is one of the
first examples of nonphenolic diarylheptanoids (Figure 1). The first isolation of alnustone was performed from
Alnus pendula by Suga et al. [2,3]. Several studies showed that alnustone (1) is a bioactive molecule in a broad
spectrum. On this basis, it has been reported to have antihepatotoxic [4], anti-inflammatory [5], antibacterial
[6], antiemetic [7], and estrogenic activity [8].
(4E ,6E)-1,7-Diphenylhepta-4,6-dien-3-ol (-) (2), a natural diarylheptanoid, was first isolated from Cur-
cuma xanthorrhiza by Claeson et al. [5] and was reported to exhibit significant antiinflammatory activity.
Jurgens et al. [9] isolated compound 2 from Curcuma comosa. The following isolation of (R)-2 was performed
by Suksamrarn et al. [8] and was reported to exhibit a good level of phytoestrogenic activity. In further studies,
Tantikanlayaporn et al. [10,11] isolated (R)-2 from Curcuma comosa and reported its very strong phytoestro-
genic activity.
∗Correspondence: hsecen@atauni.edu.tr (Chemistry); ofalgur@yahoo.com(Biology).
a
These authors contributed equally to this work.
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This work is licensed under a Creative Commons Attribution 4.0 International License.

DEMİR et al./Turk J Chem
Figure 1. Alnustone-like natural nonphenolic diarylheptanoids.
Zhang et al. [12] reported (E)-1,7-diphenyl-5-hepten-3-one (3) and compound 5 as new natural diaryl-
heptanoids with strong antibacterial activity against Helicobacter pylori.
Compounds 4 and 5 are natural nonphenolic diarylheptanoids having a dihydrocurcumin structure from
the aspect of the C-7 chain. Diarylheptanoid 4 was first isolated from the seeds of Alpinia katsumadai Hayata
by Kuroyanagi et al. [13] and later isolated from Alnus maximowiczii [14], Alpinia officinarum Hance [15], and
Curcuma ecalcarata [16]. Grienke et al. [17] reported (E ,E)-5-hydroxy-1,7-diphenyl-4,6-heptadien-3-one, the
E ,E isomer of 4, to have strong neuraminidase inhibitory activity.
Alnustone (1) itself was synthesized from several starting materials using different synthetic methods [18–
21]. In our previous studies we described an efficient method for the preparation of alnustone (1) itself [22] and
alnustone-like compounds [23], and their antitumor activities against estrogen receptor alpha-positive human
breast cancer.
Compound 4 was first synthesized by thermolysis of ethyl 3-oxo-5-phenyl-2-(cinnamoyl)pentanoate by
Borsche and Lewinsohn [24]. Kato et al. [21] synthesized compounds 2 and 4 starting from 3-phenylpropanoic
acid in many steps. A semisynthetic procedure for the preparation of (R/S)-2 was described by Yang et al.
[25] via NaBH4 reduction of alnustone (1).
To the best of our knowledge, the enantioselective synthesis of R-(2) and total synthesis of compound 3
are not known in the literature. In this study we report the first enantioselective synthesis of compound R-(2),
its enantiomer S -(2), and 3 via chemoselective reduction of alnustone (1). Moreover, we report an efficient
one-pot synthesis of compound 4 and an attempted synthesis of compound 5 (Figure 1).
2. Results and discussion
In our synthetic strategy, syntheses of compounds (R)-2, (S)-2, and 3 were based on reduction of alnustone (1).
As mentioned above, efficient synthesis of alnustone (1) was previously reported by our research group [22,23].
If one considers the relationship between alnustone (1) and (R)-2 or (S)-2, it can be readily seen that (R)-2
and (S)-2 could be obtained from enantioselective reduction of the carbonyl group of alnustone (1). Chiral
oxazaborolidines have been used as reagents or catalysts (with borane sources) for enantioselective reduction of
prochiral ketones [26]. In this manner, Corey et al. [27] efficiently used (S)-2-methyl-CBS-oxazaborolidine as a
catalyst with BH3 in the enantioselective reduction of aryl ketones to give the corresponding chiral alcohols with
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predominant R configuration (ee ~84-96.7%). We proposed that alnustone (1) itself may be successively reduced
to give the corresponding alcohol (R)-2 by following this methodology. Indeed, while (S)-2-Me-CBS-catalysed
reduction of alnustone (1) gave alcohol (R)-2 (ee 90%), (R)-2-Me-CBS-catalysed reduction gave alcohol (S)-2
(ee 90%) in good yield (80%) where the ee values were determined by chiral HPLC. The absolute configuration
of alcohol (R)-2 was determined by agreement of its specific rotation with data given in the literature for
natural (R)-2 [8]. The opposite specific rotation obtained for alcohol (S)-2 also confirmed its structure. The
NaBH4 reduction [25] of alnustone (1) also gave racemic-2 in 80% yield (Figure 2).
Figure 2. Syntheses of (R)-2, (S)-2, and (R/S)-2. i) BH3 .SMe2 , (S)-2-Me-CBS, THF, 0 °C, N2 atm, 4 h, 80%; ii)
BH3 .SMe2, (R)-2-Me-CBS, THF, 0 °C, N2 atm, 4 h, 80%; iii) NaBH4, EtOH, 0 °C, 4 h, 80%.
1
For the structure of (R)-2 or (S)-2, the H-NMR spectrum of the C7 chain showed 2 AB systems
belonging to the olefinic HC (6)- HC (7) at δ6.79 and δ6.57 and to HC (4)- HC (5) at δ5.86 and δ6.40, a
quartet belonging to HC (3) at δ4.24, and multiplets belonging to H2 C(1) at δ2.81-2.68 and H2 C(2) at δ2.05-
1.80. The absence of a carbonyl peak and the 3 aliphatic carbons at 72.2 (C(3)), 38.9 (C(1)), and 31.9 (C(2))
1
13
confirmed the reduction of the carbonyl group. Both H-NMR and C-NMR spectra of (S)-2 and (R)-2 were
in agreement with the data given for (R)-2 in the literature [5,9]. Thus, we easily synthesized enantioselectively
the natural compound (R)-2 and its enantiomer (S)-2 (Figure 2).
Mechanistically, the enantioselective formation of (R)-2 and (S)-2 is in good agreement with the results
reported by Corey et al. [27]. As seen in Figure 3, both the ethyl phenyl ketone and alnustone (1) are reduced
by hydride transformation from si faces.
We proposed that synthesis of compound 3 from alnustone (1) could be performed by a Birch reaction,
which reduces 1,3-butadienes to 2-butenes. However, classical Birch reduction of alnustone (1) with metallic
lithium in liquid NH3 yielded a mixture with many undesirable reduction products. Therefore, instead of the
classical Birch reduction conditions, the modification by Menzek et al. [28,29] was applied to obtain 3. This
modification successfully allowed reduction to the conjugated 1,3-diene moiety of aromatic compounds using
metallic lithium or sodium as the reducing agent in Et2 O and t-BuOH under NH3 (gas). Thus, reduction of
alnustone (1) with 2.5 molar eq. Na as a reducing agent afforded compound 3 in a yield of 85% via Menzek’s
method (Figure 4).
1
The H-NMR spectrum of compound 3 was in exact agreement with its structure, in which olefinic
hydrogens HC (5) at δ5.67 and HC (6) at δ5.74 arose as an AB system splitting into triplets (J5,6 = 15.4
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DEMİR et al./Turk J Chem
re face
(S)-Reagent
HO
(R)
O
H
Corey et al. (Ref.27)
attack from si face
si face
re face
(S)-Reagent
HO
Ph
H
Ph
O
attack from si face
(R)
Ph
Ph
si face
Figure 3. (S)-Oxazaborolidine-catalysed reduction of ethyl phenyl ketone and alnustone (1) with BH3 .SMe2 .
Figure 4. Preparation of compound 3. i) Na, t-BuOH, dry ether, –15 °C, NH3 atm, 15 min, 85%.
Hz, J4,5 = 6.3 Hz, J6,7 = 6.2 Hz). In this context, H2 C(4) at δ3.17 and H2 C(7) at δ3.43 also resonated
as doublets. The spectral values belonging to H2 C(4) and H2 C(7) of compound 3 are in good agreement with
allylbenzene and 4-penten-2-one, 2 similar structures. In the structures, the CH2 of 4-penten-2-one resonates
at δ3.19 ppm with J = 6.9 Hz [30], and the CH2 of allylbenzene resonates at δ3.33 ppm with J = 6.7
Hz [31] (Figure 5). In double-resonance experiments, irradiation of both olefinic protons together, HC(5) and
HC(6), converted doublets of H2 C(4) and H2 C(7) to singlets, which supports the CH2 -CH=CH-CH2 structure.
H2 C(1) at δ2.96 and H2 C(2) at δ2.81 also resonated as triplets. The HR-ESI-MS spectrum of compound 3
was also in good agreement with the structure of compound 3 (C19 H20 NaO: 287.1418). HMBC correlations of
compound 3 are given in Figure 6.
1
However, the H-NMR data of the heptenone part of compound 3 were in full disagreement with the
reported data of Zhang et al. [12]. H/C assignments of the heptenone skeleton for synthetic compound 3
1
compared with data of the isolated 3 are given in Table 1. For example, they reported H-NMR data for
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DEMİR et al./Turk J Chem
Figure 5. δ and J values of 4-penten-2-one and allylben-
zene.
Figure 6. HMBC (H → C) correlations of compound 3.
H2 C(4) at δ2.74 (d, J = 2.9 Hz, 2H) and H2 C(7) at δ2.77 (d, J = 2.9 Hz), which are also in disagreement
with 4-penten-2-one and allylbenzene.
Nonetheless, for compound 3 isolated by Zhang et al. [12], the presence of 2 phenyl rings, 1 carbonyl, 4
CH2 , 1 CH=CH, and especially the HRMS results are in agreement with C19 H20 O which implies a structural
isomer of compound 3.
Table 1. H/C assignments of the heptenone skeleton for synthetic and isolated compound 3.
O
5
1
7
3
Ph
Ph
3
2
4
6
12
H/C Synthetic 3
Isolated 3 (Ref. )
1
2
3
4
5
6
7
2.96 (t, J = 7.5) 30.0
2.81 (t, J = 7.5) 44.0
- 208.4
3.17 (d, J = 6.3) 47.1
5.67 (dt, J = 15.4, 6.3) 123.6 6.10 (dt, J = 15.3, 7.0) 127.1
5.74 (dt, J = 15.4, 6.2) 134.0 6.12 (dt, J = 15.3, 7.0) 147.3
2.87–2.95 (m) 29.8 45.7
- 210.9
2.74 (d, J = 2.9) 30.8
3.43 (d, J = 6.2) 39.3
2.77 (d, J = 2.9) 35.0
Thus, we synthesized compound 3 starting from alnustone (1) in a 1-step reaction, which is the first
reported synthetic method for compound 3.
For the simple synthesis of compound 4, we modelled a reaction described by Krishnamurty and Ghosh
[32] for synthesis of dihydrocurcumin, in which they synthesized dihydrocurcumin via C-acylation of O-protected
vanillylidene acetone with O-protected dihydroferuloyl chloride. We applied this methodology with a few
t
modifications by treatment of benzalacetone (6) with KOBu at 0 °C and reacting with 3-phenylpropanoyl
chloride to give compound 4 in a yield of 60% (Figure 7).
t
Figure 7. Synthesis of compound 4. i) KOBu , THF, 0 °C, 30 min; then 3-phenylpropanoyl chloride, rt, 12 h, 60%.
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DEMİR et al./Turk J Chem
1
In the H-NMR spectrum of compound 4 the C7 chain has an AB system belonging to HC(7) at δ7.60
and HC(6) at δ6.46, a singlet belonging to HC(4) at δ5.64, and an A2 B2 system belonging to H2 C(2) at δ2.74
1
13
and H2 C(1) at δ3.00. The H-NMR and C-NMR spectra are in agreement with the data given for natural
product 4 [13].
If we consider the similarity between compounds 4 and 5, we readily see that 5 is the alkylated
derivative of compound 4. Therefore, we proposed that we could readily obtain 5 by alkylating 4 with 2-
t
phenylethylbromide. However, alkylation of 4 to give 5 with bases such as LDA, NaH, and KOBu was not
successful. In another attempted synthesis, we proposed that an alkylation of 6 with PhCH2 CH2 Br and then
acylation with 3-phenylpropanoyl chloride could give compound 5. However, the first step of this attempted
synthesis afforded styrene, an elimination product, instead of the expected (E)-1,6-diphenylhex-1-en-3-one.
Figure 8. Attempted synthesis of compound 5. i) 2-Phenylacetaldehyde, pyrrolidine, AcOH, benzene, 80 °C reflux, 18
h, 42%; ii) H2 , Pd-C (cat), AcOEt, 25 °C, 3 h, 75%; iii) B2 O3 , benzaldehyde, morpholine, AcOH, microwave, 2450
MHz, 1 min, 34%; iv) Zn, AcOH, 118 °C reflux, 12 h, 76%; v) Zn(OAc)2 (1.1 molar eq.), AcOH, 118 °C reflux, 12 h,
70%.
Therefore, we decided to apply a different strategy, where 2,4-pentanedione was first condensed with 2-
phenylacetaldehyde in the presence of AcOH and pyrrolidine to give 8 as a sole compound (Figure 8). Catalytic
hydrogenation of 8 gave 9 as a keto-enol tautomer. Nichols et al. [33] developed a practical methodology
for solvent-free microwave-assisted synthesis of curcumin analogues based on B2 O3 -mediated condensation of
2,4-pentanedione with benzaldehydes in the presence of morpholine and AcOH. Applying this methodology to
9 with benzaldehyde gave curcuminoid 10.
Curcuminoid 10 and natural product 5 differ from each other with a hydrogenated double bond. There-
fore, we applied selective reduction of the double bonds of compound 10. Changtam et al. [34] reported an
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DEMİR et al./Turk J Chem
easy procedure for preparing dihydrocurcumin by reduction of curcumin with Zn in AcOH. However, applying
this methodology to curcuminoid 10 gave cyclic compound 11. We proposed that this cyclization might oc-
cur with Zn(OAc)2 formed in situ in the reaction medium. Indeed, an independent reaction performed with
Zn(OAc)2 supported this hypothesis with the formation of 11 from 10 in good yield (70%) (Figure 8). However,
attempted selective reduction of compound 10 with Na or Mg to give 5, failed.
The synthesized chemical compounds 1, (R)-2, (S)-2, (R/S)-2, 3, 4, 10, and 11 were applied against 2
gram-positive bacteria (Bacillus cereus and Arthrobacter agilis), 4 gram-negative bacteria (Pseudomonas aerug-
inosa, Xanthomonas campestris, Klebsiella oxytoca, and Helicobacter pylori), and 1 yeast (Candida albicans)
by disc diffusion method. The antimicrobial activity of the chemicals was variable, as seen in Table 2. All
the synthesized chemicals showed different degrees of antimicrobial activity at concentrations of 30–90 µg/disc
against the test organisms.
Table 2. Minimum inhibitory concentrations (µg/disc) of tested compounds against selected microorganisms.
Tested compounds (µg/disc)
Microorganisms
1
(S)-2 (R)-2 (R/S)-2
3
4
10 11
Gram (-) bacteria
H. pylori
X. campestris
K. oxytoca
40 40
60 60
50 50
50 60
30 40
50 40
40 60
50
60
40
60
40
40
60
50
50
50
60
30
30
50
30 70 70 60
50 70 70 60
30 70 70 60
40 70 70 60
30 80 70 70
30 70 70 60
40 90 70 70
P. aeruginosa
Gram (+) bacteria B. cereus
A. agilis
C. albicans
Yeast
Each value is expressed as mean (n = 3). Inhibition zone was greater than 7 mm. These evaluations
were carried out by diffusion disc tests.
Compound 3 was highly antibacterial against K. oxytoca, A. agilis, B. cereus, and H. pylori. Additionally,
3 and 1 were observed to have stronger inhibitory effects against C. albicans. Among the compounds, 4
was determined as the least effective against the microorganisms. Ofloxacin and nystatin are well known as
antibacterial and antifungal substances, respectively. The average inhibition zones of ofloxacin and nystatin
were found to be 22 and 20 mm, respectively.
In conclusion, we developed an easy synthesis of diarylheptanoids (R)-2 and (S)-2, 3, and 4. An
attempted synthesis of compound 5 gave a cyclocurcumin derivative (11).
The results of this study indicate that the synthesized chemicals showed dose-dependent inhibition against
the tested microorganisms. This result may suggest that alnustone (1) and dihydroalnustone (3) structures can
be developed for new antibiotic drugs.
3. Experimental
1
13
THF was used by distillation over Na. H- and C-NMR spectra were recorded with 400 (100) MHz Bruker
and Varian instruments. Interchangeable hydrogens or carbons were shown with the same letters. Elemental
analyses were performed with a LECO CHNS-932. HRMS spectra were recorded with an Agilent 6530 LC-MS
QTOF. Enantiomeric excesses were determined by HPLC analysis using a chiral column eluting n-hexane–i-
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PrOH (90:10), and detection was performed at 210–254 nm. Optical rotations were measured on a Bellingham
Stanley ADP220 589-nm spectropolarimeter. All percent yields were calculated from isolated compounds.
3.1. (4E,6E)-1,7-Diphenylhepta-4,6-dien-3-one(alnustone) (1)
Compound1was synthesized as described in our previous studies [22,23].
3.2. (R,4E,6E)-1,7-Diphenylhepta-4,6-dien-3-ol (R)-2
Under N2 atmosphere, 2 M BH3 .SMe2 in THF (0.12 mL, 0.24 mmol) was dissolved in THF (2 mL), cooled to
0 °C, and 1 M (S)-2-Me-CBS in toluene (0.05 mL, 0.050 mmol) was added. After the reaction mixture was
stirred at the same temperature for 1 h, alnustone (1) (100 mg, 0.38 mmol) was added to the reaction mixture.
The resulting mixture was stirred for 4 h at 0 °C and MeOH (3 mL) was added, stirred for 15 min, and warmed
to room temperature. The solvent was evaporated in vacuo, and a solution of saturated NH4 Cl (2 mL) was
added. The organic solution was extracted with AcOEt (3 ×25 mL) and dried (Na2 SO4). The solvent was
removed and the residue was purified by silica gel column chromatography with AcOEt/hexane (20:80) to give
compound (R)-2 as a light-yellow oil (80 mg, 80%). Enantiomeric excess: 90%. Rf (AcOEt/hexanes 2:8): 0.4.
27
27
1
[α]D = –53.3°(EtOH, c = 0.3 g/100 mL). Lit [8]: [α]D = –64.2°(EtOH, c = 0.3 g/100 mL). H-NMR (400
MHz, CDCl3): δ 7.41–7.19 (m, 10 arom. H), 6.79 (dd, HC(6), J6,7 = 15.7, J5,6 = 10.6 Hz), 6.57 (d,
HC(7), J6,7 = 15.7 Hz), 6.40 (dd, HC(5), J4,5 = 15.2, J5,6 = 10.6 Hz), 5.86 (dd, HC(4), J4,5 = 15.2,
13
J3,4 = 7.0 Hz), 4.24 (q, HC(3), J = 6.4 Hz), 2.81–2.68 (m, H2 C(1)), 2.05–1.80 (m, H2 C(2)) ppm; C-NMR
(100 MHz, CDCl3): δ142.0 (C(1”)), 137.3 (C(1’)), 136.5 (C(4)), 133.0 (C(7)), 131.2 (C(5)), 128.8 (C(3’/5’)),
128.7 (C(2”/6”)), 128.6 (C(2’/6’)), 128.4 (C(4’)), 127.8 (C(4”)), 126.6 (C(3”/5”)), 126.1 (C(6)), 72.2 (C(3)),
38.9 (C(1)), 31.9 (C(2)) ppm; Anal. Calcd. for C19 H20 O.1.3 H2 O (MW 264.37): C, 79.3; H, 7.92%. Found:
C, 78.94; H, 7.43%.
1
13
The H-NMR and C-NMR data are in agreement with data given in the literature [5,9].
3.3. (R,4E,6E)-1,7-Diphenylhepta-4,6-dien-3-ol(S)-2
The procedure given above for synthesis of (S)-2 was applied using (R)-2-Me-CBS to give compound (S)-2
27
(80 mg, 80%). Rf (AcOEt/hexanes 2:8): 0.4. Enantiomeric excess: 90%. [α]D
=
+53.3°(EtOH, c = 0.3
g/100 mL). ee: 0.90. Anal. Calcd. for C19 H20 O.1.05 H2 O (MW 264.37): C, 80.56; H, 7.86%. Found: C, 80.35;
H, 7.63%.
3.4. (4E,6E)-1,7-Diphenylhepta-4,6-dien-3-ol(R/S)-2
Alnustone (1) (300 mg, 1.14 mmol) was dissolved in EtOH and NaBH4 (50 mg, 1.31 mmol) was added, and the
mixture was stirred for 4 h, monitored by TLC. The reaction mixture was cooled down to 0 °C and saturated
aq. NH4 Cl solution (2 mL) was added. The resulting aqueous solution was extracted with AcOEt (3 ×75
mL), and the organic phase was dried (Na2 SO4). The solvent was removed and the residue was purified by
silica gel column chromatography eluting with AcOEt/hexane (20:80) to give (R/S)-2 (0.250 g, 80%). Rf
(AcOEt/hexanes 2:8): 0.5.
3.5. (E)-1,7-Diphenylhept-5-en-3-one(3)
Alnustone (1) (100 mg, 0.38 mmol) dissolved in dry Et2 O (20 mL) was put into a 50-mL double-necked flask.
A plastic balloon was connected to 1 neck of the flask and the other neck was fastened to a supply of NH3
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DEMİR et al./Turk J Chem
(gas). The solution was deoxygenated by the passing of 15 L of NH3 (gas) and kept under NH3 atmosphere
by the filled balloon. The mixture was cooled to –15 °C, and then metallic Na (20 mg, 0.95 mmol) was added.
At the same temperature, the reaction mixture was stirred for approximately 4 min, and then t-BuOH (70 mg,
0.95 mmol) was added and the reaction mixture was stirred for 16 min. At this stage, the colour of the reaction
mixture changed to dark green as monitored by TLC and the completion of the reaction was observed. EtOH
(15 mL) was added to quench the reaction mixture and then all solvents were removed under reduced pressure.
The residue was dissolved in H2 O (5 mL) and extracted with AcOEt (4 ×15 mL). The combined organic
phase was dried on Na2 SO4 and filtered. Evaporation of the solvent gave a crude product, which was then
chromatographed on a silica gel column eluting with 95:5 AcOEt/hexane solvent mixture to give light yellow
1
oily compound 3 (85 mg, 85%). Rf (AcOEt/hexanes 1:9): 0.64. H-NMR (400 MHz, CDCl3): δ7.37–7.23
(m, 10 arom. H), 5.74 (dt, A of AB, HC(6), J5,6 = 15.4 Hz, J6,7 = 6.2 Hz), 5.67 (dt, B of AB, HC(5),
J5,6 = 15.4 Hz, J4,5 = 6.3 Hz), 3.43 (d, H2 C(7), J6,7 = 6.2 Hz), 3.17 (d, H2 C(4), J4,5 = 6.3 Hz),
13
2.96 (t, H2 C(1), J = 7.5 Hz), 2.81 (t, 2H, H2 C(2), J = 7.5 Hz) ppm; C-NMR (100 MHz, CDCl3): δ208.4
(C(3)), 141.3 (C(1’)), 140.4 (C(1”)), 134.0 (C(6)), 128.80 (C(3’/5’)), 128.78 (C(3”/5”)), 128.6 (C(2’/6’)), 128.4
(C(2”/6”)), 126.4 (C(4’/4”)), 123.6 (C(5)), 47.1 (C(4)), 44.0 (C(2)), 39.3 (C(7)), 30.0 (C(1)) ppm; Anal. Calcd.
+
for C19 H20 O (MW 264.37): C, 86.32; H, 7.63%. Found: C, 86.96; H, 7.80%. HR-ESI-MS: 287.1418 [M+Na] ;
calc. 287.1406.
3.6. (4Z,6E)-5-Hydroxy-1,7-diphenylhepta-4,6-dien-3-one(4)
t
Under N2 atmosphere, a solution of KOBu (300 mg, 2.65 mmol) in anhydrous THF (15 mL) was cooled to
0 °C and (E)-4-phenylbut-3-en-2-one (6) (200 mg, 1.37 mmol) in anhydrous THF (20 mL) was added to the
solution. The mixture was stirred for 30 min, and then 3-phenylpropanoyl chloride (230 mg, 1.37 mmol) was
added. The mixture was stirred at room temperature for 12 h. An aq. sat. NH4 Cl solution (3 mL) was added
to the mixture at 0 °C. THF was evaporated, and the organic phase was extracted with AcOEt (2 ×50 mL)
and dried over Na2 SO4 . Evaporation of the solvent and silica gel column chromatography of the residue with
hexane/AcOEt 95:5 gave 4 as light-yellow crystals (228 mg, 60%). Rf (AcOEt/hexanes 1:9): 0.80. Mp 67–68
13
1
°C (Lit : 74–75 °C from hexane). 4: H-NMR (400 MHz, CDCl3): δ 15.3 (s, 1H, OH), 7.60 (d, 1H, HC(7),
J = 15.7 Hz), 7.42–7.20 (m, 10 arom. H), 6.46 (d, 1H, HC(6), J = 15.7 Hz), 5.64 (s, 1H, HC(4)), 3.00 (t, 2H,
13
H2 C(1), J = 7.8 Hz), 2.74 (t, 2H, H2 C(2), J = 7.8 Hz) ppm; C-NMR (100 MHz, CDCl3): δ 199.9 (C(3)),
a
a
176.7 (C(5)), 140.8 (C(1”)), 139.8 (C(7)), 135.1 (C(1’)), 129.9 (C(4’)), 128.9 (C(3’/5’ )), 128.5 (C(2’/6’ )),
a
a
128.3 (C(3”/5” )), 127.9 (C(2”/6” )), 126.2 (C(4”)), 122.7 (C(6)), 100.8 (C(4)), 41.9 (C(2)), 31.2 (C(1)) ppm.
1
13
The H-NMR and C-NMR data are in agreement with the data given for isolated natural product 4 [13].
Anal. Calcd. for C19 H18 O2 (MW 278.35): C, 81.99; H, 6.52%. Found: C, 82.13; H: 6.53%.
3.7. (Z)-4-Hydroxy-3-((E)-styryl)pent-3-en-2-one(8)
To pentan-2,4-dione (7) (7.000 g, 69.9 mmol) in benzene (50 mL) was added 2-phenylacetaldehyde (8.40 g,
69.9 mmol), a catalytic amount of anhydrous AcOH (0.35 mL), and pyrrolidine (0.56 mL). Using a Dean-
Stark apparatus the reaction mixture was refluxed for 18 h with monitoring by TLC. After cooling to ambient
temperature, the mixture was diluted with Et2 O (50 mL) and H2 O (25 mL). The organic layer was separated
and washed with H2 O (25 mL), 1 M HCl (2 ×25 mL), and a saturated solution of NaHCO3 (10 mL). The
organic layer was dried over Na2 SO4 . Evaporation of the solvent and column chromatography of the residue
597

DEMİR et al./Turk J Chem
1
with hexane/AcOEt 9:5 gave 8 as a dark yellow oil (5.96 g, 42%). Rf (AcOEt/hexanes 1:9): 0.60. H-NMR
(400 MHz, CDCl3): δ 16.74 (s, 1H, OH), 7.44–7.34 (m, 5 arom. H), 6.75 (d, 1H, styryl, J = 16.1 Hz), 6.42 (d,
13
1H, styryl, J = 16.1 Hz), 2.22 (s, 6H, 2 ×CH3) ppm; C-NMR (100 MHz, CDCl3): δ 191.4 (C(2/4)), 137.4
(C(1”, Ph)), 134.5 styryl (C(1)), 128.9 (C(3”/5”, Ph)), 128.0 (C(2”/6”, Ph)), 126.4 (C(4”, Ph)), 123.1 styryl
1
13
(C(2)), 111.6 (C(3)), 24.5 (C(1/5)) ppm. The H-NMR and C-NMR data are in agreement with data given
in the literature [35].
3.8. (Z)-4-Hydroxy-3-phenethylpent-3-en-2-one(9)
Pd/C (10%) (69 mg) was added to EtOAc (50 mL) cooled to 0 °C and then (Z)-4-hydroxy-3-((E)-styryl)pent-
3-en-2-one (8) (690 mg, 3.41 mmol) in AcOEt (20 mL) was added to the 100-mL double-necked flask. A
balloon filled with H2 gas (3 L) was fitted to the flask. The mixture was deoxygenated by flushing with H2
and then hydrogenated for 3 h at room temperature. When TLC analyses indicated the disappearance of the
starting material, the catalyst was removed by filtration. Removal of the solvent under reduced pressure gave
1
9 as a keto-enol tautomer and light-yellow oil ((9a):(9b) = 2:1) (520 mg, 75%). 9a: H-NMR (400 MHz,
CDCl3): δ 7.31–7.15 (m, 5 arom. H), 3.63 (t, 1H, HC(3), J = 7.3 Hz), 2.70 (t, 2H, PhCH2 CH2 , J = 7.8
13
Hz), 2.22–2.12 (CHCH2 CH2 Ph), 2.14 (s, 6H, 2×CH3) ppm; C-NMR (100 MHz, CDCl3): δ 204.3 (C(2/4)),
141.2 (C(1” of Ph)), 128.8 (C(3”/5” of Ph)), 128.8 (C(2”/6” of Ph)), 126.6 (C(4” of Ph)), 68.1 (C(3)); 33.7
1
(PhCH2 CH2), 29.9 (PhCH2 CH2), 29.4 (C(1/5)) ppm. 9b: H-NMR (400 MHz, CDCl3): δ 16.83 (s, 1H,
13
OH), 7.31-7.15 (m, 5 arom. H), 2.59–2.52 (A2 B2 system, 4H, CH2 CH2), 2.03 (s, 6H, 2 ×CH3) ppm; C-NMR
(100 MHz, CDCl3): δ 191.6 (C(2/4)), 140.8 (C(1” of Ph)), 128.8 (C(3”/5” of Ph)), 128.7 (C(2”/6” of Ph)),
126.5 (C(4” of Ph)), 109.6 (C(3)), 37.0 (PhCH2 CH2), 29.9 (PhCH2 CH2), 22.9 (C(1/5)), 2.81 (t, 2H, H2 C(2),
J = 7.5 Hz), 5.74 (dt, A of AB, HC(6), J5,6 = 15.4 Hz, J6,7 = 6.2 Hz).
3.9. (1E,4Z,6E)-5-Hydroxy-4-phenethyl-1,7-diphenylhepta-1,4,6-trien-3-one(10)
Compound 9 (1.2 g, 5.87 mmol) was mixed with boric anhydride (400 mg, 5.74 mmol) in a 250-mL Erlenmeyer
flask. Benzaldehyde (1.25 g, 1.2 mL, 11.77 mmol), morpholine (300 mg, 0.3 mL, 3.44 mmol), and acetic acid
(210 mg, 0.2 mL, 3.5 mmol) were then added to the mixture. The reaction was irradiated in a kitchen-type
microwave (2450 MHz) for 1 min. The flask was cooled and then MeOH (30 mL) was added. This mixture
was then sonicated in a sonicator for 10 min. The suspended mixture was taken onto filter paper and washed
with MeOH cooled to 0 °C, and then the MeOH-soluble part was removed. The solid part remaining on the
paper was dried in air. Thus, compound 10 was obtained as a sole enol form (0.75 g, 34%). Yellow crystal. Mp
1
151–152 °C. H-NMR (400 MHz, CDCl3): δ 17.60 (s, 1H, OH), 7.73 (d, 2H, HC(1/7), J = 15.4 Hz), 7.53–7.17
13
(m, 15 arom. H), 6.98 (d, 2H, HC(2/6), J = 15.4 Hz), 2.88 (A2 B2 , quasi s, 4H, CH2 CH2) ppm; C-NMR
(100 MHz, CDCl3): δ 183.4 (C(3/5)), 141.8 (C(1/7)), 141.0 (C(1”’)), 135.6 (C(1’/1”)), 130.2 (C(2”’/6”’)),
129.1 (C(2’/6’ and 2”/6”)), 128.9 (C(3”’/5”’)), 128.8 (C(4’/4”)), 128.4 (C(3’/5’ and C-3”/5”)), 126.6 (C(4”’)),
120.6 (C(2/6)), 110.9 (C(4)), 38.6 (PhCH2 CH2), 28.4 (PhCH2 CH2) ppm. Anal. Calcd. for C27 H24 O2 (MW
380.49): C, 85.23; H, 6.36%. Found: C, 84.96; H, 6.60%.
3.10. (E)-5-Phenethyl-2-phenyl-6-styryl-2,3-dihydro-4H-pyran-4-one(11)
Compound 10 (50 mg, 0.13 mmol) was dissolved in AcOH (10 mL). Zn (10 mg, 0.15 mmol) was added to this
solution, and the reaction mixture was refluxed for 12 h. After the mixture was cooled to room temperature, H2 O
598

DEMİR et al./Turk J Chem
(25 mL) was added. The organic phase was extracted with AcOEt (2 ×25 mL) and washed with H2 O (20 mL).
The organic layer was dried (Na2 SO4), and evaporation of the solvent and silica gel column chromatography
of the residue with hexane/AcOEt 95:5 gave 11 as a colourless oil (38 mg, 76%). Rf (AcOEt/hexanes 5:95):
1
0.6. H-NMR (400 MHz, CDCl3): δ 7.52–7.16 (m, 15 arom. H and 1H, styryl), 6.75 (d, 1H, styryl, J = 15.8
Hz), 5.41 (dd, 1H, HC(2), J = 13.9, J = 3.3 Hz), 2.94 (dd, 1H, HC(3(a)), J = 17.0, J = 13.9 Hz), 2.81–2.72
13
(m, 5H, CH2 CH2 and HC(3(b)); C-NMR (100 MHz, CDCl3): δ 192.6 (C(4)), 164.6 (C(6)); 142.0 (C(1”)),
139.2 (C(1’)), 137.4 (PhCH=CH), 136.0 (C(1”’)), 129.63 (1 arom. C), 129.04 (4 arom. C), 128.95 (2 arom.
C), 128.88 (1 arom. C), 128.62 (2 arom. C), 127.9 (2 arom. C), 126.3 (2 arom. C), 126.29 (1 arom. C),
119.0 (PhCH=CH), 116.2 (C(5)), 79.6 (C(2)), 43.7 (C(3)), 36.4 (PhCH2 CH2), 26.2 (PhCH2 CH2) ppm; Anal.
Calcd. for C27 H24 O2 (MW 380.49): C, 85.23; H, 6.36%. Found: C, 85.46; H, 6.53%.
3.11. Antimicrobial activity
The synthesized chemicals were dissolved in dimethyl sulfoxide (DMSO, 80%) at a final concentration of 10
mg/mL. Antimicrobial activities of the synthesized chemicals were tested by disc diffusion method against
Bacillus cereus BC-On [36], Arthrobacter agilis A17 [37], Pseudomonas aeruginosa OG1 [38], Xanthomonas
campestris MO-03 [39], Candida albicans, Klebsiella oxytoca (clinical isolates), and Helicobacter pylori [40]
8
(ATCC 43629). For this purpose, a suspension of the tested microorganism (0.1 mL of 10 cells per mL) was
spread on the agar plates. Mueller-Hinton agar with 5% sheep blood plates for H. pylori and tryptic soy agar
(TSA) for the other bacteria were used for testing antibacterial activities. H. pylori plates were incubated
under microaerophilic conditions in anaerobic jars [40]. Discs made of Whatman qualitative filter paper, grade
1 (6 mm diameter), containing 20–100 µg/disc of the synthesized chemicals were placed on the plates. The
plates were incubated at 37 °C for 24 h. At the end of the incubation period, a zone of inhibition of diameter
≥7 mm was considered positive. DMSO was used as the negative control. Ofloxacin and nystatin (HiMedia,
India) were used as positive standards for antimicrobial activities.
Acknowledgments
A part of this paper (synthesis of compounds 2 and 3) was produced from the MSc thesis of Şemsi Betül Demir.
We thank the Scientific and Technological Research Council of Turkey (TÜBİTAK) for financial support of this
study (Grant No: 113Z197). We also thank Prof. Dr. Nurettin Yaylı, Prof. Dr. Hamdullah Kılıç, Prof. Dr.
Ramazan Altundaş, Assoc. Prof. Dr. Murat Çakıcı, and Prof. Dr Ahmet C. Gören for helpful discussions.
Hasan Seçen thanks Bilal Altundaş and Esra Gürel for their helps on critical reading.
References
1. Claeson P, Tuchinda P, Reutrakul V. Naturally occurring 1,7-diarylheptanoids. Journal of Indian Chemical Society
1994; 71: 509-521.
2. Suga T, Asakawa Y, Iwata N. 1,7-Diphenyl-1,3-heptadien-5-one : a new ketone from Alnus pendula (Betulaceae).
Chemistry and Industry (London) 1971; 27: 766.
3. Suga T, Iwata N, Asakawa Y. Chemical constituents of the male flower of Alnus pendula (Betulaceae). Bulletin of
the Chemical Society of Japan 1972; 45: 2058-2060. doi: 10.1246/bcsj.45.2058
4. Hikino H, Kiso Y, Kato N, Hamada Y, Shioiri T et al. Antihepatotoxic actions of gingerols and diarylheptanoids.
Journal of Ethnopharmacology 1985; 14: 31-39. doi: 10.1016/0378-8741(85)90025-X
599

DEMİR et al./Turk J Chem
5. Claeson P, Panthong A, Tuchinda P, Reutrakul V, Kanjanapothi D et al. Three non-phenolic diarylheptanoids
with anti-inflammatory activity from Curcuma xanthorrhiza. Planta Medica 1993; 59: 451-454. doi: 10.1055/s-
2006-959730
6. Huang W, Dai X, Liu Y, Zhang C, Zhang M et al. Studies on antibacterial activity of flavonoids and diarylhep-
tanoids from Alpinia katsumadai. Journal of Plant Resources and Enviroment 2006; 15: 37-40.
7. Huang W, Zhang C, Zhang M, Wang Z. A New Biphenylpropanoid from Alpinia katsumadai. Journal of the Chinese
Chemical Society 2007; 54: 1553-1556. doi: 10.1002/jccs.200700218
8. Suksamrarn A, Ponglikitmongkol M, Wongkrajang K, Chindaduang A, Kittidanairak S et al. Diarylheptanoids,
new phytoestrogens from the rhizomes of Curcuma comosa: Isolation, chemical modification and estrogenic activity
evaluation. Bioorganic & Medicinal Chemistry 2008; 16: 6891-6902. doi: 10.1016/j.bmc.2008.05.051
9. Jurgens TM, Frazier EG, Schaeffer JM, Jones TE, Zink DL et al. Novel nematocidal agents from Curcuma comosa.
Journal of Natural Product 1994; 57 (2): 230-235. doi: 10.1021/np50104a006
10. Tantikanlayaporn D, Robinson LJ, Suksamrarn A, Piyachaturawat P, Blair HC. A diarylheptanoid phytoestrogen
from Curcuma comosa, 1,7-diphenyl-4,6-heptadien-3-ol, accelerates human osteoblast proliferation and differenti-
ation. Phytomedicine 2013; 20: 676-682. doi: 10.1016/j.phymed.2013.02.008
11. Tantikanlayaporn D, Wichit P, Weerachayaphorn J, Chairoungdua A, Chuncharunee A et al. Bone sparing effect
of a novel phytoestrogen diarylheptanoid from Curcuma comosa Roxb. in Ovariectomized Rats. Plos One 2013; 8
(11): e78739. doi: 10.1371/journal.pone.0078739
12. Zhang B, Dai Y, Liao Z, Ding L. Three new antibacterial active diarylheptanoids from Alpinia officinarum.
Fitoterapia 2010; 8: 948-952. doi: 10.1016/j.fitote.2010.06.015
13. Kuroyanagi M, Noro T, Fukushima S, Aiyama R, Ikuta A et al. Studies on the constituents of the seeds of Alpinia
katsumadai HAYATA. Chemical and Pharmaceutical Bulletin 1983; 31 (5): 1544-1550. doi: 10.1248/cpb.31.1544
14. Tori M, Hashimoto A, Hirose K, Asakawa Y. Diarylheptanoids, flavonoids, stilbenoids, sesquiterpenoids and a
phenanthrene from Alnus maximowıczii. Phytochemistry 1995; 40 (4): 1263-1264. doi: 10.1016/0031-9422(95)00439-
E
15. Zhu Y, Li S, Zhao S, Tian Q, Luo Y et al. Chemical constituents of Alpinia officinarum Hance. Yunnan Minzu
Daxue Xuebao, Ziran Kexueban 2013; 22 (4): 239-241. doi: 10.3969/j.issn.1672-8513.2013.04.002
16. Rameshkumar KB, Alan Sheeja DB, Nair MS, George V. Curcuma ecalcarata-new natural source of pinocembrin
and piperitenone. Natural Product Letters 2015; 29 (13): 1276-1279. doi: 10.1080/14786419.2014.994210
17. Grienk U, Schmidtke M, Kirchmair J, Pfarr K, Wutzler P et al. Antiviral potential and molecular insight into
neuraminidase inhibiting diarylheptanoids from Alpinia katsumadai. Journal of Medicinal Chemistry 2010; 53:
778-786. doi: 10.1021/jm901440f
18. Sakakibara M, Mori K, Matsui M. Synthesis of 1,7-diphenyl-1,3-heptadien-5-one, one of the components in the
fresh catkin of Alnus pendula. Agricultural and Biological Chemistry 1972; 36 (10): 1825-1827.
doi: 10.1271/bbb1961.36.1825
19. Vig OP, Ahuja VD, Sehgal VK, Vig AK. Synthesis of 1,7-diphenyl-trans, trans-1,3-heptadien-5-one (Alnustone).
Indian Journal of Chemistry 1975; 13: 1129-1130.
20. Vig OP, Bari SS, Sattar MA, Sharma S, Mahajan N. New synthesis of alnustone, tagetone and dihydrotagetone
from β -keto phosphonate. Journal of the Indian Chemical Society 1989; 66: 98-100.
21. Kato N, Hamada Y, Shioiri T. New methods and reagents in organic synthesis. A general, efficient, and convenient
synthesis of diarylheptanoids. Chemical and Pharmaceutical Bulletin 1984; 32 (8): 3323-3326.
doi: 10.1248/cpb.32.3323
600

DEMİR et al./Turk J Chem
22. Göksu S, Çelik H, Seçen H. An efficient synthesis of alnustone, a naturally occurring compound. Turkish Journal
of Chemistry 2003; 27: 31-34.
23. Küçükoğlu K, Seçinti H, Özgür A, Seçen H, Tutar Y. Synthesis, molecular docking, and antitumoral activity
of alnustone-like compounds against estrogen receptor alpha-positive human breast cancer. Turkish Journal of
Chemistry 2015; 39: 179-193. doi: 10.3906/kim-1408-72
24. Borsche W, Lewinsohn M. Constituents of the kawa root. XIV. Cinnamoylacetic ester. Berichte der Deutschen
Chemischen Gesellschaft [Abteilung] B: Abhandlungen 1933; 66B: 1792-1801 (Chem. Abstr. 1934, 28:8301).
25. Yang Y, Kinoshita K, Koyama K, Takahashi K, Kondo S et al. Structure-antiemetic-activity of some diarylhep-
tanoids and their analogues. Phytomedicine 2002; 9: 146-152. doi: 10.1078/0944-7113-00091
26. Mathre DJ, Shinkai I. Tetrahydro-1-methyl-3,3-diphenyl-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaborole. In: e-EROS En-
cylopedia of Reagents for Organic Synthesis, 2013. doi: 10.1002/047084289X.rt035s.pub3
27. Corey EJ, Bakshi RK, Shibata S, Chen C, Singh VK. A stable and easily prepared catalyst for the enantioselective
reduction of ketones. Applications to multistep syntheses. Journal of the American Chemical Society 1987; 109:
7925-7926. doi: 10.1021/ja00259a075
28. Menzek A, Karakaya GM, Kaya AA. Reductions of benzene derivatives whose benzylic positions bear oxygen
atoms under mild conditions. Helvetica Chimica Acta 2008; 91: 2299-2307. doi: 10.1002/hlca.200890250
29. Altundaş A, Menzek A, Gültekin DD, Karakaya M. Excellent and convenient procedures for reduction of benzene
and its derivatives. Turkish Journal of Chemistry 2005; 29: 513-518.
30. Hyugano T, Liu S, Ouchi A. Facile photochemical transformation of alkyl aryl selenides to the corresponding
carbonyl compounds by molecular oxygen: use of selenides as masked carbonyl groups. The Journal of Organic
Chemistry 2008; 73: 8861-8866. doi: 10.1021/jo801730j
31. Pandey SK, Greene AE, Poisson JF. Terminal olefins from aldehydes through enol triflate reduction. The Journal
of Organic Chemistry 2007; 72: 7769-7770. doi: 10.1021/jo071151o
32. Krishnamurty HG, Ghosh S. Synthesis of dihydrocurcumin. Indian Journal of Chemistry 1986; 25B: 411-412.
33. Nichols CE, Youssef D, Harris RG, Jha A. Microwave-assisted synthesis of curcumin analogs. Arkivoc 2006; (13):
64-72. doi: 10.3998/ark.5550190.0007.d07
34. Changtam C, Hongmanee P, Suksamrarn A. Isoxazole analogs of curcuminoids with highly potent multidrug-
resistant antimycobacterial activity. European Journal of Medicinal Chemistry 2010; 45: 4446-4457.
doi: 10.1016/j.ejmech.2010.07.003
35. McCarroll AJ, Walton JC. On the preparation of cyclopentadienes by a novel homolytic annulation of but-3-en-1-
ones with alkynes mediated by samarium diiodide. Arkivoc 2002; (3): 55-62. doi: 10.3998/ark.5550190.0003.305
36. Özdal M, Özdal ÖG, Sezen A, Algur ÖF. Biosynthesis of indole-3-acetic acid by Bacillus cereus immobilized cells.
Cumhuriyet Science Journal 2016; 37 (3): 212-222.
37. Ozdal M, Ozdal OG, Sezen A, Algur OF, Kurbanoglu EB. Continuous production of indole-3-acetic acid by
immobilized cells of Arthrobacter agilis. 3 Biotech 2017; 7: 23 (6 pages). doi: 10.1007/s13205-017-0605-0
38. Ozdal M, Ozdal OG, Algur OF. Isolation and characterization of α-endosulfan degrading bacteria from the
microflora of cockroaches. Polish Journal of Microbiology 2016; 65 (1): 63-68. doi: 10.5604/17331331.1197325
39. Ozdal M, Kurbanoglu, EB. Use of chicken feather peptone and sugar beet molasses as low cost substrates for
xanthan production by Xanthomonas campestris MO-03. Fermentation 2019; 5 (1): 9. doi: 10.3390/fermenta-
tion5010009
40. Kara AA, Algur ÖF, Köseoğlu MŞ. Antimicrobial activities of some herbs on Helicobacter pylori. Cumhuriyet
University Faculty of Science 2016; 37 (2): 129-140. doi: 10.17776/csj.32537
601