1H and 13C NMR spectral assignments of 2′-hydroxychalcones

Article abstract of DOI:10.1002/mrc.3949

Chalcones are of interest to medicinal chemists because their structures can be easily modified with various functional groups. The syntheses and biological activities of chalcones from natural sources are well known. In this study, 24 2′-hydroxychalcones bearing methoxy substituents were synthesized, among which five are new. The NMR data for all synthesized chalcones are described for the first time. The complete assignments of the ¹H and ¹³C NMR data can be used for the identification of newly discovered and widely isolated, synthesized chalcones. Copyright

Full text of DOI:10.1002/mrc.3949

MRC Letters
Received: 20 December 2012
Revised: 20 February 2013
Accepted: 26 February 2013
Published online in Wiley Online Library: 17 April 2013
(wileyonlinelibrary.com) DOI 10.1002/mrc.3949
1H and C NMR spectral assignments of
13
20-hydroxychalcones
Yeonjoong Yong,a Seunghyun Ahn,b Doseok Hwang,a Hyuk Yoon,a
Geunhyeong Jo,a Young Hwa Kim,c Sang Ho Kim,c Dongsoo Kohb and
Yoongho Lima*
Chalcones are of interest to medicinal chemists because their structures can be easily modified with various functional groups.
The syntheses and biological activities of chalcones from natural sources are well known. In this study, 24 20-hydroxychalcones
bearing methoxy substituents were synthesized, among which five are new. The NMR data for all synthesized chalcones are
described for the first time. The complete assignments of the 1H and 13C NMR data can be used for the identification of newly
discovered and widely isolated, synthesized chalcones. Copyright © 2013 John Wiley & Sons, Ltd.
Keywords: chalcone; flavonoid; NMR; 1H NMR; 13C NMR; 2D NMR
were monitored using silica gel thin-layer chromatography. At
the end of the reaction, ice water was added to the mixture
Introduction
Chalcones are known as precursors for flavonoids, which are found
ubiquitously in the plant kingdom. Because they show various
biological activities, such as anticancer,[1,2] antioxidant,[3,4] anti-
inflammatory,[5] and antimicrobial properties,[6] many analogs have
been reported. The 20-hydroxychalcone (Fig. 1) analogs have been
studied for its inhibition of prostaglandin E2 production, inducing
the biosynthesis of glutathione and antibacterial activities against
methicillin-resistant Staphylococcus aureus.[7–9] Methoxylation of
plant-derived polyphenols is a general modification of the
plant structure, which changes the mother compounds as well
as their biological functions. In particular, methoxylation increases
intracellular compartmentation due to increased lipophilicity.[10]
Therefore, we prepared 24 methoxylated 20-hydroxychalcone ana-
logs, including 20-hydroxychalcone, two monomethoxylated, seven
dimethoxylated, nine trimethoxylated, and five tetramethoxylated
20-hydroxychalcone derivatives (Fig. 2). Here, we report the
complete assignments of their 1H and 13C NMR data. Among
the 24 analogs, five are novel compounds, and the NMR data
of other eight compounds have not been reported. Some pub-
lished NMR data have been corrected on the basis of the current
experiments. These NMR data will be useful for identifying
hydroxymethoxychalcones by simple comparisons with their NMR
spectra.
and acidified with 6 N HCl. The precipitate was filtered and
washed with water and ethanol. When oil formed, the mixture
was extracted with chloroform, and the combined extracts
were dried over MgSO4 and filtered. The filtrate was evapo-
rated to yield a residue, which was purified by flash column
chromatography using Silica gel 60 (70–230 mesh; Merck,
Whitehouse Station, NJ). The final products were confirmed
by HREIMS.
NMR spectra
The synthetic 20-hydroxychalcones were dissolved in deuterated
1
dimethyl sulfoxide (DMSO-d6). The H and 13C chemical shifts of
the deuterated solvent were 2.50 and 39.5 ppm referenced to
OH
O
β
α
A
B
Figure 1. Structure of 20-hydroxychalcone.
*
Correspondence to: Yoongho Lim, Division of Bioscience and Biotechnology,
Konkuk University, Hwayang-Dong 1, Kwangjin-Ku Seoul 143-701, Korea.
E-mail: yoongho@konkuk.ac.kr
Experimental
Synthesis
a Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul
143-701 Korea
All 20-hydroxychalcone derivatives (1–24) were synthesized
as shown in Scheme 1. KOH (40% w/v aqueous solution, 3 ml)
b Department of Applied Chemistry, Dongduk Women’s University, Seoul
136-714 Korea
was added to
a stirred solution of the appropriate 2-
hydroxyacetophenone (10 mmol) and a methoxy-substituted
benzaldehyde (10 mmol) in ethanol (30 ml), and the mixture
was stirred at room temperature for 10–60 h. All reactions
c
Swine Science Division, National Institute of Animal Science, RDA, Cheonan
330-801 Korea
Magn. Reson. Chem. 2013, 51, 364–370
Copyright © 2013 John Wiley & Sons, Ltd.

1H and 13C NMR spectral assignments of 20-hydroxychalcones
Figure 2. Structures, names, and HREIMS data of 20-hydroxychalcones 1ꢁ24.
Scheme 1. Schematic route for preparing 20-hydroxychalcones 1ꢁ24.
TMS, respectively. The NMR samples were prepared at approxi-
mately 50 mM, and they were transferred to a 2.5mm NMR tube.
All NMR experiments were carried out on an Avance 400 spectrom-
eter system (9.4 T; Bruker, Karlsruhe, Germany) at 298 K. For the one-
1
dimensional H and 13C NMR experiments, the relaxation delays
were 1 and 3 s, and the 90ꢀ pulses were 11.8 and 15.0 ms, respec-
1
Figure 3. Important COSY and HMBC connections of derivative 16.
tively. The H and 13C spectral widths were 5555 and 20 964 Hz,
Magn. Reson. Chem. 2013, 51, 364–370
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Y. Yong et al.
wileyonlinelibrary.com/journal/mrc
Copyright © 2013 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2013, 51, 364–370

1H and 13C NMR spectral assignments of 20-hydroxychalcones
Magn. Reson. Chem. 2013, 51, 364–370
Copyright © 2013 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/mrc

Y. Yong et al.
wileyonlinelibrary.com/journal/mrc
Copyright © 2013 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2013, 51, 364–370

1H and 13C NMR spectral assignments of 20-hydroxychalcones
(A)
(D)
(E)
(F)
(B)
(C)
Figure 4. Partial HMQC spectra of derivatives 2 (A), 3 (B), 7 (C), 19 (D), 22 (E), and 16 (F) showing H-a/C-a (circle) and H-b/C-b (square) correlation.
respectively. The data point and digital resolution for the 1H were
32 K and 0.339 Hz/point, respectively. The data point and digital
resolution for the 13C were 64K and 0.640 Hz/point, respectively.
For the two-dimensional experiments, including COSY, HMQC,
and HMBC, all data were acquired with 2 K ꢂ 256 data points
(t2 ꢂ t1).[11] The long-range coupling time for HMBC was 70 ms.
Zero filling of 2 K and the sine-squared bell window function were
applied before Fourier transformation using XWin-NMR (Bruker).[12]
All NMR data were analyzed using Sparky.[13]
General experimental procedure
To confirm the structures of the synthetic compounds, mass
spectrometry was performed on a high-resolution electron
Magn. Reson. Chem. 2013, 51, 364–370
Copyright © 2013 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/mrc

Y. Yong et al.
1H NMR data of derivative 7 published previously agree well with
the current NMR data, those of derivatives 2 and 3 do not.[15,16,18]
To clarify the results, their HMQC spectra were elucidated. As
shown in Fig. 4, in derivatives 2, 3, 7, 19, and 22, the 1H chemical
shift of H-a was more deshielded than that of H-b. Although the
H-a values of five derivatives are more deshielded than the H-b
values, H-a of derivative 16 is more shielded than H-b. In five
derivatives except 16, the cross peak of H-a/C-a is observed
in the top left. It means that the 1H chemical shift of H-a is
more deshielded than that of H-b. On the contrary, in deriva-
tive 16, the cross peak of H-a/C-a is observed in the top
right. Its H-a is more shielded than H-b. The 1H NMR data
of derivative 2 published previously[15] reported that H-50
(7.51–7.46 ppm) was more deshielded than H-40 (6.96–6.91 ppm),
but our experimental results showed H-40 at 7.55 ppm and H-50
at 7.00 ppm. The HMQC spectrum (Figure 5) confirmed that our
data are correct.
Figure 5. Partial HMQC spectrum of derivative 2 showing H-40/C-40
The results in this study provide a useful tool for structural
identification of new hydroxymethoxychalcones.
(circle) and H-50/C-50 (square) regions.
impact ionization mass spectrometer (HREIMS, JMS700; JEOL Ltd.,
Tokyo, Japan) with the help of the Korea Basic Science Institute at
Daegu, Korea.
Acknowledgements
This work was supported by the Priority Research Centers
Program (NRF, 2012–0006686), Agenda program (RDA,
PJ907145), the NRF funded by MEST (2010–0020966), and the
next generation Biogreen21 program (RDA, PJ009532). Y. Yong,
S. Ahn, and D. Hwang contributed equally to this work.
Results and Discussion
The 24 structures and names of the 20-hydroxychalcone deriva-
tives are shown in Fig. 2. Among them, the novel compounds
were 10, 16, 18, 19, and 21. The 1H and/or 13C NMR data
of compounds 1–8, 13, 22, and 23 were reported previously.[14–20]
As noted earlier, eight derivatives, 9, 11, 12, 14, 15, 17, 20, and
24, were known, but their NMR data had not been reported.
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