Synthesis and complete assignment of NMR data of 20 chalcones

Article abstract of DOI:10.1002/mrc.2707

Chalcones, intermediates in flavonoid biosynthesis, can exhibit antibacterial, antiproliferative, and anti-inflammatory properties. Chalcones contain two benzene rings and both hydroxylated and methoxylated analogs are frequently produced by hydroxylases and O-methyltransferases in plant biosynthetic pathways. Assignments of NMR peaks in the spectra of hydroxylated and/or methoxylated chalcones can help in identifying novel chalcone derivatives isolated from natural sources by referencing these data against NMR spectra obtained from known chalcones. We report here the syntheses of 20 chalcones and complete assignments of ¹H and ¹³C NMR spectra. Copyright

Full text of DOI:10.1002/mrc.2707

MRC Letters
Received: 10 October 2010
Revised: 1 November 2010
Accepted: 4 November 2010
Published online in Wiley Online Library: 29 November 2010
(wileyonlinelibrary.com) DOI 10.1002/mrc.2707
Synthesis and complete assignment of NMR
data of 20 chalcones
Doseok Hwang,a Jiye Hyun,a Geunhyeong Jo,a Dongsoo Kohb∗
and Yoongho Lima∗
Chalcones, intermediates in flavonoid biosynthesis, can exhibit antibacterial, antiproliferative, and anti-inflammatory
properties. Chalcones contain two benzene rings and both hydroxylated and methoxylated analogs are frequently produced
by hydroxylases and O-methyltransferases in plant biosynthetic pathways. Assignments of NMR peaks in the spectra of
hydroxylated and/or methoxylated chalcones can help in identifying novel chalcone derivatives isolated from natural sources
by referencing these data against NMR spectra obtained from known chalcones. We report here the syntheses of 20 chalcones
and complete assignments of 1H and 13C NMR spectra. Copyright ꢀ 2010 John Wiley & Sons, Ltd.
c
Keywords: NMR; 1H NMR; 13C NMR; 2D NMR; flavonoid; chalcone
O
Introduction
O
MeO
MeO
OMe
OMe
3
OHC
CH3
1
+
2
More than 10 000 polyphenols have been identified and classified
based on their structural characteristics. Polyphenols with a
general C6–C3–C6 structure are flavonoids. Of these, compounds
in which the C3 bridge is composed of a linear chain of carbon
atoms are classified as chalcones.[1] Most flavonoids are produced
in biosynthetic pathways for secondary metabolites in plants;
chalcones are intermediates in flavanoid biosyntheses[2] and
can exhibit antibacterial, antiproliferative, and anti-inflammatory
properties.[3–5] Both hydroxylated and methoxylated analogs are
frequently produced by hydroxylases and O-methyltransferases
in the biosynthetic pathways of plants. NMR data from these
hydroxylated and/or methoxylated chalcones may help in the
identification of novel chalcone derivatives in natural sources
by comparing their NMR spectra and assignments with those of
known chalcones.[6] The current report describes the synthesis
of 20 chalcones with complete assignments of 1H and 13C
NMR data.
2'
2''
3''
3'
O
O
OMe
MeO
MeO
OMe
OMe
OMe
1 = 2'-OMe ; 2 = 3'-OMe
3 = 4'-OMe
4 = 4''-OMe ; 5 = 3''-OMe
6 = 2''-OMe ; 7 = 3'', 5''-di-OMe
OH
O
OH
O
OMe
OMe
MeO
8 = 2''-OMe ; 9 = 3''-OMe
10 = 4''-OMe ; 11 = 3'', 5''-di-OMe
12 = Naphthyl ;
13 = 2''-OMe Naphthyl
14 = 2''-OMe ; 15 = 3''-OMe
16 = 4''-OMe ; 17 = 3'', 5''-di-OMe
18 = phenyl ;
19 = 2'', 4'', 6''-tri-OMe
20 = 2'', 4''-di-OMe
Scheme 1. Synthesis of chalcones 1–20.
Experimental
Germany) at 298 K. The relaxation delays for proton and carbon
NMR analyses were 1 and 3 s, with 90◦ pulses of 10.2 and 10.3 µs,
respectively. All two-dimensional spectra such as COSY, HMQC,
Synthesis
Chalcones were synthesized via Claisen–Schmidt condensation
of substituted acetophenone or 1-hydroxy-2-aceto-naphthone
with methoxy benzaldehydes under basic conditions in ethanol
as outlined in Scheme 1.[7] Crude chalcones were purified
by recrystallization from a suitable solvent or by column
chromatography.
∗
Correspondence to: Yoongho Lim, Department of Bioscience and Biotechnol-
ogy, Konkuk University, Hwayang-Dong 1, Kwangjin-Ku, Seoul 143-701, Korea.
E-mail: yoongho@konkuk.ac.kr
Dongsoo Koh,DepartmentofAppliedChemistry,DongdukWomen’sUniversity,
Hawolgok-Dong, Seongbuk-Ku, Seoul 136-714, Korea.
E-mail: dskoh@dongduk.ac.kr
NMR spectra
a
Department of Bioscience and Biotechnology, Bio/Molecular Informatics
Center, Konkuk University, Seoul 143-701, Korea
Twenty synthetic chalcone derivatives were each dissolved in
CDCl3 and adjusted to approximately 50 mM. The solutions were
then transferred to 5-mm NMR tubes. All NMR data were collected
on an Avance 400 spectrometer system (9.4 T, Bruker, Karlsruhe,
b
DepartmentofAppliedChemistry,DongdukWomen’sUniversity,Seoul136-714,
Korea
c
Magn. Reson. Chem. 2011, 49, 41–45
Copyright ꢀ 2010 John Wiley & Sons, Ltd.

D. Hwang et al.
c
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Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2011, 49, 41–45

Synthesis and complete assignment of NMR data of 20 chalcones
R1
O
1
R10
3
R2
R3
R9
R8
1'
1'
2
R5
R6
R4
R7
R1
R2
R3
R4
R5
R6
R7
R8
H
R9
R10
H
Compound
1
2
OMe
OMe
H
H
H
H
H
H
H
H
H
H
H
H
H
H
OMe
OMe
OMe
H
OMe
H
H
H
H
H
H
H
OMe
OMe
H
H
H
3
H
OMe
H
H
4
H
OMe
OMe
OMe
OMe
H
OMe
OMe
OMe
OMe
H
5
H
H
H
OMe
6
H
H
H
H
H
H
H
H
H
OMe
H
OMe
H
H
OMe
H
H
H
7
H
H
OMe
H
8
H
OMe
OH
OH
OH
OH
OMe
OMe
OMe
OMe
9
H
H
H
H
H
H
H
H
H
OMe
H
H
H
H
10
11
OMe
H
H
H
H
H
OMe
H
OMe
H
OH
1'
O
R1
3
R2
R3
1
2'
1'
2
R5
R4
R1
R2
R3
H
R4
H
R5
H
Compound
12
13
14
15
16
17
18
OMe
H
OMe
H
H
H
H
H
H
OMe
H
H
H
H
OMe
H
OMe
H
H
H
H
H
OMe
OMe
H
OMe
OMe
H
OMe
H
H
H
O
1
3
1'
1''
2
H3CO
OH
R
Compound
R
H
19
20
OMe
Figure 1. Structures and nomenclatures of chalcones 1-20.
c
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2011, 49, 41–45
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D. Hwang et al.
Table 2. The 13C NMR chemical shifts of chalcone derivatives 1–20
δ of 13C
Position
1
2
3
4
5
6
7
8
9
10
1
193.2
127.8
143.4
129.4
158.3
111.8
133.1
120.9
130.5
137.2
106.5
161.2
102.6
161.2
106.5
55.9
–
190.4
122.8
145.0
136.9
113.1
160.1
129.7
119.4
121.2
139.7
106.5
161.2
103.0
161.2
106.5
–
188.8
122.5
144.1
131.2
131.0
114.0
163.6
114.0
131.0
137.1
106.4
161.2
102.7
161.2
106.4
–
190.9
123.1
140.7
140.7
106.6
161.0
105.1
161.0
106.6
124.1
159.0
111.4
132.0
120.9
129.4
–
190.2
122.4
144.9
136.3
106.5
161.0
105.1
161.0
106.5
140.2
113.5
160.1
130.0
116.5
121.3
–
190.2
119.9
144.9
127.7
106.4
161.0
104.9
161.9
106.4
140.7
130.4
114.6
161.9
114.6
130.4
–
190.1
122.6
145.0
136.8
106.5
161.0
105.1
161.0
106.5
140.2
106.5
161.2
102.9
161.2
106.5
–
192.6
121.0
140.2
114.4
166.2
101.2
166.7
107.7
131.4
123.9
159.0
111.4
132.1
120.9
129.6
–
192.0
120.8
144.5
114.3
166.5
101.3
166.9
108.0
131.5
136.4
113.8
160.2
130.2
116.6
121.3
–
192.0
117.9
144.4
114.3
166.2
101.2
166.7
107.7
131.3
114.3
130.5
114.6
161.9
114.6
130.5
–
2
3
1ꢁ
2ꢁ
3ꢁ
4ꢁ
5ꢁꢁ
6ꢁꢁ
1
2ꢁꢁ
3ꢁꢁ
4ꢁꢁ
5ꢁꢁ
6ꢁꢁ
2ꢁ-OMe
3ꢁ-OMe
4ꢁꢁ-OMe
5ꢁꢁ-OMe
2ꢁꢁ-OMe
3 -OMe
4ꢁꢁ-OMe
5ꢁꢁ-OMe
55.6
–
–
55.8
–
55.7
–
55.7
–
55.7
–
–
–
–
–
55.6
–
55.7
–
55.8
–
55.5
–
–
–
55.8
55.7
–
55.7
–
55.7
–
55.7
–
–
–
–
55.7
–
–
–
55.6
–
55.6
–
55.6
–
55.4
–
–
55.5
–
55.6
–
–
–
55.5
–
–
55.5
–
55.6
55.6
55.6
–
–
55.5
–
–
H-5ꢁ at 7.01 and 7.04 ppm, respectively. Long-range coupling
was observed between the C-1 and the H-6ꢁ peak at 7.62 ppm.
Assignments of H-3ꢁ, H-4ꢁ, and H-5ꢁ were made based on COSY
cross peaks. The coupling constant between H-2 and H-3 (15.9 Hz)
indicated that the conformation of the bond between C-2 and C-3
was trans.
and HMBC were acquired with 2048 data points for t2 and 256
for t1 increments. The long-ranged coupling time for HMBC was
70 ms. Prior to Fourier transformation, zero filling of 2K and a
sine-squared bell window function were applied using XWIN-NMR
(Bruker).[6]
The spectral assignments of the other chalcones followed the
same general pattern. A complete list of the 1H and 13C chemical
shifts of 1–20 is listed in Tables 1 and 2, respectively. Of these 20
chalcone derivatives, only the 1H and 13C NMR data of 4 and 10,
Results and Discussion
The structures and the nomenclatures of chalcones 1–20 are
shown in Fig. 1. The assignment of 1 is explained here in
detail. Fifteen peaks were observed in the 13C NMR spectrum
of 1. The peak at 193.2 ppm was assigned to a ketone at C-
1. Three peaks showing double intensities at 55.6, 106.5, and
161.2 ppm were attributed to 3ꢁꢁ-OMe/5ꢁꢁ-OMe, C-2ꢁꢁ/C-6ꢁꢁ, and
C-3ꢁꢁ/C-5ꢁꢁ, respectively. The peak at 55.9 ppm was assigned to
2ꢁ-OMe. In the COSY spectrum, a cross-peak between 7.32 and
7.53 ppm was observed and correlated with two 13C peaks
at 127.8 and 143.4 ppm, respectively, in the HMQC spectrum.
Therefore, these shifts were assigned to H-2/C-2 and H-3/C-
3, respectively. H-2 was long range coupled to a 13C peak at
137.2 ppm in the HMBC spectrum and attributed to C-1ꢁꢁ. The
13C peak at 102.6 ppm in the HMBC spectrum was assigned
to C-4ꢁꢁ based on long-range coupling with H-2ꢁꢁ/H-6ꢁꢁ. Four 1H
peaks at 7.01, 7.04, 7.48, and 7.62 ppm were correlated in the
COSY spectrum and assigned to H-3ꢁ, H-4ꢁ, H-5ꢁ, and/or H-6ꢁ,
respectively. These were connected directly to four 13C peaks at
111.8, 133.1, 120.9, and 130.5 ppm, respectively, in the HMQC
spectrum. The 13C peak at 158.3 ppm could be attributed to
methoxylated C-2ꢁ, which was long-range coupled with H-4ꢁ
and/or H-6ꢁ at 7.48 and 7.62 ppm, respectively, in the HMBC
spectrum. The 13C peak at 129.4 ppm was coupled to H-3ꢁ and/or
1
and the H NMR data of 19, had been previously reported;[8–10]
the literature spectra matched well with the NMR data given
herein.
Acknowledgements
This work was supported by Priority Research Centers Program
through NRF funded by MEST (2009-0093824), Agenda program
(RDA, 11-30-68), and Disease Network Research Program Grant
(NRF, 20090084183).
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