Synthesis and anti-inflammatory effect of morachalcone B, morachalcone C, and analogs

Article abstract of DOI:10.1002/jccs.201800261

An efficient method to synthesize morachalcones B and C (1 and 2) is described. Rap?Stoermer condensation and 1,3-prenyl rearrangement were used as two key synthetic methods. Morachalcone C was obtained by photo-oxygenation of morachalcone B. Morachalcone

Full text of DOI:10.1002/jccs.201800261

Received: 5 July 2018
Accepted: 5 December 2018
DOI: 10.1002/jccs.201800261
A R T I C L E
Synthesis and anti-inflammatory effect of morachalcone B,
morachalcone C, and analogs
Bo-Syuan Jhong1 | Ting-Yu Lin1 | Chien-Hsiang Kao1 | Hsi-Jung Yu1 | Tsung-Mei Chin1 |
Ching-Yang Liu1 | Yuh-Chiang Shen2 | Ming-Jaw Don1,2
1Department of Chemistry, Chinese Culture
An efficient method to synthesize morachalcones B and C (1 and 2) is described.
University, Taipei, Taiwan
2National Research Institute of Chinese Medicine,
Ministry of Health and Welfare, Taipei, Taiwan
Rap−Stoermer condensation and 1,3-prenyl rearrangement were used as two key
synthetic methods. Morachalcone C was obtained by photo-oxygenation of mora-
chalcone B. Morachalcones B and C showed moderate anti-inflammatory activity.
Correspondence
Ming-Jaw Don, National Research Institute of
Chinese Medicine, Ministry of Health and
Welfare, No. 155-1, Section 2, Li-Nong Street,
Peitou, Taipei 11221, Taiwan, R.O.C.
Email: mjdon@nricm.edu.tw
KEYWORDS
anti-inflammatory activity, morachalcone B, morachalcone C, Rap−Stoermer
condensation
Funding information
Ministry of Health and Welfare, Grant/Award
Number: MM10601-0160
2-bromo-1-(2,4-dimethoxyphenyl)ethanone (3) was prepared
1
| INTRODUCTION
from 2',4'-dimethoxyacetophenone by a known procedure.[10]
Morachalcones B and C (1 and 2), two novel chalcone deriv-
atives, were isolated and characterized from the leaves of
Mora alba L., and showed moderate cytotoxic activity
against HCT-8 and BGC823 human cancer cell lines.[1]
Leaves of M. alba L. is used in traditional Chinese medicine
for the treatment of cold, headache, diabetes, keratitis, and
otitis media.[2] Naturally occurring chalcones and synthesized
analogs have been reported to have various bioactivities such
as antioxidant, antimicrobial, antimalarial, anticancer, and
vasorelaxant.[3–7] Because of their various beneficial effects,
compounds related to chalcones have attracted attention as
synthetic targets. Previously, morachalcone A, a naturally
occurring chalcone, was synthesized and exhibited aromatase
inhibitory activity.[8,9] To our knowledge, no work has been
done on total synthesis of 1 and 2. It seems important to
develop synthetic routes of 1 and 2 for further studies on their
biological activity. Here we report a facile synthesis of 1 and
2 and evaluation of their anti-inflammatory activity.
Rap−Stoermer condensation of
3
and 2-hydroxy-
4-methoxybenzaldehyde in the presence of K2CO3 under reflux
gave 4 in moderate yield.[11] Demethylation of 4 with excess
BBr3 in CH2Cl2 provided 5. Two hydroxyl groups of 5 were
protected with chloromethyl methyl ether (MOMCl) in the
presence of N, N-diisopropylethylamine (DIPEA) in CH2Cl2 to
yield 6, which was then treated with prenyl bromide to afford
7. 1,3-Prenyl rearrangement of 7 using montmorillonite K10 as
a catalyst in CH2Cl2 gave a mixture of 8 and 9.[12,13] Deprotec-
tion of the MOM group in 8 and 9 was achieved by reaction
with H2SO4 to afford 10 and 1, respectively.[14] Finally, com-
pounds 11 and 2 were obtained from 10 and 1, respectively, by
photo-oxygenation reaction at 15ꢀC using tetraphenylporphin
(TPP) as the photosensitizer.[15] The 1H and 13C NMR data of
1, 2, 10, and 11 are summarized in Table 1. The spectroscopic
data of the synthesized 1 and 2 were identical to those of natu-
rally occurring morachalcones B and C, respectively. The cor-
1
responding H and 13C NMR spectra of 1, 2, and 4-11 are
shown in Supporting Information Figures S1 to S20.
Inhibitory effect of selected compounds 1, 2, 4, 5, 10,
and 11 in nitric oxide (NO) production in the microglia cell
line (BV2)[16] was evaluated, and results are shown in
Table 2. Ammonium pyrrolidinedithiocarbamate (PDTC), a
selective NF-κB inhibitor, was used as the positive control.
2
| RESULTS AND DISCUSSION
The synthetic strategy shown in Scheme 1 was employed for
the synthesis of morachalcones B and C (1 and 2). The starting
© 2019 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J Chin Chem Soc. 2019;1–6.
http://www.jccs.wiley-vch.de
1

2
JHONG ET AL.
HO
MeO
MeO
OH
OMe
iii
i
ii
O
O
Br
OH
O
OMe O
OMe O
5
4
3
MOMO
MOMO
OMOM
OMOM
iv
v
O
O
OH
O
O
O
7
6
4
5
5'
3a
HO
MOMO
4'
3'
6'
1'
3
MOMO
OMOM
OH
6
vi
OMOM
2
+
7a
7
O
O
1
2'
1"
2"
O
OH
O
OH O
4"
OH
O
3"
9
8
1, Morachalcone B
5"
vi
vii
HO
HO
HO
OH
HO
OH
OH
vii
O
OH
OH
O
O
O
OH
O
OH
O
11
2, Morachalcone C
10
SCHEME 1 Reagents and conditions: (i) 2-hydroxy-4-methoxybenzaldehyde, K2CO3, reflux; (ii) excess BBr3, CH2Cl2; (iii) MOMCl, DIPEA, CH2Cl2;
(iv) prenyl bromide, K2CO3, acetone, reflux; (v) montmorillonite K10, CH2Cl2; (vi) H2SO4, THF/i-PrOH; (vii) TPP, acetone, O2, hv
The 50% effective concentration (EC50) for inhibiting the
production of NO was calculated on the basis of nitrite
released into the culture media. Cell viability under this con-
dition was still >95% as measured by MTT assay, indicating
that the inhibition of nitrite production by these compounds
was not due to cell death. As shown in Table 2, compounds
1 and 2 displayed moderate effect for inhibiting NO produc-
tion. Compounds 10 and 11 strongly inhibited NO produc-
tion with EC50 values of 14.1 and 11.2 μM, respectively.
Compounds 1, 2, 4, 5, 10, and 11 were also evaluated
for antioxidant effect by a DPPH radical scavenging assay.
The results showed no free-radical scavenging activities.
spectrophotometer. Nuclear magnetic resonance spectra
were recorded on a Varian Unity Inova 500 MHz and
VNMRS 600 FT-NMR spectrometers. Chemical shifts are
reported in parts per million (δ) units relative to the internal
standard tetramethylsilane. The electron ionization mass (EI-
MS) spectra were measured with a direct insertion probe on
a Finnigan DSQ II mass spectrometer at 70 eV. High resolu-
tion mass spectra were recorded on Thermo Scientific Q
Exactive Focus Orbitrap instrument. Column chromatogra-
phy was performed with E. Merck 230–400 mesh silica gel.
3.2 | (6-Methoxybenzofuran-2-yl)
(2,4-dimethoxyphenyl)-methanone (4)
To a stirred solution of 3 (1.55 g, 6.0 mmol) in acetone
(60 mL) was added K2CO3 (2.76 g, 20.0 mmol) and
2-hydroxy-4-methoxybenzaldehyde (0.76 g, 5.0 mmol), and
the mixture was refluxed for 20 hr. After cooling, acetone
was removed using a rotavaporator, and water was added.
The mixture was extracted with EtOAc three times. The
combined organic layer was dried over Na2SO4, filtered, and
3
| EXPERIMENTAL
3.1 | General experimental procedures
Melting points were determined on a Yanaco MP-13 micro-
melting point apparatus and are uncorrected. Infrared spectra
were obtained on a Thermo Scientific Nicolet is5 FTIR

JHONG ET AL.
3
TABLE 1 NMR spectral data for 1, 2, 10, and 11 in acetone-d6
1
10
2
11
a
Position
δH
—
δC
δH
δC
δH
δC
δH
δC
2
152.7
117.2
120.5
124.7
115.3
159.8
98.5
—
152.9
116.9
120.5
124.7
115.3
159.8
98.4
—
152.6
117.3
120.5
124.7
115.3
159.8
98.5
—
152.4
117.1
120.5
124.7
115.3
159.8
98.5
3
7.71 (d, 1.0)
7.69 (s)
7.73 (s)
7.70 (s)
3a
4
—
—
—
—
7.66 (d, 8.5)
7.66 (d, 8.5)
6.97 (dd, 8.5, 2.0)
7.66 (d, 8.5)
7.65 (d, 8.5)
5
6.96 (dd, 8.5, 2.5)
6.97 (dd, 8.5, 2.0)
6.96 (dd, 8.5, 2.0)
6
—
—
—
7
7.09 (m)
7.08 (m)
—
7.10 (m)
7.08 (m)
7a
1'
2'
3'
4'
5'
6'
100
—
158.4
113.0
165.1
116.2
163.0
108.5
132.1
22.3
158.3
112.9
166.0
103.4
163.7
121.4
133.6
28.0
—
158.4
112.8
165.5
114.1
164.8
109.7
132.8
30.0
—
158.3
113.0
166.1
104.3
164.7
119.4
136.0
37.7
—
—
—
—
—
—
—
—
—
6.45 (s)
—
6.40 (s)
—
—
—
6.60 (d, 9.0)
8.26 (d, 9.0)
3.39 (d, 7.5)
6.55 (d, 8.5)
8.31 (d, 8.5)
2.93 (dd, 14.0, 8.0)
3.12 (dd, 14.0, 3.5)
4.43 (dd, 8.0, 3.5)
—
—
8.29 (s)
8.26 (s)
3.31 (d, 7.0)
2.88 (dd, 14.5, 7.5)
2.96 (dd, 14.5, 4.0)
4.43 (dd, 7.5, 4.0)
—
200
300
400
500
5.27–5.30 (m)
—
1.78 (s)b
123.1
131.7
17.9b
25.8b
5.40–5.43 (m)
—
1.76 (s)b
123.1
133.5
17.8b
26.0b
76.5
76.2
148.3
18.3
148.2
18.4
1.84 (s)
1.83 (s)
1.64 (d, 0.5)b
1.79 (d, 1.0)b
4.76–4.77 (m)
4.94–4.95 (m)
13.4 (s)
110.4
4.79–4.80 (m)
4.94–4.95 (m)
12.6 (s)
110.9
2'-OH
C=O
13.2 (s)
—
12.8 (s)
—
—
—
—
185.4
—
184.9
—
185.3
—
185.1
a
(Multiplicity, J in Hz) in ppm.
Interchangeable.
b
TABLE 2 Inhibitory effects of compounds 1, 2, 4, 5, 10, and 11 in nitric
159.6, 161.0, 163.4, 183.2; HRMS (ESI-Orbitrap) m/z
oxide production in cell line (BV2)a
313.1069 [M + H]+ (calcd for C18H17O5, 313.1071).
Compound
EC50 (μM)
29.2 0.8
33.2 3.2
29.5 4.1
>50
1
3.3 | (6-Hydroxybenzofuran-2-yl)
(2,4-dihydroxyphenyl)-methanone (5)
2
4
To a stirred solution of 4 (1.25 g, 4.0 mmol) in dry CH2Cl2
(20 mL) under N2 was added 1.0 M BBr3 in CH2Cl2
(24 mL, 24.0 mmol) at 0ꢀC, and the mixture was stirred at
room temperature for 40 hr. The reaction mixture was added
to 1:1 MeOH/H2O (20 mL) cautiously and stirred for further
2 hr. The reaction mixture was concentrated and water was
added. The mixture was extracted with EtOAc three times.
The combined organic layer was dried over Na2SO4, filtered,
and concentrated. The residue was purified by silica gel col-
umn chromatography eluting with 20% EtOAc in hexane to
give 5 (670 mg, 62%) as a yellow solid. M.p. > 300ꢀC
(EtOAc/hexane); IR (νmax, KBr) 3,320, 3,246, 3,116, 1,623,
1,595, 1,539, 1,491, 1,446, 1,337, 1,293, 1,242, 1,152,
5
10
14.1 1.6
11.2 0.7
10.7 0.3
11
PDTC
a
Results are expressed as the mean SE of triplicate tests. EC50 represented the
50% effective concentration to inhibit NO production.
concentrated. The residue was purified by silica gel column
chromatography eluting with 15% EtOAc in hexane to give
4 (800 mg, 51%) as a white solid. M.p. 88–89ꢀC
(EtOAc/hexane); Infrared (IR) (νmax, KBr) 3,017, 2,991,
2,946, 1,643, 1,608, 1,550, 1,492, 1,339, 1,307, 1,267,
1,209, 1,154, 1,112, 976, 842, 819, 761 cm−1 1H NMR
;
1,117, 892, 850, 824, 772 cm−1 1H NMR (acetone-d6,
;
(CDCl3, 600 MHz) δ 3.78 (s, 3H), 3.85 (s, 3H), 3.86 (s, 3H),
6.52–6.54 (m, 2H), 6.90 (dd, J = 8.4, 2.4 Hz, 1H), 7.04 (d,
J = 2.4 Hz, 1H), 7.23 (d, J = 0.6 Hz, 1H), 7.49 (d,
J = 8.4 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H); 13C NMR
(CDCl3, 150 MHz) δ 55.5, 55.7, 55.8, 95.6, 99.0, 104.3,
114.1, 116.4, 120.5, 121.0, 123.5, 131.7, 153.0, 157.5,
500 MHz) δ 6.42 (dd, J = 2.5 Hz, 1H), 6.54 (dd, J = 9.0,
2.5 Hz, 1H), 6.96 (dd, J = 8.5, 2.0 Hz, 1H), 7.10 (m, 1H),
7.66 (d, J = 8.5 Hz, 1H), 7.73 (d, J = 1.0 Hz, 1H), 8.41 (d,
J = 9.0 Hz, 1H), 12.9 (br s, OH); 13C NMR (acetone-d6,
125 MHz) δ 98.5, 103.7, 109.2, 113.1, 115.3, 117.2, 120.4,
124.7, 135.0, 152.6, 158.4, 159.9, 165.8, 167.3, 185.0;

4
JHONG ET AL.
HRMS (ESI-Orbitrap) m/z 269.0449 [M-H]− (calcd for
C15H9O5, 269.0444).
3.6 | (2-Hydroxy-4-(methoxymethoxy)-5-[3-methylbut-
2-enyl]phenyl)(6-[methoxy-methoxy]benzofuran-2-yl)
methanone (8) and (2-hydroxy-4-(methoxymethoxy)-
3-[3-methylbut-2-enyl]phenyl)(6-(methoxymethoxy)-
benzofuran-2-yl)methanone (9)
3.4 | (2-Hydroxy-4-[methoxymethoxy]phenyl)
(6-[methoxy-methoxy]benzofuran-2-yl)methanone (6)
To a stirred solution of 7 (550 mg, 1.29 mmol) in dry
CH2Cl2 (25 mL) was added montmorillonite K10 (550 mg)
at 0ꢀC, and the reaction mixture was stirred at 0ꢀC for 2 hr.
After completion of the reaction, the reaction mixture was
filtrated and concentrated under vacuum. The residue was
purified by silica gel column chromatography eluting with
15% EtOAc in hexane to give 8 (83 mg, 15%) and
9 (91 mg, 17%).
To a stirred solution of 5 (310 mg, 1.14 mmol) in dry
CH2Cl2 (40 mL) under N2 was added DIPEA (1 mL,
5.48 mmol) and MOMCl (0.48 mL, 2.85 mmol) at 0ꢀC, and
the mixture was stirred at 0ꢀC for 1 hr. To the reaction mix-
ture was added water and extracted with CH2Cl2 three times.
The combined organic layer was dried over Na2SO4, filtered,
and concentrated. The residue was purified by silica gel col-
umn chromatography eluting with 10% EtOAc in hexane to
give 6 (320 mg, 78%) as a yellow oil. IR (νmax, KBr) 3,078,
2,959, 2,910, 2,831, 1,620, 1,582, 1,536, 1,489, 1,370,
1,309, 1,253, 1,230, 1,150, 1,109, 1,008, 989, 952,
Compound 8: A yellow solid: M.p. 70ꢀC; IR (νmax, KBr)
3,330, 2,966, 1,623, 1,533, 1,506, 1,362, 1,274, 1,170,
1
1,120, 975, 823 cm−1; H NMR (CDCl3, 500 MHz) δ 1.74
1
829 cm−1; H NMR (acetone-d6, 500 MHz) δ 3.47 (s, 3H),
(s, 3H), 1.79 (d, J = 1.0 Hz, 3H), 3.29 (d, J = 7.5 Hz, 2H),
3.48 (s, 3H), 3.50 (s, 3H), 5.24 (s, 2H), 5.26 (s, 2H),
5.32–5.35 (m, 1H), 6.67 (s, 1H)), 7.05 (dd, J = 8.5, 2.0 Hz,
1H), 7.30 (d, J = 2.0 Hz, 1H), 7.55 (d, J = 1.0 Hz, 1H),
7.59 (d, J = 8.5 Hz, 1H), 8.20 (s, 1H), 12.6 (s, OH); 13C
NMR (CDCl3, 125 MHz) δ 17.8, 25.8, 27.8, 56.1, 56.4,
94.0, 94.9, 99.0, 102.0, 113.0, 115.2, 115.8, 121.3, 122.0,
122.2, 123.3, 132.1, 133.3, 152.6, 157.0, 158.3, 161.6,
165.0, 184.5; HRMS (ESI-Orbitrap) m/z 427.1753
[M + H]+ (calcd for C24H27O7, 427.1751).
3.48 (s, 3H), 5.32 (s, 2H), 5.33 (s, 2H), 6.63 (d, J = 3.0 Hz,
1H), 6.70 (dd, J = 9.0, 3.0 Hz, 1H), 7.11 (dd, J = 9.0,
2.0 Hz, 1H), 7.38 (m, 1H), 7.75 (d, J = 9.0 Hz, 1H), 7.80
(d, J = 1.0 Hz, 1H), 8.51 (d, J = 9.0 Hz, 1H), 12.7 (s, OH);
13C NMR (acetone-d6, 125 MHz) δ 56.3, 56.5, 94.9, 95.5,
99.5, 104.3, 109.5, 114.3, 116.3, 117.3, 122.0, 124.7, 134.6,
153.1, 157.9, 159.5, 164.8, 167.1, 185.3; HRMS (ESI-Orbi-
trap) m/z 359.1121 [M + H]+ (calcd for C19H19O7,
359.1125).
Compound 9: A yellow solid. M.p. 67–68ꢀC; IR (νmax
,
KBr) 2,971, 2,938, 1,612, 1,581, 1,509, 1,450, 1,403, 1,342,
3.5 | (2-(3-Methylbut-2-enyloxy)-4-[methoxymethoxy]
phenyl) (6-[methoxymethoxy]benzofuran-2-yl)
methanone (7)
1
1,252, 1,188, 1,120, 1,024, 1,005, 845, 769 cm−1; H NMR
(CDCl3, 500 MHz) δ 1.67 (d, J = 1.0 Hz, 3H), 1.80 (d,
J = 0.5 Hz, 3H), 3.42 (d, J = 7.0 Hz, 2H), 3.48 (s, 3H),
3.50 (s, 3H), 5.23–5.25 (m, 1H), 5.24 (s, 2H), 5.29 (s, 2H),
6.72 (d, J = 9.0 Hz, 1H), 7.04 (dd, J = 8.5, 2.0 Hz, 1H),
7.30 (m, 1H), 7.56 (d, J = 1.0 Hz, 1H), 7.59 (d, J = 8.5 Hz,
1H), 8.23 (d, J = 9.0 Hz, 1H), 12.7 (s, OH); 13C NMR
(CDCl3, 125 MHz) δ 17.8, 22.0, 25.8, 56.2, 56.3, 93.8, 94.8,
99.1, 105.2, 113.9, 115.2, 116.0, 118.4, 121.3, 121.9, 123.4,
131.1, 131.9, 152.4, 157.0, 158.3, 160.9, 163.2, 185.1;
HRMS (ESI-Orbitrap) m/z 427.1750 [M + H]+ (calcd for
C24H27O7, 427.1751).
To a stirred solution of 6 (608 mg, 1.91 mmol) in acetone
(35 mL) was added K2CO3 (790 mg, 5.73 mmol) and prenyl
bromide (0.4 mL, 2.87 mmol), and the reaction mixture was
refluxed overnight. After cooling, acetone was removed
using a rotavaporator, and water was added. The mixture
was extracted with EtOAc three times. The combined
organic layer was dried over Na2SO4, filtered, and concen-
trated. The residue was purified by silica gel column chro-
matography eluting with 15% EtOAc in hexane to give
7 (600 mg, 74%) as a yellow oil. IR (νmax, KBr) 2,954,
2,924, 2,854, 1,624, 1,579, 1,542, 1,492, 1,376, 1,338,
3.7 | (2,4-Dihydroxy-5-(3-methylbut-2-enyl)phenyl)
(6-hydroxybenzofuran-2-yl)methanone (10)
1
1,243, 1,152, 1,070, 1,059, 991, 921, 831 cm−1; H NMR
(CDCl3, 500 MHz) δ 1.61 (s, 3H), 1.63 (d, J = 0.5 Hz, 3H),
3.48 (s, 3H), 3.50 (s, 3H), 4.50 (d, J = 7.0 Hz, 2H), 5.21 (s,
4H), 5.22–5.25 (m, 1H), 6.66 (d, J = 2.0 Hz, 1H), 6.68 (dd,
J = 8.5, 2.0 Hz, 1H), 7.00 (dd, J = 8.5, 2.0 Hz, 1H), 7.24
(m, 1H), 7.27 (d, J = 1.0 Hz, 1H), 7.45 (d, J = 8.5 Hz, 1H),
7.51 (d, J = 8.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz) δ
18.2, 25.6, 56.1, 56.2, 65.8, 94.3, 94.8, 99.3, 101.8, 107.3,
114.7, 115.7, 119.2, 121.7, 122.3, 123.4, 131.5, 137.8,
153.5, 157.0, 158.1, 158.8, 160.9, 183.6; HRMS (ESI-Orbi-
trap) m/z 427.1750 [M + H]+ (calcd for C24H27O7,
427.1751).
To a stirred solution of 8 (50 mg, 0.12 mmol) in tetrahydro-
furan (THF) (6 mL) and isopropanol (1 mL) was added 98%
H2SO4 (0.5 mL) at 0ꢀC, and the reaction mixture was stirred
at room temperature for 3 hr. After completion of the reac-
tion, the reaction mixture was concentrated under vacuum.
The residue was purified by silica gel column chromatogra-
phy eluting with 15% EtOAc in hexane to give 10 (34 mg,
67%) as a yellow solid. mp 199–200ꢀC; IR (νmax, KBr)
2,971, 2,938, 1,612, 1,581, 1,509, 1,450, 1,403, 1,342,
1
1,252, 1,188, 1,120, 1,024, 1,005, 845, 769 cm−1; H and

JHONG ET AL.
5
13C NMR, see Table 1; HRMS (ESI-Orbitrap) m/z 339.1239
temperature. After completion of the reaction, the reaction
mixture was concentrated under vacuum. The residue was
dissolved in EtOAc and washed three times with 2N NaOH.
The combined aqueous layers were acidified with 2N HCl to
pH 3 and extracted with EtOAc three times. The combined
organic layer was dried over Na2SO4, filtered, and concen-
trated. The residue was purified by silica gel column chro-
matography eluting with 20% EtOAc in hexane to give
2 (61 mg, 69%) as a yellow solid. M.p. 185–187ꢀC; IR
(νmax, KBr) 3,361, 2,913, 1,617, 1,538, 1,484, 1,293, 1,249,
[M + H]+ (calcd for C20H19O5, 339.1227).
3.8 | (2,4-Ddihydroxy-3-(3-methylbut-2-enyl)phenyl)
(6-hydroxybenzofuran-2-yl)methanone (1,
morachalcone B)
To a stirred solution of 9 (70 mg, 0.16 mmol) in THF
(6 mL) and isopropanol (1 mL) was added 98% H2SO4
(0.5 mL) at 0ꢀC, and the reaction mixture was stirred at
room temperature for 3 hr. After completion of the reaction,
the reaction mixture was concentrated under vacuum. The
residue was purified by silica gel column chromatography
eluting with 15% EtOAc in hexane to give 1 (51 mg, 75%)
as a yellow solid. M.p. 191–192ꢀC; IR (νmax, KBr) 3,361,
2,913, 1,617, 1,538, 1,484, 1,293, 1,249, 1,162, 1,137,
1,116, 1,065, 1,022, 993, 837, 793 cm−1; 1H and 13C NMR,
see Table 1; HRMS (ESI-Orbitrap) m/z 339.1241 [M + H]+
(calcd for C20H19O5, 339.1227).
1
1,162, 1,137, 1,116, 1,065, 1,022, 993, 837, 793 cm−1; H
and 13C NMR, see Table 1; HRMS (ESI-Orbitrap) m/z
355.1177 [M + H]+ (calcd for C20H19O6, 355.1176).
3.11 | Determination of anti-inflammatory activity
A microglial cell line BV2 was cultured in Dulbecco's Modi-
fied Eagle Medium (DMEM, Gibco Laboratories, and Grand
Island, NY, USA). Production of NO was measured after
24 hr of lipopolysaccharide (LPS, 0.5 μg/mL) activation.
The accumulation of nitrite in the culture medium was mea-
sured by the Griess reagent for NO production.[16]
3.9 | (2,4-Dihydroxy-5-[2-hydroxy-3-methylbut-
3-enyl]- phenyl)(6-hydroxybenzofuran-2-yl)
methanone (11)
To a stirred mixture of 10 (75 mg, 0.22 mmol) in acetone
(60 mL) was added tetraphenylporphine (6 mg) as the pho-
tosensitizer. The reaction mixture was water-cooled at 15ꢀC,
and dried oxygen gas was bubbled through the mixture.
After the mixture was irradiated with a halogen lamp
(500 W) for 1.5 hr at 15ꢀC, triphenylphosphine (314 mg,
1.20 mmol) was added and stirred overnight at room temper-
ature. After completion of the reaction, the reaction mixture
was concentrated under vacuum. Then the residue was dis-
solved in EtOAc and washed three times with 2N NaOH.
The combined aqueous layers were acidified with 2N HCl to
pH 3 and extracted with EtOAc three times. The combined
organic layer was dried over Na2SO4, filtered, and concen-
trated. The residue was purified by silica gel column chro-
matography eluting with 20% EtOAc in hexane to give
11 (30 mg, 39%) as a yellow solid. M.p. 188–189ꢀC; IR
(νmax, KBr) 3,361, 2,913, 1,617, 1,538, 1,484, 1,293, 1,249,
4
| CONCLUSIONS
In conclusion, the total synthesis of morachalcones B and C
(1 and 2) was accomplished in seven steps from 3. Rap
−Stoermer condensation was used for constructing the core
skeleton of 1 and 2. Insertion of a prenyl group onto the aryl
ring was achieved by a 1,3-prenyl rearrangement after using
a prenylation reaction to establish the prenyl ether precursor.
Photo-oxidation was used for the transformation of the pre-
nyl group into the 2-hydroxy-3-methylbut-3-enyl group. Te
synthetic compounds 10 and 11 displayed similar activity as
PDTC, a NO production inhibitor, in microglial cells. It is
suggested that these compounds have strong potential in the
treatment of inflammation-associated brain disorders such as
ischemic stroke, Alzheimer's disease, etc.[16]
1
1,162, 1,137, 1,116, 1,065, 1,022, 993, 837, 793 cm−1; H
ACKNOWLEDGMENTS
and 13C NMR, see Table 1; HRMS (ESI-Orbitrap) m/z
This work was supported by the National Research Institute
of Chinese Medicine, Ministry of Health and Welfare
(MM10601-0160).
355.1175 [M + H]+ (calcd for C20H19O6, 355.1176).
3.10 | (2,4-Dihydroxy-3-[2-hydroxy-3-methylbut-
3-enyl]- phenyl)(6-hydroxybenzofuran-2-yl)methanone
(2, morachalcone C)
ORCID
Ming-Jaw Don https://orcid.org/0000-0002-2826-1013
To a stirred mixture of 1 (86 mg, 0.25 mmol) in acetone
(60 mL) was added tetraphenylporphine (6 mg) as the pho-
tosensitizer. The reaction mixture was water-cooled at 15ꢀC,
and dried oxygen gas was bubbled through the mixture.
After the mixture was irradiated with a halogen lamp
(500 W) for 2 hr at 15ꢀC, triphenylphosphine (72 mg,
0.27 mmol) was added and stirred overnight at room
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How to cite this article: Jhong B-S, Lin T-Y,
Kao C-H, et al. Synthesis and anti-inflammatory effect
of morachalcone B, morachalcone C, and analogs.
J Chin Chem Soc. 2019;1–6. https://doi.org/10.1002/
jccs.201800261