Synthesis and antioxidant activities of novel 4,4′-arylmethylene- bis(1H-pyrazole-5-ol)s from lignin

Article abstract of DOI:10.1002/cjoc.201280009

A series of novel bispyrazoles joined by arylmethylene at C-4 position were synthesized with aromatic aldehydes obtained from lignin and screened for their in vitro antioxidant activities by N,N-diphenyl-N′-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylenzothiazoline-sulphonic acid) diammonium salt (ABTS⁺) radical scavenging assays. All of these compounds exhibited good DPPH and ABST⁺ radical scavenging activities as compared to the standard, Trolox, which suggested their potential as promising agents for curing tumors or other free radical-related diseases.

Full text of DOI:10.1002/cjoc.201280009

FULL PAPER
DOI: 10.1002/cjoc.201280009
Synthesis and Antioxidant Activities of Novel
4,4'-Arylmethylene-bis(1H-pyrazole-5-ol)s from Lignin
Yang, Xiaohuia(杨晓慧)
Zhang, Pinghu*,b(张评浒)
Zhou, Yonghong*,a(周永红)
Wang, Junsongc(汪俊松)
Liu, Hongjuna(刘红军)
a Institute of Chemical Industry of Forestry Products, Chinese Academy of Forestry (CAF); National Engineering
Lab for Biomass Chemical Utilization; Key Laboratory of Forest Chemical Engineering, State Forestry Administra-
tion (SFA); Key Laboratory of Biomass Energy and Material; Nanjing 210042, China
b Jiangsu Center for New Drug Screening & National Drug Screening Laboratory; China Pharmaceutical Univer-
sity, 24 Tong Jia Xiang, Nanjing 210009, China
c Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China
A series of novel bispyrazoles joined by arylmethylene at C-4 position were synthesized with aromatic alde-
hydes obtained from lignin and screened for their in vitro antioxidant activities by N,N-diphenyl-N'-picrylhydrazyl
(DPPH) and 2,2'-azino-bis(3-ethylenzothiazoline-sulphonic acid) diammonium salt (ABTS＋) radical scavenging
assays. All of these compounds exhibited good DPPH and ABST＋ radical scavenging activities as compared to the
standard, Trolox, which suggested their potential as promising agents for curing tumors or other free radical-related
diseases.
Keywords pyrazole, microwave chemistry, aromatic aldehyde, 4,4'-arylmethylene-bis(1H-pyrazole-5-ol), lignin,
antioxidants
Introduction
erations, we report herein the synthesis and in vitro an-
tioxidant properties of novel 4,4'-arylmehtylene-
bis(1H-pyrazole-5-ol)s using the aromatic aldehydes
from lignin under microwave irradiation.
Pyrazoles and their related derivatives are an impor-
tant class of pharmaceutical compounds with a broad
spectrum of biological activities: analgesic, antipyretic,
antioxidant and antihypertensive properties and poten-
tial antifungal, antibacterial,[1,2] anti-inflammatory[3-5]
and anticancer activities.[6-8] In addition, some of the
oxy pyrazole derivatives are used in the treatment for a
variety of disorders caused by Human Immunodefi-
ciency Virus (HIV) and other genetic ailments caused
by retroviruses such as Acquired Immune Deficiency
Syndrome (AIDS).[9] Pyrazole derivatives are also
found applications as dyestuffs, analytical reagents and
agrochemicals.[3,10]
It is well-known that lots of natural and synthesized
antioxidants possessing phenolic hydroxyl groups can
improve their antioxidant activities by reacting with free
radicals.[11] Vanillin and syringaldehyde, two phenolic
hydroxyl containing compounds obtained from lignin,
are widely used as additives in food, pharmaceutical and
cosmetic industries due to their antioxidant activity be-
sides the fragrant odor and non-toxicity.[12-14] The syn-
thesis of pyrazole derivatives with vanillin and syring-
aldehyde as starting materials is expected to afford bet-
ter antioxidant properties. Starting from these consid-
Experimental
General
Vanillin, p-hydroxybenzaldehyde and syringalde-
hyde were synthesized according to previously reported
methods.[15-18] Other reagents were obtained from Sino-
pharm Chemical Reagent Co, Ltd. All reactions were
conducted in CEM Discover. All synthesized com-
1
pounds were characterized by infra-red (IR), H NMR,
13C NMR, mass spectrometry (MS) and elemental
analysis (EA). IR spectra were recorded with a Nicolet
Magna-IR 550 spectrometer. Mass spectra were re-
corded on WATERS Q-TOF Premier Mass Spectrome-
ter using electrospray ionization (ESI). 1H and 13C NMR
spectra were recorded with a Bruker DRX-300 Advance
spectrometer at 300 MHz and 75 MHz, respectively.
Elemental analyses (C, H, N, S) were conducted using a
PE-2400 (II) Elemental Analyser, and results were
found to be in good agreement (±0.2%) with the cal-
culated values.
*
E-mail: yhzhou1966@yahoo.com.cn; Tel.: ＋86-25-85482520; Fax: ＋86-25-85413445; zhangpinghu@163.com; Tel.: ＋86-25-83271043; Fax:
＋86-25-83271142
Received April 12, 2011; accepted October 24, 2011.
670
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 670—674

Synthesis and Antioxidant Activities of Novel 4,4'-Arylmethylene-bis(1H-pyrazole-5-ol)s from Lignin
[M＋Na]＋. Anal. calcd for C28H26N4O4: C 69.70, H
5.43, N 11.61; found C 69.79, H 5.33, N 11.50.
Typical procedure to synthesize aromatic aldehydes
from lignin
4,4'-[(4-Hydroxyphenyl)methylene]bis(3-methyl-1-
phenyl-1H-pyrazol-5-ol) (4c): 2.00 g, yield 88%; H
The aromatic aldehydes were synthesized according
1
to the reported procedure.[15-18] Briefly, alkali lignin
(100 g), 500 mL 2 mol•L－ sodium hydroxide and 112
1
NMR (DMSO-d6, 300 MHz) δ: 7.92 (d, J＝8.1 Hz, 4H,
Ar-H), 7.29 (t, J＝8.1 Hz, 4H, Ar-H), 7.13 (d, J＝8.4
Hz, 2H, Ar-H), 7.02 (t, J＝7.5 Hz, 2H, Ar-H), 6.56 (d,
J＝8.4 Hz, 2H, Ar-H), 4.50 (s, 1H, CH), 2.12 (s, 6H,
2×CH3); 13C NMR (DMSO-d6, 75.5 MHz) δ: 157.0,
154.6, 145.8, 140.1, 128.4, 128.2, 128.0, 123.2, 119.1,
118.8, 114.2, 33.5, 12.7; IR (KBr) v: 3646, 3435, 3045,
mL nitrobenzene were placed in a 2 L stainless steel
autoclave. The mixture was heated at 170 ℃ at 1 MPa
for 2 h. After the autoclave was cooled to room tem-
perature, the mixture was then transferred to a liq-
uid-liquid extractor for continuous extraction with
chloroform (500 mL×3) to remove any nitrobenzene
reduction product and excess of nitrobenzene. The oxi-
dation mixture was acidified with concentrated HCl to
pH 3 to 4 and further extracted with chloroform (500
mL×3). The solvent from the second chloroform solu-
tion was removed by using a rotary evaporator at 40 ℃
under reduced pressure to obtain the mixture of aro-
matic aldehydes. The residue was isolated by column
chromatography to obtain syringaldehyde, vanillin and
p-hydroxybenzaldehyde with total yield 12%—18%.
－
1
2966, 2859, 1597, 1501, 1424, 1270, 769 cm ; MS
(ESI) m/z: 453.2 [M＋H]＋, 475.2 [M＋Na]＋. Anal.
calcd for C27H24N4O3: C 71.67, H 5.35, N 12.38; found
C 71.76, H 5.27, N 12.31.
4,4'-((4-Hydroxy-3,5-dimethoxyphenyl)methylene)-
bis(1,3-diphenyl-1H-pyrazol-5-ol) (4d): 2.52 g, yield
79%; 1H NMR (DMSO-d6, 300 MHz) δ: 7.70 (d, J＝8.1
Hz, 4H, Ar-H), 7.12—7.47 (m, 16H, Ar-H), 6.60 (s, 2H,
Ar-H), 5.11 (s, 1H, CH), 3.68 (s, 6H, 2×OCH3); 13C
NMR (DMSO-d6, 75.5 MHz) δ: 147.8, 146.0, 140.2,
134.0, 132.5, 128.8, 128.5, 128.2, 127.7, 127.5, 126.8,
119.7, 119.6, 105.2, 55.3, 33.4; IR (KBr) v: 3066, 1596,
Typical procedure to synthesize 4,4'-arylmehtylene-
bis(1H-pyrazole-5-ol)s
－
1
A stirred aqueous mixture of phenylhydrazine (10
mmol) and β-ketoesters (10 mmol) was placed into a
sealed microwave oven (300 W) at 100 ℃ for 5 min.
After the mixture was cooled, aromatic aldehydes (5
mmol) were added successively at 100 ℃ for another 5
min. The reaction mixture was cooled to room tempera-
ture to afford the product as a precipitate. The solid
residue was filtered, washed with water and 5 mL of
50% ethanol, and then recrystallized from ethyl ace-
tate/ethanol (80∶20, V/V) to give products.
1500, 1455, 1408, 1313, 754, 690 cm ; MS (ESI) m/z:
637.2 [M＋H]＋. Anal. calcd for C39H32N4O5: C 73.57,
H 5.07, N 8.80; found C 73.64, H 5.01, N 8.93.
4,4'-[(4-Hydroxy-3-methoxyphenyl)methylene]bis-
(1,3-diphenyl-1H-pyrazol-5-ol) (4e): 2.56 g, yield 84%;
1H NMR (DMSO-d6, 300 MHz) δ: 8.00 (d, J＝8.1 Hz,
4H, Ar-H), 7.10—7.39 (m, 16H, Ar-H), 6.83 (s, 1H,
Ar-H), 6.61 (s, 1H, Ar-H), 5.09 (s, 1H, CH), 3.58 (s, 3H,
OCH3); 13C NMR (DMSO-d6, 75.5 MHz) δ: 157.9,
149.4, 146.8, 144.1, 140.4, 135.0, 134.9, 128.6, 128.3,
127.9, 127.8, 126.9, 123.6, 119.8, 119.7, 114.8, 112.3,
55.5, 33.6; IR (KBr) v: 3067, 3032, 1597, 1499, 1454,
4,4'-[(4-Hydroxy-3,5-dimethoxyphenyl)methylene]-
bis(3-methyl-1-phenyl-1H-pyrazol-5-ol) (4a): 2.18 g,
1
－
1
yield 85%; H NMR (DMSO-d6, 300 MHz) δ: 7.69 (d,
1406, 1311, 754, 688 cm ; MS (ESI) m/z: 607.1 [M＋
H]＋. Anal. calcd for C38H30N4O4: C 75.23, H 4.98, N
9.24; found C 75.30, H 4.91, N 9.29.
J＝8.1 Hz, 4H, Ar-H), 7.44 (t, J＝8.1 Hz, 4H, Ar-H),
7.21—7.27 (m, 2H, Ar-H), 6.60 (s, 2H, Ar-H), 4.82 (s,
1H, CH), 3.67 (s, 6H, 2×OCH3), 1.99 (s, 6H, 2×CH3);
13C NMR (DMSO-d6, 75.5 MHz) δ: 147.6, 146.1, 134.0,
132.6, 128.8, 125.5, 120.5, 105.3, 56.0, 33.3, 11.6; IR
(KBr) v: 3220, 3072, 2939, 2842, 1608, 1581, 1506,
4,4'-[(4-Hydroxyphenyl)methylene]bis(1,3-diphenyl-
1H-pyrazol-5-ol) (4f): 2.34 g, yield 81%; 1H NMR
(DMSO-d6, 300 MHz) δ: 7.59 (d, J＝7.8 Hz, 4H, Ar-H),
7.14—7.48 (m, 16H, Ar-H), 7.00 (d, J＝8.1 Hz, 2H,
Ar-H), 6.63 (d, J＝8.1 Hz, 2H, Ar-H), 5.12 (s, 1H, CH);
13C NMR (DMSO-d6, 75.5 MHz) δ: 157.8, 154.9, 149.2,
139.2, 133.4, 128.8, 128.5, 128.1, 128.0, 127.8, 127.6,
126.1, 124.5, 120.6, 120.1, 114.6, 33.0; IR (KBr) v:
－
＋
1
1455, 1113, 763 cm ; MS (ESI) m/z: 513.2 [M＋H] ,
535.2 [M＋Na]＋. Anal. calcd for C29H28N4O5: C 67.96,
H 5.51, N 10.93; found C 68.07, H 5.62, N 10.81.
4,4'-[(4-Hydroxy-3-methoxyphenyl)methylene]bis(3-
methyl-1-phenyl-1H-pyrazol-5-ol) (4b): 2.01 g, yield
83%; 1H NMR (DMSO-d6, 300 MHz) δ: 7.89 (d, J＝8.4
Hz, 4H, Ar-H), 7.30 (t, J＝8.4 Hz, 4H, Ar-H), 7.01—
7.06 (m, 3H, Ar-H), 6.76 (d, J＝8.1 Hz, 1H, Ar-H), 6.58
(d, J＝8.1 Hz, 1H, Ar-H), 4.50 (s, 1H, CH), 3.67 (s, 3H,
OCH3), 2.14 (s, 6H, 2×CH3); 13C NMR (DMSO-d6,
75.5 MHz) δ: 157.0, 146.7, 145.7, 143.8, 140.8, 138.2,
128.1, 122.7, 119.5, 118.9, 114.5, 112.2, 55.5, 34.5,
13.0; IR (KBr) v: 3354, 3527, 3070, 2950, 2841, 1596,
－
1
3609, 3063, 1596, 1567, 1501, 1454, 754, 695 cm ;
MS (ESI) m/z: 577.3 [M ＋ H] ＋ . Anal. calcd for
C37H28N4O3: C 77.07, H 4.89, N 9.72; found C 77.01, H
4.97, N 9.78.
In vitro biological evaluation
The compounds were evaluated for their in vitro free
radical scavenging activity by the 2,2'-diphenyl-1-
picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzo-
thiazoline-sulphonic acid) diammonium salt (ABTS＋)
radical scavenging method.[19-21]
－
1
1512, 1502, 1377, 1363, 1273, 1036, 750 cm ; MS
(ESI) m/z: 483.1 [M＋H]＋, 500.2 [M＋NH4]＋, 505.1
Chin. J. Chem. 2012, 30, 670—674
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
671

Yang et al.
FULL PAPER
cording to the reported methods (Scheme 1).[15-18] Due
to the high macromolecular complexity of lignin, it
must be liberated to monomers via oxidative degrada-
tion. Nitrobenzene oxidation, cupric oxidation and per-
manganate oxidation are the common delignification
methods. Cupric oxidation often leads to the production
of acetoguaiacone and acetosyringone as major com-
pounds in lignin, while permanganate oxidation pro-
duces significant amount of carboxylic acid methyl es-
ters. Therefore, nitrobenzene oxidation was used to
break down the lignin into monomers in our study since
vanillin and syringaldehyde are the major compounds
by this delignification method. The total yield of aro-
matic aldehydes using this method, up to 12%—18%;
seems low but also satisfactory considering the recycle
of the by-products, macromolecular polymers, and their
utilization in the synthesis of polymeric materials such
as polyurethane, phenolic resin, adhesive and so on.
DPPH radical scavenging assay
This assay is based on the measurement of the scav-
enging ability of compounds towards the stable
2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and per-
formed according to the reported method.[19,21] Briefly,
an ethanol solution (200 μL) of 100 μmol•L－ DPPH
1
(Aldrich, USA) was incubated at 30 ℃ with 1 μL of
compound or Trolox solutions in deionized H2O. The
－
1
final concentration of compounds was 100 μmol•L . A
decrease in absorbance was measured at 517 nm (Perkin
Elmer Lambda 2 Spectrophotometer). The rate constant
was calculated as the average value of 5 to 6 time-points
(intervals) until the absorbance diminished by 50%. The
radical scavenging activity was expressed as the reduc-
tion rate constant (k) of DPPH and calculated according
to the Eq. (1), where [DPPH]0 is the starting concentra-
tion and [DPPH]t is the concentration at the time ‘t’.
[DPPH]0[DPPH]t
k (mol－1·L·s－1)＝
(1)
Scheme 1 Preparation of aromatic aldehydes from lignin
t[DPPH]0[DPPH]t
R1
HO
HO
lignin
The percentage of scavenged DPPH was plotted
versus the concentration of antioxidants and the concen-
tration of antioxidant required obtaining 50% inhibition
(50% inhibition concentration, i.e., IC50) was obtained
from the graph.
CHO
O
nitrobenzene/OH-
autoclave
R2
R2
R1
R2
R1
OH
OH
R1 = R2 = H or OMe
ABST＋ radical cation scavenging assay
R1 = R2 = H or OMe
The concentration of ABST＋ remaining after reac-
tion with the antioxidants was determined according to
previously published procedure.[20,21] The procedure to
prepare the ABST ＋ stock solution was modified
slightly. Sufficient amounts of the diammonium salts of
ABTS＋ (Sigma, USA) and K2S2O8 (Sigma, USA) were
dissolved in 2.0 mL water to achieve concentrations of
4.00 and 1.41 mmol•L , respectively. This solution
was kept in the dark for at least 16 h to form ABST＋,
then diluted to 100 mL with 80% ethanol so that the
solution had an absorbance value (Absref) of 0.70±0.05
at 734 nm (Perkin Elmer Lambda 2 Spectrophotometer).
Various concentrations of compounds (10 μL) were
added to ABST＋ solution (200 μL) at ambient tem-
perature to reach a stable absorbance (Absdetect). The
percentage of ABST＋ scavenged was calculated using
Eq. (2).
Scheme 2 Microwave-assisted synthesis of 4,4'-arylmehtylene-
bis(1H-pyrazole-5-ol)s
O
O
MW
PhHN NH2
+
R
OEt
water
1
2
－
1
Ar
R
R
R
O
aromatic aldehydes
MW/water
N
N
N
N
N
N
OHHO
Ph
3
Ph
Ph
4
It is well-known that the formation of
4,4'-arylmehtylene-bis(1H-pyrazole-5-ol) is proposed to
involve the following tandem reactions: pyrazolone
formation by reaction between phenylhydrazine and
β-ketoesters, followed by aldol condensation of pyra-
zolone with aromatic aldehydes, and tautomerization
(Scheme 2).[22,23] Recently, the progress in the field of
reactions in aqua media is gaining significance because
of their operational simplicity and environmentally be-
nign processes.[24] Herein, we wished to develop a new
eco-friendly procedure with our continuation to the use
of the microwave technology for efficient and cata-
lyst-free synthesis of pyrazole derivatives in water be-
cause microwave irradiation can accelerate reaction rate,
shorten reaction time, and improve product yields by
transferring energy directly to the reactive species.[25,26]
The workup procedure is very simple without separation
Absdetect
ABSTs＋cavenged (%)＝(1－
)×100
(2)
Absref
The percentage of scavenged ABST＋ was plotted
versus the concentration of antioxidants and the concen-
tration of antioxidant required obtaining 50% inhibition
(50% inhibition concentration, i.e., IC50) was obtained
from the graph.
Results and Discussion
Chemistry
Aromatic aldehydes were prepared from lignin ac-
672
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 670—674

Synthesis and Antioxidant Activities of Novel 4,4'-Arylmethylene-bis(1H-pyrazole-5-ol)s from Lignin
of the intermediates, pyrazolones, which were con-
sumed in the next condensation reaction directly. So this
protocol is very simple just like “one-pot reaction”,
economical and environmentally benign.
As indicated in Table 1, the reactions were per-
formed in water at 80 ℃ within 5 min under micro-
wave irradiation without catalysts with good yielded
(≥79%). All the compounds were characterized by IR,
1H NMR, 13C NMR, MS and elemental analysis.
Table 1 Microwave-assisted synthesis of 4,4'-arylmehtylene-
bis(1H-pyrazole-5-ol)s 4a—4f in water
Entry Product
Ar
R
yielda/%
Figure 1 Radical scavenging activity of compounds 4a—4f and
Trolox in N,N-diphenyl-N′-picrylhydrazyl (DPPH) assay. Results
were expressed as reduction rate costant (k) of DPPH±S.D.
Significance was calculated according to the Student’s t-test, p＜
0.05.
1
2
3
4
5
6
4a
4b
4c
4d
4e
4f
syringyl
guaiacyl
Me
Me
Me
Ph
85
83
p-hydroxyphenyl
syringyl
88
79
guaiacyl
Ph
84
Table 2 Radical scavenging activity of compounds 4a—4f and
p-hydroxyphenyl
Ph
81
Trolox in DPPH and ABST＋ assays
a Isolated yield.
IC50/(μmol•L－
)
1
Sample
DPPH
ABST＋
In vitro biological evaluation
All the synthesized compounds were evaluated for
antioxidant activity by N,N-diphenyl-N'-picrylhydrazyl
(DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-
sulphonic acid) diammonium salt (ABTS＋) assays.
DPPH is a well-known method for determining an-
tioxidant activity of plant flavonoids. DPPH radical
scavenging activities of compounds 4b, 4c, 4e and 4f
were found to be good to moderate, while those of 4a
and 4d were found to be good to excellent as compared
to the standard Trolox (Figure 1). Especially, the radical
scavenging activity of compound 4a was almost two
times as high as that of Trolox, while compound 4d
showed nearly the same radical scavenging activity as
Trolox.
4a
4b
4.37±0.17
14.97±0.96
15.00±1.21
5.51±0.21
5.91±0.15
7.28±0.28
37.35±2.89
2.00±0.08
2.26±0.15
2.82±0.12
2.18±0.13
2.41±0.11
4.48±0.25
2.29±0.18
4c
4d
4e
4f
Trolox
In view of their good antioxidant activity, their 50%
inhibitory concentrations (IC50) against DPPH and
ABST＋ were tested (Table 2). The values of IC50 for all
the compounds were lower than that of Trolox in reac-
tion with DPPH, while the compounds 4a, 4b, 4d and
4e showed almost the same IC50 as Trolox in the
ABST＋ radical cation scavenging assays. As showed in
Figures 1 and 2, the antioxidant activities of 4a and 4d
are the best, those of 4b and 4e are middle, and those of
4c and 4f are relatively poor. It is easy to find that the
structure of 4,4'-arylmehtylene-bis(1H-pyrazole-5-ol)s
has a major influence on their antioxidant activities. The
presence of methoxy groups in aromatic groups in-
creased their antioxidant properties. Especially, anti-
oxidant activity of compounds 4a and 4d containing two
methoxy groups increased more sharply. On the other
hand, the substituted groups at C-4 position of pyrazoles
also produced an effect on their antioxidant activities,
for example, methyl substituted pyrazole 4a had much
better antioxidant property than phenyl substituted
Figure 2 The 50% inhibitory concentrations (IC50) against
DPPH and ABST＋ for compouds 4a—4f and Trolox.
pyrazole 4d. In general, the activity order of them is as
follows: syringyl (4-hydroxy-3,5-dimethoxyphenyl)
modified bis(1H-pyrazol-5-ol)s>>guaiacyl (4-hydroxy-
3-methoxyphenyl) modified bis(1H-pyrazol-5-ol)s ＞
p-hydroxyphenyl modified bis(1H-pyrazol-5-ol)s.
The strong antioxidant abilities of these compounds
indicated their potential usefulness in the drug devel-
Chin. J. Chem. 2012, 30, 670—674
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www.cjc.wiley-vch.de
673

Yang et al.
FULL PAPER
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Conclusions
A series of novel bispyrazoles having arylmethylene
substituent at the C-4 position were obtained from lignin
and screened for their in vitro biological activities. Al-
most all compounds showed good DPPH and ABST＋
radical scavenging activities. The procedure is very en-
vironmentally benign, which were performed in water
without catalysts in good to excellent yields. Com-
pounds 4a and 4d showed the best antioxidant activities
against DPPH and ABST＋. In addition, antioxidant ac-
tivities of those compounds increased markedly with the
introduce of the methoxy groups. What’s more, these
compounds were nontoxic,[3] which favored further
studies to explore them as potential chemotherapeutic
agents for tumors or other free radical induced deseases.
Synthesis of heterocyclic compounds from lignin for
pharmaceutical industry could obtain high value-added
products from lignin.
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Acknowledgement
This work was supported by Key Projects in the Na-
tional Science & Technology Pillar Program in the
Eleventh Five-year Plan Period (No. 2006BAD18B10)
and the President Foundation of the Chinese Academy
of Forestry (CAFYBB2008009).
[22] Yao, C. S.; Yu, C. X.; Tu, S. J.; Shi, D. Q.; Wang, X. S.; Zhu, Y. Q.;
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