The first total synthesis of tarennane, a potent antioxidant chalcone constituent from tarenna attenuate or Magnolia officinalis

Article abstract of DOI:10.2174/157017811795371368

The convergent total synthesis of tarennane has been accomplished in six steps starting from commercially available phloroglucinol and guaiacol; the key step of the synthesis relies on a highly regioselective Heck reaction applying iodophenol and PdCl₂(PPh₃)₂.

Full text of DOI:10.2174/157017811795371368

258
Letters in Organic Chemistry, 2011, 8, 258-263
The First Total Synthesis of Tarennane, a Potent Antioxidant Chalcone
Constituent from Tarenna Attenuate or Magnolia Officinalis
Jincheng Yang†,a,b, Tao Yang†,a, Youfu Luoa, Jun Heb, Jianyou Shic and Aihua Peng*,a
aState Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu,
Sichuan 610041, P.R. China
bWest China School of Pharmacy, Sichuan University, Chengdu, 610041, P.R. China
cSichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, 610041, P.R. China
Received September 10, 2010: Revised February 17, 2011: Accepted February 21, 2011
Abstract: The convergent total synthesis of tarennane has been accomplished in six steps starting from commercially
available phloroglucinol and guaiacol; the key step of the synthesis relies on a highly regioselective Heck reaction
applying iodophenol and PdCl2(PPh3)2.
Keywords: Tarennane, total synthesis, heck reaction, antioxidant activity.
INTRODUCTION
the lack of a facile synthetic access to this type of
compounds, since their indirect potent antioxidant effects as
well as other biological activities could be of interest in
medical and pharmaceutical science.
A variety of important biological compounds with the
central scaffold of aromatic ketone are known collectively as
chalcones. It is shown that these compounds possess
antifungal, antitumor and anti-inflammatory properties [1].
Cardamonin (2, Fig. 1), isolated from Alpinia rafflesiana,
inhibits pro-inflammatory mediators in activated RAW 264.7
cells and whole blood [2]. Cochinchinenone 3 from
Dracaena cochinchinensis shows growth inhibitory effects
against Helicobacter pylori (ATCC43504) [3]. Compound 4,
an analogue of chalcones from trunk exudates of Dalbergia
sissoo is one of the most potent NO production inhibitors
[4].
In this letter, we describe a facile synthesis of tarennane.
Retrosynthetic analysis for tarennane (Scheme 1) scaffold
can be divided into three parts: (i) ring B with one phenolic
hydroxyl group at the para-position and a methoxy group
next to it; (ii) ring A with one carbonyl group at the para-
position and three methoxy groups; (iii) one propylene chain
as the connection part.
Our synthesis started with etherification
of
phloroglucinol 7 with Me2SO4 and K2CO3 in methanol to
produce 1,3,5-Trimethoxybenzene (8; Scheme 2). Then 8
was oxidized by 30% H2O2 in the presence of K4Fe(CN)6
Tarennane 1, a novel chalcone constituent whose ring A
was converted to a quinol ether moiety, was first isolated in
2007 from the whole plants of Tarenna attenuata (Voigt)
Hutchins [5]. Xian-Wen Yang et al. reported its potent
antioxidant activities against H2O2-induced impairment in
PC12 cells in vitro [5]. In 2009, Chien-Chang Shen et al.
isolated tarennane in minor quantities from the bark of
Magnolia officinalis [6]. Therein it was wrongly regarded as
a novel compound and named as Magnolianone for its
special plant origin. To further investigate the broad
biological activities, efficient chemical syntheses of
tarennane will be necessary for both in vitro and in vivo test.
and AcOH at room temperature to get
9
[8].
Allyltrimethylsilane 10 was added into the CH2Cl2 solution
of 9 at -80°C to produce 11 in less than half an hour [9].
Experimentally, the low temperature is advantageous for the
formation of the target intermediate 11 without or with little
production
of
byproduct_
(4-allyl-2,6-dimethoxy-4-
hydroxyl-cyclohexa-2,5-dienone). However, at this step the
major isomer of 11 did not need to be separated. Then 11
was methylated directly with Me2SO4 in the mixture of
sodium hydroxide aqueous solution, toluene and
tetrabutylammonium bromide at room temperature to afford
the key intermediate 12 [10]. At this stage, the methylation
step made the minor isomer of 11 can be easily removed by
column chromatography and thus 12 was obtained in an
overall yield of 48% over two steps from 9.
However, none of the synthetic routes reported for
chalcones and the analogues [7] is probably practicable for
the type of Tarennane. To the best of our knowledge, it is
noteworthy that the connection of one aromatic ring with
another non-aromatic ring has rarely been investigated. We
speculate that the absence of tarennane in the literature
compared to the hundreds of synthesized chalcones is due to
Another key intermediate 14 was obtained from
iodization of guaiacol 13 with NaI, NaOH, NaClO in
methanol at -5°C [11]. Here the temperature control was the
one of the key factors for this reaction. Otherwise, the
undesired regioisomer 2-iodo-6-methoxyphenol and 2,4-
diiodo-6-methoxyphenol would take a heavy ratio in the
products. For instance, if the reaction was taken at room
*Address correspondence to this author at the State Key Laboratory of
Biotherapy, Chengdu, 610041, P.R. China; Tel: +862880366761;
Fax: +862885164060; E-mail: Peng_aihua@163.com
†These authors corresponding equally to this work.
1570-1786/11 $58.00+.00
© 2011 Bentham Science Publishers Ltd.

The First Total Synthesis of Tarennane
Letters in Organic Chemistry, 2011, Vol. 8, No. 4
259
OH
O
OMe
15
OMe
7
2
B
5
OMe
OH
1
14
9
3
4
10
A
8
6
HO
OMe
13
11
OMe
O
12
Tarennane / Magnolianone 1
Cardamonin 2
OMe
OH
OMe
OH
O
O
O
OMe
Cochinchinenone 3
MeO
OH
OMe
4
OMe
MeO
MeO
OH
OMe
MeO
OH
OMe
MeO
Combretastatin A-4 6
Erianin 5
Fig. (1). Tarennane 1 and its analogues.
temperature, the ratio of 2-iodo-6-methoxyphenol might rise
up to 30%.
strategy was evaluated for the antitumor effects compared
with 5 and 6 in HepG2 cell lines and A549 cell lines.
However, it did not exhibited inhibition in a certain degree
with IC50>100μM.
OMe
OMe
OMe
A
B
EXPERIMENTAL SECTION
Material and Methods
O
OMe
OH
1
All commercial chemicals and solvents are reagent grade
and were used without further treatment unless otherwise
noted. Analytical thin-layer chromatography was performed
on GF 254; Qingdao Haiyang company. Melting points were
obtained in open capillary tubes and are not corrected. The
1H NMR (400 MHz) spectra were recorded on a Varian
Mercury- 400 High Performance Digital FT-NMR with TMS
as internal standard, chemical shifts were reported in parts
per million (ppm, d) downfield from tetramethylsilane.
Proton coupling patterns were described as singlet (s),
doublet (d), triplet (t), quartet (q), multiplet (m), and broad
(br). HRMS was carried out on Waters Q-TOF Premier mass
spectrometry which coupled with an electrospray ionization
source. The electrospray ionization source was operated in
positive/negative ion mode with a spray voltage of 2.8 kV.
Source temperature was set at 90°C. Nitrogen was used as
vacuum gas and maintained at 0.36 Bar. In the analysis, the
sample was directly injected into mass spectrometry at a
flow rate of 3μl/min.
OMe
OH
O
OMe
OMe
12
I
OMe
14
O
Si
10
+
OH
MeO
OMe
OMe
O
13
9
Scheme 1. Retrosynthetic analysis.
General Synthetic Procedure
At the final connection 12 and 14, we tried several Heck
coupling conditions (Table 1). Finally, the target tarennane 1
was constructed with triethylamine, PdCl2(PPh3)2 and
lithium chloride anhydrous in DMF at 90°C for 50 h under
argon [12].
Synthesis of 1, 3, 5-trimethoxybenzene (8)
Phloroglucinol dehydrate 7 (27g, 166.67mmol) was
mixed with K2CO3 (73.6g, 533.33mmol) in the solvent of
acetone (ca 300mL). At room temperature, the dimethyl
sulfate (50.5mL, 533.33mmol) was dropped into the reaction
bottle. When adding over, the reaction temperature was kept
Since the structural similarity of tarennane 1 with erianin
5 and combretastatin A-4 6, tarennane synthesized in this

260 Letters in Organic Chemistry, 2011, Vol. 8, No. 4
Yang et al.
Table 1. The Optimization for the Last Step of Heck Coupling Reaction
Entry
Catalyst
Alkali
Solvent
Temp (°C)
Yield (%)
1
2
3
4
5
6
7
Pd(OAc)2/ PPh3
Pd(OAc)2/PPh3
Et3N
piperidine
K2CO3
K2CO3
Et3N
DMF
DMF
80
100
100
100
110
25
10
15
8
Pd(OAc)2 /PPh3
DMF
Pd(OAc)2/(o-tol)3P
Pd(OAc)2/(o-tol)3P
Pd2(dBa)3 / TBAB
PdCl2(PPh3)2/LiCl
DMF
20
12
0
Toluene
THF/EtOH
DMF
-----
Et3N
90
54
O
OH
OMe
b
a
MeO
OMe
HO
OH
MeO
OMe
O
7
8
9
OMe
OMe
d
c
O
O
OH
OMe
OMe
OMe
11
12
OH
OH
e
I
OMe
OMe
13
14
OMe
OMe
OMe
f
+
12
14
O
OMe
OH
1
Scheme 2. Reagents and conditions: (a)Me2SO4, MeOH, K2CO3, ref 90%; (b)H2O2, K4Fe(CN)6, AcOH, rt 60%; (c) allyltrimethylsilane 10,
TiCl4, DCM, -78°C to rt 80%; (d) Me2SO4, NaOH, n-Bu4NBr, tol, rt 60%; (e)NaI, NaOH, NaClO, MeOH, -5°C 70%.;(f) PdCl2(PPh3)2
10mol%, LiCl, Et3N, DMF, 90°C 54%.
at 60°C for 24 h. Then the mixture was filtered, the filtrate
was concentrated and washed with basic water (3ꢀ100mL) to
obtain 8 (25.3g, 90.2%) as a light yellow solid. TLC: Rf = 0.5
(2ꢀ100 mL) as well as 60-90°C petroleum ether (3ꢀ100
mL). The yellow solid was the product. (7.88g, 60%) TLC:
1
Rf = 0.06 (petroleum/acetone 3:1) mp. 254-256°C. H NMR
1
(petroleum/acetone 3:1) mp. 49-50°C. H NMR (400 MHz,
(400 MHz, CDCl3, ꢁ) 5.86 (s, 2H), 3.83 (s, 6H); MS (EI) m/z
168 (M+); HRMS (EI+) m/z calculated for [MNa+]
C8H8O4Na+ 191.0320, found 191.0308.
CDCl3, ꢁ) 6.08 (s, 3H), 3.77 (s, 9H); 13C NMR (100 MHz,
CDCl3, ꢁ) 161.5, 92.8, 55.3; MS (EI) m/z 168 (M+); HRMS
(EI+) m/z calculated for C9H12O3 168.0786, found 168.0784.
Synthesis of 4-allyl-4-hydroxy-3, 5-dimethoxycyclohexa-2,
5-dienone (11)
Synthesis of 2, 6-dimethoxycyclohexa-2, 5-diene-1, 4-dione
(9)
2, 6-dimethoxycyclohexa-2, 5-diene-1, 4-dione 9 (5g,
29.76 mmol) was added into DCM (ca. 20mL) under argon.
The reaction mixture was cooled to -78°C. Ten minutes later,
the solution was added TiCl4 (2mL, 14.88mmol). At this
moment, the solution became blood red. Six minutes later,
the allyltrimethylsilane 10 (4.84mL, 30.50mmol) was added.
Then the temperature of the solution rised heavily, the
1, 3, 5-trimethoxybenzene 8 (13.12g, 78.10mmol) was
dissolved in CH3COOH (ca. 50mL) and cooled with ice-
water. Then 30% H2O2 (24mL, 234.30mmol) was added into
this black solution, which turned into yellow with a little
white bubble on the surface. About 2 h later, this solution
was filtered, and the cake was washed with distilled water

The First Total Synthesis of Tarennane
Letters in Organic Chemistry, 2011, Vol. 8, No. 4
261
Table 2. The Comparison of the Synthetic Tarennane with Natural Tarennane and Natural Magnolianone
Position
natural magnolianone
natural tarennane
(CD3OD)
synthetic tarennane
(CDCl3)
(acetone-d6)
13C
1H
13C
1H
13C
1H
125MHz
500MHz
100MHz
500MHz
100MHz
400MHz
3-OCH3
10-OCH3
11,15-OCH3
13
56.2
52.3
3.78
3.03
3.80
56.3
53.0
3.79
3.08
3.82
56.3
52.7
3.87
3.14
3.80
56.5
57.0
55.9
186.4
105.1
169.6
80.0
190.0
104.8
172.3
81.0
187.1
104.4
169.2
79.2
12,14-CH
11,15
10
5.54
5.64
5.63
9-CH2
8-CH
7-CH
6-CH
5-CH
4
40.7
2.78 d(7.5)
5.67 m
41.6
2.79 d(7.6)
5.57 dt (15.6,7.6)
6.25 d(15.6)
6.66 d(8.2)
40.4
2.88 d(7.2)
5.57 m
120.1
134.7
120.2
115.7
147.2
148.3
110.4
130.3
119.0
135.8
120.8
116.6
149.0
149.4
110.5
129.8
119.1
134.0
119.9
114.3
145.4
146.5
108.2
129.5
6.29d(15.5)
6.73dd (8.0,1.5)
6.69 d(8.0)
6.29 d(15.2)
6.72 m
6.80 m
6.64 d(8.2)
3
2-CH
1
6.85 d(1.5)
6.76
tempreture was kept under -50°C. Fifiteen minutes later, the
bottle was put out to room temperature and added H2O
(30mL). The organic layer was separated and washed with
water (3ꢀ50mL) and then brine (1ꢀ50mL) and dry over
anhydrous Na2SO4. After the organic layer was evaporated
under reduced pressure, the residue was purified by silica gel
column chromatography (petroleum/acetone 5:1) to afford
11 (5.04 g, 80.6%) as khaki solid. TLC: Rf = 0.1
(petroleum/acetone 3:1) Rf = 0.4 (petroleum/acetone 1:1) mp.
Hz, 2H); NOE: correlations among peaks at 3.77 ppm, 5.60
ppm and 3.10 ppm were observed; 13C NMR (100 MHz,
CDCl3, ꢁ) 187.0, 168.9, 130.3, 119.3, 104.4, 79.0, 56.1, 52.5,
41.0; MS (EI) m/z 223(M+); HRMS (EI+) m/z calculated for
[MNa+] C12H16O4Na+ 247.0946, found 247.0948.
Synthesis of 4-iodo-2-methoxyphenol (14)
As Sushma Manda et al. [11] reported, guaiacol 13 (5mL,
45.97mmol), NaI (10.34g, 68.95mmol) and NaOH (2.76g,
68.95mmol) were dissolved in methanol (ca. 120mL) and
cooled below 0 °C. Then aq NaOCl (46mL, 68.95mmol)
solution was added dropwise over 30 min. Twenty min later,
the reaction was warmed up to room temperature and
acidified to pH=1. Then 10% Na2S2O3 (17g) was added. The
precipitate was filtered out and the filtrate was evaporated to
remove methanol. Then the aqueous solution was extracted
with ethyl acetate. The organic layer was then washed with
water, aqueous NaHCO3 and brine, dried with anhydrous
Na2SO4 and then concentrated and purified by silica gel
column chromatography (petroleum/acetone 100:1, 50:1) to
1
62-64°C H NMR (400 MHz, CDCl3, ꢁ) 5.44 (s, 2H), 5.40
(m, 1H), 5.04 (m, 2H), 3.78 (s, 6H), 2.77 (d, J=7.2 Hz, 2H);
13C NMR (100 MHz, CDCl3, ꢁ) 186.8, 157.3, 135.2, 125.0,
107.4, 58.5, 32.2; MS (EI) m/z 210 (M+); HRMS (EI+) m/z
calculated for [MNa+] C11H14O4Na+ 233.0790, found
233.0780.
Synthesis of 4-allyl-3, 4, 5-trimethoxycyclohexa-2, 5-
dienone (12)
NaOH/H2O (2g/20mL) was added to a solution of 11
(2.887g, 13.75mmol), tetrabutylammonium bromide (8.85g,
27.50mmol), and toluene (20mL) at room temperature. ten
minutes later, Me2SO4 (2.6mL) was added, and then the
solution became black. Six hours later, the solution was
evaporated under reduced pressure.The black solid was
washed with water (50mL) and ethyl acetate (3ꢀ50mL).
After dried over anhydrous Na2SO4, the organic layer was
concentrated; a brown semisolid was obtained. The residue
was purified by silica gel column chromatography
(petroleum/acetone 10:1) to afford 12 (1.85g, 60%) as white
solid. TLC: Rf = 0.32 (petroleum/acetone 3:1) mp. 102-104
1
afford the target product 14 (8.04g, 70%) mp. 38-40°C. H
NMR (400MHz, CDCl3,ꢁ) 7.18 (dd, J1=8.4Hz, J2=2Hz, 1H),
7.11 (d, J=2Hz, 1H), 6.68 (d, J=8Hz, 1H), 5.58 (s,1H); 13C
NMR (100MHz, CDCl3, ꢁ) 130.5, 119.8, 118.9, 116.9,
116.5, 80.9, 56.2; MS (EI) m/z 250 (M+); HRMS (EI+) m/z
calculated for C7H7IO2 249.9491, found 249.9494.
Synthesis of Tarennane/ Magnolianone (1)
Compound 12 (200mg, 0.8929mmol), 4-iodo-2-
methoxyphenol 14 (268mg, 1.0715mmol), PdCl2(PPh3)2
(63mg, 0.0893mmol), lithium chloride anhydrous (113mg,
2.6787mmol) and Et3N (0.4mL, 2.6787mmol) were stirred in
1
°C. H NMR (400 MHz, CDCl3, ꢁ) 5.61 (s, 2H), 5.37 (m,
1H), 5.00 (t, 2H), 3.77 (s, 6H), 3.11 (s, 3H), 2.74 (d, J=7.6

262 Letters in Organic Chemistry, 2011, Vol. 8, No. 4
Yang et al.
TiCl3-Cl
O
O
TiCl4
SiMe3
R1
R2
R1
R2
(i)
O
(ii)
TiCl3
R2
R1
TiCl3
R2 OH
R2
O
SiMe3
Cl
R1
R1
(iii)
O
(iv)
(v)
O
Cl-Cl3Ti
MeO
O
O
TiCl4
+
MeO
OMe
MeO
OMe
OMe
O
O
TiCl3-Cl
SiMe3
9
(vi)
(vii)
O
O
O
MeO
OMe
MeO
OMe
OH
MeO
OMe
O
O
TiCl3
H2O
TiCl3
Me3Si
Cl
11
(ix)
(viii)
Scheme 3. Possible region-selective mechanism in preparation compound 11.
DMF (ca 30mL) at 90°C under argon for 50h, during which
14 (123mg, 43mg) and Et3N (0.4mL plus 0.4 mL) were
added at 24h and 36h after the beginning of the reaction
respectively. The black solution was evaporated under
reduced pressure, and the residue was wash with water
(50mL). The aqueous solution was then extracted with ethyl
acetate (3ꢀ50mL). After dried with Na2SO4, the brown
organic layer was concentrated and purified by silica gel
column chromatography (petroleum/acetone 10:1, 5:1, 3:1)
to afford the target product 1 (510mg, 54%) as a yellow
powder. TLC: Rf=0.07 (petroleum/acetone 3:1) Rf=0.57
carbon bond formation leaded to
carbocation, which after loss of the trimethylsilyl group,
gave the double bond [13] (Scheme 3 i-v).
a
silyl-stabilized
The possible mechanism of the region-selectivity in the
preparation of compound 11 might be as follows: With TiCl4
in DCM, it would probably produce two parallel
intermediates vi and vii. However, in vii, there was a
structure of metal complex, which would display more
stability than the single link with 9 and TiCl4 in vi at the low
temperature (Scheme 3). This could also explain the reason
why the lower the temperature was, the higher the yield was.
The following product compound 12 was analyzed by
NOEDS spectrum for its structure, and the result matched
the assumption well.
1
(petroleum/acetone 1:1) mp. 84-86°C; H and 13C NMR
spectroscopic data, see Table 2; IR (KBr) 3419.61, 1656.14,
1593.73, 1512.76, 1375.79, 1279.14, 1243.72, 1204.77; MS
(EI) m/z 346 (M+); HRMS (EI+) m/z calculated for C19H22O6
+H+ 347.1489, found 347.1499.
CONCLUSIONS
In summary, we designed and first synthesized the
naturally occuring potent antioxidant tarennane, a Chalcone
constituent from Tarenna attenuata or Magnolia officinalis.
RESULTS AND DISCUSSION
The Sakurai allylation reaction started with the activation
of the carbonyl group by the Lewis acid. Subsequent carbon-

The First Total Synthesis of Tarennane
Letters in Organic Chemistry, 2011, Vol. 8, No. 4
263
inflammatory mediators in activated RAW 264.7 cells and whole
blood. Eur. J. Pharmacol., 2006, 538, 188-194.
Zhu, Y.D.; Zhang, P.; Yu, H.P.; Li, J.; Wang, M.W.; Zhao, W.M.
Anti-helicobacter pylori and thrombin inhibitory components from
chinese dragon’s blood, dracaena cochinchinensis. J. Nat. Prod.,
2007, 70(10), 1570-1577.
Shrestha, S. P.; Amano, Y.; Narukawa, Y.; Takeda, T. Nitric oxide
production inhibitory activity of flavonoids contained in trunk
exudates of dalbergia sissoo. J. Nat. Prod., 2008, 71(1), 98-101.
Yang, X.W.; Wang, J.S.; Wang, Y.H.; Xiao, H.T.; Hu, X.J.; Mu,
S.Z.; Ma, Y.L.; Lin, H.; He, H.P.; Li, L.; Hao, X.J. Tarennane and
tarennone, two novel chalcone constituents from Tarenna attenuate.
Planta Med., 2007, 73, 496-498.
Shen, C.C.; Ni, C.L.; Shen, Y.C.; Huang, Y.L.; Kuo, C.H.; Wu,
T.S.; Chen, C.C. Phenolic constituents from the stem bark of
Magnolia officinalis. J. Nat. Prod., 2009, 72(1), 168-171.
a) Kumar, S. K.; Hager, E.; Pettit, C.; Gurulingappa, H.; Davidson,
N. E.; Khan, S. R. Design, synthesis, and evaluation of novel
boronic-chalcone derivatives as antitumor agents. J. Med. Chem.,
2003, 46(14), 2813-2815; b) El-Feraly, F. and Hufford, C. D.
Synthesis and carbon-13 nuclear magnetic resonance assignments
of xenognosin. J. Org. Chem., 1982, 47(8), 1527-1530; c)
Kurosawa, K.; Hashiba, A.; Takahashi, H. Synthesis of 4-
cinnamylidene-2,5- cyclohexadien- 1-ones. Bull. Chem. Soc. Jpn.,
1978, 51(12), 3612-3615; d) Ito, C.; Itoigawa, M.; Kanematsu, T.;
Imamura, Y.; Tokuda, H.; Nishino, H.; Furukawa, H. Synthetic
cinnamylphenol derivatives as cancer chemopreventive agents.
Eur. J. Med. Chem., 2007, 42(7), 902-909; e) Ishikawa, T.;
Kadoya, R.; Arai, M.; Takahashi, H.; Kaisi, Y.; Mizuta, T.;
Yoshikai, K.; Saito, S. Revisiting [3+3] route to 1,3-
The key step of the synthesis relies on a highly regioselective
Heck reaction applying a free phenol iodide and a
homogeneous palladium catalyst. The outstanding features
of the last Heck coupling reaction include: (i) the phenolic
hydroxyl group is not protected, different from the literature
method [14]; (ii) the position of the isolated carbon-carbon
double bond on the molecule of intermediate 10, unlike other
common Heck reactions, is not connected to ethers, carbonyl
groups or benzene rings. The overall yield was 14%. Anti-
angiogenisis biological evaluations of the final target are
currently being investigated in model organism. The SAR
studies of the derivatives and synthetic intermediates are
underway. This is a highly convergent and flexible synthetic
strategy which not only provides access to the target
molecule 1, but also provides a new insight on the synthesis
of chalcone analogues containing a propylene linker between
an aromatic ring and a non-aromatic one.
[3]
[4]
[5]
[6]
[7]
ACKNOWLEDGEMENT
This work was supported by the National Major Program
of China during the 11th Five-Year Plan Period
(2009ZX09501-015).
cyclohexanedione
frameworks:
hidden
aspect
of
thermodynamically controlled enolates. J. Org. Chem., 2001,
66(24), 8000-8009.
REFERENCES
[1]
a) Srinivasan, B.; Johnson, T. E.; Lad, R.; Xing, C.
Structureꢀactivity relationship studies of chalcone leading to 3-
hydroxy-4,3ꢁ,4ꢁ,5ꢁ-tetramethoxychalcone and its analogues as
potent nuclear factor ꢂB inhibitors and their anticancer activities. J.
Med. Chem., 2009, 52(22), 7228-7235; b) Baba, M.; Asano, R.;
Takigami, I.; Takahashi, T.; Ohmura, M.; Okada, Y.; Sugimoto, H.;
Arika, T.; Nishino, H.; Okuyama, T. Studies on cancer
chemoprevention by traditional folk medicines XXV. Inhibitory
effect of isoliquiritigenin on azoxymethane-induced murine colon
aberrant crypt focus formation and carcinogenesis. Biol. Pharm.
Bull., 2002, 25(2), 247-250; c) Kim, D. Y.; Kim, K. H.; Kim, N. D.;
Lee, K. Y.; Han, C. K.; Yoon, J. H.; Moon, S. K.; Lee, S. S.; Seong,
B. L. Design and biological evaluation of novel tubulin inhibitors
as antimitotic agents using a pharmacophore binding model with
tubulin. J. Med. Chem., 2006, 49(19), 5664-5670; d) Modzelewska,
A.; Pettit, C.; Achanta, G.; Davidson, N. E.; Huang, P.; Khan, S. R.
Anticancer activities of novel chalcone and bis-chalcone
derivatives. Bioorg. Med. Chem., 2006, 14(10), 3491-3495; e)
Shen, K. H.; Chang, J. K.; Hsu, Y. L.; Kuo, P. L. Chalcone arrests
cell cycle progression and induces apoptosis through induction of
mitochondrial pathway and inhibition of nuclear factor kappa B
signalling in human bladder cancer cells. Basic Clin. Pharmacol.
Toxicol., 2007, 101(4), 254-261; f). Zi, X.; Simoneau, A. R.
Flavokawain A, a novel chalcone from kava extract, induces
apoptosis in bladder cancer cells by involvement of bax protein-
dependent and mitochondria-dependent apoptotic pathway and
suppresses tumor growth in mice. Cancer Res., 2005, 65(8), 3479-
3486.
[8]
[9]
Matsumoto, M.; Kobayashi, H. Hexacyanoferrate-catalyzed
oxidation of trimethoxybenzenes to dimethoxy-p-benzoquinones
with hydrogen peroxide. J. Org. Chem., 1985, 50(10), 1766-1768.
a) Hosomi, A.; Sakurai, H. Synthesis of ꢃ,ꢃ-dimethylallylsilanes, a
reagent of regiospecific prenylation of acetals and carbonyl
compounds. Tetrahedron Lett., 1978, 19(29), 2589-2592; b)
Hosomi, A. and Sakurai, H. Thermische umlagerung von
quadratsäure-bis (trimethylsilyl) ester. Tetrahedron Lett., 1976,
16(15), 1295-1296.
a) Suzuki, I.; Shigenaga, A.; Nemoto, H.; Shibuya, M.
Developments of enediyne model compounds generating biradicals
with an enhanced radical character – regulation of triggering
devices. Heterocycles, 2004, 62, 503-519; b) Stahly, G. P.;
Jackson, A. Synthesis of 2-[(perfluoroalkyl)phenyl]propionic acids.
J. Org. Chem., 1991, 56(18), 5472-5475.
Manda, S.; Nakanishi, I.; Ohkubo, K.; Uto, Y.; Kawashima, T.;
Hori, H.; Fukuhara, K.; Okuda, H.; Ozawa, T.; Ikota, N.;
Fukuzumi, S.; Anzai, K. Enhanced radical-scavenging activity of
naturally-oriented artepillin C derivatives. Chem. Commun., 2008,
626-628.
Fürstner, A.; Thiel, O. R.; Kindler, N.; Bartkowska, B. Total
syntheses of (S)-(ꢀ)-zearalenone and lasiodiplodin reveal superior
metathesis activity of ruthenium carbene complexes with imidazol-
2-ylidene ligands. J. Org. Chem., 2000, 65(23), 7990-7995.
László Kürti and Barbara Czakó. Strategic Applications of Named
Reactions in Organic Synthesis. Elsevier. 2005.
[10]
[11]
[12]
[13]
[14]
Beletskaya, I. P.; Cheprakov, A. V. The heck reaction as a
sharpening stone of palladium catalysis. Chem. Rev., 2000, 100(8),
3009-3066.
[2]
Ahmad, S.; Israf, D. A.; Lajis, N. H.; Shaari, K.; Mohamed, H.;
Wahab, A. A.; Ariffin, K. T.; Hoo, W. Y.; Aziz, N. A.; Kadir, A.
A.; Sulaiman, M. R.; Somchit, M. N. Cardamonin, inhibits pro-