A facile three-step total synthesis of tanshinone I

Article abstract of DOI:10.1080/10286020.2015.1136906

A facile synthetic approach for total synthesis of tanshinone I has been accomplished. The key precursor is a novel compound, epoxy phenanthraquinone. And this synthesis of tanshinone I is achieved in only three simple stages, which include Diels–Alder reaction, Δ²-Weitz–Scheffer-type epoxidation, and Feist–Bénary reaction from commercially available styrene.

Full text of DOI:10.1080/10286020.2015.1136906

Journal of Asian Natural Products Research
ISSN: 1028-6020 (Print) 1477-2213 (Online) Journal homepage: http://www.tandfonline.com/loi/ganp20
A facile three-step total synthesis of tanshinone I
Han-Rui Yang, Jie-Jie Wang, Peng-Peng Shao, Si-Yi Yuan & Xu-Qin Li
To cite this article: Han-Rui Yang, Jie-Jie Wang, Peng-Peng Shao, Si-Yi Yuan & Xu-Qin Li (2016):
A facile three-step total synthesis of tanshinone I, Journal of Asian Natural Products Research,
DOI: 10.1080/10286020.2015.1136906
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Date: 06 February 2016, At: 00:49

Journal of asian natural Products research, 2016
ꢁꢁp://ꢂx.ꢂꢃꢄ.ꢃꢅg/10.1080/10286020.2015.1136906
ꢀ
A facile three-step total synthesis of tanshinone I
Han-Rui Yang, Jie-Jie Wang, Peng-Peng Shao, Si-Yi Yuan and Xu-Qin Li
dꢋpꢆꢅꢁmꢋꢈꢁ ꢃꢌ cꢀꢋmꢄꢊꢁꢅy, uꢈꢄvꢋꢅꢊꢄꢁy ꢃꢌ sꢉꢄꢋꢈꢉꢋ ꢆꢈꢂ tꢋꢉꢀꢈꢃꢇꢃgy Bꢋꢄjꢄꢈg, Bꢋꢄjꢄꢈg 100083, cꢀꢄꢈꢆ
ABSTRACT
ARTICLE HISTORY
A facile synthetic approach for total synthesis of tanshinone I has
been accomplished. The key precursor is a novel compound, epoxy
phenanthraquinone. And this synthesis of tanshinone I is achieved
rꢋꢉꢋꢄvꢋꢂ 28 aꢍgꢍꢊꢁ 2015
aꢉꢉꢋpꢁꢋꢂ 24 dꢋꢉꢋmbꢋꢅ 2015
KEYWORDS
2
in only three simple stages, which include Diels–Alder reaction, Δ -
tꢆꢈꢊꢀꢄꢈꢃꢈꢋ i; ꢁꢃꢁꢆꢇ ꢊyꢈꢁꢀꢋꢊꢄꢊ;
dꢄꢋꢇꢊ–aꢇꢂꢋꢅ ꢅꢋꢆꢉꢁꢄꢃꢈ;
pꢋꢅꢃxꢄꢂꢆꢁꢄꢃꢈ; fꢋꢄꢊꢁ–Béꢈꢆꢅy
ꢅꢋꢆꢉꢁꢄꢃꢈ
Weitz–Scheffer-type epoxidation, and Feist–Bénary reaction from
commercially available styrene.
1
. Introduction
Tanshinone I (1, Figure 1) which was isolated from the roots of Salvia miltiorrhiza Bunge,
a well-known traditional Chinese medicine, is one of the major bioactive constituents
exhibiting various pharmacological activities, such as treatment of cardiovascular disease,
heart failure, and inflammatory diseases including chronic hepatitis and arthritis [1–3].
Tanshinone I is composed of four rings: naphthalene rings A and B, an ortho-quinone ring
C, and a furan ring D. Recently, tanshinones have been reported to have potent antican-
cer activity in some cancer cells [4–8], such as liver and prostate cancer cells [9–13]. e
anti-colon cancer activity of tanshinone I has also been reported [14,15]. e cytostatic effect
of dihydrotanshinone and tanshinone I has been shown to be comparable to doxorubicin,
and more potent than cisplatin, curcumin, etoposide, and retinoic acid. Dihydrotanshinone
and tanshinone I at 24-h treatment have been shown to induce oxidative stress as indi-
cated by GSH/GSSG imbalance in a concentration-dependent manner. Liu and coworkers
−1
have reported the effect of tanshinone I at dosages from 10–50 mg·ml in three different
monocytic leukemia cells (U937, THP-1, and SHI 1) [16]. erefore, increased attention
has been drawn to tanshinone I due to its unique in vitro and in vivo anticancer activities.
Since the early 1960s, several methods of achieving total synthesis of 1 have been reported
(Scheme 1). In 1968, the first total synthesis of 1 was completed by Baillie and omson
starting from the natural product podocarpic acid 3 [17]. Inouye and Kakisawa used a
Diels–Alder reaction to build the tanshinone scaffold 5 [18]; the synthetic route took four
steps and resulted in approximately 4% overall yield. Lee and Snyder later reported an ultra-
sound-promoted Diels–Alder reaction which gave a higher overall yield, but was limited to
CONTACT Xꢍ-Qꢄꢈ lꢄ
ꢇꢄxꢍqꢄꢈ@ꢍꢊꢁb.ꢋꢂꢍ.ꢉꢈ
The supplemental material for this paper is available at http://dx.doi.org/10.1080/10286020.2015.1136906.
©
2016 tꢆyꢇꢃꢅ & fꢅꢆꢈꢉꢄꢊ

2
H.ꢀR. YAꢁꢂ ꢃT AL.
Figure 1. sꢁꢅꢍꢉꢁꢍꢅꢋꢊ ꢃꢌ ꢁꢆꢈꢊꢀꢄꢈꢃꢈꢋ i ꢆꢈꢂ 8-ꢂꢋmꢋꢁꢀyꢇ ꢁꢆꢈꢊꢀꢄꢈꢃꢈꢋ i.
Scheme 1. rꢋpꢃꢅꢁꢋꢂ ꢆppꢅꢃꢆꢉꢀꢋꢊ ꢆꢈꢂ kꢋy ꢄꢈꢁꢋꢅmꢋꢂꢄꢆꢁꢋꢊ ꢌꢃꢅ ꢁꢀꢋ ꢊyꢈꢁꢀꢋꢊꢄꢊ ꢃꢌ ꢁꢆꢈꢊꢀꢄꢈꢃꢈꢋ i (1).
tanshinone IIA scaffold [19]. From 5-bromo-1-naphthoic acid 6, Danheiser et al. applied
photochemical aromatic annulations for the total synthesis of tanshinone through the key
intermediate 7 [20]. De Koning et al. developed a base-induced photochemical cyclization
for the synthesis of substituted naphthalenes and phenanthrenes 8 [21], which could be
applied to produce the key intermediate 9 in Scheme 1. Chunyong Ding et al. reported
a method for construction of 3-hydroxyphenanthrene-1,4-diones 10 from commercially
available 5-bromovanillin 11. is tandem process includes decarboxylative radical alkyla
-
tion, intramolecular C-H arylation and one-pot O-demethylation, aromatization, and syn-
thesized tanshinone I in six steps in 19% overall yields [22]. However, all of these methods
suffered from more steps and harsh reaction conditions. erefore, mild and facile synthetic
approaches to access tanshinone I and its analogs are still needed.
Here, we describe, for the first time, an efficient method of total synthesis of tanshinone
I through a three-step reaction approach, which includes Diels–Alder reaction between
2
substituted styrene and p-benzoquinone, Δ -Weitz–Scheffer-type epoxidation of 1,4-phe-
nanthrenequinone, and Feist–Bénary reaction of the key intermediate.

JꢄꢅRꢁAL ꢄF ASIAꢁ ꢁATꢅRAL PRꢄDꢅꢆTS RꢃSꢃARꢆH
3
(
a) 0°C, benzene, 94%; (b) 5N HCl/THF, 99+%; (c) Fremy's salt, 99+%;
Scheme 2. dꢋꢊꢄgꢈ ꢃꢌ ꢄꢈꢄꢁꢄꢆꢇ ꢆꢁꢁꢋmpꢁ ꢁꢃ pꢅꢋpꢆꢅꢋ ꢁꢆꢈꢊꢀꢄꢈꢃꢈꢋ i by ꢅꢋpꢃꢅꢁꢋꢂ dꢄꢋꢇꢊ–aꢇꢂꢋꢅ ꢅꢋꢆꢉꢁꢄꢃꢈ. (ꢆ) 0 °c,
bꢋꢈzꢋꢈꢋ, 94%; (b) 5 n hcꢇ/thf, 99+%; (ꢉ) fꢅꢋmy’ꢊ ꢊꢆꢇꢁ, 99+%.
(
2 2 2 3 2 4
a) H O , Na CO , r.t.; (b) 2mol/L H SO
Scheme 3. tꢀꢋ ꢅꢋꢆꢉꢁꢄꢃꢈ ꢌꢃꢅ kꢋy ꢄꢈꢁꢋꢅmꢋꢂꢄꢆꢁꢋ 5. (ꢆ) h o , nꢆ co , ꢅ.ꢁ.; (b) 2 mꢃꢇ/l h so
4
2
2
2
3
2
(
a) toluene, N
2
130°C; (b) H
2
O
2
, Na
2
CO
3
, r.t.; 2mol/L H
2 4 4
SO (c) bromo-2-propanone, NH OAc,
120 °C
Scheme 4. syꢈꢁꢀꢋꢊꢄꢊ ꢃꢌ 8-ꢂꢋmꢋꢁꢀyꢇ ꢁꢆꢈꢊꢀꢄꢈꢃꢈꢋ i. (ꢆ) ꢁꢃꢇꢍꢋꢈꢋ, n 130 °c; (b) h o , nꢆ co , ꢅ.ꢁ.; 2 mꢃꢇ/l
2
2
2
2
3
h so ; (ꢉ) bꢅꢃmꢃ-2-pꢅꢃpꢆꢈꢃꢈꢋ, nh oaꢉ, 120 °c.
2
4
4
2
. Results and discussion
As depicted in Scheme 2, we initially designed the synthesis route of tanshinone I from
ortho-quinone 14 by following a literature procedure [19].

4
H.ꢀR. YAꢁꢂ ꢃT AL.
ortho-Quinone 14 was prepared through enamine 12 condensation with p-benzoquinone
in three steps, although some tanshinones, such as tanshinone IIA, nortanshinone, and
(
i)-tanshindiol B, can be prepared by simple Diels–Alder cycloadditions of ortho-quinone
4 with appropriate dienes. In our laboratory experiment, heating styrene or 1-methyl-2-vi-
nylbenzene with ortho-quinone 14 to 90 °C for 2 h did not yield cycloadducts; longer heating
1
(
16 h) led only to decomposition of 14 (Scheme 2). Inspired by Baillie and Chunyong Ding’s
synthesis approaches, we designed a novel method using Weitz–Scheffer-type epoxidation/
epoxide cleavage [23] for the synthesis of 2-hydroxy phenanthraquinones 17 (Scheme 3).
2

e Δ -Weitz–Scheffer-type epoxidation of the endocyclic double bond was carried out in
ethanol as solvent by adding a solution of alkaline hydrogen peroxide at room temperature.
However, in the end, instead of getting the desired hydroxyl quinones, we obtained the pure
epoxide 16 in high yield. e conversion was monitored during the reaction by thin-layer
chromatography (TLC) and by high field shif of the diagnostic signals for the α,β-hydrogen
1
in the H NMR spectrum.
We imagine the epoxide product (16) can also be a good precursor, which could be
applied to produce the desired product using the reported Feist–Bénary reaction [24].
Feist–Bénary reaction enjoys a history of over a century and provides a convenient access
to highly substituted furan derivatives, using anhydrous toluene as the solvent, and treating
1
6 with bromo-2-propanone and NH OAc at 120 °C in a sealed tube for 10 h successfully
4
provided 8-demethyl tanshinone I (2).
Using this three-step procedure (Scheme 4), o-methyl styrene smoothly underwent
a Diels–Alder reaction with p-benzoquinone under pressure at 120 °C to yield directly
l,4-phenanthrenedione (15a) in 40% yield [25]. e epoxy group was introduced by an in
2
situ Δ -Weitz–Scheffer-type epoxidation with aqueous hydrogen peroxide. Af er the key
precursor, 16a had been successfully prepared, using Feist–Bénary reaction condensation
of dicarbonyl compound with α-haloketone followed by elimination to form furan ring,
we obtained the final product 1. us, the procedure turned out to be effective in achieving
total synthesis of tanshinone I. is result suggests using different substituents to replace R
(
Scheme 4), we may synthesize tanshinone derivatives in a similar fashion.
Although extensive studies have been carried out with the object of achieving total syn-
thesis of tanshinones and their analogs, facile synthetic approaches to access tanshinone
I and its analogs are still needed. In this study, we have developed a short facile synthetic
approach allowing for a total synthesis of tanshinone I. is tandem process includes Diels–
2
Alder reaction, Δ -Weitz–Scheffer-type epoxidation, and Feist–Bénary reaction. Compared
to previous approaches, our synthesis of tanshinone I is far more direct. e starting materi
-
als are simple, the reagent is more economical, and the key intermediates 2-epoxy-1,4- phe-
nanthrenequinones are novel compounds which have not been reported before.
3
. Experimental
3
.1. General experimental procedures
Melting points were determined with an X-4 digital display microscopic melting point
apparatus (Tianjin Xintian Optical Analytical Instruments Co. Ltd. Tianjin, China) and are
uncorrected. Mass spectra were recorded with Finnigan MAT TSQ 7000 (ESI) (ermo
Finnigan, California, America). We recorded NMR spectra with a Bruker Avance 400

JꢄꢅRꢁAL ꢄF ASIAꢁ ꢁATꢅRAL PRꢄDꢅꢆTS RꢃSꢃARꢆH
5
1
13
(
(
Bruker, Fallanden, Switzerland) ( H: 400.1 MHz; C: 100.6 MHz; T: 300 K) instrument
using tetramethylsilane as the internal standard). e solvent used for each spectrum is
reported. e chemical shif values are expressed in parts per million (ppm) relative to the
internal standard tetramethylsilane, and coupling constants J are given in Hz. Abbreviations
are as follows: s, singlet; d, doublet; t, triplet; m, multiplet; br, broad; dd, double doublet. e
relative numbers of protons are determined by integration. Purification was performed using
silica gel column chromatography, unless otherwise noted. Chemicals and reagents were
purchased from commercial suppliers and used without special instructions. Products were
detected by TLC on alumina plates coated with silica gel (Merck silica gel 60 F254, thickness
0
.2 mm) and visualized by UV light (Shanghai Hong Wah biochemical instrument manu-
facturing Co. Ltd. Shanghai, China) (λ 254 nm). Column chromatographic separations were
performed using silica gel (Merck silica gel Si 60, particle size 40–63 μm, 230–300 mesh).
3
.2. 1,4-phenanthrenedione (15) and 8-methylphenanthrene-1,4-dione (15a)
In a sealed tube, p-benzoquinone (1 g, 9.2 mmol), styrene (0.2175 g, 2.1 mmol), and tolu-
ene (2 ml) were refluxed to 120 °C under N for 27 h. Af er cooling to rt, the toluene was
2
stripped, and small amounts of p-benzoquinone were sublimed under vacuum from the
flask heated to its neck in hot water. e solid residue was flash chromatographed on silica
gel using petroleum ether/CH Cl (3:1) as eluent. Af er concentration in vacuo, p-benzo-
2
2
quinone sublimed from the eluted product, leaving 0.19 g (yield 44%) of 15, an orange solid.
1
Recrystallized from ethanol to constant melting point, it melted at 146–148 °C, H NMR
(
400 MHz, CDCl ): δ 9.54 (d, J = 8.1 Hz, 1H), 8.18 (s, 2H), 7.89 (d, J = 8.0 Hz, 1H), 7.73 (t,
3
13
J = 16.4, 1H), 7.64 (t, J = 16.4, 1H), 6.99–6.92 (m, 2H); C NMR (100 MHz, CDCl ): δ 188.2
3
(
(
C), 185.9 (C), 140.5 (C), 140.5 (CH), 136.6 (C), 135.8 (CH), 135.2 (CH), 132.2 (C), 130.2
CH), 129.9 (CH), 128.7 (CH), 127.9 (CH), 127.2 (C), 121.9 (CH); Starting from o-methyl
1
styrene, 15a can be obtained through similar reaction in 48% yield, mp 162–164 °C, H
NMR(400 MHz, CDCl ): δ 9.38 (d, J = 8.8, 1 H), 8.34 (d, J = 8.8, 1 H), 8.14 (d, J = 8.8, 1
H), 7.60–7.56 (m, 1 H), 7.45 (d, J = 8.1, 1 H), 6.95–6.88 (m, 2 H), 2.71 (s, 3H); C NMR
(
1
3
1
3
101 MHz, CDCl ): δ 188.2 (C), 186.0 (C), 140.8 (CH), 135.8 (CH), 135.7 (C), 134.8 (C),
3
31.8 (C), 131.0 (CH), 130.3 (C), 129.8 (CH), 129.5 (CH), 127.4 (C), 126.0 (CH), 121.7
(CH), 19.9 (CH3).
3.3. Phenanthro[2,3-b]oxirene-7,9(7aH,8aH)-dione (16) and 4-methylphenanthro[2,3-b]
oxirene-7,9(7aH,8aH)-dione (16a)
To a solution of 1,4-phenanthrenedione (0.1 g) in ethanol (10 ml), anhydrous sodium
carbonate (0.5 g) and a solution of alkaline hydrogen peroxide (4 ml, 30 wt%) were added
dropwise. e reaction mixture was stirred at room temperature, and the color turned from
yellow to orange and then to light red. e solution was carefully acidified to pH 2–3 with
2
mol/L sulfuric acid (2–3 ml), and the color turned to light yellow. e reaction mixture was
extracted with CH Cl (3×20 ml). e combined organic solution was washed with brine,
2
2
dried over anhydrous Na SO , filtered and evaporated to give a yellow residue. e residue
was further purified using chromatography developed by petroleum ether/ethyl acetate
2
4
(
10:1) to achieve the desired products 16. Light yellow powder (Yield 80%), mp 141–143 °C,
1
H NMR(400 MHz, CDCl ): δ 8.90 (d, J = 8.0, 1 H), 8.17 (d, J = 8.0, 1 H), 7.97 (d, J = 8.0, 1
3

6
H.ꢀR. YAꢁꢂ ꢃT AL.
1
3
H), 7.92 (d, J = 8.0, 1 H), 7.74–7.66 (m, 2 H), 4.16 (d, J = 4.0, 1 H), 4.11 (d, J = 4.0, 1 H); C
NMR (100 MHz, CDCl ): δ 193.4 (C), 191.9 (C), 136.6 (C), 135.1 (CH), 131.6 (C), 129.6 (C),
3
1
29.5 (C), 129.1 (CH), 128.8 (CH), 128.6 (CH), 127.1 (CH), 122.0 (CH), 54.7 (CH), 54.7
(
CH); Under similar reaction condition, 8-methylphenanthrene-1,4-dione was converted
1
to 16a in 85% yield, mp 174–175 °C, H NMR (400 MHz, CDCl ): δ 8.71 (d, J = 8.6, 1 H),
3
8
.33 (d, J = 8.8, 1 H), 7.97 (d, J = 8.8, 1 H), 7.59–7.55 (m, 1 H), 7.48 (d, J = 8.8, 1 H), 4.14 (d,
1
3
J = 4.1, 1 H), 4.08 (d, J = 4.1, 1 H), 2.71 (s, 3H); C NMR (100 MHz, CDCl ): δ 193.6 (C),
3
1
1
92.0 (C), 135.9 (C), 134.9 (C), 131.1 (C), 131.0(CH), 129.9 (C), 129.8 (CH), 129.3 (CH),
29.2 (C), 125.3 (CH), 121.8 (CH), 54.8 (CH), 54.7 (CH), 19.7 (CH3).
3
.4. 1-Methylphenanthro[1,2-b]furan-10,11-dione (2) and tanshinone 1 (1)
To 4-methyl-7a,8a-dihydrophenanthro[2,3-b]oxirene-7,9-dione (0.0240 g, 0.1 mmol) in a
sealed tube, was added bromo-2-propanone (40 μl, 65 mg, 0.47 mmol), NH OAc (0.0121 g,
4
0
.15 mmol), and anhydrous toluene (5 ml). e mixture was heated to 120 °C for 10 h in
the dark. Af er cooling to rt, the reaction mixture was acidified with 1 N HCl (3 ml) and
extracted with CH Cl (3×20 ml). e combined organic solution was washed with brine,
2
2
dried over anhydrous Na SO , filtered and evaporated to give a solid residue. e residue
was further purified using chromatography developed by petroleum ether: CH Cl to afford
2
4
2
2
1
1
0 mg product (1) as orange powder (36% yield), mp 230–232 °C, H NMR (400 MHz,
CDCl ): δ 9.23 (d, J = 8.8 Hz, 1H), 8.27 (d, J = 8.6 Hz, 1H), 7.78 (d, J = 8.7 Hz, 1H), 7.55–7.51
3
13
(
m, 1H), 7.33 (d, J = 6.9 Hz, 1H), 7.29 (s, 1H), 2.67 (s, 3H), 2.28 (s, 3H); C NMR (100 MHz,
CDCl ): δ 183.5 (C), 175.6 (C), 161.2 (C), 142.0 (CH), 135.2 (C), 133.6 (C), 132.9 (C), 132.7
3
(
CH), 130.6 (CH), 129.6 (C), 128.3 (CH), 124.8 (CH), 123.1 (C), 121.8 (C), 120.5 (C), 118.7
+
(CH), 19.8 (CH ), 8.8 (CH ). ESI-MS: m/z 276.8 [M+H ].
3
3
rough the similar procedure, 8-demethyl tanshinone I (2) was prepared from phe-
nanthro[2,3-b]oxirene-7,9(7aH,8aH)-dione (0.0224 g, 0.1 mmol) in 34% yield. Orange
1
color solid, mp 227–229 °C, H NMR (400 MHz, CDCl ): δ 9.41 (d, J = 8.0, 1 H), 8.12 (d,
3
1
2
1
2
1
J = 12.0, 1 H), 7.82 (t, J = 8.0, J = 4.0, 2 H), 7.70 (t, J = 8.0, J = 8.0, 1 H), 7.53 (t, J = 8.0,
2
13
J = 4.0, 1 H), 7.32 (s, 1 H), 2.31 (s, 3 H); C NMR (100 MHz, CDCl ): δ 183.4 (C), 175.6
3
(
(
C), 161.2 (C), 142.1 (CH), 137.1 (CH), 134.4 (C), 132.4 (CH), 131.0 (C), 130.3 (C), 129.1
CH), 127.5 (CH), 126.6 (CH), 122.9 (C), 121.9 (C), 120.6 (C), 119.0 (CH), 8.8 (CH ).
3
+
ESI-MS: m/z 262.8 [M+H ].
Acknowledgments
We thank University of Science & Technology Beijing for financial support of this work.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding

is research was financially supported by Beijing Science Nova Program [grant number 2008B20];
Fundamental Research Funds for the Central Universities [grant number FRF-BR-14-002A].

JꢄꢅRꢁAL ꢄF ASIAꢁ ꢁATꢅRAL PRꢄDꢅꢆTS RꢃSꢃARꢆH
7
References
[
[
[
[
[
1] M. Nakao, Bull. Shanghai Sci. Inst. 5, 5 (1930).
2] K. Takiura, J. Pharm. Soc. Jpn. 61, 475 (1941).
3] K. Takiura, and K. Koizumi, Chem. Pharm. Bull. 10, 112 (1962).
4] X. Wang, S.L. Morris-Natschke, and K.H. Lee, Med. Res. Rev. 27, 133 (2007).
5] W.Y.W. Lee, C.C.M. Cheung, K.W.K. Liu, K.P. Fung, J. Wong, P.B.S. Lai, and J.H.K. Yeung, J.
Nat. Prod. 73, 854 (2010).
[
[
6] C.C. Su, G.W. Chen, and J.G. Lin, Int. J. Mol. Med. 22, 613 (2008).
7] C.Y. Lee, H.F. Sher, H.W. Chen, C.C. Liu, C.H. Chen, C.S. Lin, P.C. Yang, H.S. Tsay, and J.J.
Chen, Mol. Cancer er. 7, 3527 (2008).
[8] X.H. Wang, S.L. Morris-Natschke, and K.H. Lee, Med. Res. Rev. 27, 133 (2007).
9] Z. Zhang, J. Gao, Y. Wang, T. Song, J. Zhang, G. Wu, T. Zhang, and G. Du, Biochem. Pharmacol.
[
7
8, 1316 (2009).
[
[
[
10] Y. Li, Y. Gong, L. Li, H.M. Abdolmaleky, and J.R. Zhou, Mol. Carcinog. 52, 535 (2013).
11] W.Y. Lee, K.W. Liu, and J.H. Yeung, Cancer Lett. 285, 46 (2009).
12] Y. Gong, Y.L. Li, Y. Lu, L. Li, H. Abdolmaleky, G.L. Blackburn, and J.R. Zhou, Int. J. Cancer.
1
29, 1042 (2011).
[
[
[
[
13] Y. Dong, S.L. Morris-Natschke, and K.H. Lee, Nat. Prod. Rep. 28, 529 (2011).
14] C.C. Su, G.W. Chen, and J.G. Lin, Int. J. Mol. Med. 22, 613 (2008).
15] L. Wang, A. Liu, F.L. Zhang, J.H.K. Yeung, X.Q. Li, and C.H. Cho, Chin. J. Nat. Med. 12, 1 (2014).
16] X.D. Liu, R.F. Fan, Y. Zhang, H.Z. Yang, Z.G. Fang, W.-B. Guan, D.J. Lin, R.Z. Xiao, R.W.
Huang, H.Q. Huang, P.Q. Liu, and J.J. Liu, Intl. J. Mol. Sci. 11, 2267 (2010).
17] A.C. Baillie, and R.H. omson, J. Chem. Soc. C. (1968), 48.
[
[
[
[
[
[
[
18] Y. Inouye, and H. Kakisawa, Bull. Chem. Soc. Jpn. 42, 3318 (1969).
19] J. Lee, and J.K. Snyder, J. Am. Chem. Soc. 111, 1522 (1989).
20] R.L. Danheiser, D.S. Casebier, and J.L. Loebach, Tetrahedron Lett. 33, 1149 (1992).
21] C.B. De Koning, J.P. Michael, and A.L. Rousseau, J. Chem. Soc., Perkin Trans. 1, 787 (2000).
22] M.K. Jiao, C.Y. Ding, and A. Zhang, Tetrahedron 70, 2976 (2014).
23] H.R. Nasiri, M.G. Madej, R. Panisch, M. Lafontaine, J.W. Bats, C.R.D. Lancaster, and H.
Schwalbe, J. Med. Chem. 56, 9530 (2013).
[
[
24] M.A. Calter, R.M. Phillips, and C. Flaschenriem, J. Am. Chem. Soc. 127, 14566 (2005).
25] N.D. Willmore, D.A. Hoic, and T.J. Katz, J. Org. Chem. 59, 1889 (1994).