New approach to flavonols via base-mediated cyclization: Total synthesis of 3,5,6,7-tetramethoxyflavone

Article abstract of DOI:10.1055/s-0031-1290207

A new methodology for the synthesis of flavonols is described. The key step is a base-mediated cyclization-isomerization-elimination reaction which results in the formation of flavonols. Using this strategy, three flavonols are synthesized and characteriz

Full text of DOI:10.1055/s-0031-1290207

LETTER
385
New Approach to Flavonols via Base-Mediated Cyclization: Total Synthesis of
3,5,6,7-Tetramethoxyflavone
S
ynthesis of 3,5,6,
e
7-Tetramet
ohoxyflavonerge A. Kraus,* Vinayak Gupta, Aaron Kempema
Department of Chemistry, Iowa State University, Ames, IA 50011, USA
Fax +1(515)2940105; E-mail: gakraus@iastate.edu
Received 15 August 2011
OH
OH
OH
Abstract: A new methodology for the synthesis of flavonols is de-
scribed. The key step is a base-mediated cyclization–isomerization–
elimination reaction which results in the formation of flavonols. Us-
ing this strategy, three flavonols are synthesized and characterized.
HO
O
O
HO
O
O
OH
OH
Key words: flavonols, base-mediated cyclization, 3,5,6,7-tetra-
OH
OH
methoxyflavone, LDA
kaempferol (1)
quercetin (2)
OH
Flavonoids are polyphenolic compounds that are ubiqui-
tous in nature and are categorized according to chemical
structure into nine major subgroups: flavonols, flavones,
flavanones, isoflavones, flavanediols, anthocyanidins,
chalcones, aurones, and tannins.1 They are biosynthesized
in plants and many of them possess various biological
functions such as acting as floral pigments, signal mole-
cules, and antimicrobial compounds.2 They occur in the
plants as glycosides. Plants create specific flavonoids and
thus each species often exhibits a different flower color
range.3
OH
OH
MeO
O
HO
O
MeO
OMe
OH
OMe
O
OH
O
myricetin (3)
3,5,6,7-tetramethoxyflavone (4)
Figure 2 Common flavonols
O
O
3'
RO
OH
O
RO
4'
5'
2'
1
O
C
8
A
5
O
2
7
6
1'
O
6'
B
3
OR
4
O
LG
Figure 1 General structure of flavonols
OH
O
O
O
The flavonoids (Figure 1) have aroused considerable in-
terest recently because of their potential beneficial effects
on human health. They have been reported to have antivi-
ral, antiallergic, antiplatelet, anti-inflammatory, antitu-
mor, antioxidant, and estrogenic activities.4–9 Over 5,000
flavonoids have been identified but their applications
have been hampered because they usually exist as either a
mixture of multiple compounds that are difficult to sepa-
rate or their activities are not satisfactory.10 Examples of
some well-known naturally occurring flavonols are
kaempferol (1), quercetin (2), myricetin (3), and 3,5,6,7-
tetramethoxyflavone (4, Figure 2).
RO
RO
OEt
O
OEt
O
Scheme 1 Retrosynthetic analysis
In general, flavonols are synthesized as oxidation product
of flavones which in turn are prepared by several different
ways, prominent of which are either oxidative cyclization
of various substituted 2¢-hydroxychalcones or cyclode-
hydration of 1-(2-hydroxyphenyl)-3-phenyl-propane-1,3-
diones.12 The oxidation step in flavonol synthesis usually
requires the use of strong oxidizing agents like hydrogen
peroxide, dimethyldioxirane, or potassium permanganate.
The earliest known synthesis of flavonols was via an oxi-
dative cyclization of chalcones known as Algar–Flynn–
Oyamada reaction.11
In an effort to develop a direct synthesis independent of
undesired oxidation conditions, we examined the discon-
nection shown above (Scheme 1). The synthesis began
with coupling of commercially available phenols 5–7 with
ethyl chlorooxoacetate under Friedel–Crafts acylation
SYNLETT 2012, 23, 385–388
x
x.
x
x.
2
0
1
2
Advanced online publication: 26.01.2012
DOI: 10.1055/s-0031-1290207; Art ID: S08011ST
© Georg Thieme Verlag Stuttgart · New York

386
G. A. Kraus et al.
LETTER
conditions to give keto phenols 8–10 in good yields
(Scheme 2).13–16 A base-mediated O-alkylation of phenols
8–10 with a-bromophenylacetonitrile 11 produced keto
esters 12–14.17–20
LDA, THF
–78 to 0 °C
MeO
MeO
O
CN
12
Ph
OEt
HO
MeO
O
12–14
18
O
NaBH4
EtOH
OEt
Cl
MeO
R1
OH
MeO
R1
OH
O
O
O
15
NC
Ph
TiCl4, CH2Cl2
–20 to 0 °C
OEt
R2
R2
LDA (2.2 equiv), THF
–78 °C, reflux
MeO
R1
O
MeO
R1
O
Ph
5 R1 = OMe, R2 = OMe
6 R1 = H, R2 = OMe
7 R1 = H, R2 = H
8 R1 = OMe, R2 = OMe 80%
9 R1 = H, R2 = OMe 89%
10 R1 = H, R2 = H 85%
O
acidic workup
OEt
OH
R2
OH
R2
O
15 R1 = OMe, R2 = OMe 51%
16 R1 = H, R2 = OMe 63%
17 R1 = H, R2 = H 60%
NC
Ph
CN
NaH, DMF,
0–60 °C
MeO
R1
O
Br
O
8–10
+
Scheme 3 Ring closure
OEt
11
R2
O
12 R1 = OMe, R2 = OMe 70%
13 R1 = H, R2 = OMe 25%*
14 R1 = H, R2 = H 76%*
NC
CN
O
* based on starting material recovered
LDA
(2.2 equiv)
O
O
O
RO
SM
RO
Scheme 2 Synthesis of intermediates
O
OEt
OEt
O
Unfortunately, LDA-mediated intramolecular cyclization
of 12 resulted in the formation of the corresponding dihy-
drobenzofuran adduct 18, indicating that the carbonyl site
reacts preferentially (Scheme 3).
CN
CN
O
O
O
H+
To circumvent this problem, the ketone group was selec-
tively reduced to the corresponding alcohol using sodium
borohydride to give a diastereomeric mixture of a-hy-
droxy esters. These a-hydroxy esters were column puri-
fied but the diastereomers were not separated. When these
a-hydroxy esters were subjected to base-mediated condi-
tions (2.2 equiv LDA), the desired flavonols were formed
in 51–63% yield over two steps (Scheme 3).21–24 At lower
temperatures, the starting material remained unaffected
but under reflux conditions, the a-hydroxy esters success-
fully cyclized into flavonols 15–17. The analytical data of
the flavonols were compared and found to be in excellent
agreement with the literature data.25–27
15–17
RO
RO
OH
O
O
Scheme 4 Proposed mechanism
MeO
MeO
O
O
MeO
O
O
MeI, K2CO3,
OH
acetone, reflux
80%
MeO
OMe
MeO
MeO
15
4
A mechanism of base-mediated cyclization is depicted in
Scheme 4. The first equivalent of LDA would deprotonate
the hydroxyl group, and the second equivalent would gen-
erate the benzylic anion that, in turn, reacts with the ester
to afford a keto nitrile which tautomerizes to its enol form.
Elimination of the nitrile group results in the formation of
flavonols 15–17.
Scheme 5 Total synthesis of 3,5,6,7-tetramethoxyflavone
In conclusion, a new and highly efficient strategy for the
synthesis of flavonols is developed. The key step involved
a novel base-mediated cyclization–isomerization–elimi-
nation reaction. Using this methodology, three flavonols
were synthesized in good yields.
3,5,6,7-Tetramethoxyflavone (4) is a naturally occurring
flavonol found in Gomphrena martiana28 and shows anti-
micobacterial, antitumor, and antifungal activities.28,29
This flavonol derivative was successfully synthesized in
80% yield by subjecting trimethoxyflavonol 15 to methy-
lation conditions (Scheme 5).30,31 The analytical data for
flavonol 4 matched with the reported data.32
References and Notes
(1) Winkel-Shirley, B. Plant Physiol. 2001, 126, 485.
(2) Harborne, J. B.; Williams, C. A. Phytochemistry 2000, 55,
481.
(3) Tanaka, Y. Phytochem. Rev. 2006, 5, 283.
Synlett 2012, 23, 385–388
© Thieme Stuttgart · New York

LETTER
Synthesis of 3,5,6,7-Tetramethoxyflavone
387
(4) Nijveldt, R. J.; van Nood, E.; van Hoorn, D. E. C.; Boelens,
P. G.; van Norren, K.; van Leeuwen, P. A. M. Am. J. Clin.
Nutr. 2001, 74, 418.
(5) (a) Kawai, M.; Hirano, T.; Higa, S.; Arimitsu, J.; Maruta,
M.; Kuwahara, Y.; Ohkawara, T.; Hagihara, K.; Yamadori,
T.; Shima, Y.; Ogata, A.; Kawase, I.; Tanaka, T. Allergol.
Int. 2007, 56, 113. (b) Kim, J. M.; Yun-Choi, H. S. Arch.
Pharm. Res. 2008, 31, 886.
(6) Yao, L. H.; Jiang, Y. M.; Shi, J.; Datta, N.; Singanusong, R.;
Chen, S. S. Plant Foods Hum. Nutr. 2004, 59, 113.
(7) Middleton, E. Jr.; Kandaswami, C.; Theoharides, T. C.
Pharmacol. Rev. 2000, 52, 673.
(8) Dixon, R. A.; Ferreira, D. Phytochemistry 2002, 60, 205.
(9) Katsuyama, Y.; Funa, N.; Miyahisa, I.; Horinouchi, S.
Chem. Biol. (Cambridge, MA, U.S.) 2007, 14, 613.
(10) (a) Algar, J.; Flynn, J. P. Proc. R. Ir. Acad.,Sect. B 1934, 42,
1. (b) Oyamada, B. J. Chem. Soc. Jpn. 1934, 55, 1256.
(11) (a) Kraus, G. A.; Gupta, V. Org. Lett. 2010, 12, 5278.
(b) PhD Thesis: Gupta, V. New Synthetic Methods for
Biologically Active Aromatic Heterocycles; Iowa State
University: Ames (IA / USA), 2010.
(17) General Procedure for O-Alkylation
To a slurry of NaH (1.1 equiv) in dry DMF under argon,
phenol 8, 9, or 10 (1.0 equiv) was added at 0 °C. The
resulting reaction mixture was stirred at 0 °C for 15 min
followed by the addition of 2-bromo-2-phenylacetonitrile 11
(1.1–1.5 equiv) at the same temperature. The reaction
mixture was then stirred at 60 °C for 2–10 h. After the
completion of the reaction, the reaction mixture was
quenched by adding sat. NH4Cl solution. The reaction
mixture was then extracted with EtOAc (3 ×). The combined
organic extracts were then washed with H2O and brine, dried
over anhyd MgSO4, filtered, and evaporated in vacuo. The
crude compound was purified by column chromatography to
give pure 12, 13, or 14 respectively.
(18) Spectroscopic Data for Compound 12
Yellow oil (20% EtOAc–hexanes, 70% yield). 1H NMR
(400 MHz, CDCl3): d = 7.63–7.69 (m, 2 H), 7.35–7.50 (m, 3
H), 6.62 (s, 1 H), 5.96 (s, 1 H), 4.21 (m, 2 H), 3.91 (s, 6 H),
3.83 (s, 3 H), 1.31 (t, J = 7.2 Hz, 3 H). 13C NMR (100 MHz,
CDCl3): d = 184.7, 163.6, 158.5, 155.0, 152.9, 138.5, 132.5,
130.4, 129.3, 127.9, 116.9, 114.3, 100.0, 72.4, 62.4, 62.3,
61.2, 56.6, 14.2. MS: m/z = 399 [M+], 327, 325, 283, 282,
254, 211, 210, 209. HRMS: m/z calcd for C21H21NO7:
399.1318; found: 399.1326.
(12) (a) McGarry, L. W.; Detty, M. R. J. Org. Chem. 1990, 55,
4349. (b) Gao, H.; Kawabata, J. Bioorg. Med. Chem. 2005,
13, 1661.
(13) General Procedure for Friedel–Crafts Acylation
To a solution of phenol 5, 6, or 7 (1.0 equiv) in CH2Cl2 was
added TiCl4 (1.1 equiv) at –20 °C under argon. To this dark
brown solution, ethyl chlorooxoacetate (1.1 equiv) was
added dropwise while maintaining temperature at or below
–15 °C. The resulting reaction mixture was stirred for 4 h
with a steady increase in temperature to 0 °C. After the
completion of the reaction, the reaction mixture was diluted
with CH2Cl2 and poured over cold HCl (1.0 M) solution. The
aqueous layer was separated and extracted with CH2Cl2. The
combined organic extracts were washed with HCl (1.0 M)
solution and brine followed by drying over anhyd MgSO4.
The solvent was evaporated in vacuo to obtain the crude
compound 8, 9, or 10. The crude compounds were then
purified by silica gel column chromatography.
(19) Spectroscopic Data for Compound 13
Yellow solid (50% EtOAc–hexanes, 17% yield, 25% based
on SM recovered), recrystallized from EtOAc–hexanes, mp
146 °C. 1H NMR (300 MHz, CDCl3): d = 7.67–7.64 (m, 2
H), 7.49–7.46 (m, 3 H), 6.41 (s, 1 H), 6.28 (s, 1 H), 5.95 (s,
1 H), 4.18–4.13 (m, 2 H), 3.88 (s, 3 H), 3.84 (s, 3 H), 1.28 (t,
J = 7.5 Hz, 3 H). 13C NMR (100 MHz, CDCl3): d = 184.2,
164.5, 163.9, 162.6, 158.4, 132.1, 130.4, 129.3, 127.7,
117.5, 109.1, 95.8, 93.9, 70.4, 62.0, 56.4, 55.9, 14.2. MS:
m/z = 392 [M + Na+], 370, 276, 256, 203, 144. HRMS: m/z
calcd for C20H20NO6: 370.1285; found: 370.1279.
(20) Spectroscopic Data for Compound 14
Yellow oil (33% EtOAc–hexanes, 48% yield, 76% based on
SM recovered). 1H NMR (300 MHz, CDCl3): d = 7.97 (d,
J = 8.7 Hz, 1 H), 7.62–7.60 (m, 2 H), 7.53–7.51 (m, 3 H),
6.74 (dd, J = 9.0 Hz, 2.1 Hz 1 H), 6.64 (d, J = 2.1 Hz, 1 H),
5.91 (s, 1 H), 3.90 (s, 3 H), 3.81 (q, J = 7.5 Hz, 2 H), 1.14 (t,
J = 6.6 Hz, 3 H). 13C NMR (100 MHz, CDCl3): d = 184.7,
166.4, 165.2, 158.2, 133.8, 131.5, 130.8, 129.5, 128.1,
116.7, 115.9, 108.7, 100.5, 69.0, 61.8, 56.1, 14.0. MS: m/z =
362 [M + Na+], 340, 266, 246. HRMS: m/z calcd for
C19H17NNaO5: 362.0999; found: 362.1004.
(14) Spectroscopic Data for Compound 8
Yellow solid (15% EtOAc–hexanes, 80% yield),
recrystallized from EtOAc–hexanes, mp 50–51 °C. 1H NMR
(400 MHz, CDCl3): d = 11.95 (s, 1 H), 6.25 (s, 1 H), 4.38 (q,
J = 7.2 Hz, 2 H), 3.91 (s, 3 H), 3.91 (s, 3 H), 3.77 (s, 3 H),
1.40 (t, J = 7.2 Hz, 3 H). 13C NMR (100 MHz, CDCl3): d =
189.3, 164.2, 162.9, 154.2, 134.1, 104.7, 96.0, 62.0, 61.6,
61.1, 56.5, 14.1. MS: m/z = 307 [M + Na+], 239, 211. HRMS:
m/z calcd for C13H16O7: 284.0900; found: 284.0896.
(15) Spectroscopic Data for Compound 9
(21) General Procedure for Reduction and Base-Mediated
Cyclization
In a round-bottom flask, ketone 12, 13, or 14 (1.0 equiv) was
suspended in anhyd EtOH under inert conditions in an ice–
acetone bath. To this, NaBH4 (1.1 equiv) was added, and the
reaction mixture was warmed to r.t. over 1–3 h. After the
completion of reaction, the reaction mixture was quenched
with HCl (2.0 M) solution until the gas evolution stopped.
The mixture was then diluted with H2O and extracted with
EtOAc (2 ×). The combined organic extracts were then
washed with H2O and brine, dried over anhyd MgSO4,
filtered, and evaporated in vacuo to obtain crude as a mixture
of diastereomers. The crude compounds were purified by
column chromatography and were taken to next step as
diastereomeric mixtures.
To a solution of diisopropylamine (2.3 equiv) in dry THF
under argon was added n-BuLi (2.5 M in hexanes, 2.2 equiv)
at –78 °C. The mixture was warmed to –40 °C and stirred
at this temperature for 45 min. The solution was returned to
–78 °C, and a solution of a-hydroxyester in dry THF was
added to it. The resulting reaction mixture was warmed to r.t.
Orange solid (25% EtOAc–hexanes, 89% yield),
recrystallized from EtOAc–hexanes, mp 52–53 °C. 1H NMR
(400 MHz, CDCl3): d = 12.35 (s, 1 H), 6.09 (s, 1 H), 5.92 (s,
1 H), 4.38 (q, J = 8 Hz, 2 H), 3.85 (s, 3 H), 3.80 (s, 3 H), 1.40
(t, J = 8 Hz, 3 H). 13C NMR (100 MHz, CDCl3): d = 188.5,
168.9, 168.2, 164.5, 162.5, 102.3, 94.0, 91.4, 61.9, 56.3,
56.0. 14.3. MS: m/z = 277 [M + Na+], 209, 181. HRMS: m/z
calcd for C12H15O6: 255.0863; found: 255.0863.
(16) Spectroscopic Data for Compound 10
Yellow oil (20% EtOAc–hexanes, 85% yield). 1H NMR
(300 MHz, CDCl3): d = 11.76 (s, 1 H), 7.66 (d, J = 9.0 Hz, 1
H), 6.51 (d, J = 2.4 Hz, 1 H), 6.48 (dd, J = 6.0, 2.4 Hz, 1 H),
4.45 (q, J = 7.2 Hz, 2 H), 3.88 (s, 3 H), 1.43 (t, J = 7.2 Hz, 3
H). 13C NMR (100 MHz, CDCl3): d = 188.4, 167.8, 167.1,
162.8, 133.9, 110.4, 109.0, 101.0, 62.6, 55.9, 14.2. MS: m/z
= 247 [M + Na+], 191, 170, 151. HRMS: m/z calcd for
C11H13O5: 225.0757; found: 225.0754.
© Thieme Stuttgart · New York
Synlett 2012, 23, 385–388
x

388
G. A. Kraus et al.
LETTER
and then refluxed for 8 h. After the completion of the
reaction, the reaction mixture was quenched with HCl (1.0
M) solution until acidic and then returned to neutral pH with
sat. NaHCO3 solution. Most of the THF was evaporated in
vacuo. The residue was then diluted with H2O and extracted
with EtOAc (3 ×). The combined organic extracts were then
washed with H2O and brine, dried over anhyd MgSO4,
filtered, and evaporated in vacuo. The crude compound was
then purified by column chromatography.
(26) Park, Y.; Moon, B.; Lee, E.; Hong, S.; Lim, Y. Bull. Korean
Chem. Soc. 2008, 29, 81.
(27) Buschi, C. A.; Pomilio, A. B.; Gros, E. G. Phytochemistry
1980, 19, 903.
(28) (a) Pomilio, A. B.; Vacchino, M. N.; Vitale, A. A.
Antimycobacterial and Antitumoral Activities of Argentine
Plants Belonging to the Amaranthaceae Family, In South
American Medicinal Plants as a Potential Source of
Bioactive Compounds; Martino, S. M.; Muschietti, L. V.,
Eds.; Research Signpost: Trivandrum, 2008, 73–113.
(b) Pomilio, A. B.; Buschi, C. A.; Tomes, C. N.; Viale, A. A.
J. Ethnopharmacol. 1992, 36, 155.
(22) Spectroscopic Data for Compound 15
Brown solid (40% EtOAc–hexanes, 51% yield),
recrystallized from EtOAc–hexanes, mp 150–152 °C. 1H
NMR (400 MHz, CDCl3): d = 8.21 (d, J = 8.6 Hz, 2 H), 7.51
(t, J = 6.8 Hz, 2 H), 7.44 (t, J = 7.2 Hz, 1 H), 6.79 (s, 1 H),
4.03 (s, 3 H), 3.98 (s, 3 H), 3.92 (s, 3 H). 13C NMR (100
MHz, CDCl3): d = 172.0, 158.6, 154.0, 151.9, 142.7, 140.1,
138.3, 131.3, 130.0, 128.7, 127.5, 110.0, 96.3, 62.5, 61.8,
56.6. MS: m/z = 329 [M + H+], 328, 326, 314, 313, 267, 167,
105, 77, 69. HRMS: m/z calcd for C18H17O6: 329.1011;
found: 329.1020.
(29) Tomas-Barberan, F. A.; Msonthi, J. D.; Hostettmann, K.
Phytochemistry 1988, 27, 753.
(30) Preparation of Flavonol 4
Flavonol 15 (0.04 g, 0.12 mmol) was taken in dry actone,
and anhyd K2CO3 was added to it under argon. To this, MeI
(0.03 g, 0.18 mmol) was added, and the resulting reaction
mixture was refluxed for 6 h. After the completion of
reaction, the reaction mixture was filtered through Celite and
evaporated to dryness. The residue was then diluted with
H2O and extracted with EtOAc (3 × 20 mL). The combined
organic extracts were then washed with H2O and brine, dried
over anhyd MgSO4, filtered, and evaporated in vacuo to
obtain crude 4. The crude compound was then purified by
column chromatography using 50% EtOAc–hexanes as
eluent to get pure flavonol 4 (0.03 g, 0.10 mmol) in 80%
yield.
(23) Spectroscopic Data for Compound 16
Brown solid (5% MeOH–CH2Cl2, 63% yield), recrystallized
from EtOAc–hexanes, mp 169–170 °C. 1H NMR (300 MHz,
CDCl3): d = 8.23 (d, J = 9 Hz, 2 H), 7.55–7.45 (m, 3 H), 6.59
(d, J = 3 Hz, 1 H), 6.38 (d, J = 3 Hz, 1 H), 4.00 (s, 3 H), 3.93
(s, 3 H). 13C NMR (100 MHz, CDCl3): d = 172.1, 164.6,
160.6, 159.0, 141.9, 138.4, 131.1, 129.7, 128.6, 127.3,
106.2, 95.9, 92.5, 56.5, 56.0. MS: m/z = 299 [M + H+], 237,
144. HRMS: m/z calcd for C17H15O5: 299.0914; found:
299.0919.
(31) Spectroscopic Data for Compound 4
Yellow oil. 1H NMR (400 MHz, CDCl3): d = 8.06 (dd,
J = 8.0, 2.0 Hz, 2 H), 7.45–7.53 (m, 3 H), 6.75 (s, 1 H), 4.00
(s, 3 H), 3.96 (s, 3 H), 3.91 (s, 3 H), 3.86 (s, 3 H). 13C NMR
(100 MHz, CDCl3): d = 174.0, 157.9, 153.9, 153.5, 152.6,
141.6, 140.4, 131.0, 130.6, 128.7, 128.6, 128.4, 113.4, 96.3,
62.4, 61.8, 60.3, 56.5. MS: m/z = 342, 327, 323, 297, 284,
283, 241, 195, 167, 129, 105, 88, 76, 68. HRMS: m/z calcd
for C19H18O6: 342.1103; found: 342.1108.
(24) Spectroscopic Data for Compound 17
Brown solid (2% MeOH–CH2Cl2, 60% yield), recrystallized
from EtOAc–hexanes, mp 167–169 °C. 1H NMR (300 MHz,
CDCl3): d = 8.25 (d, J = 9 Hz, 2 H), 8.16 (d, J = 9 Hz, 1 H),
7.57–7.47 (m, 3 H), 7.03–6.98 (m, 2 H), 3.95 (s, 3 H). 13
C
NMR (100 MHz, CDCl3): d = 173.0, 164.5, 157.6, 144.4,
138.3, 131.4, 130.1, 128.8, 127.7, 127.0, 115.1, 114.8,
100.1, 56.1. MS: m/z = 269 [M + H+], 239, 189, 150. HRMS:
m/z calcd for C16H13O4: 269.0808; found: 269.0808.
(25) Lee, H. S.; Park, K.; Kim, D.; Chong, Y. Bioorg. Med.
Chem. 2010, 18, 7331.
(32) Tomas-Lorente, F.; Iniesta-Sanmartin, E.; Tomas-Barberan,
F. A.; Trowitzsch-Kienast, W.; Wray, V. Phytochemistry
1989, 28, 1613.
Synlett 2012, 23, 385–388
© Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or
emailed to multiple sites or posted to a listserv without the copyright holder's express written permission.
However, users may print, download, or email articles for individual use.