Selective C-6 prenylation of flavonoids via europium(III)-catalyzed claisen rearrangement and cross-metathesis

Article abstract of DOI:10.1002/adsc.200600454

Starting from the readily available parent flavonoids, the flavanone 6-prenylnaringenin, the isoflavone 6-prenylgenistein (wighteone, erythrinin B) and a protected derivative of the flavonol 6-prenylquercetin (gancaonin P) have been synthesized in short reaction sequences featuring the title processes as key steps.

Full text of DOI:10.1002/adsc.200600454

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DOI: 10.1002/adsc.200600454
Selective C-6 Prenylation of Flavonoids via Europium(III)-
G
Catalyzed Claisen Rearrangement and Cross-Metathesis
Sandra Tischera and Peter Metza,*
a
Department of Chemistry, Technische Universität Dresden, Bergstr. 66, 01069 Dresden, Germany
Fax : (+49)-351-463-33162; e-mail: peter.metz@chemie.tu-dresden.de
Received: September 5, 2006
Dedicated to Professor Jürgen Fabian on the occasion of his 70th birthday
Abstract: Starting from the readily available parent
flavonoids, the flavanone 6-prenylnaringenin, the
isoflavone 6-prenylgenistein (wighteone, erythrinin
B) and a protected derivative of the flavonol 6-pre-
nylquercetin (gancaonin P) have been synthesized
in short reaction sequences featuring the title pro-
cesses as key steps.
Previous preparations of the antifungal[8] and anti-
bacterial[12] compound 6-prenylnaringenin (3) that
also exhibits a weak estrogenic activity[13] relied on
unselective nuclear prenylations of naringenin
(1),[8,14–17] a similarly unselective cyclization of the cor-
responding chalcone demethylxanthohumol[18] or
multi-tep total synthesis.[19] Our novel access to 3 is
depicted in Scheme 2. Chemoselective diacetyla-
tion[3,20] of 1 and subsequent Mitsunobu reaction[3,21]
of 6 with allyl alcohol gave rise to allyl ether 7, which
Keywords: Claisen rearrangement; cross-metathe-
sis; flavonoids; homogeneous catalysis; natural
products; prenylation
in turn was subjected to a europiumACHTRE(UNG III)-catalyzed
Claisen rearrangement at relatively low temperature
to provide the C-6 allylated intermediate 8 without
competing domino Claisen–Cope reaction. CM of 8
with isobutylene[5] was conveniently achieved at room
Flavonoids constitute a large class of plant metabo- temperature using the CM partner and benzene as a
lites, many of which have been shown to display mixed solvent system with a 1 mol% loading of cata-
useful physiological properties.[1] Among this group of lyst 10 to give the C-6 prenylated product 9 in good
phytochemicals, especially prenylated flavonoids have yield. Finally, potassium carbonate-catalyzed solvoly-
attracted considerable interest in the field of nutri- sis[22] smoothly afforded the natural product 3.
tion, health and medicine.[2] We have recently report-
ed an efficient four-step synthesis of the potent phy-
toestrogen 8-prenylnaringenin (2) from commercially
available naringenin (1) consisting of chemoselective
diacetylation of the C-7 and C-4’ phenolic hydroxy
À
groups, prenyl ether formation at C-5 OH, domino
Claisen–Cope rearrangement and deprotection
(Scheme 1).[3]
Here we disclose a related route that allows a com-
pletely regioselective C-6 prenylation of flavonoids be-
longing to different subgroups of these natural prod-
ucts via europiumACHTRE(UNG III)-catalyzed Claisen rearrange-
ment[4] followed by cross-metathesis (CM)[5,6] as the
key events.[7] Using this approach, the flavanone 6-pre-
nylnaringenin (3) first isolated from Humulus lupu-
lus,[8] the isoflavone 6-prenylgenistein (wighteone, er-
ythrinin B) (4) first isolated from Glycine wightii[9] and
Erythrina variegata[10] as well as a protected derivative
of the flavonol 6-prenylquercetin (gancaonin P) (5)
first isolated from Glycyrrhiza uralensis[11] have been
synthesized in short reaction sequences (Figure 1).
Scheme 1.
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147

Sandra Tischer and Peter Metz
COMMUNICATIONS
Figure 1.
Scheme 3. Reagents and conditions: a) decalin, 2008C, 1 d,
41% 8 + 11 (1:1); b) 2-methyl-2-butene, 1 mol% 10, ben-
zene, room temperature, overnight, 73% 9 + 12 (8.5:1),
71% 13 + 14 (5.6:1); c) Ac2O, pyridine, room temperature,
90%.
rangement of allyl ether 7 at the C-6 allyl stage, since
purely thermal activation afforded a 1:1 mixture of
the desired product 8 and the C-8 allylated diacetate
11 resulting from a domino Claisen–Cope process.[23]
Furthermore, CM of 8 using 2-methyl-2-butene[5] led
to a mixture of the required prenyl derivative 9 and
the methyl-substituted olefins (E)- and (Z)-12, from
which pure 9 could not be separated chromatographi-
cally. Likewise, CM of the corresponding triacetate
derived from 8 resulted in a mixture of dimethyl- and
methyl-substituted products 13 and 14 under these
conditions as well, whereas CM of 8 with isobutylene
avoids such a severe purification problem.
The reaction sequence used for the preparation of
flavanone 3 (Scheme 2) could be readily applied to
the synthesis of the antifungal[24] phytoalexin 6-prenyl-
genistein (4), too (Scheme 4). This isoflavone addi-
tionally displays considerable antibacterial activity[25]
against diverse microbes including vancomycin-resist-
ant Enterococcus species and methicillin-resistant
Staphylococcus aureus,[25b] significantly inhibits the
Na+/H+ exchange system of arterial smooth muscle
cells,[26] acts as a hepatoprotective agent[27] and shows
a potent cytotoxic activity[28] against human solid
tumor (KB) cells.[28a] So far, 4 has been prepared by
unselective nuclear prenylation of the isoflavone gen-
Scheme 2. Reagents and conditions: a) 2 equivs. Ac2O, pyri-
dine, room temperature, 89%; b) allyl alcohol, PPh3,
DEAD, THF, 08C to room temperature, 73%; c) 10mol%
EuACHTREUNG(fod)3, CHCl3, 708C (sealed tube), 16.5 h, 74%; d) isobu-
tylene, 1 mol% 10, benzene, room temperature (sealed
tube), 2 d, 78%; e) MeOH, 0.3 equivs. K2CO3, 408C, 2 h,
88%. DEAD=diethyl azodicarboxylate.
Some important observations made during the de- istein (15),[29] small-scale enzymatic C-6 prenylation of
velopment of the route discussed above are illustrated 15 using prenyltransferases[30] or multistep synthesis
in Scheme 3. Thus, europium
ACHTRE(UGN III) catalysis of the via prenylation of a 6-iodotrialkoxyisoflavone inter-
Claisen step was essential in order to stop the rear- mediate through an alkynylation/hydrogenation/dehy-
148
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EuropiumACHTREUNG(III)-Catalyzed Claisen Rearrangement and Cross-Metathesis
COMMUNICATIONS
Scheme 4. Reagents and conditions: a) 2 equivs. Ac2O, pyri-
dine, room temperature, 81%; b) allyl alcohol, PPh3,
DEAD, THF, 08C to room temperature, 53%; c) 10mol%
EuACHTREUNG(fod)3, CHCl3, 858C (sealed tube), 18 h, 57%; d) isobuty-
lene, 1 mol% 10, benzene, room temperature (sealed tube),
3 d, 86%; e) MeOH, 0.3 equivs. K2CO3, 408C, 2 h, 91%.
Scheme 5. Reagents and conditions: a) 4 equivs. Ac2O, pyri-
dine, room temperature, 7 min, 59%; b) allyl alcohol, PPh3,
DEAD, THF, 08C to room temperature, 72%; c) 10mol%
EuACHTRE(UNG fod)3, CHCl3, 808C (sealed tube), 15 h, 73%; d) isobuty-
lene, 3 mol% 25, CH2Cl2, room temperature (sealed tube),
3 d, 51%.
dration sequence.[31] Our novel route to 6-prenylgenis-
tein (4) commenced with a chemoselective diacetyla-
tion[32] of commercially available genistein (15) that
can also easily be prepared from inexpensive building might be due to the higher number of Lewis basic
blocks.[33] Allyl ether formation from 16 under Mitsu- donor groups within this substrate, application of the
(III)-catalyzed ruthenium carbene complex 25[37] in dichloromethane
nobu conditions followed by europiumACHTREUNG
Claisen rearrangement of 17 provided the substrate 18 and increasing the catalyst loading to 3 mol% accom-
for the CM event without interference by a domino plished the formation of the desired prenylated flavo-
Claisen–Cope process. After CM of 18 with isobuty- nol tetraacetate 24 in a satisfactory 51% isolated
lene using a 1 mol% loading of catalyst 10, the preny- yield. Unfortunately, the solvolysis conditions success-
lated diacetate 19 was isolated in high yield and effi- fully utilized for deacylation of acetates 9 and 19 did
ciently deblocked to give the natural product 4.
not effect complete deblocking of 24 to give the natu-
The Claisen rearrangement/CM strategy could be ral product 5, and alternative methodologies are cur-
employed for a concise preparation of the tetraace- rently being investigated.
tate 24 of the flavonol 6-prenylquercetin (5) that
In summary, we have developed an efficient strat-
shows cytotoxic activity against human oral tumor cell egy for regioselective C-6 prenylation of flavanones,
lines[34] as well (Scheme 5). During the previous syn- isoflavones and flavonols starting from the readily
thesis of 5,[35] reaction of the tetra-MOM ether of available parent flavonoids. This technology should
quercetin (20) with prenyl bromide and potassium be helpful for medicinal chemists in providing sub-
carbonate afforded only a 2% yield of the desired C- stantial amounts of prenyl flavonoids for further bio-
6 prenylated product. In our novel approach to 5, logical evaluation.
commercially available quercetin (20) was first che-
moselectively converted to the tetraacetate 21,[36]
which in turn was O-allylated using the Mitsunobu
methodology to provide 22. A subsequent europium-
Experimental Section
ACHTREUNG(III)-catalyzed Claisen rearrangement of 22 cleanly
General Procedure for Europium
Claisen Rearrangement
ACHTRE(UNG III)-Catalyzed
gave rise to the C-6 allyl derivative 23 without com-
peting C-8 allylation. While the 1 mol% loading of
catalyst 10 used before only led to low levels of con-
To a stirred suspension of a flavonoid C-5-O-allyl ether
(fod)3
version in the CM of 23 with isobutylene, which (2.0mmol) in dry CHCl 3 (3 mL) was added EuACHTREUNG
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149

Sandra Tischer and Peter Metz
COMMUNICATIONS
(0.2 mmol, 10 mol%) under an argon atmosphere. After re-
fluxing in a sealed tube at the temperature and for the time
listed in the Schemes, the solvent was removed under
vacuum, and the crude product was purified by flash chro-
matography on silica gel.
General Procedure for Cross-Metathesis with 2-
Methyl-2-butene
To a stirred solution of 10 (0.0025 mmol, 1 mol%) in dry
benzene (0.5 mL) was added the C-6 allylated flavonoid de-
rivative (0.252 mmol) in dry benzene (1.5 mL) and 2-
methyl-2-butene (0.5 mL) under an argon atmosphere. After
stirring the mixture at room temperature overnight, it was
filtered through a plug of silica gel. Following removal of
the solvent under vacuum, the crude product was purified
by flash chromatography on silica gel.
23: Rf =0.66 (pentane/ethyl acetate, 1:1); mp 187–1888C;
IR (neat): n˜ =3082 (w), 2936 (w), 2853 (w), 1771 (s, C=O),
1646 (m), 1619 (s), 1454 (m), 1370(s), 1251 (w), 1189 (s)
1
cmÀ1; H NMR (CDCl3, 500 MHz): d=2.33 (s, 3H), 2.36 (s,
3
9H), 3.38 (d, J=6.2 Hz, 2H, CH2-CH), 4.99–5.03 (m, 2H,
CH2 =CH), 5.84–5.89 (m, 1H, CH2 =CH), 6.83 (s, 1H, 8-H),
3
4
7.35 (d, J=8.4 Hz, 1H, 5’-H), 7.72 (d, J=2.0Hz, 1H, 2 ’-
H), 7.74 (dd, J=2.0Hz, 3J=8.4 Hz, 1H, 6’-H), 12.40(s, 1H,
4
1
1
5-OH); H H NOESY (CDCl3, 500 MHz): crosspeak for 8-
H with 2’-H and 6’-H, crosspeak for 5-OH with CH2-CH
and CH2 =CH and CH2 =CH; 13C NMR (CDCl3, 126 MHz):
d=20.43 (q), 20.67 (q, intense), 20.98 (q), 27.25 (t, CH2-
CH), 101.67 (d, C-8), 108.58 (s, C-4a), 115.44 (t, CH2 =CH),
115.78 (s, C-6), 123.98 (d), 124.01 (d), 126.54 (d, C-6’),
127.65 (s, C-1’), 132.05 (s, C-3), 134.59 (d, CH2 =CH), 142.21
(s, C-4’), 144.56 (s, C-3’), 153.99 (s, C-7), 154.76 (s, C-8a),
155.43 (s, C-2), 159.43 (s, C-5), 167.74 (s), 167.81 (s), 167.85
(s), 168.28 (s), 176.41 (s, C-4); MS (LC/MS, ESI): m/z (%)=
511.1 (100) [M+H+]; anal. calcd. for C26H22O11: C 61.18, H
4.34; found: C 61.17, H 4.44.
Acknowledgements
Financial support of this work by the Deutsche Forschungs-
gemeinschaft (Graduierten-Kolleg “Struktur-Eigenschafts-Be-
ziehungen bei Heterocyclen“) and EFRE is gratefully ac-
knowlegded.
References
[1] T. Iwashina, Biol. Sci. Space 2003, 17, 24–44.
[2] B. Botta, A. Vitali, P. Menendez, D. Misiti, G. Delle
Monache, Curr. Med. Chem. 2005, 12, 713–739.
[3] S. Gester, P. Metz, O. Zierau, G. Vollmer, Tetrahedron
2001, 57, 1015–1018.
[4] B. M. Trost, F. D. Toste, J. Am. Chem. Soc. 1998, 120,
815–816.
[5] A. K. Chatterjee, D. P. Sanders, R. H. Grubbs, Org.
Lett. 2002, 4, 1939–1942.
General Procedure for Cross-Metathesis with
Isobutylene
To a stirred solution of the C-6 allylated flavonoid derivative
(0.126 mmol) in dry benzene (4 mL) or dry CH2Cl2 (4 mL)
was added 10 (0.0013 mmol, 1 mol%) or 25 (0.0038 mmol, 3
mol%) as indicated in the Schemes under an argon atmos-
phere. The mixture was cooled to À788C followed by the
addition of isobutylene (3 mL). After stirring the mixture in
a sealed tube at room temperature for 2–3 d, it was filtered
through a plug of silica gel, the solvent was removed under
vacuum, and the crude product was purified by flash chro-
matography.
[6] S. J. Connon, S. Blechert, Angew. Chem. 2003, 115,
1944–1968; Angew. Chem. Int. Ed. 2003, 42, 1900–
1923.
[7] For a combination of aromatic Claisen rearrangement
and ring closing metathesis in the synthesis of benzo-
fused bicyclic compounds, see: a) W. A. L. van Otterlo,
E. L. Ngidi, E. M. Coyanis, C. B. de Koning, Tetrahe-
dron Lett. 2003, 44, 311–313; b) S. K. Chattopadhyay,
B. K. Pal, S. Maity, Chem. Lett. 2003, 32, 1190–1191;
c) S. Kotha, K. Mandal, Tetrahedron Lett. 2004, 45,
2585–2588.
24: Rf =0.35 (pentane/ethyl acetate, 3:2); mp 157–1588C;
IR (neat): n˜ =2927 (w), 1773 (s), 1647 (m), 1618 (s), 1455
(m), 1370(s), 1250(w), 1187 (s), 1153 (s), 1119 (m), 1082
(m) cmÀ1 1H NMR (CDCl3, 500 MHz): d=1.67 (s, 3H, E
;
CH3-C=CH), 1.75 (s, 3H, Z CH3-C=CH), 2.32 (s, 3H), 2.33
[8] S. Mizobuchi, Y. Sato, Agric. Biol. Chem. 1984, 48,
2771–2775.
[9] J. L. Ingham, N. T. Keen, T. Hymowitz, Phytochemistry
1977, 16, 1943–1946.
3
(s, 3H), 2.34 (s, 3H), 2.36 (s, 3H), 3.31 (d, J=7.0Hz, 2H,
3
CH2-CH), 5.11 (t, J=7.0Hz, 1H, CH 2-CH), 6.80(s, 1H, 8-
3
4
H), 7.34 (d, J=8.4 Hz, 1H, 5’-H), 7.71 (d, J=2.0Hz, 1H,
2’-H), 7.73 (dd, J=2.0Hz, 3J=8.4 Hz, 1H, 6’-H), 12.37 (s,
[10] V. H. Deshpande, A. D. Pendse, R. Pendse, Ind. J.
4
1
1
1H, 5-OH); H H NOESY (CDCl3, 500 MHz): crosspeak
for 8-H with 2’-H and 6’-H, crosspeak for 5-OH with CH2-
CH and CH2-CH; 13C NMR (CDCl3, 126 MHz): d=17.84 (q,
Z CH3-C=CH), 20.43 (q), 20.67 (q, intense), 20.96 (q), 22.26
(t, CH2-CH), 25.68 (q, E CH3-C=CH), 101.51 (d, C-8),
108.60 (s, C-4a), 117.71 (s, C-6), 120.80 (d, prenyl CH),
123.96 (d), 123.99 (d), 126.54 (d, C-6’), 127.71 (s, C-1’),
132.01 (s, C-3), 132.67 (s, prenyl C), 142.19 (s, C-3’), 144.53
(s, C-4’), 153.69 (s, C-8a), 154.55 (s, C-7), 155.33 (s, C-2),
159.35 (s, C-5), 167.75 (s), 167.82 (s), 167.85 (s), 168.38 (s),
176.43 (s, C-4); MS (LC/MS, ESI): m/z (%)=539.1 (100)
[M+H+]; anal. calcd. for C28H26O11: C 62.45, H 4.87; found:
C 62.54, H 4.98.
Chem. (Sect. B) 1977, 15B, 205–207.
[11] T. Fukai, Q. H. Wang, M. Takayama, T. Nomura, Het-
erocycles 1990, 31, 373–382.
[12] a) Y. Shirataki, N. Motohashi, S. Tani, H. Sakagami, K.
Satoh, H. Nakashima, S. K. Mahapatra, K. Ganguly,
S. G. Dastidar, A. N. Chakrabarty, Anticancer Res.
2001, 21, 275–280; b) S. G. Dastidar, S. K. Mahapatra,
K. Ganguly, A. N. Chakrabarty, Y. Shirataki, N. Moto-
hashi, In Vivo 2001, 15, 519–523.
[13] a) S. R. Milligan, J. C. Kalita, A. Heyerick, H. Rong, L.
De Cooman, D. DeKeukeleire, J. Clin. Endocrinol. Me-
tabolism 1999, 84, 2249–2252; b) K. E. Effenberger,
S. A. Johnsen, D. G. Monroe, T. C. Spelsberg, J. J. West-
150
www.asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 147 – 151

EuropiumACHTREUNG(III)-Catalyzed Claisen Rearrangement and Cross-Metathesis
COMMUNICATIONS
endorf, J. Steroid Biochem. Mol. Biol. 2005, 96, 387–
399.
[14] a) A. C. Jain, R. C. Gupta, P. D. Sarpal, Tetrahedron
1978, 34, 3563–3567; b) A. C. Jain, R. C. Gupta, P. D.
Sarpal, Chem. Lett. 1978, 995–998.
70, 685–687; c) P. Erasto, G. Bojase-Moleta, R. R. T.
Majinda, Phytochemistry 2004, 65, 875–880.
[26] M. Kobayashi, T. Mahmud, N. Yoshioka, H. Shibuya, I.
Kitagawa, Chem. Pharm. Bull. 1997, 45, 1615–1619.
[27] C.-C. Lin, H.-Y. Lee, C.-H. Chang, T. Namba, M. Hat-
tori, Phytother. Res. 1996, 10, 13–17.
[15] A. Nagar, V. K. Gujral, S. R. Gupta, Tetrahedron Lett.
1978, 19, 2031–2034.
[16] S. Tahara, Y. Katagiri, J. L. Ingham, J. Mizutani, Phyto-
chemistry 1994, 36, 1261–1271.
[17] C. Ito, T. Mizuno, M. Matsuoka, Y. Kimura, K. Sato, I.
Kajiura, M. Omura, M. Juichi, H. Furukawa, Chem.
Pharm. Bull. 1988, 36, 3292–3295.
[18] R. Hänsel, J. Schulz, Arch. Pharm. 1988, 321, 37–40.
[19] X. Y. Bu, L. Y. Zhao, Y. L. Li, Synthesis 1997, 1246–
1248.
[20] G. Baudouin, F. Tillequin, M. Koch, J. Nat. Prod. 1983,
46, 681–687.
[21] a) O. Mitsunobu, Synthesis 1981, 1–28; b) D. L.
Hughes, Org. React. 1992, 42, 335–656.
[22] K. C. Nicolaou, A. L. Smith, S. V. Wendeborn, C. K.
Hwang, J. Am. Chem. Soc. 1991, 113, 3106–3114.
[23] For a three-step solution to a similar problem involving
the use of a phenylsulfonyl substituted allyl ether, see:
T. R. R. Pettus, M. Inoue, X.-T. Chen, S. J. Danishefsky,
J. Am. Chem. Soc. 2000, 122, 6160–6168.
[24] a) G. A. Lane, O. R. W. Sutherland, R. A. Skipp, J.
Chem. Ecol. 1987, 13, 771–783; b) T. Fukai, M. Yone-
kawa, A.-J. Hou, T. Nomura, H.-D. Sun, J. Uno, J. Nat.
Prod. 2003, 66, 1118–1120; c) Y.-H. Wang, A.-J. Hou,
G.-F. Zhu, D.-F. Chen, H.-D. Sun, Planta Med. 2005, 71,
273–274; d) H. Yin, Y. Zhao, Y. Zhang, H. Zhang, L.
Xu, Z. Zou, W. Yang, J. Cheng, Y. Zhou, Biotechnol.
Lett. 2006, 28, 99–105.
[28] a) A. E. Nkengfack, A. G. B. Azebaze, A. K. Waffo,
Z. T. Fomum, M. Meyer, F. R. van Heerden, Phyto-
chemistry 2001, 58, 1113–1120; b) Y. Okamoto, A.
Suzuki, K. Ueda, C. Ito, M. Itoigawa, H. Furukawa, T.
Nishihara, N. Kojima, J. Health Sci. 2006, 52, 186–191.
[29] A. C. Jain, B. N. Sharma, J. Org. Chem. 1974, 39, 2215–
2217.
[30] a) G. Schrçder, U. Zähringer, W. Heller, J. Ebel, H.
Grisebach, Arch. Biochem. Biophys. 1979, 194, 635–
636; b) A. Vitali, B. Giardina, G. Delle Monache, F.
Rocca, A. Silvestrini, A. Tafi, B. Botta, FEBS Lett.
2004, 557, 33–38.
[31] M. M. Hossain, T. Tokuoka, K. Yamashita, Y. Kawa-
mura, M. Tsukayama, Synth. Commun. 2006, 36, 1201–
1211.
[32] N. Al-Maharik, N. P. Botting, Tetrahedron 2003, 59,
4177–4181.
[33] a) Y. C. Chang, M. G. Nair, R. C. Santell, W. G. Helfer-
ich, J. Agric. Food Chem. 1994, 42, 1869–1871; b) S.
Balasubramanian, M. G. Nair, Synth. Commun. 2000,
30, 469–484.
[34] T. Nomura, T. Fukai, T. Akiyama, Pure Appl. Chem.
2002, 74, 1199–1206.
[35] T. Fukai, T. Nomura, Heterocycles 1992, 34, 1213–1225.
[36] M. Simokoriyama, Bull. Chem. Soc. Jpn. 1941, 16, 284–
291.
[37] a) S. B. Garber, J. S. Kingsbury, B. L. Gray, A. H. Hov-
eyda, J. Am. Chem. Soc. 2000, 122, 8168–8179; b) S.
Gessler, S. Randl, S. Blechert, Tetrahedron Lett. 2000,
41, 9973–9976.
[25] a) C. C. N. Pillay, A. K. Jager, D. A. Mulholland, J. van
Staden, J. Ethnopharmacol. 2001, 74, 231–237; b) T.
Fukai, Y. Oku, Y. Hano, S. Terada, Planta Med. 2004,
Adv. Synth. Catal. 2007, 349, 147 – 151
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
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