Total synthesis of bauhinoxepin J: A biologically active dibenzo[b,f]oxepin isolated from bauhinia purpurea

Article abstract of DOI:10.1002/ejoc.201100845

Bauhinoxepin J possessing antimycobacterial, antimalarial, and tumor growth inhibitory activities was efficiently synthesized. The method involves crucial steps, including a coupling reaction of two aromatic moieties to construct the desired carbon framew

Full text of DOI:10.1002/ejoc.201100845

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201100845
Total Synthesis of Bauhinoxepin J: A Biologically Active Dibenzo[b,f]oxepin
Isolated from Bauhinia purpurea
Koichi Narita,[a] Ken Nakamura,[a] Yui Abe,[a] and Tadashi Katoh*[a]
Keywords: Natural products / Total synthesis / Biological activity / Antitumor agents
Bauhinoxepin J possessing antimycobacterial, antimalarial,
and tumor growth inhibitory activities was efficiently synthe-
a bisphenol derivative to establish a key cyclization precur-
sor, and construction of a characteristic seven-membered di-
sized. The method involves crucial steps, including a cou- hydrooxepin ring by internal cyclization to yield the target
pling reaction of two aromatic moieties to construct the de-
sired carbon framework, chemoselective phenol oxidation of
bauhinoxepin J.
ued searching for bioactive compounds and consequently
discovered eight new dibenzo[b,f]oxepins including bauhin-
oxepin J (4) from B. purpurea in 2007.[1] Although 4 appears
to have a relatively simple structure, it exhibits remarkable
biological activities including antimycobacterial activity
(MIC = 24.4 μm), antimalarial activity (IC50 = 5.8 μm), and
tumor growth inhibitory activity (KB cells: IC50 = 10.5 μm;
BC cells: IC50 = 12.1 μm).[1]
Introduction
In recent years, numerous tricyclic dibenzo[b,f]oxepins
and related compounds have been isolated from the plant
belonging to the Bauhinia genus, particularly from Bauhinia
saccocalyx and Bauhinia purpurea.[1–4] Several of these
structurally unique natural products have been reported to
exhibit attractive biological activities such as antimyco-
bacterial,[1,3] antimalarial,[1] antifungal,[1] cytotoxic,[1,2,4]
and anti-inflammatory[1] activities. In most cases, however,
further biological studies of these natural products are ex-
tremely limited, presumably because of the scarcity of sam-
ples from natural resources.[1–4] As a consequence, the de-
velopment of an efficient and reliable method for the syn-
thesis of dibenzo[b,f]oxepins is desirable and worthwhile
from the viewpoint of medicinal chemistry and pharmaceu-
ticals.
Representative examples of naturally occurring di-
benzo[b,f]oxepins are depicted in Figure 1. Bauhinoxepin A
(1) was isolated from B. saccocalyx by Kittakoop and co-
workers in 2004.[3] This compound shows antimycobacterial
activities with an MIC value of 6.25 μm.[3] Bauhiniastatin 1
(2), isolated from B. purpurea by Pettit and co-workers in
2006, exhibits significant growth inhibitory activity against
several human cancer cell lines with IC50 values at micro-
molar levels.[2] Bulbophyol B (3), isolated from Bulbophyl-
lum kwangtungense by Wu in 2006, displays growth inhibi-
tion against human epithelial carcinoma (HeLa) and hu-
man erythomyeloblastoid leukaemia (K562) cell lines in the
low micromolar range.[4] Kittakoop and co-workers contin-
Figure 1. Representative structures of naturally occurring di-
benzo[b,f]oxepins.
To date, the synthesis of naturally occurring dibenzo[b,f]-
oxepins has not been widely reported. In 2008, Yao and co-
workers reported the first total synthesis of bulbophyol B
(3) by using an intramolecular Ullmann-type biaryl ether
formation reaction (18% overall yield in 12 steps).[5] In the
following year, Kraus and co-workers reported the first to-
tal synthesis of bauhinoxepin J (4) by employing unique in-
tramolecular radical cyclization of a quinone ring (25%
overall yield in 4 steps).[6] More recently, Yoshida and co-
workers reported an approach to the dibenzo[b,f]oxepin
core of 4 by using an oxidative dearomatization/cyclization
protocol (13% overall yield in 7 steps).[7] In this study, we
describe our total synthesis of 4 by using an efficient and
convenient process.
[a] Laboratory of Synthetic and Medicinal Chemistry,
Faculty of Pharmaceutical Sciences,
Tohoku Pharmaceutical University,
4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan
Fax: +81-22-727-0135
E-mail: katoh@tohoku-pharm.ac.jp
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100845.
Eur. J. Org. Chem. 2011, 4985–4988
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K. Narita, K. Nakamura, Y. Abe, T. Katoh
SHORT COMMUNICATION
Table 1. Coupling reaction of trioxybenzene 7 and phenylacetalde-
hyde 8.
Results and Discussion
Our retrosynthetic analysis for the synthesis of bauhin-
oxepin J (4) is outlined in Scheme 1. We envisioned that
target molecule 4 could be synthesized from phenolic qui-
none 5 by the formation of a characteristic seven-membered
dihydrooxepin (B ring) through an internal nucleophilic ad-
dition/elimination sequence. To the best of our knowledge,
this type of cyclization to construct the dihydrodibenzo[b,f]-
oxepin skeleton (ABC ring) has not been previously re-
ported; thus, this approach posed a considerable challenge
from a synthetic viewpoint. Key cyclization precursor 5 was
expected to be accessible through chemoselective phenol
oxidation of bisphenol 6 by using a combination of molecu-
lar oxygen and salcomine [N,NЈ-bis(salicylidene)ethylenedi-
aminocobalt(II)].[8] In this quinone formation step, we be-
lieved that a more electron-rich phenol moiety (A ring)
would be preferentially oxidized to yield 5.[9] Intermediate
6, in turn, was to be prepared by a coupling reaction of
known trioxybenzene 7[10] (A ring moiety) with known
phenylacetaldehyde 8[11] (C ring moiety) followed by func-
tional group manipulation and deprotection.
[a] Isolated yield.
We then performed the synthesis of phenolic quinone 5,
a precursor of the key cyclization reaction (Scheme 2). Re-
moval of the hydroxy group in 9 was efficiently achieved by
trifluoroacetylation (TFAA, Et3N, DMAP, CH2Cl2, 0 °C,
30 min) followed by hydrogenolysis of the resulting trifluo-
roacetate [H2 (balloon), 10% Pd/C, EtOAc, r.t., 24 h],[8a]
thus affording deoxygenated product 10 in 77% overall
yield. By applying the conventional Barton–McCombie
procedure[16] to this deoxygenation process, a lower yield of
10 was observed (33%, 2 steps) and stilbene-type byproduct
A was obtained as the major product (44%), which was
probably generated through unfavorable elimination of the
intermediate methyl xanthate during the course of the reac-
tions.
Scheme 1. Retrosynthetic analysis for the synthesis of bauhin-
oxepin J (4).
The synthesis commenced with the coupling reaction of
7[10] with 8[11] to construct the requisite carbon framework
(7 + 8 Ǟ 9, Table 1). Site-selective lithiation at the C3 posi-
tion in 7 was achieved by treatment with nBuLi in Et2O
under reflux temperature,[12] and the aryllithium generated
in situ was allowed to react with 8 from –78 to –50 °C to
give the desired coupling product 9, albeit in 40% yield
(Table 1, Entry 1). When THF was used as the solvent, the
yield of product 9 was moderately improved to 56%
(Table 1, Entry 2). We assumed these modest yields (40–
Scheme 2. Synthesis of phenolic quinone 5. Reagents and condi-
tions: (a) TFAA, Et3N, DMAP, CH2Cl2, 0 °C, 30 min; (b) H2 (bal-
loon), 10% Pd/C, EtOAc, r.t., 24 h, 77% (2 steps); (c) 3 m HCl,
56%) to be the result of possible enolization of the formyl MeOH, r.t., 12 h, 94%; (d) salcomine, air, MeCN, r.t., 30 min, 89%.
group in 8 under basic conditions.[13] To overcome this
problem, we considered using an organocerium reagent,
which is known to have lower basicity and higher nucleo-
philicity than the corresponding organolithium reagent.[14]
TFAA = trifluoroacetic anhydride, DMAP = 4-(dimethylamino)-
pyridine, salcomine
cobalt(II).
=
N,NЈ-bis(salicylidene)ethylenediamino-
Continuing the synthesis, deprotection of the two MOM
To this end, lithiated 7 (prepared under the conditions de- groups in 10 under acidic conditions (3 m HCl, MeOH, r.t.,
scribed in Table 1, Entry 2) was treated with anhydrous ce- 12 h) gave liberated bisphenol 11 in 94% yield. The subse-
rium chloride in THF at –78 °C to yield the corresponding quent crucial chemoselective quinone formation reaction
cerium reagent,[15] which was then allowed to react with 8 was successfully achieved by exposure of 11 to air (atmo-
at the same temperature to give coupling product 9 in a spheric oxygen) in the presence of salcomine (0.5 equiv.) in
satisfactory yield (75%; Table 1, Entry 3).
MeCN at room temperature for 30 min, which resulted in
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Total Synthesis of Bauhinoxepin J
the clean formation of desired quinone 5 in high yield Entries 5–7). Eventually, the best result was obtained when
(89%). In this reaction, the use of oxygen gas instead of cyclization was performed in a highly dilute solution
air under the same conditions resulted in nonselective and (0.5 mm) of CH2Cl2 with DBU (4 equiv.) under reflux con-
excessive phenol oxidation to give the undesired bisquinone. ditions (Table 2, Entry 8), giving rise to 4 in 64% yield. The
Next, we investigated the key intramolecular ether cycli- spectroscopic properties (IR, 1H and 13C NMR, and
zation of 5 under several conditions (5 Ǟ 4, Table 2). Initial HRMS) of synthetic sample 4 were identical to those of
screening to achieve cyclization was carried out by using natural 4.[1]
some standard bases such as NaN(SiMe3)2, NaH, and
DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) in dilute solu-
tions (5 mm) of appropriate solvents (Table 2, Entries 1–3).
Among them, DBU proved to be superior from the view-
We have accomplished the total synthesis of bauhin-
point of reaction cleanliness (Table 2, Entry 3) although the
yield of 4 was not satisfactory (28%). In the case of NaN-
(SiMe3)2 and NaH (Table 2, Entries 1 and 2), the reaction
was not clean, and the yield of 4 was lower (23 and 18%,
respectively). After repeated attempts, we found that the ad-
Conclusions
oxepin J (4) in 31% overall yield in 6 steps from the starting
materials trioxybenzene 7 and phenylacetaldehyde 8. The
key steps of the synthesis involve the coupling reaction of
aromatic moieties 7 and 8 to construct the requisite carbon
framework 9 (7 + 8 Ǟ 9, Table 1), strategic salcomine oxi-
dation of bisphenolic compound 11 to yield cyclization pre-
cursor 5 (11 Ǟ 5, Scheme 2), and formation of the seven-
dition of 4 Å molecular sieves (MS, as a methanol scaven-
ger) was effective for this cyclization (Table 2, Entry 4),
which gave a higher yield of 4 (35%). To further improve
membered dihydrooxepin ring (B ring) by ring closure of
the yield, solvent effects and concentration effects were next
phenolic quinone 5 to complete the projected synthesis (5
examined under the conditions optimized in Table 2, En-
try 4. The use of THF, toluene, or 1,2-dichloroethene
(DCE) all resulted in lower yields of 4 (0–21%; Table 2,
Ǟ 4, Table 2). Compared to other reported methods,[5–7]
the main advantages of the present synthesis are the higher
yields and milder conditions. On the basis of this study, we
are currently synthesizing additional analogues of 4 [e.g.,
possessing substituent group(s) on the benzene ring moiety]
with the aim of exploring its structure–activity relationship.
In addition, further investigations to identify the action
mechanism of 4 by using the synthetic sample are in pro-
gress in our laboratories.
Table 2. Intramolecular ether cyclization of phenolic quinone 5
leading to bauhinoxepin J (4).
Experimental Section
1-[3,6-Dimethoxy-2-(methoxymethoxy)phenyl]-2-[2-(methoxy-
methoxy)phenyl]ethanol (9): A solution of nBuLi (1.60 m in hexane,
1.30 mL, 2.2 mmol) was added dropwise to a stirred solution of
1,4-dimethoxy-2-(methoxymethoxy)benzene (7;[10] 422 mg,
2.2 mmol) in dry THF (12 mL) at 0 °C under an atmosphere of
argon, and the mixture was heated at 40 °C for 2 h. After cooling,
the resulting solution was slowly added to a stirred suspension of
anhydrous CeCl3 (600 mg, 2.4 mmol) [prepared by heating
CeCl3·7H2O (finely ground powder, 911 mg, 2.4 mmol) at 140 °C
for 2 h under reduced pressure] in dry THF (12 mL) at –78 °C un-
der an atmosphere of argon. After 1 h, a solution of 2-[2-(meth-
oxymethoxy)phenyl]acetaldehyde (8)[11] in dry THF (22 mL) was
added slowly to the organocerium reagent prepared in situ above
at –78 °C, and stirring was further continued for 1 h at the same
temperature. The reaction was quenched with saturated aqueous
NH4Cl (20 mL) at –78 °C, and the resulting mixture was extracted
with EtOAc (3ϫ30 mL). The combined extracts were washed with
brine (2ϫ20 mL), then dried with Na2SO4. Concentration of the
solvent in vacuo afforded a residue, which was purified by column
chromatography (hexane/EtOAc, 2:1) to give 9 (315 mg, 75%) as a
1
colorless oil. H NMR (400 MHz, CDCl3): δ = 3.09 (dd, J = 6.1,
13.4 Hz, 1 H), 3.39 (dd, J = 8.3, 13.7 Hz, 1 H), 3.48 (s, 3 H), 3.57
(s, 3 H), 3.74 (s, 3 H), 3.77 (s, 3 H), 3.91 (br. d, J = 10.2 Hz, 1 H),
4.97 (d, J = 5.4 Hz, 1 H), 5.10 (d, J = 5.4 Hz, 1 H), 5.14 (d, J =
6.3 Hz, 1 H), 5.17 (d, J = 6.8 Hz, 1 H), 5.42–5.48 (m, 1 H), 6.57
(d, J = 9.3 Hz, 1 H), 6.75 (d, J = 9.3 Hz, 1 H), 6.85–6.89 (m, 1 H),
7.05–7.14 (m, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 37.9,
[a] Isolated yield.
Eur. J. Org. Chem. 2011, 4985–4988
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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4987

K. Narita, K. Nakamura, Y. Abe, T. Katoh
SHORT COMMUNICATION
[2] G. R. Pettit, A. Numata, C. Iwamoto, Y. Usami, T. Yamada,
H. Ohishi, G. M. Cragg, J. Nat. Prod. 2006, 69, 323–327.
[3] P. Kittakoop, S. Nopichai, N. Thongon, P. Charoenchai, Y.
Thebtaranonth, Helv. Chim. Acta 2004, 87, 175–179.
[4] B. Wu, Faming Zhuanli Shengqing Gongkai Shomingshu, CN
1458155 A 20031126, 2003.
55.7, 55.8, 56.3, 57.7, 68.2, 94.5, 99.2, 106.2, 111.2, 113.8, 121.4,
126.3, 127.3, 128.1, 131.1, 144.2, 146.6, 152.0, 155.7 ppm. IR
(neat): ν = 3540, 2993, 2938, 2905, 2835, 1589, 1489, 1257, 1234,
˜
1152, 1074, 1003, 757 cm–1. HRMS (EI): calcd. for C20H26O7
[M]+ 378.1679; found 378.1682.
[5] J. Lin, W. Zhang, N. Jiang, Z. Niu, K. Bao, L. Zhang, D. Liu,
C. Pan, X. Yao, J. Nat. Prod. 2008, 71, 1938–1941.
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1941.
3-(2-Hydroxyphenethyl)-2,5-dimethoxycyclohexa-2,5-diene-1,4-
dione (5): Salcomine [N,NЈ-bis(salicylidene)ethylenediamino-
cobalt(II)] (22.6 mg, 70 μmol) was added to a stirred solution of 10
(38.1 mg. 0.14 mmol) in dry CH3CN (15 mL) at room temperature.
The suspension was stirred under atmospheric air for 30 min at
room temperature. The reaction mixture was diluted with water
(20 mL), and the resulting mixture was extracted with Et2O
(3 ϫ 20 mL). The combined extracts were washed with brine
(20 mL), then dried with Na2SO4. Concentration of the solvent in
vacuo afforded a residue, which was purified by column chromatog-
raphy (hexane/EtOAc, 2:1) to give 5 (35.6 mg, 89%) as an orange
powder. Recrystallization (hexane/CH2Cl2, 1:1) afforded orange
[7] M. Yoshida, Y. Maeyama, K. Shishido, Heterocycles 2010, 80,
623–629.
[8] a) J. Sakurai, T. Oguchi, K. Watanabe, H. Abe, S. Kanno, M.
Ishikawa, T. Katoh, Chem. Eur. J. 2008, 14, 829–837; b) M.
Nakatani, M. Nakamura, A. Suzuki, T. Fuchikami, M. Inoue,
T. Katoh, ARKIVOC 2003, viii, 45–57; c) A. Suzuki, M. Nakat-
ani, M. Nakamura, K. Kawaguchi, M. Inoue, T. Katoh, Synlett
2003, 329–332; d) M. Nakamura, A. Suzuki, M. Nakatani, T.
Fuchikami, M. Inoue, T. Katoh, Tetrahedron Lett. 2002, 43,
6929–6932; e) T. Katoh, M. Nakatani, S. Shikita, R. Sampe,
A. Ishiwata, O. Ohmori, M. Nakamura, S. Terashima, Org.
Lett. 2001, 3, 2701–2704; f) F. Miyata, S. Yoshida, T. Yamori,
T. Katoh, Heterocycles 2001, 54, 619–622.
[9] A related example of chemoselective salcomine oxidation has
been reported, see: K. Tatsuta, A. Furuyama, T. Yano, Y. Su-
zuki, T. Ogura, S. Hosokawa, Tetrahedron Lett. 2008, 49, 4306–
4309.
[10] Compound 7 was prepared from commercially available 2-hy-
droxyphenylacetic acid in four steps, see: a) T. Capecchi, C. B.
de Koning, J. P. Michael, J. Chem. Soc. Perkin Trans. 1 2000,
2681–2688; b) U. Wriede, M. Fernandez, K. F. West, D. Har-
court, H. W. Moore, J. Org. Chem. 1987, 52, 4485–4489.
[11] Compound 8 was prepared from commercially available 2,5-
dimethoxybenzaldehyde in three steps, see: H.-S. Moon, S.-I.
Nam, S.-D. Kim, D. Y. Kim, B. J. Gwag, Y. A. Lee, S.-H. Yoon,
J. Pharm. Pharmacol. 2002, 54, 935–944.
1
prisms. M.p. 166–169 °C. H NMR (400 MHz, CDCl3): δ = 2.61–
2.70 (m, 4 H), 3.84 (s, 3 H), 4.00 (s, 3 H), 5.71 (s, 1 H), 5.93 (s, 1 H),
6.76–6.81 (m, 2 H), 7.03–7.08 (m, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 23.7, 29.3, 56.5, 61.5, 105.6, 115.8, 120.3, 126.7, 127.8,
1285, 130.1, 154.3, 156.0, 158.8, 183.1, 183.3 ppm. IR (KBr): ν =
˜
3425, 3016, 2943, 2850, 1650, 1599, 1456, 1345, 1325, 1213, 1172,
1051, 845, 754 cm–1. HRMS (EI): calcd. for C16H16O5 [M]+
288.0998; found 288.0994.
2-Methoxy-10,11-dihydrodibenzo[b,f]oxepine-1,4-dione [Bauhin-
oxepin J (4)]: A solution of 5 (18.5 mg, 64 μmol) in dry CH2Cl2
(128 mL) containing 1,8-diazabicyclo[5.4.0]undec-7-ene (38.4 μL,
0.26 mmol) and 4 Å molecular sieves (170 mg) was heated at reflux
for 24 h under an atmosphere of argon. After cooling, the reaction
was quenched with 1 m HCl (30 mL), and then diluted with CHCl3
(30 mL). The organic layer was washed with saturated aqueous
NaHCO3 (2ϫ20 mL) and brine (2ϫ20 mL), then dried with
Na2SO4. Concentration of the solvent in vacuo afforded a residue,
which was purified by column chromatography (hexane/EtOAc,
[12] G. Pavé, J.-M. Léger, C. Jarry, M.-C. Viaud-Massuard, G. Guil-
laument, J. Org. Chem. 2003, 68, 1401–1408.
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5926; b) B. M. Trost, M. K. Ameriks, Org. Lett. 2004, 6, 1745–
1748.
1
3:1) to give 4 (10.5 mg, 64%) as a pale yellow oil. The H and 13C
NMR and IR spectra and MS data (see below) are identical to
those of natural bauhinoxepin J. 1H NMR (400 MHz, CDCl3): δ =
2.72–2.75 (m, 2 H), 3.07–3.10 (m, 2 H), 3.84 (s, 3 H), 5.97 (s, 1 H),
7.13–7.17 (m, 2 H), 7.23–7.28 (m, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 26.7, 30.2, 56.9, 106.0, 121.4, 124.5, 126.4, 128.6,
[14] For a review on organocerium reagents in organic synthesis,
see: H.-J. Liu, K.-S. Shia, X. Shang, B.-Y. Zhu, Tetrahedron
1999, 55, 3803–3830.
[15] For some examples on the formation and usage of organocer-
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tard, F. Lecornue, Synlett 2009, 2761–2764; b) G. B. Dudley,
D. A. Engel, I. Ghiviriga, H. Lam, K. W. C. Poon, J. A. Single-
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Nino, G. Bartoli, M. Bosco, L. Sambri, E. Marcantoni, J. Org.
Chem. 1998, 63, 3745–3747; d) J. Barluenga, B. Baragaña, J. M.
Concellón, J. Org. Chem. 1997, 62, 5974–5977.
[16] a) T. Oguchi, K. Watanabe, H. Abe, T. Katoh, Heterocycles
2010, 80, 229–250; b) T. Oguchi, K. Watanabe, K. Ohkubo, H.
Abe, T. Katoh, Chem. Eur. J. 2009, 15, 2826–2845; c) M. Inoue,
W. Yokota, T. Katoh, Synthesis 2007, 622–637; d) T. Abe, K.
Iwasaki, M. Inoue, T. Suzuki, K. Watanabe, T. Katoh, Tetrahe-
dron Lett. 2006, 47, 3251–3255; e) T. Katoh, T. Izuhara, W.
Yokota, M. Inoue, K. Watanabe, A. Nobeyama, T. Suzuki, Tet-
rahedron 2006, 62, 1590–1608; f) K. Watanabe, K. Iwasaki, T.
Abe, M. Inoue, K. Ohkubo, T. Suzuki, T. Katoh, Org. Lett.
2005, 7, 3745–3748; g) M. Inoue, W. Yokota, M. G. Murugesh,
T. Izuhara, T. Katoh, Angew. Chem. 2004, 116, 4303–4305; An-
gew. Chem. Int. Ed. 2004, 43, 4207–4209; h) D. H. R. Barton,
S. W. McCombie, J. Chem. Soc. Perkin Trans. 1 1975, 1574–
1585.
130.5, 134.4, 153.1, 156.7, 159.8, 181.9, 182.9 ppm. IR (neat): ν =
˜
2933, 1660, 1604, 1581, 1489, 1455, 1356, 1255, 1227, 1191, 1099,
768 cm–1. HRMS (EI): calcd. for C15H12O4 [M]+ 256.0736; found
256.0743.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures and characterization data for com-
pounds 10 and 11 along with copies of the 1H and 13C NMR spec-
tra for all new compounds.
Acknowledgments
This work was supported by the Ministry of Education, Culture,
Sports, Science and Technology of Japan (MEXT) through a
Grant-in-Aid for Scientific Research (C) (No. 21590018) and a
Grant-in-Aid for Matching Fund Subsidy for Private Universities.
[1] S. Boonphong, P. Puangsombat, A. Baramee, C. Mahidol, S.
Received: June 12, 2011
Published Online: August 5, 2011
Ruchirawat, P. Kittakoop, J. Nat. Prod. 2007, 70, 795–801.
4988
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Eur. J. Org. Chem. 2011, 4985–4988