Simple synthesis of eudesmin through oxidative coupling of carbanions and reductive catalytic hydrogenation of diketo diester

Article abstract of DOI:10.1080/00397910701263882

A simple synthesis of eudesmin (1) is described. The key fragments were diol 13, dicarbethoxyethane 4, and diketo diester 5, which were prepared via reductive catalytic hydrogenation and oxidative intermolecular coupling of carbanions. This method is useful to generate the core skeleton of an endo-endo furofuran ring. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701263882

This article was downloaded by: [Monash University Library]
On: 15 May 2013, At: 05:27
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office:
Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International
Journal for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lsyc20
Simple Synthesis of Eudesmin through
Oxidative Coupling of Carbanions and
Reductive Catalytic Hydrogenation of Diketo
Diester
Jae‐Chul Jung a & Oee‐Sook Park b
a Department of Medicinal Chemistry, School of Pharmacy, University of
Mississippi, Mississippi, USA
b Department of Chemistry, Institute for Basic Sciences, College of Natural
Sciences, Chungbuk National University, Cheongju, Chungbuk, Korea
Published online: 22 May 2007.
To cite this article: Jae‐Chul Jung & Oee‐Sook Park (2007): Simple Synthesis of Eudesmin through Oxidative
Coupling of Carbanions and Reductive Catalytic Hydrogenation of Diketo Diester, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:10, 1665-1673
To link to this article: http://dx.doi.org/10.1080/00397910701263882
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any substantial
or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or
distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation that the
contents will be complete or accurate or up to date. The accuracy of any instructions, formulae,
and drug doses should be independently verified with primary sources. The publisher shall not
be liable for any loss, actions, claims, proceedings, demand, or costs or damages whatsoever or
howsoever caused arising directly or indirectly in connection with or arising out of the use of this
material.

Synthetic Communicationsw, 37: 1665–1673, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701263882
Simple Synthesis of Eudesmin through
Oxidative Coupling of Carbanions and
Reductive Catalytic Hydrogenation of
Diketo Diester
Jae-Chul Jung
Department of Medicinal Chemistry, School of Pharmacy, University
of Mississippi, Mississippi, USA
Oee-Sook Park
Department of Chemistry, Institute for Basic Sciences, College of Natural
Sciences, Chungbuk National University, Cheongju, Chungbuk, Korea
Abstract: A simple synthesis of eudesmin (1) is described. The key fragments were
diol 13, dicarbethoxyethane 4, and diketo diester 5, which were prepared via
reductive catalytic hydrogenation and oxidative intermolecular coupling of carb-
anions. This method is useful to generate the core skeleton of an endo–endo
furofuran ring.
Keywords: eudesmin, furofuran lignans, oxidative intermolecular coupling, reductive
catalytic hydrogenation
INTRODUCTION
The naturally occurring furofurans are the main representatives of a family of
lignans that exhibit a wide range of intriguing biological activities such
as antitumor,[1] antimitomic,[2] antiviral,[3] antioxidant,[4] and antihyperten-
sive,[5] properties; inhibition of platelet-activating factor (PAF);[6] Ca2þ
Received October 9, 2006
Address correspondence to Professor Oee-Sook Park, Department of Chemistry,
Institute for Basic Sciences, College of Natural Sciences, Chungbuk National Univer-
sity, Cheongju 361-763, Chungbuk, Korea. E-mail: ospark@cbnu.ac.kr
1665

1666
J.-C. Jung and O.-S. Park
channels;[7] cAMP phosphodiesterase inhibitory[8] properties; sodium
selective diuretic properties;[9] and microsomal monooxygenases inhibitory
effects for insects.[10] The variety of pharmacological activities of these
furofuran lignans, and their unique structural features including bis-tetra-
hydrofuran rings, generated a great deal of interest from synthetic chemists
and biologists. Several elegant synthetic approaches have been developed
for the furofuran lignans with two different aryl groups or the same aryl
groups[11] since the synthesis of the racemate (+)-sesamin was first
achieved by Beroza and Schechter.[12] However, most of these methods are
substrate specific, providing an entry to one particular stereochemical series,
and only a few approaches are applicable to the stereocontrolled synthesis
of furofurans as (+)-eudesmin, (+)-yangambin, and (+)-epiasarinin.
[13]
Recently, the Kise group
reported oxidative homocoupling of b-keto
esters with sodium hydride–bromine to afford stereoselective R,R-dimers.
The Aldons group[14] introduced generation of an endo–endo furofuran
skeleton through diastereocontrolled cationic cyclization and asymmetric
stereoselective reduction. Kasahara and co-workers[15] performed generation
of (2)-pinoresinol by microbial transformation of (+)-eudesmin using Asper-
gillus niger. Banerjee and Roy[16] more recently developed an enantioselec-
tive synthesis of furofuran lignans with high optical purity through
stereoselective intramolecular radical cyclization of suitably substituted
epoxy olefinic ethers using bis(cyclopentadienyl)titanium(III) chloride as
the radical initiator. In a preliminary communication, we reported[17] a stereo-
selective method to generate the core skeleton of furofuran rings by dianion
aldol condensation. In this article, we report the efficient total synthesis of
racemic eudesmin (1) by reductive catalytic hydrogenation and oxidative
intermolecular coupling of carbanions (Figure 1).
Figure 1. Structures of furofuran lignans: 1, eudesmin, R1 ¼ H, R2 ¼ R3 ¼ OMe;
2, sesamin, R1 ¼ H, R2 ¼ R3 ¼ -OCH2O-; and 3, yangambin, R1 ¼ R2 ¼ R3 ¼ OMe.
RESULTS AND DISCUSSION
Retrosynthetic analysis of eudesmin (1) reveals a convergent, short-step
sequence involving oxidative intermolecular coupling reaction of acetate 9[18]

Simple Synthesis of Eudesmin
1667
and reductive catalytic hydrogenation of diketo diester 5, followed by reduction
of diol 13 or dicarbethoxyethane 4, and intramolecular ring cyclization of tetraol
14, to furnish the target framework (Scheme 1).
The syntheses of 13 and 4 as key intermediates were accomplished as
shown in Scheme 2. We have used 3,4-dimethoxy benzoic acid (6) as a
starting material, which was reacted with thionyl chloride in toluene to give
acid chloride 7 in quantitative yield. Compound 7 was subsequently treated
with the anion of diethyl malonate to give 8 in excellent yield. In this conden-
sation reaction, we found that the magnesium ethoxide was the most effective
among bases such as sodium ethoxide, sodium hydride, potassium tert-
butoxide, sodium 3-aminopropylamide (NAPA), and potassium 3-aminopro-
pylamide (KAPA). It seems probable that the effectiveness of magnesium
ethoxide can be explained in part by a magnesium chelation effect.[19]
.
Decarboxylation of 8 with a catalytic amount of p-TsOH H2O in H2O
gave 9 and 10 in 90% and 5% yields, respectively. Compound 9 was oxida-
tively dimerized by silver oxide without intervention of their carbanions in
dimethyl sulfoxide (DMSO) to afford 5 and 11 as a mixture of trans-diketo
diester 5 and cis-diketo diester 11 (4:1 ratio, 5:11, 82% combined yield).
The ratio of 5 to 11 was determined to be 80:20 by the integration of the
1
ethoxy group signals in H NMR spectrum. The catalytic hydrogenation of
5 was examined by 10% palladium on charcoal under various hydrogenation
conditions (Table 1). Interestingly, when diketo diester 5 was treated with Pd–
C in EtOH, three reduced products were generated: dicarbethoxyethane 4,
alcohol 12, and diol 13 as syn-products, respectively (Table 1, entries 2–5).
Although these reductive hydrogenation reactions are all unsatisfactory, the
high conversion yield was obtained in reduction with Pd–C in EtOH under
40 psi (Table 1, entry 4). In these catalytic hydrogenation reactions, isolated
Scheme 1. Retrosynthetic analysis of eudesmin (1).

1668
J.-C. Jung and O.-S. Park
Scheme 2. (a) SOCl2, urea, toluene, 1008C, 3 h, 99%; (b) CH2(CO2Et)2, Mg, EtOH,
.
CCl4, toluene, rt, 30 min, 95%; (c) p-TsOH H2O/H2O, reflux, 7 h, 90%; (d) Ag2O,
DMSO, 708C, 8 h, 82%; (e) H2, Pd–C/EtOH.
three components (4, 12, and 13) were determined and characterized based on
isolation and 2D NMR study.
Reduction of dicarbethoxyethane 4 or diol 13 was achieved using lithiu-
maluminum hydride (LAH) in THF at 2258C to give tetraol 14 in 72% and
70% yields, respectively, which was readily treated with methanesulfonyl
chloride in the presence of Et3N and 4-dimethylaminopyridine (DMAP) in
CH2Cl2 to afford eudesmin (1) in 38% yield (Scheme 3).[20] The spectral
data of our synthetic diol 14 and eudesmin (1) were identical to the corre-
sponding spectral data reported for these compounds.[11f,21]
In conclusion, we have developed a simple synthesis of eudesmin (1) via
reductive catalytic hydrogenation and oxidative intermolecular coupling of
carbanions. This method is useful to generate the core skeleton of endo–
endo furofuran rings.
Table 1. Catalytic hydrogenation of 5 under various hydrogenation conditions
Hydrogenation
condition
Time
(h)
Yield
(%)b
Entry
Product
Ratioc
1
2
3
4
5
Pd–Ca/EtOH, H2, rt
16
10
5
78
81
70
85
65
(4 þ 12 þ 13) (75:22:trace)
Pd–C/EtOH, H2, 20 psi
Pd–C/EtOH, H2, 40 psi
Pd–C/EtOH, H2, 40 psi
Pd–C/EtOH, H2, 60 psi
(4 þ 12 þ 13)
(4 þ 12 þ 13)
(4 þ 12 þ 13)
(4 þ 12 þ 13)
(54:34:8)
(30:42:15)
(36:39:22)
(31:48:17)
1
1
a10% Palladium on charcoal.
bIsolated yield.
cRatio was determinded based on isolated products.

Simple Synthesis of Eudesmin
1669
Scheme 3. (a) LiAlH4/THF, 2258C, 2 h, 72%, 70%; (b) MeSO2Cl, Et3N, DMAP,
CH2Cl2, rt, 3 h, 38%.
EXPERIMENTAL
Reactions requiring anhydrous conditions were performed with the usual pre-
cautions for rigorous exclusion of air and moisture. Tetrahydrofuran was
distilled from sodium benzophenone ketyl prior to use. Thin-layer chromato-
graphy (TLC) was performed on precoated silica-gel G and GP uniplates from
Analtech and visualized with a 254-nm UV light. Flash chromatography was
carried out on silica gel 60 [Scientific Adsorbents Incorporated (SAI), particle
size 32–63 mm pore size 60 A]. H NMR and 13C NMR spectra were
1
˚
recorded on a Bruker DPX 400 at 400 MHz and 100 MHz and a Bruker
DPX 500 at 500 MHz and 125 MHz, respectively. The chemical shifts were
reported in parts per million (ppm) downfield from tetramethylsilane, and J
values are in Hertz. Infrared (IR) spectra were obtained on an ATI Mattson
FT/IR spectrometer. GC was performed by Hewlett Packard 5890 series II
gas chromatograph. Mass spectra were recorded with a Waters Micromass
ZQ LC–Mass system, and high resolution mass spectra (HRMS) were
measured with a Bruker BioApex FTMS system by direct injection using an
electrospray interface (ESI). When necessary, chemicals were purified
according to the reported procedures.[22]
Diethyl (3,4-Dimethoxybenzoyl)malonate (8)
Thionyl chloride (8.6 g, 72.0 mmol) was added to a well-stirred suspension of
acid 6 (10.0 g, 55.0 mmol) and urea (0.14 g) in toluene (50 mL). The reaction
mixture was heated in an oil bath at 1008C for 3 h, then cooled to room

1670
J.-C. Jung and O.-S. Park
temperature. The mixture of diethyl malonate (8.8 g, 55.0 mmol), magnesium
(1.47 g, 60.5 mmol), ethanol (8.4 g, 181.5 mmol), carbon tetrachloride
(1.2 ml), and toluene (90 mL) was stirred at room temperature for 1 h and
refluxed for 1 h. The reaction mixture was cooled to 08C, and the former
solution was cannulated into the latter. The resulting reaction mixture was
stirred at room temperature for 30 min. The aqueous 10% hydrochloric acid
solution (20 mL) was added, and then the mixture was extracted with ether
(100 mL ꢀ 2). The organic layer was washed with saturated aqueous
NH4Cl solution (120 mL) and brine (100 mL). The organic layer was
separated, dried over anhydrous MgSO4, filtered, and concentrated under
reduced pressure. The residue was purified by flash column chromatography
(silica gel, 33% ethyl acetate in hexanes) to give 8 (16.9 g, 95%) as a white
crystal. Rf ¼ 0.4 (hexanes–EtOAc, 3:1); mp 688C; IR (neat, NaCl) 3084,
2983, 2843, 1752, 1735, 1681, 1595, 1420, 1303, 1275, 1156, 1021 cm21
;
1H NMR (400 MHz, CDCl3) d 7.51 (s, 1H), 7.45 (d, J ¼ 8.0 Hz, 1H), 6.87
(d, J ¼ 12.0 Hz, 1H), 5.25 (s, 1H), 4.25 (q, J ¼ 6.8 Hz, 4H), 3.94 (s, 3H),
3.91 (s, 3H), 1.25 (t, J ¼ 7.2 Hz, 6H); 13C NMR (100 MHz, CDCl3) d
187.8, 165.4, 154.5, 149.7, 128.9, 123.7, 110.8, 110.6, 62.6, 61.9, 56.5,
56.3, 14.3; HRMS calcd. for C16H21O7: 325.1287 M þ Hþ, found: 325.1291.
Ethyl 3,4-Dimethoxybenzoylacetate (9)[23]
To a stirred solution of malonate 8 (5.5 g, 17.0 mmol) in water (70 mL) was
.
added p-TsOH H2O (0.18 g, 0.9 mmol) at room temperature, and the
mixture was refluxed for 7 h. The reaction mixture was cooled to room temp-
erature and extracted with ethyl acetate (120 mL). The organic layer was
washed with aqueous 2% sodium bicarbonate solution (70 mL) and brine
(100 mL). The organic layer was separated, dried over anhydrous MgSO4,
filtered, and concentrated under reduced pressure. The residue was purified
by flash column chromatography (silica gel, 33% ethyl acetate in hexanes)
to give 9 (3.85 g, 90%) as a white crystal. Rf ¼ 0.4 (hexanes–EtOAc, 3:1);
mp 658C; IR (neat, NaCl) 3084, 2982, 2843, 1752, 1735, 1680, 1595, 1464,
1
1342, 1275, 1155, 1021 cm21; H NMR (400 MHz, CDCl3) d 7.54–7.48
(m, 2H), 6.86 (d, J ¼ 7.3 Hz, 1H), 4.18 (q, J ¼ 7.5 Hz, 2H), 3.90 (s, 8H),
1.22 (t, J ¼ 7.5 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 191.4, 168.1,
154.2, 149.6, 129.7, 123.9, 110.7, 110.5, 61.8, 56.5, 56.4, 46.1, 14.5;
HRMS calcd. for C13H17O5: 253.1076 M þ Hþ, found: 253.1082.
Preparation of Diketo Diester 5 and Its Structure Isomer (11)
To a stirred solution of acetate 9 (2.5 g, 10.0 mmol) in DMSO (10 mL), Ag2O
(2.3 g, 10.0 mmol) was added at room temperature, and the mixture was
heated at 708C for 8 h. The reaction mixture was filtered through Celitew

Simple Synthesis of Eudesmin
1671
and washed with chloroform (2 mL ꢀ 2). The filtrate was poured into H2O
(30 mL) and extracted with chloroform (30 mL ꢀ 2). The organic phase
was washed with saturated aqueous NH4Cl solution (30 mL), and combined
organic layer was dried over anhydrous MgSO4, filtered, and concentrated
under reduced pressure to give diketo diesters, which were purified by flash
column chromatography (silica gel, 45% ethyl acetate in hexanes) to afford
5 and its structure isomer 11 as semisolid: Rf ¼ 0.4 (hexanes–EtOAc, 1:1);
IR (neat, NaCl) 3082, 2981, 2939, 2842, 1726, 1662, 1593, 1514, 1420,
1
1343, 1269, 1175, 1020 cm21; H NMR (500 MHz, CDCl3) d 7.61 (s, 1H),
7.57–7.48 (m, 2H), 7.26 (d, J ¼ 4.4 Hz, 1H), 6.91 (d, J ¼ 8.4 Hz, 1H), 6.84
(d, J ¼ 8.4 Hz, 1H), 4.27 (q, J ¼ 7.2 Hz, 4/5 ꢀ 4H), 4.05 (q, J ¼ 7.2 Hz,
1/5 ꢀ 4H), 3.96 (s, 3H), 3.95 (s, 3H), 3.92 (s, 3H), 3.83 (s, 3H), 1.24
(t, J ¼ 7.2 Hz, 4/5 ꢀ 6H), 0.97 (t, J ¼ 7.2 Hz, 1/5 ꢀ 6H); 13C NMR
(125 MHz, CDCl3) d 189.2, 188.5, 163.4, 162.6, 154.2, 153.9, 149.3, 148.9,
141.7, 140.7, 129.0, 128.5, 125.8, 124.6, 110.3, 110.2, 110.1, 109.7, 62.8,
62.7, 56.4, 56.3, 56.2, 14.3, 13.9; HRMS calcd. for C26H28O10Na: 523.1580
M þ Naþ, found: 523.1586:
General Procedure of Catalytic Hydrogenation Reaction
A solution of the diketo diester 3 (0.5 g, 1.0 mmol) in ethanol (80 mL) was
hydrogenated over 10% palladium on charcoal (0.2 g) using a Parr hydroge-
nator. The reaction mixture was filtered through Celitew and evaporated to
give a dark brown oil, which was purified by flash column chromatography
(silica gel, 50% ethyl acetate in hexanes) to afford 4, 12–13. Compound 4:
Rf ¼ 0.6 (hexanes–EtOAc, 1:1); mp 145–1468C; [a]2D4 –12.0 (c 0.15,
CHCl3); IR (neat, NaCl) 3083, 2979, 2938, 2841, 1735, 1670, 1594, 1516,
1419, 1274, 1154, 1022 cm21 1H NMR (500 MHz, CDCl3) d 7.91 (dd,
;
J ¼ 8.5, 2.5 Hz, 2H), 7.62 (d, J ¼ 6.0 Hz, 1H), 7.52 (d, J ¼ 6.0 Hz, 1H),
7.03–6.91 (m, 2H), 5.60–5.47 (m, 2H), 4.18–4.09 (m, 2H), 3.96 (s, 3H),
3.95 (s, 3H), 3.94 (s, 3H), 3.93 (s, 3H), 3.91–3.84 (m, 2H), 1.17
(t, J ¼ 7.0 Hz, 3H), 0.98 (t, J ¼ 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3)
d 191.8, 190.9, 167.6, 167.1, 153.8, 148.8, 147.7, 129.0, 128.7, 124.7,
124.6, 111.0, 110.1, 62.2, 62.1, 56.3, 56.2, 56.1, 54.0, 53.3, 14.3, 14.1.
HRMS calcd. for C26H31O10: 503.1917 M þ Hþ, found: 503.1922.
Compound 12: Rf ¼ 0.5 (hexanes–EtOAc, 1:1); [a]2D4 –10.4 (c 0.23,
CHCl3); IR (neat, NaCl) 3507, 3084, 2981, 2938, 2839, 1731, 1677, 1598,
1
1517, 1420, 1268, 1154, 1025 cm21; H NMR (500 MHz, CDCl3) d 7.51
(d, J ¼ 8.5 Hz, 1H), 7.49 (s, 1H), 6.82 (dd, J ¼ 10.5, 10.5 Hz, 4H), 4.99
(t, J ¼ 5.0 Hz, 1H), 4.72 (d, J ¼ 8.5 Hz, 1H), 4.01 (q, J ¼ 7.0 Hz, 2H), 3.99
(q, J ¼ 7.0 Hz, 2H), 3.93 (s, 3H), 3.90 (s, 3H), 3.86 (s, 3H), 3.80 (s, 3H),
3.74 (dd, J ¼ 5.5, 5.5 Hz, 1H), 3.54 (d, J ¼ 5.0 Hz, 1H), 1.16
(t, J ¼ 7.0 Hz, 3H), 1.03 (t, J ¼ 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3)
d191.7, 172.2, 168.2, 153.6, 148.8, 148.6, 148.4, 133.2, 129.0, 123.8, 118.3,

1672
J.-C. Jung and O.-S. Park
110.8, 110.6, 109.9, 109.2, 72.8, 62.0, 61.2, 56.3, 56.1, 55.9, 53.1, 52.6, 14.3,
14.1. HRMS calcd. for C26H32O10Na: 527.1893 M þ Naþ, found: 527.1895.
Compound 13: Rf ¼ 0.4 (hexanes–EtOAc, 1:1); [a]2D2 –5.4 (c 0.22,
CHCl3); IR (neat, NaCl) 3507, 3081, 2980, 2938, 2837, 1731, 1607, 1595,
1
1518, 1465, 1421, 1263, 1154, 1056 cm21; H NMR (500 MHz, CDCl3)
d 6.76 (dd, J ¼ 8.0, 8.0 Hz, 2H), 6.69 (d, J ¼ 7.5 Hz, 2H), 6.55
(d, J ¼ 8.5 Hz, 2H), 5.00 (d, J ¼ 5.5 Hz, 2H), 4.30–4.14 (m, 4H), 3.87
(s, 3H), 3.86 (s, 3H), 3.71 (s, 3H), 3.70 (s, 3H), 3.08 (d, J ¼ 4.5 Hz, 2H),
2.63 (d, J ¼ 8.0 Hz, 2H), 1.32 (t, J ¼ 7.0 Hz, 6H); 13C NMR (125 MHz,
CDCl3) d 172.5, 148.8, 148.6, 132.7, 119.7, 110.6, 109.3, 73.4, 61.5, 56.1,
55.8, 52.3, 14.6. HRMS calcd. for C26H34O10Na: 529.2050 M þ Naþ,
found: 529.2054.
ACKNOWLEDGMENTS
This work was supported by Korea Science and Engineering Foundation
(KOSEF) (Grant No. RO5-2004-000-10742–0).
REFERENCES
1. (a) Teles, H. L.; Hemerly, J. P.; Paulettit, P. M.; Pandolfi, J. R. C.; Araujot, A. R.;
Valentini, S. R.; Young, M. C.; Bolzani, M. V. S.; Silva, D. H. S. Nat. Prod. Res.
2005, 19 (4), 319–323; (b) Chiung, Y. M.; Hayashi, H.; Matsumoto, H.; Otani, T.;
Yoshida, K.; Huang, M. Y.; Chen, R. X.; Liu, J. R.; Nakayama, M. J. Antibiot.
1994, 47 (4), 487–491.
2. (a) De Leon, E. J.; Olmedo, D. A.; Solis, P. N.; Gupta, M. P.; Terencio, M. C.
Planta Med. 2002, 68 (12), 1128–1131; (b) Serra, M. F.; Diaz, B. L.;
Barreto, E. O.; Pereira, A. P. B.; Lima, M. C. R.; Barbosa-Filho, J. M.;
Cordeiro, R. S. B.; Martins, M. A.; De Silva, P. M. R. Planta Med. 1997,
63 (3), 207–212.
3. (a) Hoang, V. D.; Tan, G. T.; Zhang, H. J.; Tamez, P. A.; Nguyen, V. H.;
Nguyen, M. C.; Soejarto, D. D.; Fong, H. H. S.; Pezzuto, J. M. Phytochemistry
2002, 59 (3), 325–329; (b) Asano, J.; Chiba, K.; Tada, M.; Yoshi, T. Phyto-
chemistry 1996, 42 (3), 713–717.
4. (a) MacRae, W. D.; Towers, G. H. N. Phytochemistry 1984, 23 (6), 1207–1220;
(b) Seligmann, B. O.; Wagner, H. Phytochemistry 1991, 30 (9), 3087–3089.
5. Brown, R. C.; Bataille, C. J.; Bruton, G.; Hinks, J. D.; Swain, N. A. J. Org. Chem.
2001, 66 (20), 6719–6728.
6. Iwakami, S.; Ebizuka, Y.; Sankawa, U. Heterocycles 1990, 30 (2), 795–798;
(b) Iwakami, S.; Wu, J. B.; Ebizuka, Y.; Sankawa, U. Chem. Pharm. Bull. 1992,
40 (5), 1196–1198.
7. Ichikawa, K.; Kinoshita, T.; Nishibe, S.; Sankawa, U. Chem. Pharm. Bull. 1986,
34 (8), 3514–3517.
8. Nikaido, T.; Ohmoto, T.; Kinoshita, T.; Sankawa, U.; Nishibe, S.; Hisada, S.
Chem. Pharm. Bull. 1981, 29 (12), 3586–3592.
9. Plante, G. E.; Prevost, C.; Chainey, A.; Braquet, P.; Sirois, P. Am. J. Physiol. 1987,
253, R375–378.

Simple Synthesis of Eudesmin
1673
10. Bernard, C. B.; Arnason, J. T.; Philogene, B.; Lam, J. R.; Waddell, J. T.
Phytochem. 1989, 28 (5), 1373–1377.
11. (a) Brown, R. C. D.; Bataille, C. J. R.; Hinks, J. D. Tetrahedron Lett. 2001, 42,
473–475; (b) Van Oeveren, A.; Jansen, J. F. G. A.; Feringa, B. L. J. Org.
Chem. 1994, 59, 5999–6007; (c) Ogiku, T.; Yoshida, S. I.; Ohmizu, H.;
Iwasaki, T. J. Org. Chem. 1995, 60, 1148–1153; (d) Yoda, H.; Kimura, K.;
Takabe, K. Synlett 2001, 400–402; (e) Aldous, D. J.; Dalencon, A. J.;
Steel, P. G. Org. Lett. 2002, 4 (7), 1159–1162; (f) Roy, S. C.; Rana, K. K.;
Guin, C. J. Org. Chem. 2002, 67 (10), 3242–3248; (g) Swain, N. A.;
Brown, R. C. D.; Bruton, G. J. Org. Chem. 2004, 69 (1), 122–129;
(h) Fry, J. L.; Orfanopoulos, M.; Adlington, M. G., Jr.; Dittman, W. P., Jr.;
Silverman, S. B. J. Org. Chem. 1978, 43 (2), 374–375; (i) Taylor, E. C.;
Andrade, J. G.; Rall, G. J. H.; Steliou, K.; Jagdmann, G. E., Jr.; McKillop, A.
J. Org. Chem. 1981, 46 (15), 3078–3081; (j) Takano, S.; Ohkawa, T.;
Tamori, S.; Satoh, S.; Ogasawara, K. J. Chem. Soc., Chem. Commun. 1988,
189–191; (k) Orito, K.; Yorita, K.; Suginome, H. Tetrahedron Lett. 1991,
32 (42), 5999–6002; (l) Suginome, H.; Ishikawa, M.; Yorita, K.;
Shimoyama, N.; Sasaki, T.; Orito, K. J. Org. Chem. 1995, 60 (10), 3052–3064;
(m) Takeya, T.; Ara, Y.; Tobinaga, S. Chem. Pharm. Bull. 1995, 43 (11),
1970–1976; (n) Samizu, K.; Ogasawara, K. Chem. Lett. 1995, 543–544;
(o) Hull, H. M.; Jones, R. G.; Knight, D. W. J. Chem. Soc. Perkin Trans. 1998,
1, 1779–1788; (p) Quideau, S.; Ralph, J. J. Chem. Soc., Perkin Trans. 1 1993,
653–659.
12. Beroza, M.; Schechter, M. S. J. Am. Chem. Soc. 1956, 78, 1242–1247.
13. Kise, N.; Fujimoto, A.; Ueda, N. Tetrahedron Asymmetry 2002, 13, 1845–1847.
14. Aldous, D. J.; Dalencon, A. J.; Steel, P. G. J. Org. Chem. 2003, 68, 9159–9161.
15. Kasahara, H.; Miyazawa, M.; Kameoka, H. Phytochemistry 1997, 44 (8),
1479–1482.
16. Banerjee, B.; Roy, S. C. Synthesis 2005, 2913–2919.
17. Kim, J. C.; Kim, K. H.; Jung, J. C.; Park, O. S. Tetrahedron Asymmetry 2006,
17 (1), 3–6.
18. (a) Ito, Y.; Fujii, S.; Konoike, T.; Saegusa, T. Synth. Commun. 1976, 6 (6),
429–433; (b) Wu, A.; Zhao, Y.; Chen, N.; Pan, X. Synth. Commun. 1997,
27 (2), 331–336.
19. Little, R. D.; Russu, W. A. J. Org. Chem. 2000, 65 (23), 8096–8099.
20. (a) Pelter, A.; Ward, R. S.; Watson, D. J.; Collins, P.I.; Kay, T. J. Chem. Soc.
Perkin Trans. 1, 1982, 175–181.
21. (a) Pelter, A.; Ward, R. S.; Watson, D. J.; Jack, I. R. J. Chem. Soc., Perkin Trans. 1,
1982, 183–190; (b) Pelter, A.; Ward, R. S.; Nishino, C. Tetrahedron Lett. 1977,
18 (47), 4137–4140.
22. Perrin, D. D.; Armarego, L. F.; Perrin, D. R. Purification of Laboratory Chemicals,
2nd edn.; Pergamon Press: New York, 1980.
23. Balaji, B. S.; Chanda, B. M. Tetrahedron 1998, 54 (43), 13237–13252.