Total syntheses of the coumarin-containing natural products pimpinellin and fraxetin using Au(I)-catalyzed intramolecular hydroarylation (IMHA) chemistry

Article abstract of DOI:10.1021/jo401583q

The title natural products (1 and 2, respectively) have been synthesized by Au(I)-catalyzed intramolecular hydroarylation (IMHA) of the relevant aryl propiolate esters (e.g., 13), which were themselves formed by reaction of the corresponding phenols with either 3-(trimethylsilyl)propiolic acid or propiolic acid and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride or dicyclohexylcarbodiimide. (±)-Purpurasol (3) was readily derived from fraxetin (2) by established procedures.

Full text of DOI:10.1021/jo401583q

Article
pubs.acs.org/joc
Total Syntheses of the Coumarin-Containing Natural Products
Pimpinellin and Fraxetin Using Au(I)-Catalyzed Intramolecular
Hydroarylation (IMHA) Chemistry
Aymeric Cervi,†,‡ Paul Aillard,† Nourallah Hazeri,†,∥ Laurent Petit,† Christina L. L. Chai,‡,§
Anthony C. Willis,† and Martin G. Banwell*,†
†Research School of Chemistry, Institute of Advanced Studies, The Australian National University, Canberra,
Australian Capital Territory 0200, Australia
‡Institute of Chemical and Engineering Sciences, 8 Biomedical Grove, #07-01 Neuros, Singapore 138665
§Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543
S
* Supporting Information
ABSTRACT: The title natural products (1 and 2, respectively)
have been synthesized by Au(I)-catalyzed intramolecular hydroarylation
(IMHA) of the relevant aryl propiolate esters (e.g., 13), which were
themselves formed by reaction of the corresponding phenols
with either 3-(trimethylsilyl)propiolic acid or propiolic acid and
N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride or
dicyclohexylcarbodiimide. ( )-Purpurasol (3) was readily derived
from fraxetin (2) by established procedures.
in certain cell lines.11 It probably also serves as a biosynthetic
INTRODUCTION
■
precursor to a range of other coumarin-containing natural pro-
Coumarins (benzo-α-pyrones) have been isolated from a
ducts, including the co-occurring purpurasol (3).12 Certainly, it
diverse range of plant sources as well as certain microorganisms
and animals.1 These natural products display an extraordinarily
has been shown that naturally derived 2 is an effective starting
material for the chemical synthesis of compound 313 as well as
wide range of biological activities and, as a result, it has been
certain other coumarin-containing natural products.14
suggested that their therapeutic potential is “immense”.2 The
size of and structural diversity within the class has led to the
identification of various subgroups, two important ones being
the furocoumarins3 and the 6,7-dihydroxycoumarins.4 Certain
members of these act as, inter alia, phytoalexins, antimitotic
agents, vasodilators, and antibacterial agents and/or have been
used in photochemotherapy for treating vitiligo, psoriasis, and
atopic dermatitis.5 Pimpinellin (1),6 for example, is an angular furo-
coumarin, the structure of which has recently been confirmed
by single-crystal X-ray analysis.7 It has been isolated from a
Despite the therapeutic potential of natural products 1 and 2,
only the former compound has been the subject of total syn-
thesis studies, with the single such effort involving its assembly
from diethyl squarate in 13 steps, including an elegant ther-
range of plant sources,6 including Pimpinella saxifraga L. and
members of the Umbelliferae family, and serves as a phytoalexin
in parsley and celery as well as acting as an inhibitor of tricho-
mally induced electrocyclic ring-opening/ring-closure proc-
thecene toxin biosynthesis and nitric oxide synthase.8 Fraxetin
ess.15 In view of this, and given our ongoing interest16 in the
development of methods for the synthesis of coumarins using
(2),9 on the other hand, is a 6,7-dihydroxycoumarin derivative.
It has been obtained by extraction of a diverse range of plants,
including those belonging to the genus Pulicaria (Compositae)
and the Mexican Tarragon (Tagetes lucida), or through acid-
promoted hydrolysis of the glycosylated derivative fraxin, itself
Au(I)-catalyzed intramolecular hydroarylation (IMHA) reac-
tions of phenyl propiolates,17 we now report total syntheses of
the title natural products 1 and 2 along with that of 3.
obtained from the bark of trees such as the common European
RESULTS AND DISCUSSION
■
ash (Fraxinus excelsior L.) or the horse chestnut tree (Aesulus
hippcastanum L.).9,10 Fraxetin not only acts against a range of
Total Synthesis of Pimpinellin. The fully substituted
nature of the benzenoid core associated with pimpinellin
bacteria, including Vibrio cholerae, but also exhibits hypour-
icemic and renal protective actions, inhibits inflammatory cytokine-
mediated apoptosis in osteoblast cells (and may thus have
potential in preventing osteoporosis), and acts as an antioxidant
Received: July 21, 2013
Published: August 26, 2013
© 2013 American Chemical Society
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presents a significant synthetic challenge, not least because this
bears annulated furan and α-pyrone rings. The demonstrated
utility of the above-mentioned IMHA process in forming
coumarins from phenolic scaffolds together with ability of
o-hydroxyphenylacetylenes to participate in 5-endo-dig cycliza-
tion reactions, thus generating benzofurans,18 prompted consid-
eration of an approach wherein an appropriately substituted
arene was used as the starting material. Sequential annulation of
the five- and six-membered heterocyclic rings would then
follow, with any regiochemical issues being addressed by ex-
ploiting the normally well-defined directing effects of substit-
uents attached to the arene core. It was hoped that the pro-
tocols developed in the course of this work might ultimately
find use in the assembly of other angular furocoumarins as well
as their linear counterparts.
arene 8 (84%), the structure of which was confirmed by single-
crystal X-ray analysis22 (see the Supporting Information for
details), was then subjected to a Sonogashira cross-coupling23
reaction with triisopropylsilylacetylene. This produced a 1:8
mixture of acetylene 9 (5%) and the isomeric benzofuran 10
(39%) which were chromatographically separable, thereby
allowing each to be subjected to comprehensive character-
ization. However, for synthetic purposes it was more con-
venient to treat the mixture with tetra-n-butylammonium
fluoride (TBAF) thereby generating the desilylated benzofuran
11, which was obtained as a colorless crystalline solid in 80%
yield. The rather modest yields associated with the conversion
8 → 9 + 10 may be attributed to competitive oxidative coupling
of the triisopropylsilylacetylene, although the (likely volatile)
product of such a process was not detected in the crude pro-
duct mixture.
On the basis of the foregoing considerations, the route
pursued in efforts to prepare pimpinellin (1) started with
vanillin (4). Regioselective bromination of the latter com-
pound using molecular bromine in acetic acid afforded the
previously reported19,20 bromoarene 5 (69%) (Scheme 1).
The completion of the synthesis of pimpinellin from
compound 11 required installation of the lactone ring, and
this proved to be a straightforward matter. Aldehyde 11 was
subjected to a Baeyer−Villiger oxidation using m-chloroperoxy-
benzoic acid (m-CPBA), and the ensuing formate ester was
cleaved with ammoniacal methanol to give phenol 12 in 68%
yield. Treatment of the latter compound with 3-(trimethylsilyl)-
propiolic acid in the presence N-(3-dimethylaminopropyl)-N′-
ethylcarbodiimide hydrochloride (EDC·HCl)24 afforded ester
13 (79% yield at 48% conversion) with accompanying loss of
the TMS group associated with the alkyne (an event that
probably took place during chromatographic purification).
Upon treatment with a 5 mol % loading of Echavarren’s gold(I)
catalyst25 in dichloromethane at 25 °C, compound 13 afforded
pimpinellin (1) as a colorless, crystalline solid in 72% yield. All
of the spectroscopic data derived from this material were
consistent with the assigned structure and accorded well with
those reported for the natural product.15,26 Relevant compar-
Scheme 1
1
isons of the 13C and H NMR data are presented in Table 1.
1
Table 1. Comparison of the 13C and H NMR Data
Recorded for Synthetically-Derived Compound 1 with
Those Reported for Pimpinellin
13C NMR (δC)
1H NMR (δH)
a
b
c
d
1
pimpinellin
1
pimpinellin
161.1
150.0
145.6
144.7
143.4
140.1
135.4
114.4
114.0
109.7
104.6
62.6
160.4
149.7
145.4
144.4
143.1
139.8
134.9
115.5
113.8
109.3
104.1
62.2
8.06 (d, J = 9.7 Hz, 1H) 8.08 (d, J = 9.7 Hz, 1H)
7.64 (d, J = 2.2 Hz, 1H) 7.65 (d, J = 2.2 Hz, 1H)
7.07 (d, J = 2.2 Hz, 1H) 7.08 (d, J = 2.2 Hz, 1H)
6.35 (d, J = 9.7 Hz, 1H) 6.37 (d, J = 9.7 Hz, 1H)
4.13 (s, 3H)
4.02 (s, 3H)
4.15 (s, 3H)
4.06 (s, 3H)
61.5
61.1
This was subjected to reaction with copper powder in the
presence of aqueous sodium hydroxide using a modification
of a protocol reported by Ellis and Lenger20 to afford catechol
6 (93%), which could be selectively monomethylated using
dimethyl sulfate in the presence of sodium carbonate to afford
ether 721 (87%).
As a prelude to establishing the furan ring of target 1, bro-
mination of compound 7 at C2 was accomplished using N-
bromosuccinimide (NBS), and the ensuing pentasubstituted
a
b
Recorded in CDCl3 at 100 MHz. Obtained from ref 26; recorded in
CDCl3 at 22.6 MHz. Recorded in CDCl3 at 400 MHz. Obtained
from ref 15; recorded in CDCl3 at 300 MHz.
c
d
Total Synthesis of Fraxetin. In principle at least, fraxetin
(2) represents a less challenging synthetic target than congener
1 given the absence of an associated furan residue and the
presence of five rather than six substituents on the benzenoid
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1
Table 2. Comparison of the 13C and H NMR Data
core. As such, the most notable task that needed to be ad-
dressed in establishing a route to compound 2 was the incor-
poration of the two free hydroxyl residues associated with the
catechol substructure. In view of the utility of isopropyl ethers
as protecting groups for phenolic OH groups,27 the synthetic
plan that was pursued (Scheme 2) started with the generation
of an arene incorporating two such residues on adjacent
benzenoid carbons.
Recorded for Synthetically-Derived Compound 2 with
Those Reported for Fraxetin
13C NMR (δC)
1H NMR (δH)
a
b
c
d
2
fraxetin
2
fraxetin
163.7
147.1
146.7
140.7
140.6
134.0
112.3
112.2
101.0
56.8
164.0
147.0
146.7
140.8
140.7
134.0
112.6
112.2
101.3
56.8
7.82 (d, J = 8.8 Hz, 1H)
6.70 (s, 1H)
7.84 (d, J = 9.6 Hz, 1H)
6.72 (s, 1H)
6.19 (d, J = 8.8 Hz, 1H)
3.89 (s, 3H)
6.23 (d, J = 9.6 Hz, 1H)
3.87 (s, 3H)
Scheme 2
a
b
Recorded in CD3OD at 100 MHz. Obtained from ref 29; recorded
c
in CD3OD at 100 MHz. Recorded in CD3OD at 400 MHz.
d
Obtained from ref 29; recorded in CD3OD at 400 MHz.
Scheme 3
2,3,4-Trimethoxybenzaldehyde (14) was treated with an
excess of boron trichloride according to a protocol defined by
Hase et al.,28 thereby producing catechol 15 in 76% yield.
Treatment of the latter compound with ca. 2.5 molar equiv
of isopropyl bromide in the presence of Hunig’s base then
̈
gave the required bisether 16 in 73% yield. Subjection of the
latter aldehyde to Baeyer−Villiger oxidation with m-CPBA in
the presence of sodium bicarbonate gave the expected formate
ester, which was immediately cleaved with ammoniacal meth-
anol to afford phenol 17 (93% over two steps), the structure of
which was confirmed by single-crystal X-ray analysis22 (see the
Supporting Information for details). Coupling of the latter
compound with propiolic acid in the presence of dicyclohex-
ylcarbodiimide (DCC) then gave ester 18 (98%), which readily
engaged in the required IMHA reaction upon exposure to
3 mol % Echavarren’s catalyst in dichloromethane at 25 °C for
5 h. By such means the bisether of fraxetin, 19, was obtained in
96% yield. Finally, treatment of compound 19 with 3 equiv of
boron trichloride at 18 °C in dichloromethane resulted in the
selective cleavage of the two isopropyl ether residues, affording
crystalline fraxetin (2) in 76% yield. The derived spectroscopic
data were in complete accord with the assigned structure and
proved to be a good match with those reported for the natural
mixture of the regioisomeric prenyl ethers 21 (12%) and 2230
(40%) (Scheme 3), the structures of which were confirmed
by comparison of the derived spectroscopic data with those
reported previously.13 The preferential formation of the latter
ether in this reaction has been attributed to selective de-
protonation of the more acidic and lactone-carbonyl-conjugated
C7 phenolic group within fraxetin.13 Epoxidation of compound
22 with m-CPBA in ethyl acetate at between 0 and 18 °C for
48 h afforded purpurasol (3) in 69% yield, presumably via
6-exo-tet cyclization of the intermediate epoxide. Compound 3
was obtained as a colorless, crystalline solid. The associated
physical and spectroscopic properties were in accord with those
reported by De Kimpe and co-workers.13
product.29 A comparison of the two sets of 13C and H NMR
1
spectroscopic data is presented in Table 2.
Total Synthesis of Purpurasol. The reaction sequence
shown in Scheme 2 provided a ready means for generating sig-
nificant quantities of fraxetin (2). Therefore, we sought to ex-
ploit this material for the purposes of generating fully synthetic
samples of purpurasol (3) for biological testing. Accordingly,
following the protocol reported by De Kimpe et al.,13 an
acetone solution of 2 containing triethylamine was treated with
prenyl bromide to afford a chromatographically separable
CONCLUSION
■
The synthetic sequences detailed in Schemes 1 and 2 serve to
emphasize the utility of Echavarren’s catalyst in effecting the
IMHA of phenyl propiolates under mild conditions, thereby
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hydrogen phosphate (273 mg, 1.924 mmol), and the resulting mixture
was heated at reflux for 1 h and then cooled and filtered. The filtrate
was treated with HCl (30 mL of a 1.0 M aqueous solution) and then
extracted with ethyl acetate (3 × 150 mL). The combined organic
layers were washed with EDTA (1 × 100 mL of a saturated aqueous
solution) and brine (1 × 100 mL) before being dried (MgSO4),
filtered, and concentrated under reduced pressure. The light-yellow oil
thus obtained was subjected to flash chromatography (silica, 2:1 v/v →
1:1 v/v hexane/ethyl acetate gradient elution) to afford, after con-
centration of the relevant fractions (Rf = 0.25 in 1:1 ethyl acetate/
hexane), 3-methoxy-4,5-dihydroxybenzaldehyde (6)20 (3.00 g, 93%) as
a light-brown solid, mp 132 °C (lit.20 132−133 °C) [Found: (M +
delivering highly substituted coumarins in good yield. There-
fore, given the likely ready (and regiocontrolled) access to rel-
evant precursor phenols, the protocols described here should
be capable of straightforward extension to a range of other
biologically interesting coumarins and furocoumarins.
EXPERIMENTAL SECTION
■
General Experimental Procedures. Unless otherwise specified,
1H and 13C NMR spectra were recorded at 18 °C in base-filtered
CDCl3 on a spectrometer operating at 400 MHz for 1H and 100 MHz
1
for 13C. For H NMR spectra, signals arising from the residual protio
1
1
Na)+, 191.0318; C8H8NaO4 requires 191.0315]. H NMR (400 MHz,
forms of the solvent were used as the internal standards. H NMR
data are recorded as follows: chemical shift δ (in ppm) [multiplicity,
coupling constant(s) J, relative integral], where the symbols repre-
senting the multiplicity are defined as follows: s = singlet; d = doublet;
t = triplet; q = quartet; m = multiplet or combinations of the above.
The signal due to residual CHCl3 appearing at δH 7.26 and the central
resonance of the CDCl3 “triplet” appearing at δC 77.0 were used to
CDCl3) δ 9.77 (s, 1H), 7.12 (d, J = 1.7 Hz, 1H), 7.06 (d, J = 1.7 Hz,
1H), 5.93 (s, 1H), 5.42 (broad s, 1H), 3.94 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 191.2, 147.5, 144.2, 138.5, 129.3, 113.3, 103.0,
56.7; νmax (KBr) 3345, 1673, 1595, 1514, 1463, 1335, 1205, 1142,
1093, 1003 cm−1; MS (EI, 70 eV) m/z 168 (M+•, 100%), 167 (97).
Compound 7. A magnetically stirred suspension of aldehyde 6
(2.15 g, 12.8 mmol), dimethyl sulfate (1.2 mL, 14.1 mmol), and
sodium carbonate (1.61 g, 2.8 mmol) in acetone (50 mL) was heated
at reflux for 5 h. The cooled reaction mixture was concentrated under
reduced pressure, and the ensuing residue was dissolved in ethyl
acetate (60 mL). The resulting solution was extracted with NaOH (1 ×
30 mL of a 1.0 M aqueous solution), and the separated aqueous phase
was acidified with HCl (70 mL of a 2 M aqueous solution) and
extracted with ethyl acetate (3 × 150 mL). The combined organic
layers were dried (MgSO4), filtered, and concentrated under reduced
pressure to give a light-yellow oil. Subjection of this material to flash
chromatography (silica, 1:1 v/v mixture of hexane/ethyl acetate
elution) then afforded, after concentration of the relevant fractions
(Rf = 0.5), 3-hydroxy-4,5-dimethoxybenzaldehyde (7)21 (2.02 g, 87%)
as a light-yellow oil [Found: (M + Na)+, 205.0478; C9H10NaO4
requires 205.0472]. 1H NMR (400 MHz, CDCl3) δ 9.80 (s, 1H), 7.09
(d, J = 1.8 Hz, 1H), 7.03 (d, J = 1.8 Hz, 1H), 5.90 (broad s, 1H), 3.97
(s, 3H), 3.90 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 191.4, 152.9,
149.8, 141.0, 132.3, 111.7, 104.0, 61.3, 56.3; νmax (KBr) 3400, 2943,
2843, 1688, 1587, 1505, 1464, 1431, 1392, 1339, 1241, 1203, 1133,
1106 cm−1; MS (EI, 70 eV) m/z 182 (M+•, 100%), 167 (53).
Compound 8. A magnetically stirred solution of compound 7
(1.83 g, 10.0 mmol) in dry THF (50 mL) maintained under nitrogen
was cooled to 0 °C and then treated, in portions, with NBS (1.82 g,
10.2 mmol). The ensuing mixture was allowed to warm to 18 °C over
16 h and then concentrated under reduced pressure. The light-yellow
solid thus obtained was subjected to flash chromatography (silica,
1:1 v/v hexane/ethyl acetate elution) to afford, after concentration of
the relevant fractions (Rf = 0.6), 2-bromo-3-hydroxy-4,5-dimethox-
ybenzaldehyde (8) (2.21 g, 84%) as a light-yellow solid, mp 55−56 °C
[Found: (M + Na)+, 282.9582; C9H979BrNaO4 requires 282.9577]. 1H
NMR (400 MHz, CDCl3) δ 10.26 (s, 1H), 7.47 (s, 1H), 3.93 (s, 3H),
3.91 (s, 3H) (one signal obscured or overlapping); 13C NMR (100 MHz,
CDCl3) δ 191.2, 151.7, 147.1, 141.1, 128.8, 106.9, 104.7, 61.5, 56.4;
νmax (KBr) 3369, 1681, 1587, 1486, 1426, 1346, 1330, 1262, 1199,
1146, 1110, 1018, 993 cm−1; MS (EI, 70 eV) m/z 262 and 260 (M+•,
99 and 100%, respectively).
1
reference the H and 13C NMR spectra, respectively. Samples were
analyzed by IR spectroscopy (νmax) as thin films on KBr plates.
Samples for attenuated total reflectance (ATR) IR spectra were
prepared by allowing a CDCl3 solution of these to evaporate on the
sampling plate before the spectrum was acquired. Low-resolution ESI
mass spectra were recorded on a single-quadrupole liquid chromato-
graph−mass spectrometer, while high-resolution measurements were
conducted on a time-of-flight instrument. Low- and high-resolution
electron impact (EI) mass spectra were recorded on a magnetic-sector
machine. Melting points are uncorrected. Analytical thin-layer chro-
matography (TLC) was performed on aluminum-backed 0.2 mm thick
silica gel 60 F254 plates. Eluted plates were visualized using a 254 nm
UV lamp and/or by treatment with a suitable dip followed by heating.
These dips included phosphomolybdic acid/ceric sulfate/sulfuric acid
(conc.)/water (37.5 g/7.5 g/37.5 g/720 mL) or potassium
permanganate/potassium carbonate/5% sodium hydroxide aqueous
solution/water (3 g/20 g/5 mL/300 mL). Flash chromatographic
separations were carried out following protocols defined by Still et al.31
with silica gel 60 (40−63 μm) as the stationary phase and the
indicated AR- or HPLC-grade solvents. Starting materials, reagents,
drying agents, and other inorganic salts were generally commercially
available and were used as supplied. Tetrahydrofuran (THF),
methanol, and dichloromethane (DCM) were dried using a solvent
purification system based upon a technology originally described by
Grubbs and co-workers.32 Where necessary, reactions were performed
under an argon atmosphere. All microwave irradiation experiments
were carried out in a microwave apparatus operating at a frequency of
2.45 GHz with continuous irradiation power from 0 to 300 W utilizing
the standard absorbance level of 300 W maximum power. Each re-
action was carried out in a 10 mL sealed vessel that had a working
volume of 7 mL and was equipped with a magnetic stirrer. The tem-
perature was measured with a fiber optic temperature sensor immersed
in the reaction vessel. After the irradiation period, the reaction vessel
was cooled rapidly (1−2 min) to ambient temperature by jet cooling
using nitrogen gas.
Compound 5. A solution of molecular bromine (7.4 mL,
144.6 mmol) in acetic acid (40 mL) was added dropwise to a
magnetically stirred suspension of vanillin (4) (20.0 g, 131.5 mmol) in
acetic acid (120 mL). The ensuing mixture was stirred at 18 °C for 1 h
before being treated with sodium hydrogen sulfate (20 mL of a
saturated aqueous solution) and then filtered to afford 5-bromovanillin
(5)19 (21.8 g, 69%) as a colorless crystalline solid, mp 176−178 °C
(lit.19a 179 °C). 1H NMR (400 MHz, CDCl3) δ 9.77 (s, 1H), 7.62 (d,
J = 1.7 Hz, 1H), 7.35 (d, J = 1.7 Hz, 1H), 6.47 (s, 1H), 3.97 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 189.9, 149.1, 147.9, 130.3, 130.3,
108.4, 108.2, 56.8.
Compound 6. A magnetically stirred solution of vanillin 5 (4.6 g,
19.2 mmol) and sodium hydroxide (7.70 g, 192.4 mmol) in deoxy-
genated water (200 mL) was treated with copper powder (61 mg,
0.96 g-atom, 5 mol %), and the ensuing mixture was heated at reflux
for 24 h. The cooled reaction mixture was treated with disodium
Compounds 9 and 10. A tube suitable for placement in a
microwave reactor was charged with aldehyde 8 (51 mg, 0.20 mmol),
PdCl2(dppf)·CH2Cl2 (8 mg, 5 mol %), and copper(I) iodide (2 mg,
5 mol %). The tube and its contents were flushed with nitrogen for
0.17 h, after which dry acetonitrile (0.75 mL) was added, and nitrogen
was bubbled through the resulting solution for 0.08 h. Triethylamine
(0.50 mL) was then added to the reaction mixture, which was again
flushed with nitrogen for 0.08 h. Finally, triisopropylsilylacetylene
(130 μL, 0.59 mmol) was added dropwise, and nitrogen was bubbled
through the resulting solution for 0.02 h. The dark-red solution thus
obtained was immediately subjected to microwave irradiation (100 W,
internal pressure of 200 psi) at 120 °C for 1.5 h before being cooled
and then subjected to flash chromatography (silica, 4:1 v/v → 2:1 v/v
hexane/ethyl acetate elution) to afford two fractions, A and B.
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Concentration of fraction A [Rf = 0.4(6) in 2:1 v/v hexane/ethyl
acetate] gave compound 9 (4 mg, 5%) as colorless needles, mp 98−
99 °C [Found: (M + H)+, 363.1988; C20H31O4Si requires 363.1987].
1H NMR (400 MHz, CDCl3) δ 10.41 (s, 1H), 7.07 (s, 1H), 6.17 (s,
1H), 3.95 (s, 3H), 3.90 (s, 3H), 1.13 (broad s, 21H); 13C NMR
(100 MHz, CDCl3) δ 190.6, 153.4, 151.5, 140.6, 132.0, 108.7, 103.8,
102.4, 96.9, 61.2, 56.4, 18.9, 11.5; νmax (KBr) 3327, 2943, 2865, 2145,
1682, 1587, 1492, 1464, 1426, 1389, 1358, 1325, 1268, 1242, 1212,
1197, 1131, 1074, 1014, 882 cm−1; MS (ESI) m/z 385 [(M + Na)+,
100%], 363 [(M + H)+, 15].
Concentration of fraction B [Rf = 0.4(7) in 2:1 v/v hexane/ethyl
acetate] gave compound 10 (30 mg, 39%) as a clear yellow oil [Found:
(M + H)+, 363.1986; C20H31O4Si requires 363.1987]. 1H NMR
(400 MHz, CDCl3) δ 10.13 (s, 1H), 7.72 (s, 1H), 7.43 (s, 1H), 4.46
(s, 3H), 4.03 (s, 3H), 1.54−1.39 (complex m, 3H), 1.20 (d, J = 7.3 Hz,
18H); 13C NMR (100 MHz, CDCl3) δ 190.1, 164.3, 148.6, 147.4,
140.1, 125.5, 120.9, 117.1, 113.7, 60.9, 57.7, 18.7, 11.2; νmax (KBr)
2944, 2866, 1684, 1603, 1582, 1528, 1495, 1463, 1370, 1306, 1292,
1234, 1195, 1159, 1133, 1103, 1026, 987, 883 cm−1; MS (EI, 70 eV)
m/z 362 (M+•, 48%), 320 (43), 319 (100).
Compound 11. A magnetically stirred solution of the crude
mixture of compounds 9 and 10 (460 mg, 1.27 mmol, obtained from
the above-mentioned Sonogashira cross-coupling reaction) in THF
(2 mL) maintained at 0 °C was treated with TBAF (7.6 mL of a 1.0 M
solution in THF). The ensuing mixture was stirred for 1 h at 0 °C and
then for a further 3 h at 18 °C before being concentrated under
reduced pressure. The light-yellow oil thus obtained was subjected to
flash chromatography (silica, 4:1 → 2:1 v/v hexane/ethyl acetate
gradient elution) to give, after concentration of the relevant fractions
(Rf = 0.2 in 2:1 v/v hexane/ethyl acetate), benzofuran 11 (210 mg,
80%) as a light-yellow powder, mp 77−78 °C [Found: (M + H)+,
207.0652; C11H11O4 requires 207.0652]. 1H NMR (400 MHz, CDCl3)
δ 10.07 (s, 1H), 7.70 (d, J = 2.2 Hz, 1H), 7.42 (d, J = 2.2 Hz, 1H), 7.38
(s, 1H), 4.35 (s, 3H), 3.97 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
189.9, 147.7, 147.4, 145.9, 140.2, 124.5, 121.4, 113.8, 106.1, 61.0, 57.4;
νmax (KBr) 3143, 3109, 2958, 2849, 1680, 1588, 1536, 1509, 1461,
1394, 1376, 1347, 1298, 1247, 1212, 1187, 1131, 1078, 1047, 1015,
851, 781 cm−1; MS (ESI) m/z 207 [(M + H)+, 20%], 186 (100).
Compound 12. A magnetically stirred solution of benzofuran 11
(210 mg, 1.02 mmol) in dichloromethane (4 mL) maintained at 0 °C
was treated with anhydrous NaHCO3 (291 mg, 3.46 mmol) and then
m-CPBA (211 mg of ca. 77% peracid, 1.22 mmol). The ensuing mix-
ture was stirred at 0 °C for 1 h and then concentrated under reduced
pressure. The residue so formed was dissolved in ammonia-saturated
methanol (12 mL), and the resulting mixture was maintained, with
magnetic stirring, in a sealed vessel for 1 h at 18 °C before being
opened to the atmosphere. After a further 0.18 h, the reaction mixture
was concentrated under reduced pressure, and the resulting light-
yellow residue was subjected to flash chromatography (silica, 2:1 v/v
hexane/ethyl acetate elution) to give, after concentration of the rel-
evant fractions (Rf = 0.2), 6,7-dimethoxybenzofuran-4-ol (12) (135 mg,
68%) as a pale-cream solid, mp 142−143 °C [Found: (M + Na)+,
217.0477; C10H10NaO4 requires 217.0472]. 1H NMR (400 MHz,
CDCl3) δ 7.47 (d, J = 2.1 Hz, 1H), 6.72 (d, J = 2.1 Hz, 1H), 6.37 (s,
1H), 4.81 (broad s, 1H), 4.01 (s, 3H), 3.87 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 149.6, 148.7, 143.9, 143.7, 129.5, 112.0, 103.5,
96.6, 61.5, 57.5; νmax (KBr) 3290, 2976, 2850, 1640, 1618, 1545, 1520,
1471, 1448, 1429, 1364, 1290, 1227, 1210, 1149, 1135, 1080, 1046,
1012 cm−1; MS (ESI) m/z 217 [(M + Na)+, 15%], 186 (100).
Compound 13. A magnetically stirred solution of phenol 12
(50 mg, 0.257 mmol) and 3-(trimethylsilyl)propiolic acid (38 mg,
0.31 mmol) in dichloromethane (2 mL) was treated with N-(3-
dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (59 mg,
0.309 mmol). The resulting mixture was stirred at 18 °C for 24 h and
then concentrated under reduced pressure, and the residue so obtained
was subjected to flash chromatography (silica, 3:1 v/v hexane/ethyl
acetate elution) to give two fractions, A and B.
Concentration of fraction B (Rf = 0.5) afforded propiolate ester 13
(24 mg, 79% at 48% conversion) as a light-brown solid, mp 72−73 °C
(Found: M+•, 246.0526; C13H10O5 requires 246.0523]. 1H NMR
(400 MHz, CDCl3) δ 7.52 (d, J = 2.3 Hz, 1H), 6.75 (s, 1H), 6.61 (m,
1H), 4.11 (s, 3H), 3.88 (s, 3H), 3.11 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 150.8, 148.8, 147.8, 145.0, 136.4, 133.6, 116.5, 104.0, 103.1,
77.4, 74.2, 61.3, 57.5; νmax (ATR) 2938, 2847, 2123, 1734, 1636, 1506,
1448, 1399, 1336, 1189, 1146, 1124, 1077, 1043 cm−1; MS (EI, 70 eV)
m/z 246 (M+•, 67%), 194 (45), 193 (100).
Pimpinellin (1). A magnetically stirred solution of ester 13 (20 mg,
0.081 mmol) in dichloromethane maintained at 18 °C was treated
with Echavarren’s catalyst (3 mg, 0.004 mmol, 5 mol %). The resulting
mixture was stirred at 18 °C for 0.5 h and then filtered through a pad
of TLC-grade silica gel. The filtrate was concentrated under reduced
pressure, and the residue thus obtained was subjected to flash chro-
matography (silica, 3:1 v/v hexane/ethyl acetate elution). Concen-
tration of the relevant fractions (Rf = 0.5) gave pimpinellin (1)6,7 (16
mg, 72%) as a colorless powder, mp 117−119 °C (lit.6a 117−119 °C)
(Found: M+•, 246.0528; C13H10O5 requires 246.0523). 1H NMR
(400 MHz, CDCl3) δ, see Table 1; 13C NMR (100 MHz, CDCl3) δ,
see Table 1; νmax (ATR) 2986, 2948, 1737, 1626, 1579, 1482, 1451,
1419, 1388, 1340, 1323, 1156, 1125, 1114, 1092, 1063, 1035, 1013,
821, 748 cm−1; MS (EI, 70 eV) m/z 246 (M+•, 100%), 231 (81).
Compound 15. A magnetically stirred solution of 2,3,4-
trimethoxybenzaldehyde (14) (4.04 g, 20.6 mmol) in dry dichloro-
methane (50 mL) maintained under nitrogen at 18 °C was treated
dropwise with boron trichloride (20 mL, 20 mmol), and the ensuing
mixture was stirred at 18 °C for 2 h. Additional boron trichloride
(40 mL, 40 mmol) was then added, and stirring was continued at
18 °C for a further 16 h. The ensuing mixture was then poured into
NaHCO3 (100 mL of a saturated aqueous solution), and the separated
aqueous layer was acidified with HCl (50 mL of a 2.0 M aqueous
solution) before being extracted with diethyl ether (3 × 100 mL). The
combined organic layers were washed with water (1 × 100 mL) and
brine (1 × 100 mL) and then dried (MgSO4), filtered, and con-
centrated under reduced pressure. The resulting yellow oil was
subjected to flash chromatography (silica, 15:5:2 v/v/v ethyl acetate/
hexane/methanol elution) to afford, after concentration of the
appropriate fractions (Rf = 0.3 in 7:3 v/v hexane/ethyl acetate), 2,3-
dihydroxy-4-methoxybenzaldehyde (15)28 (2.65 g, 76%) as a light-
yellow solid, mp 113−114 °C (lit.28 113−114 °C) (Found: M+•,
1
168.0423; C8H8O4 requires 168.0418). H NMR (400 MHz, CDCl3)
δ 11.11 (s, 1H), 9.75 (s, 1H), 7.14 (d, J = 8.8 Hz, 1H), 6.61 (d, J =
8.8 Hz, 1H), 5.51 (s, 1H, OH), 3.98 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 195.2, 153.0, 149.0, 133.0, 126.1, 116.1, 103.6, 56.4; νmax
(KBr) 3370, 2914, 2848, 1647, 1506, 1454, 1276, 1104, 1028, 775,
699 cm−1; MS (EI, 70 eV) m/z 168 (M+•, 100%), 167 (63), 122 (50).
Compound 16. A magnetically stirred solution of benzaldehyde 15
(2.61 g, 15.5 mmol) in DMF (30 mL) maintained under nitrogen was
treated with anhydrous potassium carbonate (6.44 g, 45.6 mmol) and
2-bromopropane (5.73 mL, 46.6 mmol). The ensuing reaction mixture
was heated at 90 °C for 16 h and then diluted with water (50 mL) and
extracted with dichloromethane (3 × 100 mL). The combined organic
phases were then washed with water (1 × 100 mL) and brine (1 ×
100 mL) before being dried (MgSO4), filtered, and concentrated
under reduced pressure. The resulting light-yellow oil was subjected to
flash chromatography (silica, 3:7 v/v ethyl acetate/hexane elution) to
give, after concentration of the relevant fractions (Rf = 0.4), 2,3-
diisopropoxy-4-methoxybenzaldehyde (16) (3.05 g, 73%) as a light-
yellow liquid [Found: (M + Na)+, 275.1259; C14H20NaO4 requires
275.1254]. 1H NMR (400 MHz, CDCl3) δ 10.21 (s, 1H), 7.54 (d, J =
8.8 Hz, 1H), 6.69 (d, J = 8.8 Hz, 1H), 4.75 (m, 1H), 4.38 (m, 1H),
3.84 (s, 3H), 1.22 (m, 12H); 13C NMR (100 MHz, CDCl3) δ 189.6,
159.8, 155.3, 139.7, 124.8, 123.5, 107.2, 75.9, 75.4, 56.1, 22.4, 22.2;
νmax (KBr) 2975, 2930, 2852, 1680, 1586, 1491, 1444, 1381, 1332,
1287, 1259, 1224, 1194, 1168, 1139, 1092, 1001, 965, 910, 810 cm−1;
MS (EI, 70 eV) m/z 252 (M+•, 33%), 168 (100), 167 (45), 122 (55).
Compound 17. A magnetically stirred solution of compound 16
(1.06 g, 4.41 mmol) in dichloromethane (100 mL) was cooled to 0 °C
and then treated sequentially with potassium hydrogen carbonate
Concentration of fraction A (Rf = 0.2) gave the starting phenol 12
(26 mg, 52% recovery) as a pale-cream solid that was in all respects
identical to an authentic sample.
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Article
(1.26 g, 12.6 mmol) and m-CPBA acid (4.12 g of ca. 77% peracid,
16.84 mmol). The ensuing mixture was allowed to warm to 18 °C and
then was stirred at this temperature for 16 h before being concentrated
under reduced pressure. The residue so obtained was dissolved in
methanol (100 mL), and the resulting solution was treated with
ammonium acetate (3.44 g, 44.7 mmol) and then stirred at 18 °C for
16 h. The ensuing mixture was diluted with water (100 mL) and then
extracted with diethyl ether (2 × 100 mL). The combined organic
phases were washed with water (1 × 100 mL) and brine (1 × 100 mL)
before being dried (MgSO4), filtered, and concentrated under reduced
pressure to afford 2,3-diisopropoxy-4-methoxyphenol (17) (980 mg,
93%) as a colorless crystalline solid, mp 28 °C (Rf = 0.5 in 7:3 v/v
hexane/ethyl acetate) [Found: (M + Na)+, 263.1256; C13H20NaO4
requires 263.1254]. 1H NMR (400 MHz, CDCl3) δ 6.59 (d, J =
8.8 Hz, 1H), 6.51 (d, J = 8.8 Hz, 1H), 5.39 (broad s, 1H), 4.74 (m,
1H), 4.41 (m, 1H), 3.76 (s, 3H), 1.24 (m, 12H); 13C NMR (100 MHz,
CDCl3) δ 147.8, 144.6, 140.4, 138.9, 108.1, 107.4, 75.4, 56.6, 22.7(3),
22.7(0) (one signal obscured or overlapping); νmax (KBr) 3529, 3457,
2975, 2933, 2835, 1490, 1467, 1382, 1372, 1332, 1268, 1182, 1159,
1108, 1089, 1035, 967, 901, 793, 738 cm−1; MS (ESI) m/z 263 [(M +
Na)+, 50%], 225 (100), 199 (95).
(30 mL of a 2 M aqueous solution) before being extracted using
diethyl ether (3 × 50 mL). The combined organic phases were washed
with water (1 × 20 mL) and brine (1 × 20 mL) and then dried
(MgSO4), filtered, and concentrated under reduced pressure. The
ensuing residue was subjected to flash chromatography (silica, 1:2 v/v
acetone/dichloromethane elution), and concentration of the relevant
fractions (Rf = 0.3 in 4:1 v/v ethyl acetate/hexane) afforded fraxetin
(2)9 (53 mg, 76%) as a light-yellow solid, mp 224−226 °C (lit.9
228 °C) [Found: (M + H)+, 209.0451; C10H9O5 requires 209.0445].
1H NMR (400 MHz, CD3OD) δ, see Table 2; 13C NMR (100 MHz,
CD3OD) δ, see Table 2; νmax (KBr) 3353, 1680, 1605, 1580, 1511,
1468, 1416, 1313, 1158, 1120, 1030 cm−1; MS (ESI) m/z 209 [(M +
H)+, 100%].
Compounds 21 and 22. A magnetically stirred solution of
fraxetin 2 (247 mg, 1.1 mmol,) in acetone (30 mL) maintained under
nitrogen at 18 °C was treated with triethylamine (330 μL, 2.37 mmol)
and 4-bromo-2-methyl-2-butene (280 μL, 2.37 mmol). The resulting
mixture was stirred at 18 °C for 24 h and then concentrated under re-
duced pressure. The ensuing residue was subjected to flash chro-
matography (silica, 1:2 v/v hexane/diethyl ether elution) to afford two
fractions, A and B.
Compound 18. A magnetically stirred solution of DCC (2.83 g,
13.7 mmol) in THF (40 mL) was cooled to 0 °C and then treated
with propiolic acid (962 mg, 13.7 mmol), and the resulting suspension
allowed to stand for 2 h. In a separate flask, a magnetically stirred
solution of phenol 17 (1.00 g, 5.43 mmol) in THF (50 mL) was
cooled to 0 °C, treated with NaH (183 mg of a 60% dispersion in min-
eral oil, 7.63 mmol), and also allowed to stand for 2 h. The solution so
formed was then added to the suspension in the first flask, and the
resulting mixture was stirred at 18 °C for 16 h and then concentrated
under reduced pressure. The resulting solid was treated with ace-
tonitrile (50 mL), and the suspension thus obtained was filtered and
concentrated under reduced pressure. Subjection of the resulting light-
yellow oil to flash chromatography (silica, 1:5 v/v mixture of diethyl
ether/hexane elution) afforded, after concentration of the relevant
fractions (Rf = 0.3), 2,3-diisopropoxy-4-methoxyphenyl propiolate
(18) (1.20 g, 98%) as a clear, colorless oil [Found: (M + H)+, 293.1389;
C16H21O5 requires 293.1384]. 1H NMR (400 MHz, CDCl3) δ 6.80 (d,
J = 8.8 Hz, 1H), 6.61 (d, J = 8.8 Hz, 1H), 4.53 (m, 1H), 4.45 (m, 1H),
3.82 (s, 3H), 3.03 (s, 1H), 1.27 (m, 12H); 13C NMR (100 MHz,
CDCl3) δ 153.1, 151.1, 144.3, 141.7, 138.1, 116.3, 106.2, 76.7, 76.2,
75.9, 74.5, 56.2, 22.7 (one signal obscured or overlapping); νmax (KBr)
2976, 2933, 2122, 1736, 1644, 1589, 1484, 1458, 1442, 1382, 1373,
1340, 1310, 1241, 1187, 1141, 1092, 1023, 969, 902, 791 cm−1; MS
(EI, 70 eV) m/z 292 (M+•, 40%), 208 (100), 193 (37), 165 (55), 156
(50), 155 (56).
Compound 19. A magnetically stirred solution of propiolate 18
(1.20 g, 4.11 mmol) in dichloromethane (50 mL) was treated with
Echavarren’s catalyst (95 mg, 0.12 mmol). The ensuing mix-
ture was stirred at 18 °C for 5 h and then filtered through a pad of
TLC silica gel, and the filtrate was concentrated under reduced pres-
sure. The resulting light-yellow oil was subjected to flash chroma-
tography (silica, 1:4 v/v diethyl ether/hexane elution) to afford, after
concentration of the relevant fractions (Rf = 0.1), 7,8-diisopropoxy-6-
methoxy-2H-chromen-2-one (19) (1.15 g, 96%) as a colorless crys-
talline solid, mp 97−98 °C [Found: (M + H)+, 293.1391; C16H21O5
requires 293.1384]. 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J =
8.8 Hz, 1H), 6.64 (s, 1H), 6.31 (d, J = 8.8 Hz, 1H), 4.62 (m, 2H), 3.86
(s, 3H), 1.33 (m, 12H); 13C NMR (100 MHz, CDCl3) δ 160.9, 151.2,
145.1, 144.1, 143.7, 140.2, 115.3, 114.5, 103.5, 76.6(0), 76.5(7), 56.4, 22.8
(one signal obscured or overlapping); νmax (KBr) 2968, 2928, 1701, 1604,
1562, 1484, 1453, 1434, 1409, 1381, 1371, 1347, 1290, 1237, 1197, 1161,
1125, 1105, 1082, 1040, 954, 922, 909, 866, 817 cm−1; MS (ESI) m/z 315
[(M + Na)+, 27%], 293 [(M + H)+, 58], 251 (100), 209 (98).
Concentration of fraction A (Rf = 0.3 in 1:2 v/v hexane/diethyl
ether) gave compound 21 (39 mg, 12%) as a light-yellow solid, mp
123−124 °C (lit.13 126.5 °C) (Found: M+•, 276.0997; C15H16O5 re-
quires 276.0993). 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 9.5 Hz,
1H), 6.65 (s, 1H), 6.26 (d, J = 9.5 Hz, 1H), 6.13 (s, 1H), 5.54 (t, J =
7.4 Hz, 1H), 4.80 (d, J = 7.4 Hz, 2H), 3.93 (s, 3H), 1.75 (s, 3H), 1.70
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.6, 144.6, 143.9, 143.3,
143.0, 140.7, 133.3, 119.4, 113.4, 111.2, 103.5, 70.4, 56.5, 25.9, 18.1; νmax
(KBr) 3262, 2968, 1689, 1567, 1498, 1455, 1411, 1320, 1245, 1190, 1155,
1121, 1087, 1019, 842 cm−1; MS (ESI) m/z 299 [(M + Na)+, 100%].
Concentration of fraction B (Rf = 0.3 in 1:2 v/v hexane/diethyl
ether) gave capensin (22) (130 mg, 40%) as a light-yellow solid, mp
132−133 °C (lit.13 135 °C) [Found: (M + H)+, 277.1077; C15H17O5
requires 277.1071]. 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J =
9.5 Hz, 1H), 6.49 (s, 1H), 6.34 (d, J = 9.5 Hz, 1H), 5.51 (t, J = 8.9 Hz,
1H), 4.69 (d, J = 7.5 Hz, 2H), 3.89 (s, 3H), 1.76 (s, 3H), 1.68 (s, 3H)
(one signal obscured or overlapping); 13C NMR (100 MHz, CDCl3) δ
160.3, 149.8, 143.6, 140.6, 138.1, 138.0, 137.8, 119.5, 115.4, 114.4,
100.1, 70.0, 56.2, 25.9, 18.0; νmax (KBr) 3324, 1702, 1571, 1494, 1414,
1302, 1152, 1117, 1076, 1032 cm−1.
Purpurasol (3). A solution of compound 22 (20 mg, 0.07 mmol)
in ethyl acetate (1 mL) was cooled to 0 °C and then treated with m-
CPBA acid (30 mg of ca. 77% material, 0.07 mmol). The ensuing mix-
ture was stirred at 18 °C for 48 h and then concentrated under re-
duced pressure. The residue thus obtained was dissolved in dichlo-
romethane (10 mL), and the resulting solution was washed with
sodium bicarbonate (1 × 10 mL of a saturated aqueous solution) and
water (1 × 10 mL) before being dried (MgSO4), filtered, and con-
centrated under reduced pressure to give purpurasol (3) (12 mg, 69%)
as a colorless crystalline solid, mp 145−147 °C (lit.13 148 °C) (Found:
1
M+•, 292.0948; C15H16O6 requires 292.0942). H NMR (400 MHz,
CDCl3) δ 7.59 (d, J = 9.6 Hz, 1H), 6.50 (s, 1H), 6.29 (d, J = 9.6 Hz,
1H), 4.64 (dd, J = 1.9 and 11.3 Hz, 1H), 4.11 (dd, J = 9.1 and 11.3 Hz,
1H), 3.97 (dd, J = 1.9 and 9.1 Hz, 1H), 3.91 (s, 3H), 2.73 (br s, 1H),
1.44 (s, 3H), 1.37 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.9,
145.8, 143.8, 139.0, 136.7. 132.4, 114.1, 111.6, 100.2, 79.1, 70.6, 65.6,
56.4, 26.0, 25.2; νmax (KBr) 3442, 2971, 1703, 1573, 1414, 1302, 1133,
1040, 954, 833, 731 cm−1; MS (EI, 70 eV) m/z 292 (M+•, 15%), 234
(15), 220 (40), 205 (100).
ASSOCIATED CONTENT
* Supporting Information
Crystallographic data (CIFs), anisotropic displacement ellip-
soid plots, and unit cell packing diagrams derived from the
■
S
Fraxetin (2). A magnetically stirred solution of coumarin 19
(210 mg, 0.72 mmol) in dry dichloromethane (20 mL) maintained
under nitrogen at 18 °C was treated dropwise with boron trichloride
(2.16 mL, 2.16 mmol). The ensuing mixture was stirred at 18 °C for
3 h and then poured into NaHCO3 (20 mL of a saturated aqueous
solution), and the separated aqueous phase was acidified with HCl
1
single-crystal analysis of compounds 8, 9, and 17 and H and
13C NMR spectra for compounds 1−3, 6−13, 15−19, 21, and
22. This material is available free of charge via the Internet at
http://pubs.acs.org.
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The Journal of Organic Chemistry
Article
(8) (a) Shimomura, H.; Sashida, Y.; Nakata, H.; Kawasaki, J.; Ito, Y.
Phytochemistry 1982, 21, 2213. (b) Desjardins, A. E.; Plattner, R. D.;
Spencer, G. F. Phytochemistry 1988, 27, 767. (c) Desjardins, A. E.;
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(10) (a) Yasuda, Y.; Fukui, M.; Nakazawa, T.; Hoshikawa, A.;
Ohsawa, K. J. Nat. Prod. 2006, 69, 755. (b) Venkateswarlu, K.;
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AUTHOR INFORMATION
Corresponding Author
*mgb@rsc.anu.edu.au
Notes
The authors declare no competing financial interest.
∥On leave from the Chemistry Department, Faculty of Science,
University of Sistan and Baluchestan, Zahedan, Iran.
■
ACKNOWLEDGMENTS
■
We thank the Australian Research Council and the Institute of
Advanced Studies for generous financial support. N.H. is grateful
to the Government of Iran for the financial support provided
during his sabbatical leave at the ANU. Ms. Amy Turnbull is
thanked for carrying out some preliminary experiments. The
authors are indebted to Dr. Brett Schwartz for much useful
advice.
Chim. Acta 2008, 91, 2081. (c) Ces
́
pedes, C. L.; Avila, J. G.; Martínez,
A.; Serrato, B.; Calderon-Mugica, J. C.; Salgado-Garciglia, R. J. Agric.
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