Total synthesis of enantiopure 1,3-dimethylpyranonaphthoquinones including ventiloquinones E, G, L and eleutherin

Article abstract of DOI:10.1039/b607366b

A new synthetic approach to enantiopure pyranonaphthoquinones is described. (S)-Mellein 10, prepared in 6 steps from (S)-propylene oxide 16, is converted stereospecifically to the (1R,3S)-dimethylpyran 15. The pyran 15 is then converted to the benzoquinone 14, which undergoes regiospecific Diels-Alder reactions with a variety of oxygenated butadienes to give pyranonaphthoquinones including ventiloquinones E, G, L, eleutherin and ent-deoxyquinone A. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b607366b

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Total synthesis of enantiopure 1,3-dimethylpyranonaphthoquinones including
ventiloquinones E, G, L and eleutherin
Leonie M. Tewierik,a Christian Dimitriadis,a Christopher D. Donner,*a,b Melvyn Gill†a and Brendan Willemsa
Received 24th May 2006, Accepted 28th June 2006
First published as an Advance Article on the web 31st July 2006
DOI: 10.1039/b607366b
A new synthetic approach to enantiopure pyranonaphthoquinones is described. (S)-Mellein 10,
prepared in 6 steps from (S)-propylene oxide 16, is converted stereospecifically to the
(1R,3S)-dimethylpyran 15. The pyran 15 is then converted to the benzoquinone 14, which undergoes
regiospecific Diels–Alder reactions with a variety of oxygenated butadienes to give
pyranonaphthoquinones including ventiloquinones E, G, L, eleutherin and ent-deoxyquinone A.
as natural products.1 Examples include the ventiloquinone fam-
ily of which there are 15 members. Amongst this group are
Introduction
Pyranonaphthoquinones are widespread in nature having been
ventiloquinones E 2 and G 6 isolated from the plant Ventilago
isolated from plant, insect, bacterial and fungal sources.1 Members
of this family of compounds display a range of biological activities2
and have also been proposed to act as bioreductive alkylating
agents.3 This has stimulated considerable effort towards their total
synthesis.4 One of the simplest members of this group is eleutherin
1, a topoisomerase II inhibitor5 first isolated from the bulbs of
Eleutherine bulbosa (Iradaceae).6 Eleutherin 1 has been the subject
of total synthesis a number of times, but only in racemic form.4
maderaspatana7 and ventiloquinone L 8 from V. goughii.8
A
number of racemic syntheses of members of the ventiloquinone
group have been reported.4,9 A rare example of the total synthesis
of 1,3-dimethylpyranoquinones in enantiopure form has been
reported by Giles10 and involved the synthesis of all 8 stereoisomers
of quinone A 9, a natural derivative of the aphid insect pigments.11
Herein we wish to report full details12 of our approach to
pyranoquinones that makes available enantiopure ventiloquinones
E 2, G 6, L 8, eleutherin 1 and related pyranoquinones.
Results and discussion
We have previously reported the synthesis of both enantiomers
of the natural product mellein 10 beginning from the appro-
priate stereoisomer of propylene oxide.13 We have since used
(S)-mellein 10 as an intermediate in the first total synthesis
of the fungal pigment (1R,3S)-thysanone 1114 and felt that
this methodology could be extended to the synthesis of 1,3-
dimethylpyranonaphthoquinones in enantiopure form.
Our planned approach to pyranonaphthoquinones is shown
retrosynthetically in Scheme 1. Thus, quinones of the type
12 with variously substituted aromatic rings may be formed
by Diels–Alder cycloaddition between appropriately oxygenated
butadienes 13 and the benzoquinone 14, which itself may be
available from the dimethylpyran 15. The key dimethylpyran 15
should be available from (S)-mellein 10 by use of the method
by Kraus et al.,15 which involves introduction of the alkyl group
at C-1 followed by stereospecific reduction with hydride. In
order to pursue this method, quantities of (S)-mellein 10 were
firstly prepared from ethyl (S)-lactate 17 via (S)-propylene oxide
16 according to the method we have described earlier.13 The
spectroscopic data, including specific rotation, for (S)-mellein
Numerous other 1,3-dimethylpyranoquinones possessing a va-
riety of oxygenation patterns in the quinone moiety are known
aSchool of Chemistry, University of Melbourne, Victoria, Australia 3010
bBio21 Molecular Science and Biotechnology Institute, University of
Melbourne, Victoria, Australia 3010. E-mail: cdonner@unimelb.edu.au;
Fax: +61 3 9347 8189; Tel: +61 3 8344 2411
† In memoriam of Dr Melvyn Gill, under whose guidance this work was
undertaken.
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stereochemistry at C-1 as (R) since we know the stereochemistry
at C-3 is (S) since it originates from (S)-propylene oxide 16.
Bromination of the benzopyran 15 with N-bromosuccinimide
(2 equivalents) in N,N-dimethylformamide gave, upon crystalliza-
tion of the crude material, (1R,3S)-dibromobenzopyran 18 for
the first time as fine colourless needles in 82% yield and with
22
[a]D +155. The incorporation of two bromine atoms into the
molecule was confirmed by the presence of a proton singlet (d 7.55)
in the 1H NMR spectrum and in the mass spectrum, a molecular
ion measured at m/z 334.9291 for the pseudomolecular ion {[M +
H]+, 79Br2}. Oxidation was effected by adding an aqueous solution
of cerium(IV) ammonium nitrate to the dibromobenzopyran 18
in acetonitrile to give the (1R,3S)-benzoquinone 14 as a yellow
solid in 86% yield. The benzoquinone 14 has the potential to act
as a versatile dienophile in Diels–Alder reactions. This ability is
demonstrated by the successful reaction of benzoquinone 14 with
a range of oxygenated butadienes as summarised in Scheme 3.
Firstly, the (1R,3S)-benzoquinone 14 was exposed to 1-
methoxy-1-trimethylsiloxybuta-1,3-diene 22 in benzene at room
temperature. After filtration through silica, chromatographic
purification gave a single product as yellow needles. This pig-
ment exhibited a strong positive optical rotation measurement,
Scheme 1
obtained in this way were consistent with those described in the
literature.13,16
The lactone 10 was treated with methyllithium in tetrahydro-
◦
furan at −78 C according to the method of Kraus et al.15 The
intermediate addition product was isolated and exposed immedi-
ately to trifluoroacetic acid and triethylsilane in dichloromethane
at −80 ◦C (Scheme 2). The required 1,3-dimethylpyran 15 was
isolated in yields as high as 83%, over 2 steps, after hydrolysis of a
silylated derivative. However, inconsistent yields were obtained us-
ing this method. Reproducible results were obtained by treatment
of the lactone 10 with methyl magnesium bromide in ether at 0 ◦C
followed by reduction with trifluoroacetic acid and triethylsilane
as before.15 Thus, the ether 15 was isolated as colourless plates
21
[a]D +190, and a high resolution mass measurement on the
pseudomolecular ion {[M − H]−} led to the molecular formula
C15H14O4. Signals in the 1H NMR spectrum include a sharp singlet
at d 12.01 due to a chelated hydroxyl proton, a set of 3 contiguous
aromatic protons at d 7.63 (dd, J 7.6 and 1.5 Hz), 7.60 (dd, J
8.0 and 7.6 Hz) and 7.24 (dd, J 8.0 and 1.5 Hz) and a set of
signals with chemical shifts and coupling constants17 consistent
with the presence of a 1,3-diequatorial substituted pyran ring
(Experimental). These data were consistent with the structure
19, however, the naphthoquinone 19 was obtained in a moderate
10% yield. Treatment of the benzoquinone 14 with 1-methoxy-1,3-
cyclohexadiene 23 in benzene, followed by pyrolysis, proceeded
only slightly more readily to give eleutherin 1 as yellow needles
(mp 140–145 ◦C) in 13% yield. The EI mass spectrum for this
product exhibited a molecular ion at m/z 272 consistent with
26
with [a]D +206 in 92% yield from 10.
1
the formula C16H16O4, whilst the H NMR spectrum includes 3
aromatic proton signals and a methoxy signal (Table 1). All other
spectroscopic data for the synthetic material 1 (Experimental) is
in complete accord with the assigned structure.
The spectroscopic data for synthetic eleutherin 1 also agrees
closely with those reported for the natural product (Table 1)17 as
well as those recorded using an authentic sample of eleutherin
1. Significantly, the optical rotation measurement of synthetic
Scheme 2 Reagents and conditions: (a) MeLi, THF, −80 ◦C, 3 h; or
MeMgBr, ether, 0 ◦C → rt, 1 h; (b) Et3SiH, CF3CO2H, CH2Cl2, −80 ◦C →
rt, 2 h; (c) NBS (2 eq.), DMF, rt, 18 h; (d) CAN, MeCN, H2O, rt, 20 min.
22
eleutherin 1 {[a]D +291} agrees well with that recorded for
The 1,3-diequatorial disposition of the methyl groups in the
pyran 15 was established by analysis of the chemical shifts
of the 1-H and 3-H methine protons. Previous studies17 have
natural eleutherin 1 {[a]D15 +346} from Eleutherine bulbosa.6 This
agreement is consistent with the absolute configuration of the
synthetic compound 1 being (1R,3S) as expected from its synthesis
from ethyl (S)-lactate 17. The absolute configuration of eleutherin
1 is known to be (1R,3S) by the chemical degradation of the
natural product and comparison with 3-hydroxybutyric acid.18
Many racemic, but not enantiopure, syntheses of eleutherin 1 have
been reported,4 this is the first synthesis of enantiomerically pure
eleutherin 1.
1
ascertained that there are significant differences in the H NMR
spectra of cis-1,3-dimethyl (diequatorial) versus trans-1,3-dimethyl
(axial/equatorial) 3,4-dihydropyrans. It is consistently observed
that 1-H and 3-H are deshielded for trans-isomers relative to their
cis counterpart. Particularly diagnostic is the signal associated
with 3-H that, although pseudo axial in both cis- and trans-
isomers, resonates at <d 3.75 for cis-isomers and >d 3.95 for
trans-isomers. For benzopyran 15 the 1-H (d 5.07) and 3-H (d
The bromoquinone 14 was then reacted with 1-methoxy-3-
trimethylsiloxybuta-1,3-diene 24 in dry benzene at 60 ◦C for
24 hours. Preparative thin layer chromatography gave a single
bright yellow compound that was purified by gel filtration. The
1
3.71) signals in the H NMR spectrum are consistent with a cis-
1,3-dimethyl arrangement. Thus, we can confidently assign the
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Scheme 3 Reagents and conditions: (a) 22, benzene, rt, 3.5 h (for 19); (i) 23, benzene, 80 ◦C, 1 h; (ii) CH2Cl2, NEt3, rt, 18 h; (iii) 150 ◦C, 30 min (for 1);
(b) 24, benzene, 60 ◦C, 24 h; (c) 25, benzene, 60 ◦C, 100 min (for 8); 26, benzene, rt, 18 h (for 21); (d) 27, benzene, rt, 18 h.
Table 1 1H NMR data [d, multiplicity and coupling constants (Hz)] for synthetic and naturally occurring eleutherin 1 and ventiloquinone L 8 in CDCl3
Proton(s)
Synthetic eleutherin 1a
Natural eleutherin 1b
Synthetic ventiloquinone L 8a
Natural ventiloquinone L 8b
1-H
3-H
4-Hax
4-Heq
6-H
7-H
8-H
1-Me
3-Me
7-OMe
9-OH
9-OMe
4.85 (m)
3.58 (m)
4.85 (m)
3.58 (m)
2.19 (ddd, J 18, 10, 4)
2.75 (dt, J 18, 2.5)
7.72 (m)
7.63 (m)
7.27 (m)
1.53 (d, J 6.5)
1.36 (d, J 6)
—
4.82 (ddq, J 3.9, 2.6, 6.6)
3.57 (ddq, J 10.2, 2.6, 6.4)
2.22 (ddd, J 18.6, 10.2, 3.9)
2.73 (dt, J 18.6, 2.6)
7.15 (d, J 2.4)
—
6.61 (d, J 2.4)
1.57 (d, J 6.6)
1.36 (d, J 6.4)
3.89 (s)
4.81 (ddq, J 3.9, 2.6, 6.6)
3.57 (ddq, J 10.2, 2.6, 6.6)
2.22 (ddd, J 18.0, 10.2, 3.9)
2.73 (dt, J 18.0, 2.6)
7.15 (d, J 2.6)
—
6.61 (d, J 2.6)
1.57 (d, J 6.6)
1.35 (d, J 6.6)
3.88 (s)
2.20 (ddd, J 18.3, 10.3, 3.7)
2.75 (dt, J 18.3, 2.7)
7.73 (d, J 7.8)
7.64 (dd, J 8.5, 7.8)
7.27 (d, J 8.5)
1.53 (d, J 6.6)
1.36 (d, J 6.3)
—
—
3.99 (s)
—
3.99 (s)
12.25 (s)
—
12.22 (s)
—
a Synthetic eleutherin 1 and ventiloquinone L 8 recorded at 400 MHz. b Natural eleutherin 117 and ventiloquinone L 88 recorded at 300 MHz and 360 MHz,
respectively.
product (1R,3S)-7-hydroxynaphthoquinone 20 was isolated as a
yellow solid with [a]D15 +290 in 49% yield. The 1H NMR spectrum
of 20 includes three aromatic proton signals at d 7.98 (d, J 8.4 Hz),
d 7.50 (d, J 2.6 Hz) and d 7.14 (dd, J 8.4 and 2.6 Hz), consistent
with the substitution pattern in 20.
To the bromoquinone 14 dissolved in benzene was added 1-
methoxy-1,3-bis(trimethylsiloxy)buta-1,3-diene 26. After stirring
overnight, silica was added and the suspension was purified to
give a single product as yellow needles. A high resolution mass
measurement on the molecular ion at m/z 274 led to the formula
C15H14O5. The 1H NMR indicated the presence of a chelated
hydroxy proton (d 12.19) as well as a free phenolic proton (d
7.09), a pair of meta-coupled aromatic protons (d 7.15 and 6.62,
J 1.8 Hz) and a set of signals consistent with the presence of
an intact 1,3-dimethyl substituted pyran ring. Combining all of
the spectroscopic data leads to the new structure (1R,3S)-7,9-
dihydroxynaphthoquinone 21, which was isolated in 24% yield.
This pigment 21 is not itself found in nature but its C-3 epimer
(1R,3R)-deoxyquinone A 28 is known as a degradation product
of deoxyprotoaphin 29.20
The next diene to be pursued, 1,3-dimethoxy-1-trimethyl-
siloxybuta-1,3-diene 25, was introduced to a solution of the
bromoquinone 14 in dry benzene and heated at 60 ◦C for
100 minutes. A small amount of silica was added to the solution to
ensure complete aromatization. After chromatographic purifica-
tion the product was isolated as orange needles in 41% yield with
26
[a]D +420. The EI mass spectrum for the product exhibited a
molecular ion at m/z 288, a high resolution mass measurement of
which gave the molecular formula C16H16O5. The pigment was
identified as (1R,3S)-ventiloquinone L 8 by inspection of the
spectroscopic data (Table 1 and Experimental). Comparison of the
spectroscopic data for synthetic ventiloquinone L 8 with the corre-
sponding data recorded for naturally occurring ventiloquinone L
8 (Table 1 and [a]D30 +387)8 establishes the identity of the synthetic
and natural materials. Although racemic ventiloquinone L 8
has been synthesized previously,9a,19 this is the first synthesis in
enantiopure form and establishes unequivocally for the first time
the (1R,3S) absolute stereochemistry of the natural product 8.
Epimerisation of the C-1 methyl group in quinone 21 was
achieved using boron tribromide7 and gave the trans-pyran 30 as an
18
orange solid with [a]D −210, albeit in low (11%) yield. Full details
of the optical rotation measurement of the (1R,3R)-compound 28
have not been reported, it has been noted however that the 7,9-
dimethyl ether of 28 is dextrorotatory.19 As noted earlier, Giles has
prepared all 8 stereoisomers of quinone A 9, also using lactate
from the chiral pool as a source of asymmetry.10 The method
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described here provides a distinctly different approach for the
construction of the pyran ring in quinones such as 21.
6-hydroxy-7-methoxyeleutherin 5, is a constituent of Karwinskia
humboldtiana.23 The fact that the 1H NMR data for the dimethyl
ethers 3 and 4 are distinctly different from the spectrum of
the isomer 5,23 excludes 5 from the possible products from the
reaction of diene 27 and reduced the structural possibilities of
the final two yellow quinones to 3 and 4. The isomers 3 and
1
4 could be differentiated by the observation that the H NMR
spectrum of 3 contains two methoxy singlets and a non-chelated
hydroxy resonance (d 6.68), while the spectrum of 4 exhibits
two methoxy singlets and one strongly chelated phenolic hydroxy
resonance (d 13.04). This reaction provides three natural products,
the ventiloquinones E 2, G 6 and L 8, in one pot, albeit in low
yield. This is the first report of the enantiopure synthesis of these
natural products.
Conclusions
The chemistry described here demonstrates a versatile new
route to enantiopure 1,3-dimethylpyranonaphthoquinones. The
synthetic method has led to the first total synthesis of a variety
of pyranonaphthoquinones including ventiloquinones E 2, G
6, L 8 and eleutherin 1 unequivocally establishing the absolute
stereochemistry of these natural products. The method contains
further versatility when it is recognized that the C-3 alkyl group is
dependent on the choice of chiral oxirane starting material and the
C-1 substituent derives from the choice of organometallic reagent,
providing the ability to incorporate numerous different functional
groups at C-1 and C-3. The realization of this potential will be
reported in due course.
The next diene to be combined with the bromoquinone 14 was
the more highly oxygenated butadiene 27 (Scheme 3). Thus, to
the bromoquinone 14 in benzene was added 1,3,4-trimethoxy-1-
trimethylsiloxybuta-1,3-diene27 and after stirring at room temper-
ature overnight silica was added and the dark orange suspension
was filtered through a short silica pad and an orange band was
collected. Chromatographic analysis revealed the presence in this
mixture of at least 6 pigments that were separated and each purified
by extensive chromatography. The first compound was obtained
only in trace amounts and was identified as ventiloquinone L
8. The pigment was found to be chromatographically, physically
and spectroscopically indistinguishable from the sample described
earlier.
Experimental
Melting points were determined on a hot-stage apparatus and
are uncorrected. Infrared (IR) spectra were recorded using a
Perkin-Elmer 983 G spectrophotometer for samples as potassium
bromide discs. Electronic spectra were recorded on a Shimadzu
UV-2401PC spectrophotometer using either ethanol or methanol
solutions in a 10 mm quartz cell. NMR spectra were recorded with
JEOL JNM-GX-400 and Varian Unity 400 spectrometers (1H at
400 MHz and 13C at 100 MHz) for solutions in CDCl3 unless stated
otherwise. Chemical shifts are relative to tetramethylsilane with J
values given in Hz. Mass spectra were recorded on a Shimadzu
GCMS-QP505A spectrometer at 70 eV [probe; electron ionisation
(EI)] and a Micromass QUATTRO II [electrospray ionisation
(ESI)]. Specific rotations were measured using a JASCO DIP-
1000 polarimeter and are given in units of 10−1 deg cm2 g−1.
Thin-layer chromatography (TLC) and preparative TLC (PLC)
were performed on Merck pre-coated silica gel 60 F254 and Merck
Kieselgel 60 GF254 (20 g silica gel spread on 20 × 20 cm glass
plates), respectively. Visualisation was under ultraviolet (UV) light
(254 or 366 nm).
The next two quinone products, 6 and 7, were identified as
naphthazarin derivatives from the UV–vis spectra that exhibited
long wavelength absorption at 519 and 553 nm and 502 and
535 nm, respectively.21 The 1H NMR data from quinone 6 reveal
the presence of an isolated quinonoid proton, one non-chelated
and two chelated hydroxy protons and a set of methyl, methylene
and methine protons consistent with the dimethylpyran ring
system (Experimental). That the quinone 6 exists predominantly
in the tautomeric form shown follows from the characteristic shift
of the quinone proton (d 6.35).22 The quinone 6 proved identical
in all respects, including the sign of the specific rotation, with
ventiloquinone G 6 isolated from Ventilago maderaspatana.7 The
second red quinone was identified as the 7-O-methyl ether 7 of
ventiloquinone G 6 from the spectroscopic data, principally by
1
comparison of the H NMR spectrum of the entirely synthetic
material with that of the naturally derived material.7
The remaining three orange/yellow quinones were identified
as ventiloquinone E 2 and its isomeric 7- and 9-desmethyl ethers
1
3 and 4, respectively, from the H NMR data (Experimental).
(1R,3S)-8-Hydroxy-1,3-dimethyl-3,4-dihydro-1H-2-benzopyran
15
Ventiloquinone E 2 occurs along with several other quinones
in the root bark of Ventilago maderaspatana.7 Comparison of
the 1H NMR spectra of the synthetic and natural products
established the identity of the two. The 7- and 9-desmethyl
derivatives 3 and 4, respectively, of ventiloquinone E 2, are
not themselves natural products but their structural isomer,
To a solution of (S)-mellein 10 (502 mg, 2.8 mmol) in anhydrous
ether (15 mL) at 0 ◦C was added methylmagnesium bromide (2 M
in ether, 5 mL, 10 mmol) dropwise over 5 min. The mixture
was stirred for 30 min at 0 ◦C, then for a further 60 min at
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room temperature. The reaction was quenched with sat. aq.
ammonium chloride and the mixture was extracted with ether
(3 × 30 mL). The combined extracts were dried (MgSO4) and
concentrated under reduced pressure to give a colourless solid
that was dissolved in dichloromethane (10 mL) and cooled to
−80 ◦C. Trifluoroacetic acid (0.65 mL, 8.4 mmol) and then
triethylsilane (1.4 mL, 8.8 mmol) were added dropwise and the
resulting solution was stirred for 30 min followed by warming to
room temperature over 90 min. The solution was concentrated
under reduced pressure, then treated overnight in a mixture of
tetrahydrofuran (5 mL), acetic acid (10 mL) and water (5 mL).
The solution was neutralized with sat. aq. sodium bicarbonate
and extracted with ether (3 × 30 mL). The combined ethereal
extracts were washed with sat. aq. sodium bicarbonate (20 mL),
dried (MgSO4) and concentrated under reduced pressure. Column
chromatography (dichloromethane then ether) gave (1R,3S)-
dimethylpyran 15 (464 mg, 92%), as colourless plates, mp 166–
169 ◦C (ether–hexanes) (subl., ◦morphological changes at 110 ◦C)
0.100, CHCl3); found: C, 74.0; H, 7.8%; [M + Na]+, 201.0893.
C11H14O2 requires: C, 74.1; H, 7.9%; [M + Na]+, 201.0891; mmax
(KBr) 3248, 2970, 2935 and 2851 cm−1; dH(400 MHz) 1.35 (3H, d,
J 6.0, 3-Me), 1.61 (3H, d, J 6.3, 1-Me), 2.59 (1H, dd, J 15.6 and
2.0, 4-Hax), 2.71 (1H, dd, J 15.6 and 10.6, 4-Heq), 3.71 (1H, ddq, J
10.6, 2.0 and 6.0, 3-H), 5.07 (1H, br q, J 6.3, 1-H), 5.12 (1H, br s,
8-OH), 6.57 (1H, d, J 8.0, 7/5-H), 6.68 (1H, d, J 7.7, 5/7-H) and
7.02 (1H, t, J 7.8, 6-H). dC(100 MHz) 21.47, 21.53, 37.2, 69.7, 70.8,
113.2, 121.0, 126.1, 126.8, 136.8 and 152.1; m/z (EI) 178 {[M]+,
4}, 163 (100), 145 (26) and 91 (20).
benzopyran 18 (53 mg, 0.16 mmol) in acetonitrile (7 mL). After
stirring for 20 min the solution was poured into water (20 mL)
and extracted with chloroform (3 × 20 mL). The combined
organic extracts were washed with water (3 × 30 mL), dried
(MgSO4) and concentrated under reduced pressure. The resultant
oil was purified by gel filtration (Sephadex LH20, methanol–
dichloromethane, 1 : 1) to give (1R,3S)-benzoquinone 14 (37 mg,
86%), as a yellow solid, which was used immediately and without
further purification; dH(400 MHz) 1.33 (3H, d, J 6.1, 3-Me), 1.49
(3H, d, J 6.6, 1-Me), 2.16 (1H, ddd, J 18.8, 10.0 and 4.2, 4-Hax),
2.60 (1H, dt, J 18.8 and 2.6, 4-Heq), 3.55 (1H, ddq, J 10.0, 2.6 and
6.1, 3-H), 4.70 (1H, ddq, J 4.2, 2.6 and 6.6, 1-H) and 7.25 (1H, s,
6-H).
(1R,3S)-9-Hydroxy-1,3-dimethyl-3,4,5,10-tetrahydro-1H-
naphtho[2,3-c]pyran-5,10-dione 19
A
solution of 1-methoxy-1-trimethylsiloxybuta-1,3-diene 22
26
(lit.15b mp [( )-form] 111–112 C, ether–hexanes); [a]D +206 (c
(42 mg, 0.24 mmol) in benzene (2 mL) was added dropwise to
a solution of the (1R,3S)-benzoquinone 14 (22 mg, 0.081 mmol)
in benzene (2 mL). The reaction was stirred at room temperature
for 3.5 h, silica gel (1.0 g) was added and the solvent was evaporated
at reduced pressure. Column chromatography (dichloromethane–
1% formic acid) and gel filtration (Sephadex LH20, methanol–
dichloromethane, 1 : 1) gave (1R,3S)-naphthoquinone 19 as yellow
◦
21
microneedles (2 mg, 10%), mp 83–86 C (MeOH); [a]D +190 (c
0.030, CHCl3); CD kextrema(MeOH) 256 (De +0.55), 283 (+3.03),
340 (+1.17), 437 (−0.59) and 482 nm (−0.15); found: [M − H]−,
257.0818. C15H14O4 requires: [M − H]−, 257.0814; kmax(MeOH) 212
(log e 4.25), 246 (3.72), 273 (3.76) and 417 nm (3.27); dH(400 MHz)
1.37 (3H, d, J 6.3, 3-Me), 1.58 (3H, d, J 6.6, 1-Me), 2.24 (1H, ddd,
J 18.8, 10.0 and 3.9, 4-Hax), 2.74 (1H, dt, J 18.8 and 2.5, 4-Heq),
3.59 (1H, ddq, J 10.0, 2.5 and 6.3, 3-H), 4.85 (1H, ddq, J 3.9, 2.5
and 6.6, 1-H), 7.24 (1H, dd, J 8.0 and 1.5, 8-H), 7.60 (1H, dd, J 8.0
and 7.6, 7-H), 7.63 (1H, dd, J 7.6 and 1.5, 6-H) and 12.01 (1H, s,
9-OH); m/z (EI) 258 {[M]+, 7}, 115 (26), 92 (28), 77 (24), 71 (24),
69 (40), 67 (27), 65 (34), 64 (24), 63 (52), 57 (99), 56 (33), 55 (100),
53 (30) and 51 (38); m/z (ESI–) 257.0 [M − H]−.
(1R,3S)-5,7-Dibromo-8-hydroxy-1,3-dimethyl-3,4-dihydro-1H-2-
benzopyran 18
To a solution of (1R,3S)-benzopyran 15 (144 mg, 0.81 mmol)
in dimethylformamide (10 mL) was added N-bromosuccinimide
(288 mg, 1.62 mmol). The solution was stirred at room temperature
in the dark for 18 h. After dilution with water (50 mL), the
solution was extracted with dichloromethane (3 × 20 mL) and
the combined organic extracts were washed with water (4 ×
20 mL), dried (MgSO4) and concentrated under reduced pressure.
Crystallization from dichloromethane–hexanes gave (1R,3S)-
dibromobenzopyran 18 (223 mg, 82%) as colourless needles, mp
(1R,3S)-9-Methoxy-1,3-dimethyl-3,4,5,10-tetrahydro-1H-
naphtho[2,3-c]pyran-5,10-dione (eleutherin) 1
153–155 ◦C; [a]D +155 (c 1.00, CHCl3); found: C, 39.3; H, 3.6%;
To a solution of (1R,3S)-benzoquinone 14 (55 mg, 0.20 mmol)
in benzene (1 mL) was added 1-methoxy-1,3-cyclohexadiene 23
(69 mg, 0.63 mmol) and the mixture was heated at reflux for
1 h. After removal of the solvent under reduced pressure, the
residual oil was dissolved in dichloromethane (2 mL), triethy-
lamine (0.2 mL) was added and the mixture stirred at room
temperature overnight. The solution was washed with 1 M HCl
(2 × 1 mL), dried (MgSO4) and concentrated under reduced
pressure. The crude adduct was heated at 150 ◦C for 30 min and,
after cooling, the residual oil was purified by preparative thin layer
chromatography (dichloromethane–ethyl acetate 95 : 5) followed
by gel filtration (Sephadex LH20, methanol–dichloromethane, 1 :
1) and crystallization from methanol to give eleutherin 1 as yellow
needles (7 mg, 13%), mp 140–145 ◦C (lit.6 mp 175 ◦C); [a]D22 +291
(c 0.10, CHCl3) {lit.6 [a]D15 +346 (c 1.01, CHCl3)}; mmax (KBr) 3055,
2985, 1699, 1660 and 1587 cm−1; kmax(MeOH) 245 (log e 4.18), 272
(3.94), 348 (3.47) and 391 nm (3.45); dH(400 MHz) 1.36 (3H, d, J
22
{[M + H]+, 79Br2}, 334.9291; {[M]+, 79Br2}, 333.9193. C11H12O2Br2
requires: C, 39.3; H, 3.6%; {[M + H]+, 79Br2}, 334.9283; {[M]+,
79Br2}, 333.9205; mmax (KBr) 3409, 3078, 2977, 2928 and 2843 cm−1;
dH(400 MHz) 1.37 (3H, d, J 6.3, 3-Me), 1.57 (3H, d, J 6.3, 1-Me),
2.43 (1H, ddd, J 16.6, 10.7 and 1.5, 4-Hax), 2.72 (1H, br d, J 16.6,
4-Heq), 3.61 (1H, ddq, J 10.7, 2.3 and 6.3, 3-H), 4.98 (1H, br q, J
6.3, 1-H), 5.60 (1H, s, 8-OH) and 7.55 (1H, s, 6-H); dC(100 MHz)
21.0, 21.4, 37.6, 69.3, 71.1, 108.5, 115.1, 129.7, 131.8, 135.9 and
147.7; m/z (EI) 336 {[M]+, 21}, 323 (51), 321 (100), 319 (50), 292
(36), 224 (24), 222 (24), 132 (34), 131 (26) and 77 (31).
(1R,3S)-7-Bromo-1,3-dimethyl-3,4-dihydro-1H-2-benzopyran-5,8-
dione 14
A solution of cerium(IV) ammonium nitrate (268 mg, 0.49 mmol)
in water (7 mL) was added dropwise to (1R,3S)-dibromo-
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6.3, 3-Me), 1.53 (3H, d, J 6.6, 1-Me), 2.20 (1H, ddd, J 18.3, 10.3
and 3.7, 4-Hax), 2.75 (1H, dt, J 18.3 and 2.7, 4-Heq), 3.58 (1H, m,
3-H), 3.99 (3H, s, 9-OMe), 4.85 (1H, m, 1-H), 7.27 (1H, d, J 8.5,
8-H), 7.64 (1H, dd, J 8.5 and 7.8, 7-H) and 7.73 (1H, d, J 7.8,
6-H); dC(100 MHz) 20.8, 21.2, 29.9, 56.5, 68.7, 70.3, 117.7, 119.0,
120.3, 134.0, 134.6, 139.9, 148.7, 159.4, 183.8 and 184.1; m/z (EI)
272 {[M]+, 17}, 257 (30), 76 (25), 45 (35), 44 (21), 43 (100) and 41
(22).
10.2, 2.6 and 6.4, 3-H), 3.89 (3H, s, 7-OMe), 4.82 (1H, ddq, J 3.9,
2.6 and 6.6, 1-H), 6.61 and 7.15 (each 1H, d, J 2.4, 6-H and 8-H)
and 12.25 (1H, s, 9-OH); dC(100 MHz) 21.19, 21.20, 30.6, 56.0,
68.6, 69.8, 106.2, 107.6, 109.6, 133.3, 143.2, 146.7, 164.3, 165.8,
183.1 and 187.5; m/z (EI) 288 {[M]+, 100}, 273 (55), 259 (30), 255
(20), 244 (20) and 69 (29).
(1R,3S)-7,9-Dihydroxy-1,3-dimethyl-3,4,5,10-tetrahydro-1H-
naphtho[2,3-c]pyran-5,10-dione (3-epi-4-deoxyquinone A) 21
(1R,3S)-7-Hydroxy-1,3-dimethyl-3,4,5,10-tetrahydro-1H-
naphtho[2,3-c]pyran-5,10-dione 20
To
a
solution of (1R,3S)-benzoquinone 14 (140 mg,
0.52 mmol) in benzene (5 mL) was added 1-methoxy-1,3-
bis(trimethylsiloxy)buta-1,3-diene 26 (900 mg, 3.46 mmol) in
benzene (3 mL) and the reaction mixture was stirred at room
temperature overnight. Silica (1.0 g) was added and the suspension
was stirred for 18 h. The suspension was concentrated under
reduced pressure and column chromatography (ethyl acetate then
ethyl acetate–1% formic acid) gave a yellow band that was collected
and concentrated under reduced pressure. The residual oil was
dissolved in dichloromethane (20 mL) and washed sequentially
with sodium bicarbonate (3 × 20 mL) and 3.0 M sodium hydroxide
(3 × 20 mL). The combined basic extracts were acidified with
conc. hydrochloric acid and extracted with dichloromethane (3 ×
20 mL). Drying (MgSO4) and concentration of the solution
gave an oil that was purified by column chromatography (light
petroleum → ethyl acetate) to give 3-epi-4-deoxyquinone A 21 as
yellow needles (34 mg, 24%), mp 127–129 ◦C (dichloromethane–
light petroleum); [a]D23 +526 (c 0.050, CHCl3); CD kextrema(MeOH)
240 (De +1.98), 262 (+0.38), 297 (+5.46), 410 (−0.26) and 452 nm
(+0.57); found: [M]+, 274.0834. C15H14O5 requires: [M]+, 274.0841;
mmax (KBr) 3414, 2978, 2936, 2901, 2873, 2855, 1637 and 1609 cm−1;
kmax(CHCl3) 270 (log e 4.16), 288 (3.97) and 433 nm (3.57);
dH(400 MHz) 1.37 (3H, d, J 6.1, 3-Me), 1.58 (3H, d, J 6.6, 1-
Me), 2.24 (1H, ddd, J 18.6, 10.0 and 3.9, 4-Hax), 2.72 (1H, dt, J
18.6 and 2.5, 4-Heq), 3.60 (1H, ddq, J 10.0, 2.5 and 6.1, 3-H), 4.84
(1H, ddq, J 3.9, 2.5 and 6.6, 1-H), 7.09 (1H, br s, 7-OH), 6.62 and
7.15 (each 1H, d, J 1.8, 6-H and 8-H) and 12.19 (1H, s, 9-OH);
dC(100 MHz) 21.1, 21.2, 30.5, 68.7, 69.9, 108.3, 108.6, 109.7, 133.5,
142.9, 147.1, 162.7, 164.3, 183.5 and 187.3; m/z (EI) 274 {[M]+,
100}, 259 (59), 245 (38), 241 (24), 231 (26), 230 (30), 229 (21), 213
(22), 137 (21), 69 (43) and 51 (28).
To a solution of (1R,3S)-benzoquinone 14 (32 mg, 0.12 mmol) in
dry benzene (2 mL) was added 1-methoxy-3-trimethylsiloxybuta-
1,3-diene 24 (41 mg, 0.24 mmol). The mixture was stirred at
60 ◦C for 24 h, concentrated and purified by preparative thin
layer chromatography (toluene–ethyl formate–formic acid, 50 :
49 : 1) followed by gel filtration (Sephadex LH20, methanol–
dichloromethane, 1 : 1) to give (1R,3S)-7-hydroxynaphthoquinone
20 (15 mg, 49%), isolated as a yellow solid, mp 228 ◦C (dec.)
15
(MeOH); [a]D +290 (c 0.050, EtOH); CD kextrema(MeOH) 270
(De +0.25), 285 (+7.36), 375 (+0.51), 428 (−0.68) and 482 nm
(+0.02); found: [M − H]−, 257.0812. C15H14O4 requires: [M − H]−,
257.0814; kmax(MeOH) 208 (log e 4.20), 266 (4.16) and 395 nm
(3.05); dH(400 MHz) 1.37 (3H, d, J 6.2, 3-Me), 1.55 (3H, d, J 6.6,
1-Me), 2.25 (1H, ddd, J 18.4, 10.2 and 3.9, 4-Hax), 2.75 (1H, dt, J
18.4 and 2.6, 4-Heq), 3.60 (1H, ddq, J 10.2, 2.6 and 6.2, 3-H), 4.85
(1H, ddq, J 3.9, 2.6 and 6.6, 1-H), 6.09 (1H, s, 7-OH), 7.14 (1H,
dd, J 8.4 and 2.6, 8-H), 7.50 (1H, d, J 2.6, 6-H) and 7.98 (1H, d,
J 8.4, 9-H); dC(100 MHz) 20.9, 21.2, 30.3, 68.8, 70.2, 112.4, 120.9,
125.8, 129.3, 133.7, 142.0, 147.2, 161.0, 183.1 and 184.4; m/z (EI)
258 {[M]+, 65}, 243 (52), 229 (29), 225 (35), 215 (26), 213 (27), 197
(42), 187 (23), 185 (20), 157 (33), 141 (20), 131 (23), 129 (21), 128
(43), 127 (25), 121 (40), 120 (27), 115 (48), 93 (23), 92 (64), 77 (33),
69 (22), 66 (21), 65 (61), 64 (37), 63 (100), 62 (24), 57 (33), 55 (46),
53 (39) and 51 (46); m/z (ESI–) 257.1 [M − H]−.
(1R,3S)-9-Hydroxy-7-methoxy-1,3-dimethyl-3,4,5,10-tetrahydro-
1H-naphtho[2,3-c]pyran-5,10-dione (ventiloquinone L) 8
To a solution of (1R,3S)-benzoquinone 14 (37 mg, 0.14 mmol) in
benzene (2 mL) was added 1,3-dimethoxy-1-trimethylsiloxybuta-
1,3-diene 25 (83 mg, 0.41 mmol) in benzene (2 mL). The mixture
was stirred at 60 ◦C for 100 min, then silica gel (0.5 g) was
added and the suspension was stirred for a further 2.5 h at room
temperature. The mixture was filtered and the filter cake was
washed with ethyl acetate (20 mL). The filtrate was concentrated
under reduced pressure and the residual oil was purified by column
chromatography (dichloromethane–1% formic acid) followed by
gel filtration (Sephadex LH20, methanol–dichloromethane, 1 : 1)
to give (1R,3S)-ventiloquinone L 8 (16 mg, 41%) as orange need◦les,
mp 116–118 ◦C from methanol–dichloromethane (lit.8 mp 126 C,
(1S,3S)-7,9-Dihydroxy-1,3-dimethyl-3,4,5,10-tetrahydro-1H-
naphtho[2,3-c]pyran-5,10-dione (ent-deoxyquinone A) 30
(1R,3S)-Pyranonaphthoquinone 21 (7 mg, 0.03 mmol) in
dichloromethane (10 mL) was cooled to −78 ◦C. To this solution
was added boron tribromide (1.2 M in dichloromethane, 0.5 mL)
over 2 min. The mixture was allowed to stir for 5 min at
−78 ◦C, then was warmed to 0 ◦C and stirred for a further
5 min. The reaction was quenched by the addition of sat. aq.
sodium bicarbonate (10 mL) and extracted with chloroform
(3 × 20 mL). The combined organic extracts were washed with
brine (1 × 20 mL), dried (MgSO4) and concentrated at reduced
pressure. The orange residue was purified by preparative thin layer
chromatography (75 : 24 : 1 toluene–ethyl formate–formic acid)
to give two fractions. The most mobile fraction was identified
as unreacted (1R,3S)-pyranoquinone 21 (0.6 mg, 9%). The less
mobile fraction was identified as ent-deoxyquinone A 30 (0.8 mg,
benzene–hexane); [a]D +420 (c 0.009, CHCl3) {lit.8 [a]D +387.1
(c 0.01, CHCl3)}; CD kextrema(MeOH) 268 (De +0.21), 296 (+5.26),
409 (−0.09) and 451 nm (+0.47); found: [M]+, 288.0997. C16H16O5
requires: [M]+, 288.0998; kmax(MeOH) 220 (log e 4.46), 270 (4.09),
290 sh (3.93) and 423 nm (3.51); dH(400 MHz) 1.36 (3H, d, J 6.4,
3-Me), 1.57 (3H, d, J 6.6, 1-Me), 2.22 (1H, ddd, J 18.6, 10.2 and
3.9, 4-Hax), 2.73 (1H, dt, J 18.6 and 2.6, 4-Heq), 3.57 (1H, ddq, J
26
30
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11%), isolated as an orange solid, mp 147–149 ◦C (acetone); [a]D
206 (log e 3.79), 243 (3.55), 308 (3.04), 490 sh (2.97), 519 (3.09),
553 (3.05) and 590 sh nm (2.65); dH(400 MHz) 1.40 (3H, d, J 6.4,
3-Me), 1.64 (3H, d, J 6.3, 1-Me), 2.42 (1H, ddd, J 17.6, 10.5 and
2.7, 4-Hax), 2.88 (1H, dt, J 17.6 and 2.2, 4-Heq), 3.63 (1H, ddq,
J 10.5, 2.2 and 6.4, 3-H), 5.04 (1H, tq, J 2.5 and 6.3, 1-H), 6.35
(1H, s, 8-H), 7.35 (1H, br s, 7-OH), 11.96 and 13.48 (each 1H, s,
5- and 10-OH); m/z (ESI–) 289.1 [M − H]−; (1R,3S)-7-desmethyl
ventiloquinone E 3, which was isolated as an orange solid (0.4 mg,
0.2%); [a]D23 +370 (c 0.020, MeOH); kmax(MeOH) 220 (log e 4.29),
267 (4.00), 292 sh (3.89) and 454 nm (3.29); dH(400 MHz) 1.35 (3H,
d, J 6.1, 3-Me), 1.52 (3H, d, J 6.6, 1-Me), 2.13 (1H, ddd, J 18.1,
10.2 and 3.6, 4-Hax), 2.75 (1H, dt, J 18.1 and 2.4, 4-Heq), 3.55 (1H,
ddq, J 10.2, 2.4 and 6.1, 3-H), 3.90 and 3.93 (each 3H, s, 6- and 9-
OMe), 4.82 (1H, tq, J 3.6 and 6.6, 1-H), 6.68 (1H, br s, 7-OH) and
6.88 (1H, s, 8-H); dC(100 MHz) 20.7, 21.3, 29.7, 56.6, 62.1, 68.8,
70.1, 104.3, 113.7, 125.1, 139.9, 140.5, 148.0, 155.9, 158.0, 182.5
and 183.7; (1R,3S)-ventiloquinone G 7-O-methyl ether 7 (0.5 mg,
18
−210 (c 0.0028, EtOH); CD kextrema(MeOH) 226 (De +2.15), 247
(−0.94), 256 (−0.66), 265 (−0.93), 268 (−0.77), 276 (−1.15), 311
(+0.16), 355 (−0.35), 406 (−0.20) and 445 nm (−0.34); found:
[M]+, 274.0848. C15H14O5 requires: [M]+, 274.0841; kmax(MeOH)
219 (log e 4.21), 231 sh (3.94), 273 (3.87), 290 (3.80) and 441 nm
(4.3); dH(400 MHz) 1.35 (3H, d, J 6.4, 3-Me), 1.56 (3H, d, J 6.8,
1-Me), 2.22 (1H, ddd, J 19.3, 10.0 and 2.0, 4-Hax), 2.72 (1H, dd,
J 19.3 and 3.4, 4-Heq), 3.99 (1H, ddq, J 10.0, 3.4 and 6.4, 3-H),
5.00 (1H, dq, J 2.0 and 6.8, 1-H), 6.03 (1H, br s, 7-OH), 6.61 and
7.10 (each 1H, d, J 2.4, 6-H and 8-H) and 12.22 (1H, s, 9-OH);
dC(100 MHz) 19.8, 21.5, 29.9, 62.4, 67.0, 108.1, 108.3, 109.7, 133.7,
141.9, 146.8, 162.3, 164.3, 183.2 and 186.8; m/z (EI) 274 {[M]+,
28}, 259 (26), 137 (22), 108 (30), 91 (29), 83 (21), 81 (25), 79 (24),
77 (38), 71 (32), 69 (100), 67 (30), 65 (37), 63 (31), 57 (81), 55 (86),
53 (43), 52 (24), 51 (64) and 50 (24); m/z (ESI–) 274.1 [M]− and
273.1 [M− H]−.
0.3%), a red pigment with mp 225 ◦C (dec.) (MeOH); [a]D +271
22
(c 0.025, CHCl3); CD kextrema(MeOH) 225 (De +2.36), 248 (+0.49),
261 (+0.64), 304 (−1.47), 387 (+0.81) and 454 nm (−0.02); found:
[M]+, 304.0955. C16H16O6 requires: [M]+, 304.0947; kmax(MeOH)
227 (log e 4.23), 302 (3.59), 502 (3.50), 535 (3.42) and 570 sh nm
(3.09); dH(400 MHz) 1.39 (3H, d, J 6.1, 3-Me), 1.64 (3H, d, J 6.3,
1-Me), 2.40 (1H, ddd, J 17.6, 10.3 and 2.5, 4-Hax), 2.88 (1H, dt, J
17.6 and 2.2, 4-Heq), 3.62 (1H, ddq, J 10.3, 2.2 and 6.1, 3-H), 3.94
(3H, s, 7-OMe), 5.01 (1H, tq, J 2.5 and 6.3, 1-H), 6.21 (1H, s, 8-H),
12.76 and 13.36 (each 1H, s, 5- and 10-OH); m/z (EI) 304 {[M]+,
7}, 71 (28), 69 (61), 67 (30), 59 (25), 57 (95), 56 (29), 55 (100) and
51 (24); m/z (ESI–) 303.1 [M − H]−; and the yellow trimethyl ether
(1R,3S)-ventiloquinone E 2 (trace); dH(300 MHz) 1.34 (3H, d, J
6.1, 3-Me), 1.50 (3H, d, J 6.6, 1-Me), 2.11 (1H, ddd, J 18.3, 10.3
and 3.7, 4-Hax), 2.78 (1H, dt, J 18.3 and 2.4, 4-Heq), (∼3.6 signal
obscured), 3.87 (3H, s, 7-OMe), 3.97 (6H, s, 6- and 9-OMe), 4.80
(1H, ddq, J 3.7, 2.4 and 6.6, 1-H) and 6.72 (1H, s, 8-H).
Diels–Alder reaction of (1R,3S)-benzoquinone 14 with diene 27
To
a
solution of (1R,3S)-benzoquinone 14 (140 mg,
0.52 mmol) in benzene (5 mL) was added 1,3,4-trimethoxy-1-
trimethylsiloxybuta-1,3-diene 27 (840 mg, 3.62 mmol) in ben-
zene (2 mL). The reaction was stirred at room temperature
overnight then silica gel (0.5 g) was added and the suspension
was stirred for 70 min, filtered through a silica pad (ethyl
acetate–1% formic acid) and the orange band was collected
and concentrated under reduced pressure. The resulting oil
was purified by repeated column chromatography (toluene–ethyl
formate–formic acid, 50 : 49 : 1, light petroleum–ethyl acetate
and ethyl acetate–1% formic acid) and gel filtration (Sephadex
LH20, 100% methanol or methanol–dichloromethane, 1 : 1) to
give a total of six compounds with differing spectroscopic data,
listed below in order of decreasing mobility when subjected to
thin layer chromatography (toluene–ethyl formate–formic acid,
50 : 49 : 1).
Acknowledgements
Ventiloquinone L 8 (trace), the spectroscopic data for this
compound matched both those recorded for the independently
synthesized material described earlier and data reported for the
natural product;8 (1R,3S)-9-desmethyl ventiloquinone E 4, an
orange solid (0.5 mg, 0.3%), mp 180 ◦C (dec.) (MeOH); [a]D22 +270
(c 0.025, CHCl3); CD kextrema(MeOH) 232 (De −0.31), 256 (+1.36),
277 (+0.62), 296 (+1.38), 417 (−0.12) and 449 nm (+0.01); found:
[M]+, 318.1105. C17H18O6 requires: [M]+, 318.1103; kmax(MeOH)
223 (log e 4.32), 275 (3.90) and 442 nm (3.41); dH(400 MHz) 1.36
(3H, d, J 6.3, 3-Me), 1.57 (3H, d, J 6.6, 1-Me), 2.20 (1H, ddd, J
18.8, 10.3 and 3.6, 4-Hax), 2.79 (1H, ddd, J 18.8, 2.7 and 2.4, 4-
Heq), 3.56 (1H, ddq, J 10.3, 2.4 and 6.3, 3-H), 3.87 and 3.94 (each
3H, s, 6- and 7-OMe), 4.82 (1H, ddq, J 3.6, 2.7 and 6.6, 1-H),
6.65 (1H, s, 8-H) and 13.04 (1H, s, 9-OH); m/z (EI) 318 {[M]+,
33}, 303 (37), 273 (23), 260 (22), 259 (27), 257 (26), 245 (28), 241
(24), 217 (23), 115 (37), 95 (21), 91 (27), 77 (37), 69 (100), 67 (25),
66 (33), 65 (47), 63 (31), 59 (51), 55 (37), 53 (71) and 51 (32);
m/z (ESI–) 317.1 [M − H]−; (1R,3S)-ventiloquinone G 6, a red
solid (1.2 mg, 0.8%), mp 220 ◦C (dec.) (MeOH) (lit.7 mp 183 ◦C,
methanol–light petroleum); [a]D28 +115 (c 0.0075, methanol) {lit.7
L. M. T. is grateful for a Melbourne Research Scholarship; M. G.
is thankful for generous financial support from the Australian
Research Council. We thank Professor D. W. Cameron, University
of Melbourne, for kindly providing an authentic sample of
eleutherin.
References
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18
[a]D +720 (c 0.10, MeOH)}; CD kextrema(MeOH) 273 (De +0.23),
311 (−0.10), 358 (+0.12) and 388 nm (−0.01); found: [M − H]−,
289.0725. C15H14O6 requires: [M − H]−, 289.0712; kmax(MeOH)
8 S. R. Jammula, S. B. Pepalla, H. Telikepalli, K. V. J. Rao and R. H.
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Org. Biomol. Chem., 2006, 4, 3311–3318 | 3317
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3318 | Org. Biomol. Chem., 2006, 4, 3311–3318
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