Regioselective synthesis of o-methyl derivatives morindone and nataloe-emodnr of the trihydroxy anthraquinones

Article abstract of DOI:10.1071/CH99106

Cycloaddition chemistry of dichloronaphthoquinones has led to regioselective syntheses of all regioisomeric α-O-methyl derivatives of morindone (2) and nataloe-emodin (4), including the natural anthraquinone ethers (1) and (3).

Full text of DOI:10.1071/CH99106

C S I R O P U B L I S H I N G
Australian Journal
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Volume 52, 1999
© CSIRO Australia 1999
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Aust. J. Chem., 1999, 52, 941–948
Regioselective Synthesis of O-Methyl Derivatives
of the Trihydroxy Anthraquinones
Morindone and Nataloe-Emodin
Donald W. CameronA,B and D. Ross CollerA
A School of Chemistry, The University of Melbourne, Parkville, Vic. 3052.
B Author to whom correspondence should be addressed.
Cycloaddition chemistry of dichloronaphthoquinones has led to regioselective syntheses of all regioisomeric ␣-O-
methyl derivatives of morindone (2) and nataloe-emodin (4), including the natural anthraquinone ethers (1) and (3).
The plant anthraquinone morindone 5-methyl ether (1)1–4
was structurally assigned largely by spectroscopic compari-
son with its parent, morindone (2). Another natural
monomethyl ether (3)5–8 has a parallel relationship to the iso-
meric nataloe-emodin series represented by (4). Though
described as the 8-methyl ether, compound (3) is actually the
1-methyl ether in terms of IUPAC numbering. The assigned
structures (1) and (3) are both based on a 1,2-dioxy
anthraquinone, possessing a further ␣-oxy group in the oppo-
site ring and having one of the two ␣-oxy groups O-methy-
lated.
Differentiating the two possible ␣-O-methyl derivatives of
each of the parents (2) and (4) is not trivial. The first part of
this paper does so by synthesizing the natural morindone
ether (1) and its regioisomer (5), together with the corre-
sponding pair of regioisomers (6) and (7), in which the sub-
stituents of the two outer rings have the opposite orientation
to one another, relative to the first pair. The second part
describes the synthesis of an analogous nataloe-emodin series
based on (3), together with its regioisomers (8), (9) and (10).
Access to these compounds was investigated by cycload-
dition chemistry of 2,3-dichloronaphthoquinones, developed
here earlier.9 In conjunction with further ␣-hydroxy or ␣-
methoxy substituents these dienophiles underwent regiocon-
trolled addition of Danishefsky’s diene (11)10 to give
respective desilylated adducts (12) or (13). These aromatized
with incorporation of an external oxy nucleophile to give
1,2-dioxy anthraquinones (14), as shown in Scheme 1. The
versatility of this approach is extended by adducts (12) and
(13) being stable enough to allow modification of benzenoid
substituents prior to aromatization. Accordingly, the hydroxy
group of adducts (12) can be methylated and the correspond-
ing methoxy group of adducts (13) demethylated, without
serious accompanying decomposition. An earlier
Diels–Alder synthesis of derivatives of morindone (2)11
differs from the present investigation in involving conven-
tional monochloro naphthoquinonoid dienophiles and in
having led to ␤-methoxy products.
Derivatives of Morindone (2)
Treatment of the angelate-derived diene (15)12 with
trichloro-1,4-benzoquinone (16) gave selective addition to
the monochloro side, as expected.9 Thermal aromatization of
the cycloadduct in boiling xylenes gave the new dienophile
(17) (46%). Alternative acidic or basic aromatization was
accompanied by considerable decomposition. The 1H n.m.r.
spectrum of the product showed an ␣-hydroxy resonance at
␦ 12.01 along with two ortho-coupled aromatic doublets
(␦ 7.52, 7.65, J 7.7 Hz). Reaction of (17) with diene (11) then
gave the desilylated trione (18) (62%). The methine proton
(H 4) of the newly formed ring resonated at ␦ 4.18 as a
doublet of doublets (J 3.2, 2.7 Hz) coupled to both neigh-
bouring methylene protons. The latter appeared at ␦ 2.78 and
3.14, additionally showing geminal coupling of 16.1 Hz.
Cross-carbonyl coupling (J 2.0 Hz) was observed between
H1␣ and H 3␣.
Consistent with Scheme 1, treatment of (18) with sodium
methoxide in methanol gave morindone 5-methyl ether (1)
1
virtually quantitatively. Its H n.m.r. spectrum showed a
chelated hydroxy resonance (␦ 13.02) along with a broad
D2O-exchangeable ␤-hydroxy signal at ␦ 6.73. The new
methoxy substituent resonated at ␦ 4.02 and a pair of dou-
blets (␦ 7.34, 8.14, J 8.5 Hz) confirmed formation of the new
aromatic ring. A similar pair of doublets (␦ 7.51, 7.70, J 7.6
Hz) corresponded to the original aromatic system, with
appropriate broadening through benzylic coupling to the C-
methyl group.
Formation of the regioisomeric anthraquinone (6)
required reversing the orientation of addition to the naphtho-
quinone. This followed methylation of (17) with methyl
iodide and silver(I) oxide to give the methoxy quinone (19)
efficiently. Its reaction with diene (11) gave a new trione (20)
(68%). On selective demethylation with aluminium trichlo-
ride in dichloromethane at room temperature it gave the
trione (21) (62%), isomeric with (18). Reaction was accom-
panied by replacement of the aromatic methoxy resonance (␦
3.83) of the starting material by a chelated hydroxy reso-
Manuscript received 31 August 1999
© CSIRO 1999
0004-9425/99/100941
10.1071/CH99106

942
D. W. Cameron and D. R. Coller
nance (␦ 11.03) in the 1H n.m.r. spectrum of the product. This
latter resonance was markedly different from that of its
regioisomer (18) (␦ 12.07) as has been observed for other
parallel pairs.9
The remaining anthraquinone isomers (5) and (7) were
readily accessible from the triones (18) and (20) respec-
tively. Access to (5) required prior methylation of the
hydroxy group of (18) with methyl iodide/silver(I) oxide.
Without purification, the relatively unstable product (22)
was treated with sodium acetate in acetic acid, to effect
aromatization with incorporation of acetate as the nucle-
ophile.9 The derived anthraquinone (23) (73%) reflected the
expected, accompanying acetyl migration from ␣- to the ␤-
oxy group, releasing a chelated hydroxy group, which res-
onated at ␦ 12.72. Treatment with sodium methoxide then
gave the anthraquinone (5) virtually quantitatively.
Treatment of (21) with sodium methoxide then gave the
new anthraquinone (6), isomeric with (1). The new methoxy
1
group was associated with a H n.m.r. resonance at ␦ 4.03,
and the new aromatic ring with an ortho-coupled pair of dou-
blets (␦ 7.36, 8.12, J 8.5 Hz).
Formation of the remaining anthraquinone (7) from trione
(20) was more straightforward, since the latter possessed the
required ␣-methoxy substituent already in place. Thus treat-
ment with sodium acetate followed by basic hydrolysis of
the intermediate acetate (24) gave (7) efficiently, completing
the isomeric series with (1), (5) and (6).
The 1H n.m.r. spectra of the four isomers (1), (5), (6) and
(7) were mostly similar. As expected,13 the ␣-hydroxy reso-
nance of (7) (␦ 13.20), being peri to a methoxy carbonyl

O-Methyl Derivatives of Morindone and Nataloe-Emodin
943
system, was deshielded relative to its counterpart in (5) (␦
12.72). Similar deshielding was observed for the ␣-hydroxy
proton of (6) (␦ 13.12) relative to that of (1) (␦ 13.02), though
its magnitude was much less. Possibly the latter resonance
experiences some separate deshielding through the conjuga-
tive effect of the ␤-hydroxy group in (1). For all four
anthraquinones the ␣-aromatic proton para to the methoxy
group (␦ 8.05–8.14) was deshielded relative to the corre-
sponding ␣-proton para to the ␣-hydroxyl (␦ 7.70–7.80).
This effect held irrespective of whether the methoxy group
was part of the C-methyl-containing ring, as in (5) and (7), or
of the opposite one, as in (1) and (6). Differentiating aro-
matic proton signals of the C-methyl-containing ring was
simplified by identifiable benzylic coupling to the methyl
protons.
meta-coupled aromatic doublets at ␦ 7.13 and 7.58 (J 1 Hz).
Methylation with methyl iodide/silver(I) oxide then gave the
1
methoxy quinone (29) efficiently. Its H n.m.r. spectrum
resembled that of (28), with appropriate replacement of the
chelated hydroxy signal by a methoxy singlet at ␦ 4.01.
Reaction of (29) with diene (11) led to the tricyclic trione
1
(30) (64%). Its H n.m.r. spectrum resembled those of the
analogous triones described earlier and was amenable to
first-order analysis. With a view to synthesizing the assigned
structure (3) for the natural nataloe-emodin ether,5–8 the
trione (30) was selectively O-demethylated with aluminium
trichloride to give the hydroxy trione (31) efficiently. Its 1H
n.m.r. spectrum showed a new chelated hydroxy signal (␦
10.72) and a single methoxy resonance (␦ 2.93). On treat-
ment with sodium methoxide it gave (3) almost quantita-
tively. The 1H n.m.r. spectrum of this product showed a new
pair of ortho-coupled doublets (␦ 7.36, 8.12, J 8.6 Hz).
Access to the parent system nataloe-emodin (4) readily
resulted from demethylation of (3) in molten aluminium
chloride/sodium chloride. Its 1H n.m.r. spectrum showed two
chelated ␣-hydroxy resonances (␦ 11.91, 12.31) and a broad
␤-hydroxy signal (␦ 6.25) in agreement with values reported
for natural (4).16
Of the four synthesized anthraquinones (1), (5), (6) and
(7), spectroscopic data for (1) agreed most closely overall
with values cited for the natural morindone methyl ether,
thereby supporting the assignment of structure (1) to the
latter.1–4 This was despite some differences between data
from the different natural sources and particularly between
the ␦ value for the broadened ␤-hydroxy resonance of syn-
thetic (1) (6.73) and the only cited value for this proton from
natural material (10.0).2 However, this signal may not be
diagnostic due to its dynamic nature, compared with the
characteristic usefulness of resonances for chelated
With the methoxy quinone (3) thus obtained, attention
was directed towards synthesizing its isomers (8), (9) and
(10), by procedures analogous to those used in the
morindone series. Compound (8) was obtained by treatment
of the methoxy trione (30) with sodium acetate. This pro-
ceeded through the acetyl-migrated anthraquinone (32),
which gave (8) on hydrolysis with sodium methoxide.
Alternative aromatization of the trione (30) with sodium
1
␣-hydroxy protons.14 The H n.m.r. spectra of synthetic (1)
and (6) were very similar indeed, corresponding resonances
differing by no more than 0.1 ppm. However, the isomers
were clearly differentiated by their long-wavelength elec-
tronic absorption maxima in base (493 and 468 nm respec-
tively), the former value more closely corresponding to that
cited for the natural product.1–3
1
methoxide gave the dimethyl ether (33). Its H n.m.r. spec-
trum showed two methoxy signals (␦ 4.02, 4.04) and a D2O-
exchangeable ␤-hydroxy singlet (␦ 6.61).
A further O-methyl derivative of morindone (2), the 1,5-
dimethyl ether (25), has been reported from morindonin, a
natural 6-O-glycoside of morindone, by permethylation and
hydrolysis.15 Structure (25) was further substantiated by sep-
arate synthesis from morindone itself.15 It has also been
obtained independently in the present investigation, as has its
regioisomer (26).
Synthesis of (25) (84%) involved treatment of the trione
(22) with sodium methoxide. Its 1H n.m.r. spectrum showed
two methoxy resonances (␦ 3.92, 4.02) and the absence of an
␣-hydroxy resonance, along with the presence of signals
appropriate for the remainder of the molecule. The isomeric
dimethyl ether (26) was similarly obtained by the action of
sodium methoxide on the isomeric trione (20). As expected,
the 1H n.m.r. spectra of (25) and (26) were very similar, with
less than 0.1 ppm difference between corresponding signals.
Obtaining the remaining anthraquinone isomers (9) and
(10) required reversing the orientation of addition of diene
(11), in forming the tricyclic system. This was expected to be
achieved by addition of (11) to the hydroxy quinone (28).
1
However, this reaction gave a solid which proved by H
n.m.r. spectroscopy to consist of two isomeric triones (3 : 1).
Since the spectrum of the minor component was indistin-
guishable from that of (31), it was inferred that the major
component was the desired adduct (34), a conclusion sup-
ported by chemistry described in the following paragraphs.
Thus, in this nataloe-emodin series the regioselectivity of
cycloaddition was significantly reduced. The methyl sub-
stituent of (28) evidently opposed the electronic effect of the
chelated hydroxy substituent, in contrast to the absence of
appreciable regiochemical leakage for the isomeric hydroxy
naphthoquinone (17).
Derivatives of Nataloe-Emodin (4)
All attempts at efficiently separating the two desilylated
triones (34) and (31) were unsuccessful. However, repeated
recrystallization of a sample of the mixture gave the major
isomer (34) in pure form. Its 1H n.m.r. spectrum showed an
␣-hydroxy resonance (␦ 11.71) which differed substantially
from that of (31) (␦ 10.72).
Treatment of trichloro-1,4-benzoquinone (16) with the
diene (27)11 and aromatization of the cycloadduct with
sodium acetate in acetic acid gave the dichloronaphtho-
quinone (28) (71%). The ease of aromatization in this series
contrasted with that of the corresponding step leading to the
1
6-methyl isomer (17). The H n.m.r. spectrum of (28)
Aromatization of the mixed triones (34) and (31) with
sodium methoxide gave the desired new anthraquinone (9)
included a chelated hydroxy signal (␦ 11.62) together with

944
D. W. Cameron and D. R. Coller
with a minor proportion of its isomer (3), isolated earlier,
However, these isomers proved as inseparable as their trione
precursors. The anthraquinone mixture was therefore treated
with acetic anhydride/pyridine, which allowed chromato-
graphic separation of the major diacetate (35) in 56% yield
monomethyl ether, supporting the assignment of that struc-
ture to the latter.5–8 As for morindone 5-methyl ether (1), the
chief discrepancy lay in non-diagnostic ␦ values for the ␤-
hydroxy group. For synthesized (3) this resonated as a broad-
ened singlet at ␦ 6.70, compared with the reported value of ␦
7.24 for natural material.7
1
from the original mixture of triones (34) and (31). Its H
n.m.r. spectrum showed two acetoxy resonances (␦ 2.39,
2.47) in addition to the C-methyl singlet (␦ 2.51), the latter
broadened by benzylic coupling. Hydrolysis of this diacetate
with sodium methoxide then gave (9) virtually quantita-
tively. Its 1H n.m.r. spectrum showed a chelated hydroxy res-
onance at ␦ 12.63 and a broad D2O-exchangeable ␤-hydroxy
signal at ␦ 6.73.
The final anthraquinone monomethyl ether (10) was also
synthesized from the mixture of trione isomers (34) and (31).
Methylation with methyl iodide/silver(I) oxide gave an
inseparable and relatively unstable mixture of products (36)
and (30). This was immediately aromatized in the presence
of sodium acetate. The derived anthraquinones were able to
be separated into the desired acetate (37) (55%) and a minor
amount of its isomer (32) (18%). In their respective 1H n.m.r.
spectra the ␣-hydroxy resonance of (32) (␦ 13.22) was sig-
nificantly deshielded relative to that for (37) (␦ 12.64), the
former hydroxy group being peri to a methoxy carbonyl
system.13 Deacetylation of (37) with sodium methoxide then
efficiently gave (10).
For spectra of the four isomers (3), (8), (9) and (10) the
most diagnostic signals were those for the chelated
␣-hydroxy groups.14 Thus, the ␣-hydroxy proton of (8)
(␦ 13.35), peri to a methoxy carbonyl system,13 was consid-
erably deshielded relative to that of its regioisomer (10)
(␦ 12.62). The same qualitative trend was observed for the
␣-hydroxy proton of (3) (␦ 12.74) relative to that of (9)
(␦ 12.63) but here the effect was less marked, possibly
because the latter proton experiences some independent
deshielding through the conjugative effect of the ␤-hydroxy
group of (9). For all four isomers the ␣-aromatic proton para
to the methoxy group was deshielded relative to the analo-
gous proton para to the ␣-hydroxyl. Thus, the ␣-aromatic
proton of the dioxy ring, when para to the methoxy group as
in (3) and (9), resonated at ␦ 8.12–8.13; whereas, when para
to hydroxy as in (8) and (10) it resonated at ␦ 7.79 in both
cases. The corresponding proton of the C-methyl-containing
ring, when para to methoxy as in (8) and (10), resonated at
␦ 7.79–7.81; whereas, when para to hydroxy as in (3) and (9)
it resonated at ␦ 7.59–7.61.
Other anthraquinones regioisomeric with nataloe-emodin
derivatives were also prepared, from intermediates already
described. Brief treatment of the methyl ether (9) in molten
aluminium chloride/sodium chloride gave the nataloe-
emodin isomer (38) almost quantitatively. This product was
also obtained with greater overall efficiency from trione
(34), the synthetic precursor of (9). Thus, treatment of the
trione mixture (34) and (31) with sodium acetate in acetic
acid gave a chromatographically separable mixture of
acetate (39) (80%) and a minor component, assumed to be
the acetate (40). The major component (39) (␦OH 12.58,
12.84) on deacetylation efficiently gave (38), indistinguish-
able from the product above. Its 1H n.m.r. spectrum closely
resembled that of its isomer, nataloe-emodin (4), except for
the two ␣-hydroxy resonances. Those for (38), a 1,5-dihy-
droxy anthraquinone, were characteristically deshielded13 by
0.6–0.9 ppm relative to those in the 1,8-dihydroxy system of
(4).
Experimental
General
Melting points were determined on a Kofler hot-stage and are
uncorrected. Microanalyses were carried out by National Analytical
Laboratories, Melbourne, or by Chemical and Microanalytical
Services, Geelong. Electronic spectra were recorded in methanol con-
taining 1% formic acid unless otherwise stated, by using
a
Perkin–Elmer Lambda 2 spectrophotometer. Infrared spectra were
recorded as potassium bromide disks, with a Perkin–Elmer 983G
Grating spectrophotometer. Proton nuclear magnetic resonance (1H
n.m.r.) spectra were recorded with a Varian Unity 300 spectrometer.
The solvent was (D)chloroform unless otherwise stated. High- and low-
resolution mass spectra were recorded by using either a V.G. Micromass
7070F or a JEOL AX-505H instrument at 70 eV. The mass of each ion
is given followed by its relative intensity. In general, only peaks greater
than 20% are quoted. Flash chromatography was carried out with
Merck silica No. 9385 containing 2% oxalic acid. Thin-layer chro-
matography (t.l.c.) was carried out on glass plates coated with Merck
silica gel containing 2% oxalic acid. The separated compounds were
recovered by using ethyl acetate or dichloromethane, washing the
extract twice with water and then drying it before evaporation. All sol-
vents used were of analytical reagent (A.R.) grade or were redistilled
prior to use. Dried solvents were used for all cycloaddition reactions
and manipulations of cycloadducts. Petrol refers to the fraction boiling
in the range 60–80°. Organic extracts were generally dried over mag-
nesium sulfate before evaporation at reduced pressure.
The dimethyl ether (41), regioisomeric with (33), was
then derived by treating the mixture of O-methylated triones
(36) and (30) with sodium methoxide. Chromatographic sep-
aration of the product gave the new anthraquinone (41)
(60%), along with a minor proportion of its isomer (33)
(20%) identical with material synthesized earlier. The two
1
dimethyl ethers (41) and (33) had practically identical H
2,3-Dichloro-5-hydroxy-6-methyl-1,4-naphthoquinone (17)
Diene (15)12 (750 mg) was added to a solution of quinone (16) (710
mg) in benzene (20 cm3) and heated at reflux for 1 h. Xylenes (50 cm3)
were added and the solution was kept at reflux for a further 2 days. The
solution was then cooled to room temperature and sodium acetate (200
mg) and methanol (100 cm3) were added. After stirring for 15 min the
mixture was acidified with 1 M hydrochloric acid, poured into water
(250 cm3) and extracted with ethyl acetate (2×150 cm3). The combined
extracts were washed with water (2×100 cm3) and dried, and the solvent
n.m.r. spectra, corresponding resonances of the respective
isomers differing by less than 0.1 ppm.
The 1H n.m.r. spectra of the isomeric monomethyl ethers
(3), (8), (9) and (10) showed considerable similarities. Their
differences largely paralleled those discussed earlier for the
morindone series (1), (5), (6) and (7). Data for (3) agreed
most closely with values cited for the natural nataloe-emodin

O-Methyl Derivatives of Morindone and Nataloe-Emodin
945
3.0%). ␭max (log⑀) 255, 283, 370 nm (4.82, 4.09, 3.49). ␯max 1674 cm–1.
␦ 2.42, s, Me; 3.89, s, OMe; 7.60, d, J 7.8 Hz, H7; 7.93, d, J 7.8 Hz, H8.
m/z 274 (M[37Cl2], 8%), 272 (M[37Cl35Cl], 48), 270 (M[35Cl2], 75), 255
(21), 252 (24), 235 (52), 207 (56), 205 (100), 199 (22), 179 (40), 177
(58), 149 (32), 136 (24), 89 (23), 87 (30), 75 (21), 74 (21), 62 (25).
was evaporated. Preparative t.l.c. of the residue, with petrol as eluent,
gave a major orange band (RF 0.2) which afforded the naphthoquinone
(17) (400 mg, 46%) as an orange solid. Recrystallization from chloro-
form/petrol gave red needles, m.p. 145–147° (Found: C, 51.3; H, 2.3.
C11H6Cl2O3 requires C, 51.4; H, 2.4%). ␭max (log⑀) 250sh, 290, 436 nm
(3.79, 3.98, 3.56). ␯max 1679, 1631 cm–1. ␦ 2.37, s, Me; 7.52, d, J 7.7 Hz,
H7; 7.65, d, J 7.7 Hz, H 8; 12.01, s, OH. m/z 260 (M[37Cl2], 12%), 258
(M[37Cl35Cl], 67), 256 (M[35Cl2], 100), 223 (32), 222 (29), 221 (91),
193 (35), 51 (25).
(4␣,4a␤,9a␤)-4a,9a-Dichloro-4,8-dimethoxy-7-methyl-3,4,4a,9a-
tetrahydroanthracene-2,9,10(1H)-trione (20)
Diene (11) (640 mg) was added to the naphthoquinone (19) (200
mg) in benzene (10 cm3), and the solution was heated to reflux for 2
days. The solvent was evaporated and the residue was subjected to
preparative t.l.c., with toluene/ethyl acetate (7: 3) as eluent. Isolation of
the major pale yellow band (RF 0.7; purple staining to ammonia) yielded
a clear oily residue which upon trituration with petrol precipitated the
anthracenetrione (20) (186 mg, 68%) as a pale yellow powder.
Recrystallization from ethyl acetate/petrol gave colourless needles,
m.p. dec. >130° (Found: M+•, 370.0379. C17H16Cl2O5 requires M+•,
370.0375). ␭ (log⑀) (CHCl3) 243, 281, 325 nm (4.32, 3.91, 3.59).
(4␣,4a␤,9a␤)-4a,9a-Dichloro-5-hydroxy-4-methoxy-6-methyl-
3,4,4a,9a-tetrahydroanthracene-2,9,10(1H)-trione (18)
The naphthoquinone (17) (100 mg) and diene (11)10 (320 mg) in
benzene (5 cm3) were heated to reflux for 48 h. The solvent was
removed and the oily residue was subjected to preparative t.l.c. using
toluene/ethyl acetate (9 : 1) as eluent. The major colourless band (RF 0.8;
purple staining to ammonia) was isolated to yield the trione (18) (86
mg, 62%) as a colourless powder. Recrystallization from ethyl
acetate/petrol gave colourless needles, m.p. 136–138° (Found: C, 53.8;
␯
max 1719, 16m9a4x cm–1. ␦ 2.41, s, Me; 2.77, ddd, J 16.2, 2.5, 2.0 Hz, H3␣;
H, 4.0. C16H14Cl2O5 requires C, 53.8; H, 4.0%). ␭ (log⑀) (CHCl3)
max
2.96, s, 4-OMe; 3.07, d, J 15.1 Hz, H 1␤; 3.09, dd, J 16.2, 3.4 Hz, H3␤;
3.62, dd, J 15.1, 2.0 Hz, H1␣; 3.83, s, 8-OMe; 4.22, dd, J 3.4, 2.5 Hz,
H4; 7.54, d, J 7.8 Hz, H 6; 7.92, d, J 7.8 Hz, H5. m/z 374 (M[37Cl2],
2%), 372 (M[37Cl35Cl], 12), 370 (M[35Cl2], 18), 337 (30), 335 (86), 305
(26), 303 (72), 293 (30), 277 (56), 268 (23), 119 (21), 91 (27), 85 (100).
248, 268sh, 292sh, 367 nm (4.29, 3.97, 3.79, 3.81). ␯ 1734, 1709,
max
1642 cm–1. ␦ 2.37, s, Me; 2.78, ddd, J 16.1, 2.7, 2.0 Hz, H3␣; 2.95, s,
OMe; 3.07, d, J 15.1 Hz, H 1␤; 3.14, dd, J 16.1, 3.2 Hz, H3␤; 3.72, dd,
J 15.1, 2.0 Hz, H 1␣; 4.18, dd, J 3.2, 2.7 Hz, H 4; 7.55, s, H 7, H8; 12.07,
s, OH. m/z 360 (M[37Cl2], 3%), 358 (M[37Cl35Cl], 14), 356 (M[35Cl2],
22), 321 (25), 265 (33), 263 (100), 254 (29), 236 (22), 235 (23), 207
(25), 85 (87), 56 (33), 55 (21).
(4␣,4a␤,9a␤)-4a,9a-Dichloro-8-hydroxy-4-methoxy-7-methyl-
3,4,4a,9a-tetrahydroanthracene-2,9,10(1H)-trione (21)
Trione (20) (75 mg) in dichloromethane (10 cm3) was added to a
suspension of aluminium trichloride (150 mg) in dichloromethane (50
cm3) at 0°, and stirred for 15 min. The mixture was stirred for a further
1.5 h at room temperature, and then aqueous oxalic acid (5%, 10 cm3)
was added. The mixture was poured into water (100 cm3) and extracted
with ethyl acetate (2×50 cm3). The combined extracts were washed with
water (2×50 cm3) and dried, and the solvent was evaporated to afford
1,6-Dihydroxy-5-methoxy-2-methyl-9,10-anthraquinone
(Morindone 5-Methyl Ether) (1)
Trione (18) (50 mg) in methanol (10 cm3) was treated with sodium
methoxide (300 mg) for 15 min. The solution was acidified with dilute
hydrochloric acid until the red solution became yellow, then poured into
water (100 cm3) and extracted with ethyl acetate (2×50 cm3). The
extracts were combined, washed with water (2×50 cm3), dried and
evaporated to give the anthraquinone (1) (39 mg, 98%) as a yellow
solid. Recrystallization from ethyl acetate/petrol gave (1) as yellow
microneedles, m.p. 243–245° (Found: C, 67.5; H, 4.2. Calc. for
the hydroxy anthracenetrione (21) as
a pale yellow solid.
Recrystallization from ethyl acetate/petrol (charcoal) gave colourless
needles (45 mg, 62%), m.p. dec. >135° (Found: C, 54.0; H, 3.8.
C16H14Cl2O5 requires C, 53.8; H, 4.0%). ␭
(log⑀) (CHCl3) 251,
max
C16H12O5: C, 67.6; H, 4.3%). ␭
(log⑀) 224, 267, 292sh, 414 nm
max
270sh, 292sh, 362 nm (4.19, 3.84, 3.70, 3.73). ␯ 1730, 1705, 1656
max
(4.41, 4.27, 4.05, 3.85). ␭max (log⑀) (MeOH/NaOH) 235, 251, 314, 394,
cm–1. ␦ 2.37, s, Me; 2.76, ddd, J 15.9, 2.8, 1.8 Hz, H3␣; 2.92, s, 4-OMe;
3.11, d, J 15.0 Hz, H1␤; 3.17, dd, J 15.9, 3.1 Hz, H3␤; 3.77, dd, J 15.0,
1.8 Hz, H1␣; 4.15, dd, J 3.1, 2.8 Hz, H4; 7.51, d, J 7.7 Hz, H 6; 7.69,
d, J 7.7 Hz, H 5; 11.03, s, OH. m/z 360 (M[37Cl2], 3%), 358
(M[37Cl35Cl], 12), 356 (M[35Cl2], 18), 289 (31), 288 (27), 285 (20), 268
(26), 263 (50), 254 (72), 253 (30), 115 (21), 85 (58), 77 (26), 56 (100).
493 nm (4.26, 4.34, 4.18, 3.53, 3.91). ␯ 3404, 1664, 1625 cm–1. ␦
max
2.37, s, Me; 4.02, s, OMe; 6.73, br s, 6-OH; 7.34, d, J 8.5 Hz, H 7; 7.51,
d, J 7.6 Hz, H 3; 7.70, d, J 7.6 Hz, H4; 8.14, d, J 8.5 Hz, H 8; 13.02, s,
1-OH. m/z 284 (M, 100%), 269 (32), 266 (46), 241 (22), 238 (58).
Requested samples of natural (1)1–3 proved unavailable. Reported1
␭
(EtOH) 224, 255sh, 268, 285sh, 294sh, 322, 415 nm. ␭
max
max
(EtOH/OH–) 515 nm. ␯max 3450, 1660, 1625, 1575 cm–1. ␦ 2.35, s, Me;
4.01, s, OMe; 7.35, d, J 9 Hz, H7; 7.60, d, J 9 Hz, H3; 7.75, d, J 9 Hz,
1,7-Dihydroxy-8-methoxy-2-methyl-9,10-anthraquinone (6)
H4; 8.16, d, J 9 Hz, H 8; 13.0, s, 1-OH. Reported2 m.p. 223°. ␭
Trione (21) (26 mg) was treated with sodium methoxide (200 mg) in
methanol, as for the formation of (1), giving the dihydroxy
anthraquinone (6) (20 mg, 97%) as a yellow solid. It sublimed (180°,
1×10–4 Torr) as orange-yellow needles, m.p. 228–231° (Found: C, 67.5;
max
(log⑀) (MeOH) 222, 264, 280, 288sh, 410 nm (4.54, 4.49, 4.33, 4.26,
4.10). ␭
(log⑀) (MeOH/NaOH) 215, 232, 248, 312, 394, 490 nm
(4.37, 4.m4a0x, 4.49, 4.31, 3.57, 4.03). ␯max 1650, 1610 cm–1. ␦ 2.35, br s,
Me; 4.02, s, OMe; 7.38, d, J 8.5 Hz, H 7; 7.52, br d, J 7.5 Hz, H 3; 7.72,
d, J 7.5 Hz, H4; 8.17, d, J 8.5 Hz, H 8; 10.0, br s, 6-OH; 12.98, s, 1-OH.
m/z 284 (M, 100%), 269 (38), 266 (42), 258 (32), 255 (28), 254 (24),
H, 4.2. C16H12O5 requires C, 67.6; H, 4.3%). ␭ (log⑀) 272, 294sh,
max
410 nm (4.43, 4.12, 3.97). ␭ (log⑀) (MeOH/NaOH) 240, 291, 316,
max
468 nm (4.48, 4.20, 4.23, 4.03). ␯max 3351, 1648, 1624 cm–1. ␦ 2.37, s,
Me; 4.03, s, OMe; 6.73, br s, 7-OH; 7.36, d, J 8.5 Hz, H6; 7.52, d, J 7.7
Hz, H3; 7.72, d, J 7.7 Hz, H 4; 8.12, d, J 8.5 Hz, H5; 13.12, s, 1-OH.
m/z 284 (M, 100%), 266 (93), 238 (56), 237 (20), 129 (21), 117 (22), 89
(32), 77 (23).
238 (62), 149 (40). Reported3 ␭
(MeOH) 220, 271, 441 nm. ␭
(MeOH/OH–) 230sh, 242sh, 309,m5a0x0 nm. ␯max 3420, 2920, 2850, 1660,
1625 cm–1. ␦ 2.38, s, Me; 4.02, s, OMe; 7.35, d, J 8.6 Hz, H7; 7.51, d,
J 7.8 Hz, H 3; 7.70, d, J 7.8 Hz, H4; 8.14, d, J 8.6 Hz, H8; 13.1, s, OH.
m/z 284 (M, 100%), 266 (45), 238 (48), 60 (30).
max
2-Acetoxy-1-hydroxy-5-methoxy-6-methyl-9,10-anthraquinone (23)
2,3-Dichloro-5-methoxy-6-methyl-1,4-naphthoquinone (19)
Methyl iodide (3 cm3), silver(I) oxide (400 mg) and trione (18) (24
mg) were stirred, away from light, for 27 h. The mixture was filtered
and to the filtrate were added acetic acid (50 cm3) and sodium acetate
(200 mg). The solution was heated at 100° for 2 h, then poured into
water (250 cm3) and extracted with ethyl acetate (2×50 cm3). The com-
bined extracts were washed with water (2×100 cm3), dried and evapo-
rated. The residue was chromatographed, with toluene/ethyl acetate
(9: 1) as eluent. The major yellow band (RF 0.5) was isolated giving the
The naphthoquinone (17) (180 mg), dissolved in dichloromethane
(25 cm3), was stirred with silver(I) oxide (650 mg) and methyl iodide
(10 cm3), away from light, for 24 h. The suspension was filtered and the
filtrate evaporated to afford 2,3-dichloro-5-methoxy-6-methyl-1,4-
naphthoquinone (19) (183 mg, 96%) as a yellow-orange solid, which
recrystallized from chloroform/petrol as yellow-orange needles, m.p.
149–150° (Found: C, 53.1; H, 2.9. C12H8Cl2O3 requires C, 53.2; H,

946
D. W. Cameron and D. R. Coller
acetoxy anthraquinone (23) (16 mg, 73%) as a yellow solid.
Recrystallization from ethyl acetate/petrol gave yellow needles, m.p.
201–204° (Found: C, 66.0; H, 4.2. C18H14O6 requires C, 66.3; H, 4.3%).
1636 cm–1. ␦ 2.40, s, OAc; 2.45, s, Me; 3.92, s, OMe; 7m.4ax5, d, J 8.2 Hz,
H3; 7.63, d, J 7.9 Hz, H 7; 7.82, d, J 8.2 Hz, H 4; 8.06, d, J 7.9 Hz, H8;
12.72, s, OH. m/z 326 (M, 4%), 284 (100), 267 (57).
2-Hydroxy-1,8-dimethoxy-7-methyl-9,10-anthraquinone (26)
Trione (20) (35 mg) was dissolved in methanol (20 cm3) and sodium
methoxide was added. After 30 min the solution was acidified with
dilute hydrochloric acid. The mixture was poured into water (200 cm3)
and extracted with ethyl acetate (2×100 cm3). The combined extracts
were washed with water (2×100 cm3) and dried, and solvent was
removed to yield the anthraquinone (26) (27 mg, 96%) as a yellow
solid. It sublimed (180°, 1×10–4 Torr) as yellow microneedles, m.p.
202–204° (Found: C, 68.5; H, 4.7. C17H14O5 requires C, 68.5; H, 4.7%).
␭
max
(log⑀) 260, 274sh, 412 nm (4.48, 4.18, 4.11). ␯ 1757, 1671,
1,2-Dihydroxy-5-methoxy-6-methyl-9,10-anthraquinone (5)
␭
max (log⑀) 270, 366 nm (4.45, 3.80). ␯max 3317, 1665 cm–1. ␦ 2.42, s,
The anthraquinone (23) (15 mg) was treated with a solution of
sodium methoxide (60 mg) in methanol for 15 min. The solution was
then acidified with dilute hydrochloric acid until a colour change was
observed. The solution was poured into water (100 cm3) and extracted
with ethyl acetate (2×100 cm3). The combined extracts were washed
with water (2×100 cm3), dried and evaporated to afford the dihydroxy
anthraquinone (5) (13 mg, 99%). It sublimed (180°, 1×10–4 Torr) as an
orange solid, m.p. 249–251° (Found: C, 67.9; H, 4.3%. C16H12O5
requires C, 67.6; H, 4.3%). ␭max (log⑀) 230, 259, 288sh, 411 nm (4.45,
4.38, 4.14, 3.95). ␯ 3425, 1661, 1636 cm–1. ␦ 2.44, s, Me; 3.92, s,
OMe; 6.16, br s, 2-mOaHx ; 7.26, d, J 8.4 Hz, H 3; 7.60, d, J 7.9 Hz, H 7;
7.79, d, J 8.4 Hz, H4; 8.05, d, J 7.9 Hz, H 8; 12.72, s, 1-OH. m/z 284
(M, 100%), 266 (85), 238 (57), 139 (30), 128 (20).
Me; 3.95, 4.04, s, s, 2×OMe; 6.65, br s, OH; 7.29, d, J 8.6 Hz, H3; 7.57,
d, J 7.9 Hz, H 6; 7.98, d, J 7.9 Hz, H 5; 8.05, d, J 8.6 Hz, H 4. m/z 298
(M, 81%), 283 (100), 105 (63), 77 (37).
2,3-Dichloro-5-hydroxy-7-methyl-1,4-naphthoquinone (28)
A solution of diene (27)11 (1.00 g) in benzene (3 cm3) was added to a
stirred solution of trichloro-1,4-benzoquinone (16) (500 mg) in benzene
(3 cm3). After 4 h, acetic acid (3 cm3) was added and the solution was
stirred for 5 min before the addition of sodium acetate (300 mg) and
methanol (50 cm3). After a further 4 h, the orange solution was poured
into water and extracted with ethyl acetate (2×200 cm3). The combined
organic extracts were washed with water (2×200 cm3), dried and evapo-
rated to an oily orange-red solid. Recrystallization from
chloroform/petrol gave the naphthoquinone (28) (455 mg, 71%) as red-
orange needles, m.p. 177–179° (Found: C, 51.6; H, 2.2. C11H6Cl2O3
2-Acetoxy-1-hydroxy-8-methoxy-7-methyl-9,10-anthraquinone (24)
requires C, 51.4; H, 2.4%). ␭ (log⑀) 242, 290, 432 nm (3.64, 3.85,
Sodium acetate was added to a solution of trione (20) (36 mg) in
acetic acid (10 cm3) and the solution was heated at 100° for 3 h. The
solvent was removed under vacuum and the residue was suspended in
water (200 cm3). Ethyl acetate extraction (2×100 cm–3) afforded a
yellow solution which was washed with water (2×100 cm3), dried and
evaporated to give the acetoxy anthraquinone (24) (31 mg, 98%).
Recrystallization from ethyl acetate/petrol gave yellow-orange needles,
m.p. 189–191° (Found: C, 66.4; H, 4.4. C18H14O6 requires C, 66.3; H,
4.3%). ␭ (log⑀) 258, 282sh, 388 nm (4.36, 3.89, 3.76). ␯ 1766,
max
3.38). ␯max 1677, 1635 cm–1. ␦ 2.46, s, Me; 7.13, d, J 1 Hz, H6; 7.58, d,
J 1 Hz, H8; 11.62, s, OH. m/z 260 (M[37Cl2], 13%), 258 (M[37Cl35Cl],
79), 256 (M[35Cl2], 94) 223 (42), 221 (100), 193 (61), 102 (20), 101 (20).
2,3-Dichloro-5-methoxy-7-methyl-1,4-naphthoquinone (29)
The naphthoquinone (28) (100 mg) was dissolved in
dichloromethane (30 cm3), and methyl iodide (3 cm3) and silver(I)
oxide (150 mg) were added. The suspension was stirred away from light
for 24 h, then filtered and evaporated to give the methoxy naphtho-
quinone (29) (105 mg, 99%) as a brown-orange solid. Recrystallization
from ethyl acetate/petrol gave brown-yellow needles, m.p. 208–209°
max
max
1664, 1632 cm–1. ␦ 2.41, s, OAc; 2.44, s, Me; 3.92, s, OMe; 7.43, d, J
8.2 Hz, H 3; 7.65, d, J 7.9 Hz, H6; 7.82, d, J 8.2 Hz, H 4; 8.06, d, J 7.9
Hz, H 5; 13.13, s, OH. m/z 326 (M, 2%), 284 (95), 267 (21), 266 (100).
(Found: C, 53.2; H, 2.7. C12H8Cl2O3 requires C, 53.2; H, 3.0%). ␭
max
(log⑀) 250, 285, 415 nm (4.03, 4.15, 3.61). ␯max 1675 cm–1. ␦ 2.50, s,
Me; 4.01, s, OMe; 7.13, br s, H 6; 7.66, br s, H 8. m/z 274 (M[37Cl2],
12%), 272 (M[37Cl35Cl], 67), 270 (M[35Cl2], 100), 241 (20), 235 (47),
207 (48), 205 (56), 179 (25), 177 (36).
1,2-Dihydroxy-8-methoxy-7-methyl-9,10-anthraquinone (7)
Treatment of quinone (24) (33 mg) with sodium methoxide as for
the formation of (5) afforded the dihydroxy anthraquinone (7) (28 mg,
97%) as an orange solid. Sublimation (180°, 1×10–4 Torr) gave an
orange solid, m.p. 186–188° (Found: C, 67.7; H, 4.2. C16H12O5 requires
C, 67.6; H, 4.3%). ␭max (log⑀) 257, 356, 430 nm (4.29, 3.50, 3.65). ␯
3357, 1654, 1630 cm–1. ␦ 2.44, s, Me; 3.93, s, OMe; 6.29, br s, 2-OmHax;
7.24, d, J 8.2 Hz, H3; 7.64, d, J 7.9 Hz, H 6; 7.80, d, J 8.2 Hz, H4; 8.07,
d, J 7.9 Hz, H 5; 13.20, s, 1-OH. m/z 284 (M, 91%), 267 (23), 266 (100),
238 (37), 71 (25), 69 (26), 56 (68), 53 (33).
(4␣,4a␤,9a␤)-4a,9a-Dichloro-4,8-dimethoxy-6-methyl-3,4,4a,9a-
tetrahydroanthracene-2,9,10(1H)-trione (30)
Diene (11)10 (640 mg) was added to the naphthoquinone (29) (200
mg) in benzene (10 cm3), and the solution was boiled under reflux for
2 days. The solvent was evaporated and the residue was chro-
matographed in toluene/ethyl acetate (7: 3). The major pale yellow
band (RF 0.6; purple staining to ammonia) was isolated to give the
anthracenetrione (30) (176 mg, 64%). Recrystallization from ethyl
acetate/petrol gave colourless needles, m.p. dec. >140° (Found: C,
2-Hydroxy-1,5-dimethoxy-6-methyl-9,10-anthraquinone (25)
Trione (18) (20 mg) was dissolved in methyl iodide (3 cm3), and
silver(I) oxide (400 mg) was added. The suspension was stirred, away
from light, for 27 h, and then filtered. The filtrate was added to
methanol (50 cm3) and treated with sodium methoxide for 15 min. The
solution was then acidified with dilute hydrochloric acid, poured into
water (100 cm3) and extracted into ethyl acetate (2×50 cm3). The
extracts were combined, washed with water (2×50 cm3) and dried, and
the solvent was evaporated. The residue was subjected to preparative
t.l.c., with toluene/ethyl acetate (9: 1) as eluent. Isolation of the major
yellow band (RF 0.1) yielded the anthraquinone (25) (14 mg, 84%) as a
yellow solid. Sublimation (180°, 1×10–4 Torr) gave yellow micronee-
dles, m.p. 224–226° (lit.15 219–220°) (Found: C, 68.3; H, 4.8. Calc. for
54.7; H, 4.2. C17H16Cl2O5 requires C, 55.0; H, 4.3%). ␭
(log⑀)
(CHCl3) 243, 265sh, 278sh, 352 nm (4.26, 4.09, 3.87, 3.73). m␯amxax 1734,
1708 cm–1. ␦ 2.50, s, Me; 2.76, ddd, J 16.1, 2.6, 1.8 Hz, H3␣; 2.97, s,
4-OMe; 3.03, d, J 15.0 Hz, H1␤; 3.07, dd, J 16.1, 3.7 Hz, H3␤; 3.65,
dd, J 15.0, 1.8 Hz, H1␣; 3.96, s, 8-OMe; 4.21, dd, J 3.7, 2.6 Hz, H4;
7.12, br s, H7; 7.64, br s, H5. m/z 374 (M[37Cl2], 1%), 372
(M[37Cl35Cl], 4), 370 (M[35Cl2], 6), 337 (35), 336 (20), 335 (100), 305
(31), 304 (22), 303 (87), 293 (23), 277 (49), 90 (29), 85 (73).
(4␣,4a␤,9a␤)-4a,9a-Dichloro-8-hydroxy-4-methoxy-6-methyl-
3,4,4a,9a-tetrahydroanthracene-2,9,10(1H)-trione (31)
Asolution of trione (30) (100 mg) in dichloromethane (40 cm3) at 0°
was treated with aluminium trichloride (200 mg) with stirring for 15
min. The solution was then allowed to warm to room temperature and
stirring was continued for 1.5 h. The reaction was then quenched with
aqueous oxalic acid (5%, 10 cm3). The mixture was poured into water
C17H14O5: C, 68.5; H, 4.7%). ␭ (log⑀) 268, 288sh, 358 nm (4.35,
max
4.20, 3.79). ␯
3464, 1664 cm–1. ␦ 2.42, s, Me; 3.92, 4.02, s, s,
2×OMe; 6.56,mbarx s, OH; 7.34, d, J 8.5 Hz, H 3; 7.58, d, J 7.9 Hz, H7;
7.99, d, J 7.9 Hz, H 8; 8.08, d, J 8.5 Hz, H 4. m/z 298 (M, 100%), 284
(29), 283 (92), 280 (22), 266 (23), 255 (21), 119 (39), 56 (38).

O-Methyl Derivatives of Morindone and Nataloe-Emodin
947
(200 cm3) and extracted with dichloromethane (2×100 cm3). The com-
bined extracts were washed with water (2×100 cm3) and dried, and the
solvent was evaporated to give the hydroxy anthracenetrione (31) as a
pale yellow solid (95 mg, 98%). Recrystallization from ethyl
acetate/petrol gave colourless needles, m.p. dec. >135° (Found: M+•,
2-Acetoxy-1-hydroxy-8-methoxy-6-methyl-9,10-anthraquinone (32)
A solution of trione (30) (30 mg) in acetic acid (50 cm3) was treated
with sodium acetate (200 mg) at 100° for 2 h. The orange solution was
poured into water (200 cm3) and extracted with ethyl acetate (2×100
cm3). The combined extracts were washed with water (2×100 cm3) and
dried, and the solvent was removed to afford the anthraquinone (32) (26
mg, 98%) as a yellow-orange solid. Recrystallization from ethyl
acetate/petrol gave orange microneedles, m.p. 188–191° (Found: C,
66.3; H, 4.4. C18H14O6 requires C, 66.3; H, 4.3%). ␭max (log⑀) 224, 260,
282sh, 412 nm (4.78, 4.42, 4.14, 4.03). ␯max 1765, 1670, 1632 cm–1. ␦
2.39, s, OAc; 2.52, s, Me; 4.06, s, OMe; 7.16, br s, H7; 7.40, d, J 8.2
Hz, H 3; 7.79, d, J 8.2 Hz, H4; 7.79, br s, H5; 13.22, s, OH. m/z 326 (M,
5%), 284 (100), 266 (58).
356.0229. C16H14Cl2O5 requires M+•, 356.0218). ␭ (log⑀) (CHCl3)
max
250, 361 nm (4.27, 3.78). ␯ 1730, 1695, 1660 cm–1. ␦ 2.46, s, Me;
2.76, ddd, J 16.0, 2.6, 2.0 Hmza,xH3␣; 2.93, s, OMe; 3.10, d, J 15.0 Hz,
H1␤; 3.17, dd, J 16.0, 3.2 Hz, H 3␤; 3.77, dd, J 15.0, 2.0 Hz, H1␣;
4.16, dd, J 3.2, 2.6 Hz, H 4; 7.13, br s, H 7; 7.58, br s, H 5; 10.72, s, OH.
m/z 358 (M[37Cl35Cl], 1%), 356 (M[35Cl2], 2), 290 (26), 289 (34), 288
(68), 263 (38), 207 (36), 197 (35), 141 (23), 139 (49), 135 (21), 134
(24), 115 (71), 106 (42), 89 (22), 85 (100), 78 (23), 77 (59), 75 (24), 64
(23), 62 (50), 57 (26), 51 (30), 50 (38).
1,2-Dihydroxy-8-methoxy-6-methyl-9,10-anthraquinone (8)
2,8-Dihydroxy-1-methoxy-6-methyl-9,10-anthraquinone
(Nataloe-Emodin 1-Methyl Ether) (3)
A solution of the anthraquinone (32) (17 mg) in methanol (25 cm3)
was treated with sodium methoxide (50 mg) for 15 min, as for the for-
mation of (5), to afford dihydroxy anthraquinone (8) (14 mg, 98%) as a
yellow-orange solid. It sublimed (180°, 1×10–4 Torr) to give an orange-
red solid, m.p. 251–253° (Found: C, 67.3; H, 4.2. C16H12O5 requires C,
67.6; H, 4.3%). ␭max (log⑀) 258, 284sh, 412 nm (4.36, 4.05, 3.97). ␯
3391, 1659, 1630 cm–1. ␦ 2.52, s, Me; 4.07, s, OMe; 6.28, br s, 2-OmHax;
7.13, br s, H 7; 7.21, d, J 8.4 Hz, H 3; 7.79, d, J 8.4 Hz, H 4; 7.81, br s,
H5; 13.35, s, 1-OH. m/z 284 (M, 100%), 266 (81), 238 (39).
Trione (31) (65 mg) was treated with sodium methoxide (150 mg) in
methanol, as for the formation of (1), to afford the anthraquinone (3) (49
mg, 95%) as an orange solid. Recrystallization from ethyl acetate/petrol
gave (3) as orange needles, m.p. 240–241° (Found: C, 67.5; H, 4.2.
Calc. for C16H12O5: C, 67.6; H, 4.3%). ␭max (log⑀) 222, 273, 294sh, 401
nm (4.80, 4.42, 4.21, 4.01). ␯max 3398, 1648, 1635 cm–1. ␦ 2.45, s, Me;
4.03, s, OMe; 6.70, br s, 2-OH; 7.09, br s, H7; 7.36, d, J 8.6 Hz, H3;
7.61, br s, H 5; 8.12, d, J 8.6 Hz, H 4; 12.74, s, 8-OH. m/z 284 (M,
100%), 266 (84), 238 (29).
Reaction of (28) and Diene (11)
Reported7 for natural (3), m.p. 234–235°. ␦ 2.45, s, Me; 4.03, s,
OMe; 7.09, dd, J 2, 1 Hz, H 7; 7.24, br s, 2-OH; 7.36, d, J 9 Hz, H3;
7.61, dd, J 2, 1 Hz, H5; 8.11, d, J 9 Hz, H 4; 12.74, s, 8-OH. m/z 284
(M, 100%), 266 (80), 255 (14), 241 (9), 238 (80), 237 (20), 223 (8), 213
(19), 210 (14), 185 (20), 182 (12), 181 (16), 142 (5). Reported17 for (3)
derived by ferric chloride oxidation of homonataloin, m.p. 235–236°.
The naphthoquinone (28) (100 mg) and diene (11)10 (320 mg) in
benzene (5 cm3) were boiled under reflux for 2 days. The solvent was
evaporated and the residue was subjected to preparative t.l.c., with
toluene/ethyl acetate (19 : 1) as eluent. Isolation of the colourless band
(RF 0.5; purple staining to ammonia) gave a colourless oil. This was
diluted with dichloromethane (1 cm3) followed by petrol (50 cm3) and
the solution was chilled overnight. This caused deposition of a colour-
less powder (95 mg, 68%) which contained two regioisomeric com-
pounds (34) and (31) (3: 1). ␦ (major isomer) 2.46, s, Me; 2.78, ddd, J
16.1, 2.7, 2.0 Hz, H3␣; 2.96, s, OMe; 3.08, d, J 15.2 Hz, H1␤; 3.14, dd,
J 16.1, 3.2 Hz, H3␤; 3.72, dd, J 15.2, 2.0 Hz, H1␣; 4.18, dd, J 3.2, 2.7
Hz, H4; 7.08, br s, H 6; 7.43, br s, H 8; 11.71, s, OH. ␦ (minor isomer)
2.48, s, Me; 2.76, apparent dt, spacing 16.1, 2.7 Hz, H3␣; 2.93, s, OMe;
3.10, d, J 15.2 Hz, H1␤; 3.16, dd, J 16.1, 3.2 Hz, H3␤; 3.77, dd, J 15.2,
2.0 Hz, H 1␣; 4.15, apparent t, spacing 2.9 Hz, H4; 7.13, br s, H 7; 7.58,
br s, H 5; 10.73, s, OH.
␭
max (log⑀) 228, 275, 295, 400 nm (4.36, 4.22, 4.02, 3.80). ␯max 3350,
1658, 1638 cm–1.
1,2,8-Trihydroxy-6-methyl-9,10-anthraquinone
(Nataloe-Emodin) (4)
The anthraquinone (3) (15 mg) was added to a mixture of aluminium
chloride (5 g) and sodium chloride (1 g) at 140°. After 5 min the reac-
tion mixture was poured into water (100 cm3) containing concentrated
hydrochloric acid (5 cm3), and briefly warmed. The solution was then
extracted with ethyl acetate (2×100 cm3). The combined extracts were
washed with water (2×100 cm3), dried and evaporated to afford nataloe-
emodin (4) (14 mg, 98%) as an orange solid. Sublimation (180°, 1×10–4
Torr) gave orange microneedles, m.p. 209–211° (Found: C, 66.7; H,
3.9. Calc. for C15H10O5: C, 66.7; H, 3.7%). ␭max (log⑀) (CH3CN) 230,
The major isomer was isolated in pure form by repeated recrystal-
lization of a sample from ethyl acetate/petrol, which gave the
anthracenetrione* (34) as colourless needles, m.p. dec. >135° (Found:
M+•, 356.0222. C16H14Cl2O5 requires M+•, 356.0218). ␭
(log⑀)
max
260, 270sh, 284sh, 295, 424 nm (4.51, 4.41, 4.36, 4.20, 4.16, 4.01). ␯
max
(CHCl3) 249, 295sh, 361 nm (4.32, 3.86, 3.84). ␯max 1722, 1644, 1612
3398, 1623 cm–1. ␦ 2.47, s, Me; 6.25, br s, 2-OH; 7.08, br s, H7; 7.27,
d, J 8.3 Hz, H 3; 7.67, br s, H 5; 7.84, d, J 8.3 Hz, H 4: 11.91, 12.31, s,
s, 2×␣-OH. m/z 270 (M, 75%), 149 (100), 71 (20), 69 (24), 56 (52), 54
(37).
1
cm–1. H n.m.r. data were identical with those for the major isomer
quoted in the preceding paragraph. m/z 358 (M[37Cl35Cl], 4%), 356
(M[35Cl2], 6), 265 (20), 263 (59), 235 (20), 207 (52), 134 (23), 115 (55),
106 (36), 85 (100), 77 (48), 65 (21), 62 (28), 57 (32), 51 (27), 50 (30).
Reported for natural nataloe-emodin,16 m.p. 212–214°. ␭
max
(CH3CN) 231, 259, 288, 426 nm. ␯ 3550, 3200, 1660, 1625 cm–1.
2.45, s, Me; 6.20, br s, 2-OH; 7.05, Jm1a.x8 Hz, H 7; 7.25, d, J 8.5 Hz, H 3;
7.65, J 1.8 Hz, H 5; 7.82, d, J 8.5 Hz, H 4; 11.88, 12.28, s, s, 2×␣-OH.
2,5-Diacetoxy-1-methoxy-7-methyl-9,10-anthraquinone (35)
A solution of the crude solid (90 mg) from the cycloaddition of (28)
and (11), dissolved in methanol (40 cm3), was treated with sodium
methoxide for 15 min. Workup as for (1) gave a yellow solid which was
dissolved in acetic anhydride (20 cm3) and pyridine (5 cm3) and the
solution was heated on a steam bath for 6 h. The mixture was then
poured into water (200 cm3) and extracted with ethyl acetate (2×100
cm3). The extracts were washed with 1 M hydrochloric acid (2×100
cm3), then with water (100 cm3), dried and evaporated. The residue was
subjected to preparative t.l.c., with toluene/ethyl acetate (9: 1) as eluent.
Isolation of the major yellow band (RF 0.6) afforded the anthraquinone
(35) (52 mg, 56%). Recrystallization from ethyl acetate/petrol gave
yellow-orange needles, m.p. 174–176° (Found: C, 65.6; H, 4.3.
2-Hydroxy-1,8-dimethoxy-6-methyl-9,10-anthraquinone (33)
Trione (30) (20 mg), dissolved in methanol (10 cm3), was treated
with sodium methoxide (100 mg) for 15 min. Workup as for (1)
afforded the anthraquinone (33) (16 mg, 98%) as a yellow solid. It sub-
limed (180°, 1×10–4 Torr) as a yellow solid, m.p. 251–253° (Found: C,
68.9; H, 4.7%. C17H14O5 requires C, 68.5; H, 4.7%). ␭ (log⑀) 269,
max
286sh, 376 nm (4.43, 4.24, 3.97). ␯max 3228, 1658 cm–1. ␦ 2.49, s, Me;
4.02, 4.04, s, s, 2×OMe; 6.61, br s, 2-OH; 7.10, br s, H 7; 7.27, d, J 8.4
Hz, H 3; 7.70, br s, H 5; 8.03, d, J 8.4 Hz, H4. m/z 298 (M, 100%), 283
(95), 280 (25), 265 (21), 255 (24).
C20H16O7 requires C, 65.2; H, 4.4%). ␭ (log⑀) 258, 278sh, 345 nm
max
* (4␣,4a␤,9a␤)-4a,9a-Dichloro-5-hydroxy-4-methoxy-7-methyl-3,4,4a,9a-tetrahydroanthracene-2,9,10(1H)-trione.

948
D. W. Cameron and D. R. Coller
(4.56, 4.05, 3.79). ␯max 1756, 1670 cm–1. ␦ 2.39, 2.47, s, s, 2×OAc; 2.51,
s, Me; 3.94, s, OMe; 7.20, br s, H6; 7.47, d, J 8.5 Hz, H 3; 8.01, br s,
H8; 8.07, d, J 8.5 Hz, H 4. m/z 368 (M, 11%), 347 (45), 326 (36), 284
(100), 266 (34), 238 (22), 134 (24), 133 (39), 105 (88), 104 (44), 91
(92), 77 (23).
Workup as for (32) was followed by preparative t.l.c. with toluene/ethyl
acetate (9 : 1) as eluent. The major yellow band (RF 0.4) afforded the
anthraquinone (37) (25 mg, 55%) as a yellow solid. Recrystallization
from ethyl acetate/petrol gave orange needles, m.p. 232–235° (Found:
C, 66.2; H, 4.3. C18H14O6 requires C, 66.3; H, 4.3%). ␭max (log⑀) 226sh,
258, 278sh, 435 nm (4.36, 4.40, 4.16, 3.76). ␯
1761, 1668, 1635
max
cm–1. ␦ 2.40, s, OAc; 2.52, s, Me; 4.04, s, OMe; 7.17, br s, H 6; 7.43, d,
J 8.4 Hz, H3; 7.78, br s, H8; 7.81, d, J 8.4 Hz, H4; 12.64, s, OH. m/z
326 (M, 1%), 283 (100), 267 (29), 266 (28), 255 (28), 238 (20).
The minor yellow band (RF 0.5) afforded the anthraquinone (32) (8
mg, 18%) identical to that isolated previously.
2,5-Dihydroxy-1-methoxy-7-methyl-9,10-anthraquinone (9)
A solution of the anthraquinone (35) (50 mg) in methanol (20 cm3)
was treated with sodium methoxide. Workup as for (5) yielded the dihy-
droxy anthraquinone (9) (37 mg, 96%) as a yellow solid. A small
sample sublimed as an orange solid, m.p. 209–211°. Recrystallization
from ethyl acetate/petrol gave orange microneedles, m.p. 217–219°
1,2-Dihydroxy-5-methoxy-7-methyl-9,10-anthraquinone (10)
(Found: C, 67.6; H, 4.3. C16H12O5 requires C, 67.6; H, 4.3%). ␭
max
3380,
The anthraquinone (37) (14 mg) was treated with sodium methox-
ide (100 mg), as for the formation of (5), to give the dihydroxy
anthraquinone (10) (12 mg, 98%) as an orange solid. It sublimed (180°,
1×10–4 Torr) as orange microneedles, m.p. 263–266° (Found: C, 67.4;
(log⑀) 223, 265, 293sh, 414 nm (4.53, 4.38, 4.16, 3.92). ␯
max
1664, 1630 cm–1. ␦ 2.46, s, Me; 4.02, s, OMe; 6.73, br s, 2-OH; 7.08,
br s, H 6; 7.36, d, J 8.5 Hz, H 3; 7.59, br s, H 8; 8.13, d, J 8.5 Hz, H4;
12.63, s, 5-OH. m/z 284 (M, 100%), 266 (38), 238 (59).
H, 4.0. C16H12O5 requires C, 67.6; H, 4.3%). ␭
(log⑀) 227, 258,
280sh, 434 nm (4.61, 4.64, 4.42, 4.02). ␯max 3409,m1a6x33 cm–1. ␦ 2.52, s,
Me; 4.03, s, OMe; 6.12, br s, 2-OH; 7.16, br s, H6; 7.25, d, J 8.3 Hz,
H3; 7.79, d, J 8.3 Hz, H4; 7.79, br s, H8; 12.62, s, 1-OH. m/z 284 (M,
100%), 266 (49).
1,2,5-Trihydroxy-7-methyl-9,10-anthraquinone (38)
(A) The anthraquinone (9) (16 mg) was demethylated with alu-
minium chloride/sodium chloride as for (4), to yield the trihydroxy
anthraquinone (38) (15 mg, 99%) as an orange solid. Sublimation
(180°, 1×10–4 Torr) gave orange-red needles, m.p. 284–286° (Found: C,
66.7; H, 3.7. C15H10O5 requires C, 66.7; H, 3.7%). ␭max (log⑀) (CH3CN)
229, 260, 287, 298sh, 360sh, 441 nm (4.31, 4.31, 4.00, 3.95, 3.40, 3.81).
Acknowledgments
We acknowledge the financial support of the Australian
Research Council and an Australian Postgraduate Research
Award (to D.R.C.). We are grateful to Dr P. G. Griffiths for
discussion. We thank the Research School of Chemistry,
A.N.U., for a Visiting Fellowship (to D.W.C.), during which
part of this paper was written.
␯
max 3318, 1622, 1608 cm–1. ␦ 2.47, s, Me; 6.30, br s, 2-OH; 7.13, br s,
H6; 7.27, d, J 8.2 Hz, H 3; 7.65, br s, H 8; 7.84, d, J 8.2 Hz, H 4; 12.81,
12.87, s, s, 2×␣-OH. m/z 270 (M, 100%), 242 (15), 135 (19).
(B) The anthraquinone (39) (15 mg) was dissolved in methanol (20
cm3) and treated with sodium methoxide as for the formation of (5),
yielding the trihydroxy anthraquinone (38) (13 mg, 100%) as an orange
solid. Sublimation (180°, 1×10–4 Torr) gave orange-red needles spec-
troscopically indistinguishable from the material from (A).
References
2-Acetoxy-1,5-dihydroxy-7-methyl-9,10-anthraquinone (39)
1
Gonzalez, A. G., Cardona, R. J., Lopez Dorta, H., Medina, J. M., and
The crude mixture of triones (34) and (31) (3: 1, 50 mg) was dis-
solved in acetic acid (10 cm3) and treated with sodium acetate with stir-
ring at 100° for 1 h. Workup as for (32) was followed by preparative
t.l.c., with toluene/ethyl acetate (9: 1) as eluent. The major yellow band
(RF 0.8) was isolated to give the anthraquinone (39) (31 mg, 71%) as an
orange solid. Recrystallization from ethyl acetate/petrol gave yellow-
orange prisms, m.p. 208–211° (Found: C, 65.5; H, 3.8. C17H12O6
Rodriguez, L. F., An. Quim., 1977, 73, 869.
2
Demagos, G. P., Baltus, W., and Höfle, G., Z. Naturforsch., B, 1981,
36, 1180.
3
Wijnsma, R., Verpoorte, R., Mulder-Krieger, T., and Baerheim
Svendson, A., Phytochemistry, 1984, 23, 2307.
4
Ismail, N. H., Ali, A. M., Aimi, N., Kitajima, M., Takayama, H., and
Lajis, N. H., Phytochemistry, 1997, 45, 1723.
requires C, 65.4; H, 3.9%). ␭ (log⑀) 259, 290, 443 nm (4.40, 4.12,
max
5
3.95). ␯max 3464, 1767, 1623 cm–1. ␦ 2.41, s, OAc; 2.48, s, Me; 7.14, br
s, H6; 7.47, d, J 8.2 Hz, H 3; 7.67, br s, H 8; 7.87, d, J 8.2 Hz, H4; 12.58,
12.84, s, s, 2×␣-OH. m/z 271 (17%), 270 (M, 100), 242 (7), 135 (7).
Niyonzima, D.-D., Rev. Univ. Burundi, Ser.: Sci. Exactes, 1993, 16,
41 (Chem. Abstr., 1994, 120, 212593s).
6
Rauwald, H.-W., and Niyonzima, D.-D., Z. Naturforsch., C, 1991,
46, 177.
7
2-Hydroxy-1,5-dimethoxy-7-methyl-9,10-anthraquinone (41)
Delle Monache, G., de Rosa, M. C., Scurria, R., Monacelli, B.,
Pasqua, G., dall’Olio, G., and Botta, B., Phytochemistry, 1991, 30,
The crude regioisomeric mixture of quinones (34) and (31) (3: 1, 50
mg), methyl iodide (4 cm3) and silver(I) oxide (500 mg) were stirred
away from light for 27 h. The suspension was filtered and the filtrate
was treated with sodium methoxide (400 mg) in methanol (50 cm3) for
15 min. Workup as for (1) gave a yellow solid which was subjected to
preparative t.l.c., with toluene/ethyl acetate (7: 3) as eluent. Isolation of
the major yellow band (RF 0.6) afforded the anthraquinone (41) (25 mg,
60%) as a yellow solid, which sublimed (180°, 1×10–4 Torr) as yellow-
orange needles, m.p. 215–218° (Found: C, 68.3; H, 4.8. C17H14O5
1849.
8
van Oudtshoorn, M. C. B., Phytochemistry, 1964, 3, 383.
9
Cameron, D. W., Feutrill, G. I., and Keep, P. L. C., Tetrahedron Lett.,
1989, 30, 5173.
10
Danishefsky, S., and Kitahara, T., J. Am. Chem. Soc., 1974, 96,
7807.
11
Savard, J., and Brassard, P., Tetrahedron, 1984, 40, 3455.
12
Cameron, D. W., Looney, M. G., and Pattermann, J. A., Tetrahedron
requires C, 68.5; H, 4.7%). ␭ (log⑀) 221, 270, 393 nm (4.46, 4.34,
max
Lett., 1995, 36, 7555.
3.77). ␯
3421, 1664, 1642 cm–1. ␦ 2.50, s, Me; 4.01, 4.03, s, s,
2×OMe;m6ax.53, br s, 2-OH; 7.11, br s, H6; 7.33, d, J 8.6 Hz, H 3; 7.72,
br s, H8; 8.08, d, J 8.6 Hz, H 4. m/z 298 (M, 100%), 267 (23), 222 (21).
The minor yellow band (RF 0.7) afforded the anthraquinone (33) (8
mg, 20%) identical to that isolated previously.
13
Cameron, D. W., Gan, C.-Y., Griffiths, P. G., and Pattermann, J. A.,
Aust. J. Chem., 1998, 51, 421.
14
Lillie, T. J., and Musgrave, O. C., J. Chem. Soc., Perkin Trans. 1,
1977, 355.
15
Balakrishna, S., Seshadri, T. R., and Venkataramani, B., J. Sci. Ind.
2-Acetoxy-1-hydroxy-5-methoxy-7-methyl-9,10-anthraquinone (37)
Res., Sect. B, 1960, 19, 433 (Chem. Abstr., 1961, 55, 14401i).
16
Alemayehu, G., Abegaz, B., Snatzke, G., and Duddeck, H.,
The crude mixture of triones (34) and (31) (3: 1, 50 mg) was stirred
with methyl iodide (3 cm3) and silver(I) oxide (500 mg) away from light
for 27 h. The suspension was filtered, and the filtrate was then treated
with sodium acetate (300 mg) in acetic acid (25 cm3) at 100° for 2 h.
Phytochemistry, 1993, 32, 1273.
17
Haynes, L. J., Henderson, J. I., and Tyler, J. M., J. Chem. Soc., 1960,
4879.