Synthesis of coruscanones A and B, metabolites of piper coruscans, and related compounds

Article abstract of DOI:10.1007/s11172-010-0048-9

Base-catalyzed rearrangements of both individual 4-(acylmethylidene) butenolides and their mixtures prepared by condensation of citraconic anhydride with various phosphoranes occur successfully only in the presence of 5.2% MeONa in MeOH (molar ratio MeONa

Full text of DOI:10.1007/s11172-010-0048-9

Russian Chemical Bulletin, International Edition, Vol. 59, No. 1, pp. 81—90, January, 2010
81
Synthesis of coruscanones A and B,
metabolites of Piper coruscans, and related compounds
O. P. Shestak and V. L. Novikov
Pacific Institute of Bioorganic Chemistry, FarꢀEast Division of the Russian Academy of Sciences,
159 prosp. 100 Let Vladivostoku, 690022 Vladivostok, Russian Federation.
Fax: +7 (423 2) 31 4050. Eꢀmail: shestak@piboc.dvo.ru
Baseꢀcatalyzed rearrangements of both individual 4ꢀ(acylmethylidene)butenolides and their
mixtures prepared by condensation of citraconic anhydride with various phosphoranes occur
successfully only in the presence of 5.2% MeONa in MeOH (molar ratio MeONa : substꢀ
rate ≤ 10 : 1, room temperature, 1—2 h). Under these conditions, the yields of 2ꢀcinnamoylꢀ4ꢀ
methylcyclopentꢀ4ꢀeneꢀ1,3ꢀdione (coruscanone B) and 2ꢀacetylꢀ4ꢀmethylcyclopentꢀ4ꢀeneꢀ
1,3ꢀdione are 56 and 65%, respectively. With a considerable increase in the reaction temperaꢀ
ture or the molar ratio MeONa : substrate, formal addition of MeOH to the C(4)=C(5) double
bond of these triketones becomes an appreciable (or predominant) process. A reaction of
coruscanone B with CH2N2 in ether gives coruscanone A as a ~3 : 2 mixture of (Z)ꢀ and
(E)ꢀmethyl enolates (43%); other products (10%) result from the expansion and aromatization
of the fiveꢀmembered ring of the triketone. The simplest analog of coruscanone B, 2ꢀacetylꢀ4ꢀ
methylcyclopentꢀ4ꢀeneꢀ1,3ꢀdione, reacts with CH2N2 in a similar way.
Key words: citraconic anhydride, the Wittig reaction, 4ꢀ(acylmethylidene)butenolides, baseꢀ
catalyzed rearrangements, 2ꢀacylcyclopentꢀ4ꢀeneꢀ1,3ꢀdiones, coruscanones A and B, Oꢀalkylaꢀ
tion, diazomethane.
In the last few years, many biochemical and pharmaꢀ
cological investigations have been focused on cyclopenꢀ
tene β,β´ꢀtriketones (2ꢀacylcyclopentꢀ4ꢀeneꢀ1,3ꢀdiones)
and methyl ethers of the corresponding enols produced by
higher plants of the genera Calythrix, Lindera, and Piper.
Some of them proved to be efficient antifungal,1—3 antituꢀ
mor,2,4 and antiinflammatory agents,5,6 as well as chiꢀ
mase,7 chitin synthase 2,3 and farnesylꢀprotein transferase
inhibitors.4
fluconazoleꢀresistant strains Candida albicans and Cryptoꢀ
coccus neoformans, which are the main opportunistic fungi
that attack AIDS patients with lowered immunity.1,2
Two known routes to coruscanone B (1) start from
citraconic anhydride1,2 and 2ꢀacetylfuran.14 The former
method is simpler and more efficient, involving the conꢀ
version of citraconic anhydride into the corresponding
4ꢀylidenebutenolide and its baseꢀcatalyzed rearrangement
into the target triketone 1.
During our systematic studies8—13 of the physicochemꢀ
ical and biological properties of 2ꢀacetylcyclopentꢀ4ꢀeneꢀ
1,3ꢀdiones, we needed to compare the biological activities
of coruscanone B (1), its methyl enolate, coruscanone
A (2) (both are the metabolites of Piper coruscans1), and
their simplest synthetic analogs 3 and 4. Coruscanone A (2)
showed potent in vitro antifungal activity against the
The goal of the present work was to obtain coruscanone
B (1) and its simplest analog, triketone 3, according to the
aforementioned approach1,2 and further conversion of
triketones 1 and 3 into their methyl enolates 2 (corusꢀ
canone A) and 4, respectively. Earlier, triketone 3 has not
been synthesized in this way.
This approach was first employed for the synthesis of
2ꢀisobutyroylꢀ4,5ꢀdimethylcyclopentꢀ4ꢀeneꢀ1,3ꢀdione
(calythrone) and related cyclopentene β,β´ꢀtriketones.15,16
In our experiments, the Wittig reaction of anhydride 5
with phosphorane 6 (benzene, 11ꢀh reflux, Scheme 1) ocꢀ
curred regiospecifically at the unhindered carbonyl group
of the substrate to give a ~9 : 1 mixture of known1,2
(E)ꢀbutenolide 8 and undocumented (Z)ꢀbutenolide 10 in
a total yield of 76%. These butenolides were isolated in the
individual state by column chromatography on SiO2. The
column chromatography revealed no trace amounts of
R = H (1, 3), Me (2, 4)
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 82—91, January, 2010.
1066ꢀ5285/10/5901ꢀ0081 © 2010 Springer Science+Business Media, Inc.

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Shestak and Novikov
products that would result from an attack of phosphorane
6 at the sterically hindered carbonyl group of anhydride 5.
The Wittig reaction of anhydride 5 with a less bulky and
less reactive phosphorane 7 (toluene, 16ꢀh reflux) was reꢀ
gioselective, mainly occurring at the less hindered carbonyl
group. However, apart from products 9 and 11, their
regioisomers 12 and 13 were also obtained in noticeꢀ
able amounts (total yield of 14%). Compound 12 has
not been documented hitherto. The ratio of butenoꢀ
lides 9 : 11 : 12 : 13 in the final mixture is 26 : 11 : 1 : 6
(1H NMR data). The total yield of butenolides 9 and
11—13 was 89%.
spectively, while the corresponding signals in the spectra
of (E)ꢀbutenolide 9 and (Z)ꢀbutenolide 11 appear at δ 2.10
1
and 2.11, respectively. When comparing the H NMR
spectra of butenolides 8 and 10 with those of butenolides 9
and 11, one can see that compounds 8 and 9 are (E)ꢀisomers
and compounds 10 and 11 are (Z)ꢀisomers with respect to
1
the exocyclic double bond C(5)=C(1´). The H NMR
spectra of these compounds show characteristic signals
for H(4) and H(1´). In the spectra of (E)ꢀbutenolides 8
and 9, the signals for H(4) appear at δ 8.11 and 7.98
(as a result of the deshielding effect of the carbonyl dipole
of the COMe group), while the signals for H(1´) appear at
δ 6.48 and 6.17, respectively (as a result of the deshielding
effect of the cisoid O atom of the heterocycle). In the
spectra of (Z)ꢀbutenolides 10 and 11, the H(4) atoms resꢀ
onate at δ 7.19 and 7.17 and the H(1´) atoms resonate at
δ 5.71 and 5.49, respectively.
Scheme 1
Baseꢀcatalyzed rearrangements of 4ꢀylidenebutenolides
into the corresponding cyclopentene β,β´ꢀtriketones unꢀ
der the action of MeONa in MeOH were first described
in Refs 15, 16. Three (Z)ꢀ4ꢀylidenebutenolides with
structurally different ylidene side chains were obtained
from dimethylmaleic anhydride and rearranged according
to a general procedure under the following conditions:
freshly prepared 0.8% MeONa in anhydrous MeOH,
MeONa : substrate = 7.2—10.5 (mol/mol), 1ꢀh reflux.
The yields of triketones were 78—90%.
3
Using this procedure for rearrangement of (E)ꢀbutenoꢀ
lide 8 (0.78% MeONa in MeOH, MeONa : substrate =
= 10.5 : 1, 1ꢀh reflux), we unexpectedly obtained a mixꢀ
ture of coruscanone B (1) (21% yield) and undocumented
methoxy triketone 14 (56% yield) (see Scheme 1). Under
the conditions employed in Ref. 1 (5.2% MeONa in
MeOH, MeONa : substrate = 10.0 : 1, room temperature,
3 h), the yield of coruscanone B (1) increased to 47%
(against 62% in Ref. 1); however, methoxy triketone 14
was also obtained (9%).
Monitoring of the course of the reaction by chromaꢀ
tography revealed that the formation of coruscanone B is
completed in 1 h. The yields of compounds 1 and 14 were
52 and 5%, respectively. These conditions for the rearꢀ
rangement of (E)ꢀbutenolide 8 seem to be nearly optimum
since the yield of coruscanone B (1) decreases under other
conditions. For instance, for 2.5% MeONa in MeOH and
MeONa : substrate = 5.0 : 1 (room temperature, 1 h), the
yields of products 1 and 14 were 43 and 3%, respectively;
for 8.2% MeONa in MeOH and MeONa : substrate =
= 18.0 : 1 (room temperature, 1 h), the correspondꢀ
ing yields were 40 and 33%. As shown above, the forꢀ
mation of compound 14 is best promoted at elevated
temperatures.
Butenolides 9 and 11—13 were isolated in the individꢀ
ual state by column chromatography on SiO2. Compounds
12 and 13 can easily be distinguished from their regioisoꢀ
mers 9 and 11 by 1H NMR spectroscopy. In the spectra of
(E)ꢀbutenolide 12 and (Z)ꢀbutenolide 13, the protons of
the Me group in the βꢀposition of the carbonylꢀconjugated
double bond C(3)=C(4)* resonate at δ 2.35 and 2.20, reꢀ
Methoxy triketone 14 can easily be transformed into
coruscanone in 67% yield when treated with dry 6% HCl
in MeOH at room temperature for 1 h. This makes the
synthesis of coruscanone B (1) more efficient. Moreover,
* Numbering of the C atoms is shown on the structural formulas
of the compounds.

Coruscanones A and B
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 1, January, 2010
83
Scheme 2
the latter can be obtained not only from pure (E)ꢀbutenoꢀ
lide 8. Rearrangement of a mixture of (E)ꢀ and (Z)ꢀbutenoꢀ
lides 8 and 10 under optimum conditions (5.1% MeONa
in MeOH, MeONa : substrate = 10.0 : 1, room temperaꢀ
ture, 1 h) afforded coruscanone B (1) in 56% yield, the
yield of methoxy triketone 14 being 6%. Upon the converꢀ
sion 14 → 1, the total yield of coruscanone B was inꢀ
creased to 60%.
Rearrangement of less reactive acetonylidenebutenꢀ
olide 9 (freshly prepared 5.5% MeONa in MeOH,
MeONa : substrate = 5.0 : 1, room temperature, 2 h) gave
a mixture of known triketone 3 (50% yield) and undocuꢀ
mented methoxy triketone 15 (2% yield). Under the same
conditions (except that the ratio MeONa : substrate was
increased to 10.0 : 1), the yield of triketone 3 was 61% and
the yield of product 15 was 4%.
As in the synthesis of triketone 1, triketone 3 can be
obtained not only from pure (E)ꢀbutenolide 9. Rearrangeꢀ
ment of a mixture of butenolides 9 and 11—13 under the
aforementioned optimum conditions gave triketone 3 in
65% yield. The yield of triketone 15 was 8%.
Because compounds 1 and 14 have close Rf values,
their chromatographic separation is difficult. So we tried
to separate them by extraction from a solution in CHCl3
with aqueous saturated NaHCO3. These triketones are both
fully enolized in CHCl3 and either can theoretically exist
as a mixture of four enol species A—D (Scheme 2). Beꢀ
cause each tautomer contains a fragment of a vinylogous
carboxylic acid, these compounds exhibit pronounced acid
properties. However, it turned out that methoxy triketone
14 is a stronger acid than triketone 1 and when treated
with a solution of NaHCO3 can easily be extracted from
the organic phase as the corresponding salt. Treatment of
the bicarbonate extract with 10% HCl liberated triketone
14. Products 3 and 15 were separated in a similar way.
The spectroscopic characteristics of compound 1 fully
agree with those of both natural1,17 and earlier prepared
i. Slowly. ii. Rapidly.
R = CH=CHPh (1, 14), Me (3, 15)
1
synthetic coruscanone B.1,2,14 In the H NMR spectrum
of coruscanone B (1), each signal for the Me, OH, and
H(5) protons appears as a set of two similar signals, which
suggests the presence of two enol forms of this compound
in CDCl3. One form is slightly dominant: the integral
intensity ratio for analogous signals is ~11 : 9 in our case
and 1.2 : 1 in natural coruscanone B.1 The rate of exꢀ
change between tautomers A and B (see Scheme 2) in
a solution of coruscanone B is two orders of magnitude
higher than the NMR time scale and hence these tauꢀ
tomers cannot be differentiated spectroscopically. The
same relates to tautomers C and D. At the same time, the
rate of exchange between tautomers A and C or between
tautomers B and D is comparable with the NMR time
scale, which allows these equilibria to be seen in the specꢀ
trum. Earlier,18 we found that triketone 3 obtained, like
compound 1, according to Scheme 1 exists in CDCl3 as an
equilibrium mixture of tautomers A and C in a ratio
of ~3 : 2. Quantumꢀchemical DFT calculations at the
B3LYP/6ꢀ31G(d) level showed that enolization of trikeꢀ
tone 3 should occur almost completely in the side chain
since the total Gibbs energies (GH) of tautomers A and C
are lower by 5—6 kcal mol–1 than the corresponding
GH values of tautomers B and D. The difference in the
GH values between tautomers A and C is small, speꢀ
cies A being slightly more favorable (GH(C) – GH(A)
≈
1
≈ 0.8—1.0 kcal mol–1). When comparing the H and 13C
chemical shifts in the corresponding NMR spectra of trikeꢀ
tone 3 and coruscanone B (1), one can conclude that
triketone 1 also exists as an equilibrium mixture of tauꢀ
tomers A and C (see Scheme 2), the former being domiꢀ
nant. Tautomers A and C may be regarded as geometrical
(E)ꢀ and (Z)ꢀisomers, respectively, with respect to the
double bond C(2)=C(1´).

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Shestak and Novikov
Scheme 3
The structure of undocumented methoxy triketone 14
was determined from H and 13C NMR, IR, and mass
spectra. According to 1H and 13C NMR spectra, triketone
14 in CDCl3 exists as an equilibrium mixture of two tauꢀ
tomers. A large difference between the 1H chemical shifts
of the CH2 protons and the C(4)Me and OMe protons for
these species suggests that the observed equilibrium is beꢀ
tween tautomers B and D (~3 : 2, see Scheme 2) rather
than between tautomers A and C as in the case of corusꢀ
canone B (1).
1
This conclusion is true for related methoxy triketone
15 also existing as an equilibrium ~3 : 2 mixture of tauꢀ
tomers B and D (1H NMR data).
1
Interestingly, the H and 13C NMR spectra of comꢀ
pound 14 in DMSOꢀd6 show only one set of signals. Such
a spectral pattern is probably explained by a much higher
rate of exchange between DMSOꢀsolvated enol forms B
and D, which seems to pass through a triketone intermeꢀ
diate (in DMSO, the formation of this species is very
likely19). Apparently, the rate of this exchange is highꢀ
er than the NMR time scale and hence the 1H and
13C NMR spectra show signals for an average form of
compound 14.
The formation of considerable amounts of methoxy
triketone 14 in the synthesis of coruscanone B promptꢀ
ed us to study the reaction scheme leading to this byꢀ
product. Fundamentally, it can form in two ways. Acꢀ
cording to the first way (Scheme 3), the methoxide anion
attacks the electrophilic C(3) center of butenolide 8
and another MeONa molecule attacks the electrophilic
C(2) center of intermediate 16. The resulting double salt
17a undergoes cyclization, through its tautomer 17b, into
salt 18. Acid hydrolysis of the latter gives methoxy triꢀ
ketone 14.
An alternative way involves an initial attack of the
methoxide anion on butenolide 8 at the C(2) rather than
C(3) atom (Scheme 4). The resulting coruscanone B salt
20 can be transformed, via conjugated addition of a secꢀ
ond MeONa molecule, into double salt 18 and further
into product 14 (acid hydrolysis).
To verify this assumption, we treated coruscanone
B (1) with freshly prepared 5.2% MeONa in MeOH
(MeONa : substrate = 10.0 : 1) in an inert atmosphere at
room temperature for 1 h. Upon acid hydrolysis, the yield
of methoxy triketone 14 was only 10%. Therefore, the
formation of product 14 predominantly involves the conꢀ
version sequence 8 → 16 → 17 → 18 → 14 (see Scheme 3).
Under similar conditions, triketone 3 reacted with
MeONa as well; however, the yield of product 15 was very
low (~2%).
Our study of baseꢀcatalyzed rearrangements of 4ꢀyliꢀ
denebutenolides 8, 10 and 9, 11—13 revealed the two most
important conditions for the successful synthesis of trikeꢀ
tones 1 and 3: the reaction temperature must be ~20 °C
and the molar ratio MeONa : substrate should not exceed
12 : 1 (an optimal value is 10 : 1). The reaction time is less
important (1—2 h). When the reaction is carried out in
boiling methanol, the fractions of methoxy triketones 14
and 15 increase substantially (note that rearrangements of
4ꢀylidenebutenolides prepared from dimethylmaleic anꢀ
hydride produce no such compounds15,16).
To obtain coruscanone A (2), which is methyl enolate
of coruscanone B (1), first we tried out relatively simple
and rapid Oꢀmethylation with CH2N2. Diazomethane is
known to be often employed earlier for the preparation of
methyl enolates of cyclopentane β,β´ꢀtriketones, includꢀ
ing natural ones.20—23 However, a reaction of coruscanone
B (1) with diazomethane gave a mixture of several prodꢀ
ucts (Scheme 5), which were separated by column chroꢀ
matography on SiO2.
The target coruscanone A (2) was isolated as a ~3 : 2
mixture of (Z)ꢀ and (E)ꢀmethyl ethers 2A and 2C in 43%
yield. The ratio of the isomers (relative to the double bond
1
C(2)=C(1´)) was determined from the H NMR specꢀ
trum in CDCl3. Natural coruscanone A (2) exists in CDCl3
as a ~1 : 1 mixture of (Z)ꢀ and (E)ꢀisomers.1 Apart from
coruscanone A (2), we isolated a ~5 : 2 mixture of regioꢀ
isomers 21 and 22 (2ꢀcinnamoylꢀ4ꢀmethoxyꢀ5(6)ꢀmethꢀ

Coruscanones A and B
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 1, January, 2010
85
Scheme 4
C(3) atoms, respectively, of the fiveꢀmembered ring of
coruscanone B (1), which is followed by ring expansion
and aromatization and Oꢀmethylation of the free OH
group of the resulting hydroquinone (earlier,24 this transꢀ
formation was discussed in detail for a reaction of CH2N2
with 2ꢀacetylindaneꢀ1,3ꢀdione). The ratio 21 : 22 indiꢀ
cates that the carbene mainly attacks the less hindered
carbonyl group of coruscanone B (1). Another product of
this reaction was compound 23 (8%) identified as methyl
octatrienoate from 1H and 13C NMR, IR, and mass specꢀ
tra. The (Z)ꢀconfiguration of the double bond C(2)=C(3)
of this compound was determined from a strong NOE in
the 2D NOESY spectrum of ester 23 between the spins of
the C(2)Me and H(3) protons. The (E)ꢀconfiguration of
the double bond C(7)=C(8) is evident from JH(7),H(8)
=
1
= 15.9 Hz in the H NMR spectrum. Apparently, this
compound is produced by a reaction of very unstable
cyclopentadienone enolate 26 with a water molecule
(Scheme 6).
Scheme 6
Scheme 5
The presence of water traces in the reaction mixture is
due to incomplete drying of a rapidly prepared solution of
CH2N2 in ether. When the solution was dried thoroughly,
product 23 was not formed.
Model β,β´ꢀtriketone 3 reacted with CH2N2 in a simiꢀ
lar way; however, the yields and ratio of products differed
from those in the case of coruscanone B (1) (Scheme 7).
A difficultꢀtoꢀseparate mixture of nearly equal amounts
of (Z)ꢀ and (E)ꢀenolates 4A and 4C (relative to the double
7
7
R1 = Me, R2 = H (21); R1 = H, R2 = Me (22)
ylphenols) in 10% yield. The position of the methyl
group (at the C(5) or C(6) atom) in their structures and
the (E)ꢀconfiguration of the double bond C(2´)=C(3´)
(J(H2´),H(3´) = 15.4 Hz) were determined from the 1H NMR
spectrum. Apparently, the formation of these products reꢀ
sults from an attack of a carbene on the carbonyl C(1) and

86
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Shestak and Novikov
Scheme 7
in anhydrous benzene (50 mL). The reaction mixture was reꢀ
fluxed for 11 h. The solvent was removed and the residue
was chromatographed on SiO2. Elution with hexane—acetone
((30 : 1)—(20 : 1)) gave butenolide 8 (2.2 g, 68%) as yellow neeꢀ
dles, m.p. 158—159 °C (chloroform—ethanol, 1 : 1) (cf. Ref. 1:
m.p. 160—161 °C). IR, νmax/cm–1: 1786 (C=O), 1652 (C=O),
1628 (C=C), 1617 (C=C), 1598 (C=C), 1577 (C=C). 1H NMR
(CDCl3), δ: 2.11 (dd, 3 H, C(3)Me, J = 1.7 Hz, J = 0.6 Hz); 6.48
(quint, 1 H, H(1´), J = 0.6 Hz); 6.88 (d, 1 H, H(3´), J = 16.0
Hz); 7.42 (m, 3 H, H(7´), H(8´), H(9´)); 7.60 (m, 2 H, H(6´),
H(10´)); 7.65 (d, 1 H, H(4´), J = 16.0 Hz); 8.11 (dq, 1 H, H(4),
J = 1.7 Hz, J = 0.6 Hz).
Elution with hexane—acetone ((20 : 1)—(15 : 1)) gave butꢀ
enolide 10 (0.245 g, 8%) as yellow needles, m.p. 190—192 °C
(chloroform—ethanol, 1 : 1). IR, νmax/cm–1: 1798 (C=O), 1663
(C=O), 1630 (C=C), 1621 (C=C), 1600 (C=C), 1581 (C=C).
1H NMR (CDCl3), δ: 2.12 (dd, 3 H, C(3)Me, J = 1.7 Hz,
J = 1.0 Hz); 5.71 (quint, 1 H, H(1´), J = 1.0 Hz); 6.80 (d, 1 H,
H(3´), J = 16.0 Hz); 7.19 (dq, 1 H, H(4), J = 1.7 Hz, J = 1.0 Hz);
7.43 (m, 3 H, H(7´), H(8´), H(9´)); 7.59 (m, 2 H, H(6´), H(10´));
7.78 (d, 1 H, H(4´), J = 16.0 Hz). Found (%): C, 75.12; H, 4.99.
C15H12O3. Calculated (%): C, 74.99; H, 5.03.
7
7
R1 = Me, R2 = H (28); R1 = H, R2 = Me (29)
bond C(2)=C(1´)) was isolated in ~50% yield. The yield
of a ~3 : 2 mixture of regioisomers 28 and 29 (2ꢀacetylꢀ4ꢀ
methoxyꢀ5(6)ꢀmethylphenols) was 25%. In this case, no
product of the type 23 was detected.
A more suitable procedure for the synthesis of corusꢀ
canone A (2) involves methylation of coruscanone B (1)
with Me2SO4 in dry acetone in the presence of anhydrous
K2CO3. The yield of coruscanone A (2) as a ~3 : 2 mixture
of (E)ꢀ and (Z)ꢀmethyl enolates was 77%; no byꢀproducts
were detected. At the same time, methylation of model
triketone 3 under similar conditions gave product 4 as
a ~3 : 2 mixture of (E)ꢀ and (Z)ꢀmethyl enolates only in
20% yield.
(5E) 3 Methyl 5 (2 oxopropylidene)furan 2(5H) one (9),
(5Z) 3 methyl 5 (2 oxopropylidene)furan 2(5H) one (11),
(5E) 4 methyl 5 (2 oxopropylidene)furan 2(5H) one (12), and
(5Z) 4 methyl 5 (2 oxopropylidene)furan 2(5H) one (13). A soꢀ
lution of citraconic anhydride 5 (1.12 g, 10 mmol) in toluene
(10 mL) was added under argon to a boiling solution of phosphoꢀ
rane 7 (3.18 g, 10 mmol) in anhydrous toluene (90 mL). The
reaction mixture was refluxed for 16 h. The solvent was removed
and the residue was chromatographed on SiO2. Elution with
hexane—acetone (45 : 1) gave butenolide 9 (0.8 g, 53%) as light
yellow needles, m.p. 88—90 °C (ether—hexane, 1 : 1) (cf. Refs
26, 27: m.p. 88—89 °C). IR, νmax/cm–1: 1788 (C=O), 1720
Hence, the nature of the acyl substituent at the C(2)
atom in triketones 1 and 3 substantially influences the
outcomes of their reactions with CH2N2 and Me2SO4.
Experimental
1
(C=O), 1655 (C=C), 1615 (C=C). H NMR (CDCl3), δ: 2.10
(dd, 3 H, C(3)Me, J = 1.5 Hz, J = 0.5 Hz); 2.34 (s, 3 H, COMe);
6.17 (quint, 1 H, H(1´), J = 0.5 Hz); 7.98 (dq, 1 H, H(4), J = 1.5 Hz,
J = 0.5 Hz).
Elution with hexane—acetone (38 : 1) gave butenolide 12
(0.027 g, 2%) as a viscous oil. IR, νmax/cm–1: 1815 (C=O), 1795
(C=O), 1725 (C=O), 1660 (C=C), 1618 (C=C). 1H NMR
(CDCl3), δ: 2.33 (s, 3 H, COMe); 2.35 (d, 3 H, C(4)Me,
J = 1.6 Hz); 6.21 (quint, 1 H, H(3), J = 1.6 Hz); 6.35 (d, 1 H,
H(1´), J = 1.6 Hz). Found (%): C, 63.29; H, 5.32. C8H8O3.
Calculated (%): C, 63.16; H, 5.26.
Elution with hexane—acetone (35 : 1) gave butenolide 11
(0.33 g, 22%) as light yellow needles, m.p. 123—124 °C (ether—heꢀ
xane, 1 : 1) (cf. Ref. 27: m.p. 125 °C). IR, νmax/cm–1: 1798
(C=O), 1724 (C=O), 1659 (C=C), 1617 (C=C). 1H NMR
(CDCl3), δ: 2.11 (dd, 3 H, C(3)Me, J = 1.5 Hz, J = 1.0 Hz); 2.55
(s, 3 H, COMe); 5.49 (quint, 1 H, H(1´), J = 1.0 Hz); 7.17 (dq, 1 H,
H(4), J = 1.5 Hz, J = 1.0 Hz).
Elution with hexane—acetone (33 : 1) gave butenolide 13
(0.18 g, 12%) as light yellow needles, m.p. 91—93 °C (ether—heꢀ
xane, 2 : 1) (cf. Ref. 27: m.p. 92—94 °C). IR, νmax/cm–1: 1805
(C=O), 1789 (C=O), 1701 (C=O), 1671 (C=O), 1649 (C=C),
1622 (C=C). 1H NMR (CDCl3), δ: 2.20 (d, 3 H, C(4)Me,
J = 1.4 Hz); 2.57 (s, 3 H, COMe); 5.59 (d, 1 H, H(1´), J = 0.5 Hz);
6.18 (dq, 1 H, H(3), J = 1.4 Hz, J = 0.5 Hz).
Melting points were determined on a Boetius hot stage and
are given uncorrected. IR spectra were recorded on a Bruker
Vector 22 spectrophotometer in CHCl3. 1H and 13C NMR specꢀ
tra were recorded on a Bruker Avance DPXꢀ300 spectrometer
(300.13 (1H) and 75.47 MHz (13C)) in CDCl3 with Me4Si as the
internal standard. Mass spectra (EI) were measured on an AMD
604 S instrument (8 kW, direct inlet probe, ionizing energy 70 eV).
The course of the reactions was monitored, and the purity of the
products was checked, by TLC on Silufol UV 254 plates in benꢀ
zene—acetone systems from 15 : 1 to 2 : 1. The products were
isolated in the individual state by column chromatography on
SiO2 (Alfa Aesar, 70—230 μm) with hexane—acetone mixtures
as eluents. Elemental analysis was carried out on a Flash E1112
C, H, Nꢀanalyzer.
Freshly distilled citraconic anhydride 5 (b.p. 85 °C, 5 Torr)
was used. Phosphoranes 6 (see Ref. 1) and 7 (see Ref. 25) were
prepared according to known procedures. A solution of diazoꢀ
methane in ether was prepared in a separatory funnel by decomꢀ
position of NꢀmethylꢀNꢀnitrosourea with aqueous NaOH; the
organic layer was dried over anhydrous Na2SO4.
(5E) 3 Methyl 5 (2 oxo 4 phenylbut 3 en 1 ylidene)furan
2(5H) one (8) and (5Z) 3 methyl 5 (2 oxo 4 phenylbut 3 en 1
ylidene)furan 2(5H) one (10). A solution of citraconic anhydride
5 (1.8 g, 16.1 mmol) in benzene (10 mL) was added under argon
to a boiling solution of phosphorane 6 (5.5 g, 13.5 mmol)
(2Z) [(2E) 1 Hydroxy 3 phenylprop 2 en 1 ylidene] 4 me
thylcyclopent 4 ene 1,3 dione (1A) and (2E) [(2E) 1 hydroxy

Coruscanones A and B
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 1, January, 2010
87
3 phenylprop 2 en 1 ylidene] 4 methylcyclopent 4 ene 1,3 di
one (1C, coruscanone B), (2E) 2 cinnamoyl 3 hydroxy 5 meth
oxy 5 methylcyclopent 2 en 1 one (14B) and (2E) 2 cinnamoyl
3 hydroxy 4 methoxy 4 methylcyclopent 2 en 1 one (14D).
A solution of MeONa freshly prepared from metallic Na (0.664 g)
in MeOH (20 mL) was added dropwise to a solution of butenꢀ
olide 8 (0.7 g, 2.8 mmol) in dry MeOH (9 mL). The reaction
mixture was stirred at room temperature for 1 h, poured into
a mixture of ice and water (45 mL), and acidified with 2 M HCl
to pH 1.0. The solvent was removed under reduced pressure and
the product was extracted from the aqueous suspension with
chloroform (4×15 mL). The combined organic extracts were
washed with a saturated aqueous solution of NaHCO3 (3×20 mL)
and brine (3×15 mL), dried over anhydrous Na2SO4, and conꢀ
centrated. The crude product was chromatographed on SiO2.
Elution with hexane—acetone (30 : 1) gave coruscanone B (1)
(0.364 g, 52%), m.p. 127 °C (hexane) (cf. Ref. 1: m.p. 125 °C).
A mixture of tautomers 1A and 1C. IR, νmax/cm–1: 3400—2600
(OH), 1709 (C=O), 1650 (C=O), 1631 (C=O, C=C), 1590
(C=C), 1573 (C=C). Major tautomer 1A ((Z)ꢀisomer). 1H NMR
(CDCl3), δ: 2.11 (d, 3 H, C(4)Me, J = 1.7 Hz); 6.69 (q, 1 H,
H(5), J = 1.7 Hz); 7.41 (m, 3 H, H(6´), H(7´), H(8´)); 7.65
(m, 2 H, H(5´), H(9´)); 7.72 and 7.80 (both d, 1 H each, H(3´),
H(2´), J = 16.0 Hz); 12.10 (br.s, 1 H, C(1´)OH). 13C NMR
(CDCl3), δ: 11.4 (C(6)); 103.1 (C(2)); 117.5 (C(2´)); 128.6
(C(5´), C(9´)); 129.0 (C(6´), C(8´)); 130.7 (C(7´)); 134.8 (C(4´));
137.0 (C(5)); 143.2 (C(3´)); 158.0 (C(4)); 167.9 (C(1´)); 192.2
(C(3)); 200.7 (C(1)). Tautomer 1C ((E)ꢀisomer). 1H NMR
(CDCl3), δ: 2.10 (d, 3 H, C(4)Me, J = 1.7 Hz); 6.61 (q, 1 H,
H(5), J = 1.7 Hz); 7.41 (m, 3 H, H(6´), H(7´), H(8´)); 7.65 (m, 2 H,
H(5´), H(9´)); 7.71 and 7.80 (both d, 1 H each, H(3´), H(2´),
J = 16.0 Hz); 11.99 (br.s, 1 H, C(1´)OH). 13C NMR (CDCl3), δ:
10.6 (C(6)); 103.4 (C(2)); 117.6 (C(2´)); 128.7 (C(5´), C(9´));
129.0 (C(6´), C(8´)); 130.7 (C(7´)); 134.8 (C(4´)); 140.7 (C(5));
143.3 (C(3´)); 154.1 (C(4)); 167.7 (C(1´)); 191.7 (C(1)); 201.2
(C(3)). Coruscanone B (1). MS (EI, 70 eV), m/z (Irel (%)): 241
[M + 1]+ (10), 240 [M]+ (50), 239 [M – 1]+ (6), 225 (4), 223 (3),
222 (4), 212 (12), 211 (27), 198 (9), 197 (44), 196 (16), 195 (100),
194 (10), 171 (33), 165 (13), 144 (13), 138 (15), 115 (25), 104
(13), 103 (20), 77 (23), 69 (18), 32 (90).
7.71 (m, 2 H, H(5´), H(9´)); 7.92 and 8.04 (both d, 1 H each,
H(3´), H(2´), J = 16.0 Hz); 12.20 (br.s, 1 H, C(1´)OH).
13C NMR (CDCl3), δ: 22.0 (C(6)); 47.5 (C(5)); 52.1 (C(7)); 79.0
(C(4)); 110.5 (C(2)); 118.9 (C(2´)); 129.1 (C(5´), C(9´)); 129.5
(C(6´), C(8´)); 131.6 (C(7´)); 135.0 (C(4´)); 148.1 (C(3´)); 181.7
(C(1´)); 196.9 (C(1)); 207.2 (C(3)). Triketone 14. 1H NMR
(DMSOꢀd6), δ: 1.37 (s, 3 H, C(4)Me); 2.69 and 2.90 (both d,
1 H each, H(5), J = 18.8 Hz); 3.17 (s, 3 H, C(4)OMe); 7.51
(m, 3 H, H(6´), H(7´), H(8´)); 7.76 (m, 2 H, H(5´), H(9´)); 7.81
and 7.97 (both d, 1 H each, H(3´), H(2´), J = 16.0 Hz); 10.30
(br.s, 1 H, C(1´)OH). 13C NMR (DMSOꢀd6), δ: 21.7 (C(6));
43.7 (C(5)); 51.3 (C(7)); 79.6 (C(4)); 110.0 (C(2)); 119.7 (C(2´));
129.0 (C(5´), C(9´)); 129.3 (C(6´), C(8´)); 131.7 (C(7´)); 134.2
(C(4´)); 146.0 (C(3´)); 181.5 (C(1´)); 200.9 (C(1)); 201.4 (C(3)).
MS, m/z (Irel (%)): 272 [M]+ (12), 243 (17), 242 (100), 200 (22),
172 (8), 171 (20), 144 (18), 138 (43), 131 (33), 116 (17), 115 (20),
103 (18), 77 (10), 73 (21), 69 (12), 43 (13), 42 (14), 41 (12), 32
(35). Found (%): C, 70.67; H, 5.89. C16H16O4. Calculated (%):
C, 70.57; H, 5.92.
Rearrangement of a mixture of butenolides 8 and 10. A ~9 : 1
mixture of (E)ꢀbutenolide 8 and (Z)ꢀbutenolide 10 (0.7 g,
2.8 mmol) in dry MeOH (10 mL) and MeONa freshly prepared
from metallic Na (0.664 g) in MeOH (20 mL) were stirred at
room temperature for 1 h. The workup described above gave
coruscanone B (1) (0.392 g, 56%) and triketone 14 (0.046 g, 6%).
Conversion of triketone (14) into coruscanone B (1). A mixꢀ
ture of triketone 14 (0.095 g, 0.35 mmol) and a 6% solution of
dry gaseous HCl in anhydrous MeOH (5 mL) was stirred at room
temperature for 1 h. The reaction mixture was diluted with waꢀ
ter (20 mL) and the product was extracted with chloroform
(3×5 mL). The combined extracts were dried over anhydrous
Na2SO4 and concentrated. The crude product was chromatoꢀ
graphed on SiO2. Elution with hexane—acetone (30 : 1) gave
coruscanone B (1) (0.057 g, 67%), which is identical with the
aforementioned sample.
(2Z) 2 (1 Hydroxyethylidene) 4 methylcyclopent 4 ene 1,3
dione (3A) and (2E) 2 (1 hydroxyethylidene) 4 methylcyclopent
4 ene 1,3 dione (3C), 2 acetyl 3 hydroxy 5 methoxy 5 methyl
cyclopent 2 en 1 one (15B) and 2 acetyl 3 hydroxy 4 methoxy
4 methylcyclopent 2 en 1 one (15D). A solution of MeONa
freshly prepared from metallic Na (2.3 g) in MeOH (58 mL) was
added dropwise to a solution of butenolide 9 (1.52 g, 10.0 mmol)
in dry MeOH (40 mL). The reaction mixture was stirred at room
temperature for 2 h, poured into a mixture of ice and water, and
acidified with 2 M HCl. The acidic solution was treated as deꢀ
scribed above for the rearrangement of butenolide 8. The prodꢀ
uct was chromatographed on SiO2. Elution with hexane—aceꢀ
tone (25 : 1) gave triketone 3 (0.92 g, 61%) as light yellow plates,
m.p. 43—47 °C (hexane) (cf. Ref. 28: m.p. 45—50 °C). A mixture
of tautomers 3A and 3C. IR, νmax/cm–1: 3235—2300 (OH), 1718
(C=O), 1659 (C=O), 1630 (C=O), 1616 (C=O, C=C), 1590
(C=C). Major tautomer 3A ((Z)ꢀisomer). 1H NMR (CDCl3), δ:
2.07 (d, 3 H, C(4)Me, J = 1.7 Hz); 2.39 (s, 3 H, C(1´)Me); 6.63
(q, 1 H, H(5), J = 1.7 Hz); 12.28 (br.s, 1 H, OH). 13C NMR
(CDCl3), δ: 11.3 (C(6)); 18.2 (C(2´)); 104.4 (C(2)); 136.3 (C(5));
157.9 (C(4)); 177.2 (C(1´)); 192.3 (C(3)); 200.1 (C(1)). Tauꢀ
tomer 3C ((E)ꢀisomer). 1H NMR (CDCl3), δ: 2.06 (d, 3 H,
C(4)Me, J = 1.7 Hz); 2.40 (s, 3 H, C(1´)Me); 6.56 (q, 1 H, H(5),
J = 1.7 Hz); 11.97 (br.s, 1 H, OH). 13C NMR (CDCl3), δ: 10.4
(C(6)); 18.2 (C(2´)); 104.6 (C(2)); 140.6 (C(5)); 153.4 (C(4));
177.0 (C(1´)); 191.8 (C(1)); 200.6 (C(3)). Triketone 3. MS,
Aqueous sodium bicarbonate phase used for washing the orꢀ
ganic extract was acidified with 2 M HCl to pH 1.0 and the product
was extracted with chloroform (4×5 mL). The combined organꢀ
ic extracts were washed with brine (4×5 mL), dried over anꢀ
hydrous Na2SO4, and concentrated. The crude product was
chromatographed on SiO2. Elution with hexane—acetone
((25 : 1)—(20 : 1)) gave triketone 14 (0.038 g, 5%) as light yellow
crystals, m.p. 68—72 °C. A mixture of tautomers 14B and 14D.
IR, νmax/cm–1: 3300—2200 (OH), 1702 (C=O), 1620 (C=O,
C=C), 1597 (C=O, C=C), 1580 (C=C), 1554 (C=C). Major
tautomer 14B. 1H NMR (CDCl3), δ: 1.47 (s, 3 H, C(4)Me); 2.67
and 2.95 (both d, 1 H each, H(5), J = 19.1 Hz); 3.32 (s, 3 H,
C(4)OMe); 7.45 (m, 3 H, H(6´), H(7´), H(8´)); 7.69 (m, 2 H,
H(5´), H(9´)); 7.92 and 8.03 (both d, 1 H each, H(3´), H(2´),
J = 16.0 Hz); 12.35 (br.s, 1 H, C(1´)OH). 13C NMR (CDCl3), δ:
21.7 (C(6)); 44.1 (C(5)); 52.0 (C(7)); 80.4 (C(4)); 110.0 (C(2));
118.6 (C(2´)); 129.1 (C(5´), C(9´)); 129.5 (C(6´), C(8´)); 131.5
(C(7´)); 134.3 (C(4´)); 147.9 (C(3´)); 182.0 (C(1)); 199.5 (C(3));
1
205.9 (C(1´)). Tautomer 14D. H NMR (CDCl3), δ: 1.54 (s, 3
H, C(4)Me); 2.53 and 2.84 (both d, 1 H each, H(5), J = 18.4
Hz); 3.34 (s, 3 H, C(4)OMe); 7.44 (m, 3 H, H(6´), H(7´), H(8´));

88
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 1, January, 2010
Shestak and Novikov
m/z (Irel (%)):153 [M + 1]+ (8), 152 [M]+ (84), 138 (6), 137 (79),
135 (2), 134 (5), 124 (3), 123 (5), 110 (3), 109 (6), 108 (3),
107 (2), 106 (3), 105 (3), 95 (7), 83 (7), 81 (19), 69 (43), 57 (12),
55 (12), 53 (12), 44 (26), 40 (20), 35 (28), 32 (100).
57 (5). Found (%): C, 76.23; H, 6.07. C17H16O3. Calculated (%):
C, 76.10; H, 6.01.
Elution with hexane—acetone (45 : 1) gave methyl (2Z,
4E,7E) 4 hydroxy 2 methyl 6 oxo 8 phenylocta 2,4,7 tri
enoate (23) (0.010 g, 8%) as light yellow crystals, m.p. 68—70 °C
(ethanol). IR, νmax/cm–1: 1717 (C=O), 1633 (C=O), 1580
(C=C), 1575 (C=C), 1449, 1437, 1262, 1200, 1143, 1118.
1H NMR (CDCl3), δ: 2.37 (d, 3 H, C(2)Me, J = 1.5 Hz); 3.82
(s, 3 H, COOMe); 5.84 (s, 1 H, H(5)); 6.60 and 7.68 (both d, 1 H
each, H(7), H(8), J = 15.9 Hz); 6.94 (q, 1 H, H(3), J = 1.5 Hz);
7.40 (m, 3 H, Ph); 7.55 (m, 2 H, Ph); 15.75 (s, 1 H, C(4)OH).
13C NMR (CDCl3), δ: 14.7 (C(15)); 52.6 (C(16)); 104.7 (C(5));
123.9 (C(7)); 128.2 (C(11), C(13)); 129.0 (C(10), C(14));
130.4 (C(12)); 132.2 (C(3)); 134.8 (C(9)); 139.9 (C(2)); 141.5
(C(8)); 168.1 (C(1)); 183.2 (C(4)); 184.5 (C(6)). MS, m/z
(Irel (%)): 273 [M + 1]+ (13), 272 [M]+ (88), 257 (6), 241 (23),
240 (100), 239 (8), 214 (9), 213 (73), 212 (21), 211 (9), 197 (10),
195 (13), 173 (29), 171 (15), 165 (9), 164 (18), 145 (20), 141 (20),
131 (74), 128 (26), 127 (22), 103 (35), 77 (24), 69 (26), 32 (18).
Found (%): C, 70.69; H, 5.96. C16H16O4. Calculated (%):
C, 70.57; H, 5.92.
Elution with hexane—acetone (15 : 1) gave triketone 15
(0.07 g, 4%) as light yellow crystals, m.p. 80—83 °C (benzene).
A mixture of tautomers 15B and 15D. IR, νmax/cm–1: 3215—2210
(OH), 1710 (C=O), 1651 (C=O), 1634 (C=O), 1611 (C=O,
C=C), 1585 (C=C). Major tautomer 15B ((Z)ꢀisomer). 1H NMR
(CDCl3), δ: 1.43 (s, 3 H, C(4)Me); 2.54 (s, 3 H, COMe); 2.66
and 2.94 (both d, 1 H each, H(5), J = 18.6 Hz); 3.29 (s, 3 H,
C(4)OMe); 11.90 (br.s, 1 H, OH). 13C NMR (CDCl3), δ: 21.2
(C(6)); 26.9 (C(2´)); 43.9 (C(5)); 51.8 (C(7)); 80.1 (C(4)); 109.7
(C(2)); 181.1 (C(1)); 198.7 (C(3)); 203.6 (C(1´)). Tautomer 15D
((E)ꢀisomer). 1H NMR (CDCl3), δ: 1.54 (s, 3 H, C(4)Me);
2.55 (s, 3 H, COMe); 2.45 and 2.76 (both d, 1 H each, H(5),
J = 18.2 Hz); 3.30 (s, 3 H, C(4)OMe); 11.90 (br.s, 1 H, OH).
13C NMR (CDCl3), δ: 21.6 (C(6)); 26.6 (C(2´)); 46.9 (C(5));
51.9 (C(7)); 78.9 (C(4)); 110.1 (C(2)); 180.7 (C(3)); 196.1 (C(1));
205.0 (C(1´)). Triketone 15. MS, m/z (Irel (%)): 184 [M]+ (10),
155 (16), 154 (100), 112 (59), 111 (9), 84 (11), 83 (30), 52 (48),
43 (8), 42 (26), 32 (39). Found (%): C, 58.73; H, 6.59. C9H12O4.
Calculated (%): C, 58.69; H, 6.57.
Elution with hexane—acetone (20 : 1) gave a ~3 : 2 mixture
of 2 (1 methoxy 3 phenylprop 2(E) en 1(Z) ylidene) 4 methyl
cyclopent 4 ene 1,3 dione (2A) and 2 (1 methoxy 3 phenylprop
2(E) en 1(E) ylidene) 4 methylcyclopent 4 ene 1,3 dione (2C,
coruscanone A) (0.055 g, 43%) as small yellow crystals, m.p.
84 °C (hexane—acetone, 10 : 1) (cf. Ref. 1: m.p. 86 °C). A mixꢀ
ture of 2(Z)ꢀ and 2(E)ꢀisomers. IR, νmax/cm–1: 1711 (C=O),
1666 (C=O), 1615 (C=C), 1578 (C=C), 1547 (C=C), 1445, 1309,
1279, 1222, 1208, 1181, 1057. 2(Z)ꢀIsomer of coruscanone A.
1H NMR (CDCl3), δ: 2.09 (d, 3 H, C(4)Me, J = 1.6 Hz); 4.21
(s, 3 H, C(1´)OMe); 6.72 (q, 1 H, H(5), J = 1.6 Hz); 7.39 (m, 3 H,
Ph); 7.62 (m, 2 H, Ph); 7.63 and 7.99 (both d, 1 H each, H(9),
H(8), J = 15.9 Hz). 13C NMR (CDCl3), δ: 11.2 (C(6)); 64.7
(C(7)); 108.7 (C(2)); 121.1 (C(2´)); 128.5 (C(5´)); 128.9 (C(6´),
C(9´)); 129.7 (C(8´)); 130.4 (C(7´)); 135.4 (C(4´)); 140.6 (C(5));
142.9 (C(3´)); 156.4 (C(4)); 169.0 (C(1´)); 192.7 (C(3)); 194.2
Rearrangement of a mixture of butenolides 9 and 11—13.
A ~26 : 11 : 1 : 6 mixture of (E)ꢀbutenolide 9, (Z)ꢀbutenolide 11,
(E)ꢀbutenolide 12, and (Z)ꢀbutenolide 13 (1.52 g, 10.0 mmol) in
dry MeOH (40 mL) and MeONa freshly prepared from metallic
Na (2.3 g) in MeOH (60 mL) were stirred at room temperature
for 2 h. The workup described above gave triketone 3 (0.98 g,
65%) and triketone 15 (0.14 g, 8%).
Reaction of coruscanone B (1) with diazomethane. A 2% soluꢀ
tion of CH2N2 in anhydrous ether (20 mL) was added in one
portion to a solution of coruscanone B (1) (0.12 g, 0.5 mmol) in
anhydrous ether (10 mL). The reaction mixture was kept at room
temperature for 1 h. The solvent was removed and the residue
was chromatographed on SiO2. Elution with hexane—acetone
(50 : 1) gave a 3 : 2 mixture of (2E) 2 cinnamoyl 4 methoxy 5
methylphenol (21) and (2E) 2 cinnamoyl 4 methoxy 6 meth
ylphenol (22) (0.013 g, 10%) as a light yellow viscous oil.
A mixture of isomers 21 and 22. IR, νmax/cm–1: 3400—2400
(OH), 1713 (C=O), 1642 (C=O), 1628 (C=C), 1584 (C=C),
1575 (C=C), 1498, 1466, 1451, 1430, 1356, 1292, 1278, 1259,
1253, 1200, 1182, 1172, 1086, 1061. Ether 21. 1H NMR (CDCl3),
δ: 2.27 (s, 3 H, C(5)Me); 3.87 (s, 3 H, C(4)OMe); 6.85 and 7.19
(both s, 1 H each, H(6), H(3)); 7.45 (m, 2 H, Ph); 7.67 (m, 3 H,
Ph); 7.57 and 7.92 (both d, 1 H each, H(2´), H(3´), J = 15.4 Hz);
12.61 (s, 1 H, C(1)OH). 13C NMR (CDCl3), δ: 15.9 (C(7)); 56.1
(C(8)); 110.0 (C(3)); 118.8 (C(2)); 120.6 (C(2´)); 125.2 (C(6));
128.6 (C(5´), C(9´)); 128.9 (C(5)); 129.0 (C(6´), C(8´)); 130.8
(C(7´)); 134.7 (C(4´)); 145.3 (C(3´)); 151.1 (C(4)); 156.8 (C(1));
193.6 (C(1´)). Ether 22. 1H NMR (CDCl3), δ: 2.30 (s, 3 H,
C(6)Me); 3.83 (s, 3 H, C(4)OMe); 7.05 and 7.21 (both d, 1 H
each, H(5), H(3), J = 2.8 Hz); 7.45 (m, 2 H, Ph); 7.67 (m, 3 H,
Ph); 7.61 and 7.92 (both d, 1 H each, H(2´), H(3´), J = 15.4 Hz);
12.74 (s, 1 H, C(1)OH). 13C NMR (CDCl3), δ: 16.9 (C(7)); 56.1
(C(8)); 108.9 (C(3)); 117.4 (C(2)); 120.4 (C(2´)); 120.5 (C(5));
128.6 (C(5´), C(9´)); 129.0 (C(6´), C(8´)); 130.8 (C(7´)); 134.8
(C(4´)); 138.8 (C(6)); 145.0 (C(3´)); 150.4 (C(4)); 158.5 (C(1));
192.8 (C(1´)). A mixture of isomers 21 and 22. MS, m/z (Irel (%)):
269 [M + 1]+ (17), 268 [M]+ (100), 267 [M – 1]+ (20), 191 (11),
165 (8), 164 (48), 149 (12), 136 (8), 121 (6), 103 (5), 77 (5),
1
(C(1)). 2(E)ꢀIsomer of coruscanone A. H NMR (CDCl3), δ:
2.10 (d, 3 H, C(4)Me, J = 1.6 Hz); 4.22 (s, 3 H, C(1´)OMe);
6.71 (q, 1 H, H(5), J = 1.6 Hz); 7.39 (m, 3 H, Ph); 7.62 (m, 2 H,
Ph); 7.63 and 7.97 (both d, 1 H each, H(9), H(8), J = 15.9 Hz).
13C NMR (CDCl3), δ: 11.3 (C(6)); 64.8 (C(7)); 108.7 (C(2));
121.3 (C(2´)); 128.5 (C(5´)); 128.9 (C(6´), C(9´)); 129.7 (C(8´));
130.7 (C(7´)); 135.4 (C(4´)); 140.3 (C(5)); 142.8 (C(3´)); 156.9
(C(4)); 168.8 (C(1´)); 191.9 (C(1)); 195.4 (C(3)). A mixture of
2A and 2C. MS (EI, 70 eV), m/z (Irel (%)): 255 [M + 1]+ (13),
254 [M]+ (77), 253 [M – 1]+ (6), 240 (3), 239 (11), 226 (6), 225
(25), 223 (15), 213 (12), 212 (72), 211 (16), 210 (22), 199 (8), 198
(20), 197 (18), 196 (10), 195 (9), 189 (15), 188 (100), 185 (13),
167 (11), 166 (12), 165 (25), 158 (22), 155 (11), 153 (12), 152
(12), 137 (13), 128 (37), 127 (27), 115 (33), 103 (20), 102 (18),
77 (26), 45 (21), 32 (61).
Reaction of triketone 3 with diazomethane. A 2% solution of
CH2N2 in anhydrous ether (20 mL) was added in one portion to
a solution of triketone 3 (0.304 g, 2.0 mmol) in anhydrous ether
(20 mL). The reaction mixture was kept at room temperature for
20 h. The solvent was removed and the residue was chromatoꢀ
graphed on SiO2. Elution with hexane—acetone (50 : 1) gave
a ~3 : 2 mixture of 2 acetyl 4 methoxy 5 methylphenol (28) and
2 acetyl 4 methoxy 6 methylphenol (29) (0.090 g, 25%) as light
yellow needles, m.p. 65—72 °C. A mixture of isomers 28 and 29.

Coruscanones A and B
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 1, January, 2010
89
IR, νmax/cm–1: 3200—2400 (OH), 1641 (C=O), 1620 (C=C),
05ꢀ149 and the Joint Grant of the FarꢀEast, Siberian,
and Ural Divisions of the Russian Academy of Sciences
09ꢀIIꢀSUꢀ05ꢀ001).
1583 (C=C), 1494, 1466, 1429, 1370, 1328, 1284, 1259, 1223,
1
1209, 1176, 1061. Ether 28. H NMR (CDCl3), δ: 2.23 (s, 3 H,
C(5)Me); 2.59 (s, 3 H, C(2)COMe); 3.77 (s, 3 H, C(4)OMe);
6.98 (s, 2 H, H(3), H(6)); 12.02 (s, 1 H, C(1)OH). 13C NMR
(CDCl3), δ: 15.7 (C(7)); 26.8 (C(2´)); 55.8 (C(8)); 110.5 (C(3));
118.5 (C(2)); 125.3 (C(6)); 128.8 (C(5)); 150.4 (C(4)); 157.3
(C(1)); 204.1 (C(1´)). Ether 29. 1H NMR (CDCl3), δ: 2.23 (s, 3 H,
C(6)Me); 2.58 (s, 3 H, C(2)COMe); 3.80 (s, 3 H, C(4)OMe);
6.76 and 6.98 (both d, 1 H each, H(5), H(3), J = 1.5 Hz); 12.19
(s, 1 H, C(1)OH). 13C NMR (CDCl3), δ: 16.9 (C(7)); 26.5
(C(2´)); 55.8 (C(8)); 109.5 (C(3)); 117.0 (C(2)); 120.2 (C(5));
138.4 (C(6)); 151.1 (C(4)); 155.7 (C(1)); 203.1 (C(1´)). A mixꢀ
ture of isomers 28 and 29. MS, m/z (Irel (%)): 181 [M + 1]+ (9),
180 [M]+ (80), 166 (10), 165 (100), 162 (7), 147 (12), 137 (7),
119 (4). Found (%): C, 66.70; H, 6.73. C10H12O3. Calculatꢀ
ed (%): C, 66.65; H, 6.71.
References
1. X.ꢀC. Li, D. Ferreira, M. R. Jacob, Q. Zhang, S. I. Khan, H.
N. ElSohly, D.G. Nagle, T. J. Smillie, I. A. Khan, L. A.
Walker, A. M. Clark, J. Am. Chem. Soc., 2004, 126, 6872.
2. K. S. Babu, X.ꢀC. Li, M. R. Jacob, Q. Zhang, S. I. Khan,
D. Ferreira, A. M. Clark, J. Med. Chem., 2006, 49, 7877.
3. E. I. Hwang, Y. M. Lee, S. M. Lee, W. H. Yeo, J. S. Moon,
T. H. Kang, K. D. Park, S. U. Kim, Planta Med., 2007,
73, 679.
4. H. M. Oh, S. K. Choi, J. M. Lee, S. K. Lee, H. Y. Kim,
D. C. Han, H. M. Kim, K. H. Son, B. M. Kwon, Bioorg.
Med. Chem., 2005, 13, 6182.
5. S. Y. Wang, X. Y. Lan, J. H. Xiao, J. C. Yang, Y. T. Kao,
S. T. Chang, Phytother. Res., 2008, 22, 213.
6. S. Kumar, K. Jayabal, S. Y. Wang, Planta Med., 2008, 74, 956.
7. Y. Aoyama, T. Konoike, A. Kanda, N. Naya, M. Nakajima,
Bioorg. Med. Chem. Lett., 2001, 11, 1695.
8. O. P. Shestak, Ph.D. (Chem.) Thesis, Tikhookeansk. Inst.
Bioorg. Khim. DVO RAN, Vladivostok, 1987, 210 pp.
(in Russian).
9. O. P. Shestak, V. L. Novikov, S. I. Stekhova, I. A. Gorshꢀ
kova, Khim.ꢀFarm. Zh., 1999, 33, 1, 18 [Pharm. Chem. J.
(Engl. Transl.), 1999, 33, No. 1, 18].
10. O. P. Shestak, V. L. Novikov, N. G. Prokof´eva, E. L. Chaikiꢀ
na, Khim.ꢀFarm. Zh., 1999, 33, 12, 5 [Pharm. Chem. J.
(Engl. Transl.), 1999, 33, 631].
11. V. L. Novikov, O. P. Shestak, V. V. Logachev, M. M. Anisiꢀ
mov, Rastitel´nye resursy [Plant Resources], 2003, 39, No. 4,
87 (in Russian).
12. L. A. Lapshina, O. P. Shestak, A. V. Reunov, V. L. Novikov,
M. M. Anisimov, Rastitel´nye resursy [Plant Resources], 2006,
44, No. 1, 107 (in Russian).
13. O. P. Shestak, E. A. Martyyas, M. M. Anisimov, V. L. Noꢀ
vikov, Tezisy dokladov Mezhdunarodnoi nauchnoi konferenꢀ
tsii "Khimiya, tekhnologiya i meditsinskie aspekty prirodnykh
soedinenii" (Almaty, Kazakhstan, 10—13 oktyabrya 2007 g.)
[Abstrs Int. Scientific Conf. "Chemistry, Technology, and Meꢀ
dicinal Aspects of Natural Compounds" (Almaty, Kazakhstan,
October 10—13, 2007)], Almaty, 2007, p. 250 (in Russian).
14. L. C. Diaz, S. B. Shimokomaki, R. T. Shiota, J. Braz. Chem.
Soc., 2005, 16, 482.
15. D. R. Gedge, G. Pattenden, J. Chem. Soc., Chem. Commun.,
1978, 20, 880.
16. N. G. Clemo, D. R. Gedge, G. Pattenden, J. Chem. Soc.,
Perkin Trans. 1, 1981, 5, 1448.
17. V. A. Facundo, A. L. Sa, S. A. Silva, S. M. Morais, C. R.
Matos, R. BrazꢀFilho, J. Braz. Chem. Soc., 2004, 15, 140.
18. D. V. Berdyshev, V. P. Glazunov, V. L. Novikov, Teziꢀ
sy dokladov VI Vserossiiskogo nauchnogo seminara "Khimiya
i meditsina" (Ufa, 26—29 noyabrya 2007 g.) [Abstrs,
VI AllꢀRussia Scientific Seminar "Chemistry and Medicine"
(Ufa, November 26—29, 2007)], Ufa, Gilem, 2007, Pꢀ133
(in Russian).
Elution with hexane—acetone (8 : 1) gave a ~1 : 1 mixture of
(2Z) 2 (1 methoxyethylidene) 4 methylcyclopent 4 ene 1,3 di
one (4A) and (2E) 2 (1 methoxyethylidene) 4 methylcyclopent
4 ene 1,3 dione (4C) (0.166 g, 50%) as pale yellow crystals, m.p.
78—80 °C (hexane). A mixture of 4A and 4C. IR, νmax/cm–1
:
1720 (C=O), 1699 (C=O), 1668 (C=O), 1624 (C=C), 1606
(C=C), 1579, 1376, 1316, 1246, 1073. (Z)ꢀIsomer 4A. 1H NMR
(CDCl3), δ: 2.02 (d, 3 H, C(4)Me, J = 1.7 Hz); 2.60 (s, 3 H,
C(1´)Me); 3.99 (s, 3 H, C(1´)OMe); 6.59 (q, 1 H, H(5), J = 1.7 Hz).
13C NMR (CDCl3), δ: 11.0 (C(6)); 14.3 (C(2´)); 56.1 (C(7));
107.4 (C(2)); 140.0 (C(5)); 155.4 (C(4)); 174.2 (C(1´)); 193.3
(C(3)); 194.8 (C(1)). (E)ꢀIsomer 4C. 1H NMR (CDCl3), δ: 2.03
(d, 3 H, C(4)Me, J = 1.7 Hz); 2.59 (s, 3 H, C(1´)Me); 4.00 (s, 3 H,
C(1´)OMe); 6.57 (q, 1 H, H(5), J = 1.7 Hz). 13C NMR (CDCl3),
δ: 11.2 (C(6)); 14.3 (C(2´)); 56.2 (C(7)); 107.4 (C(2)); 139.3
(C(5)); 156.1 (C(4)); 173.9 (C(1´)); 192.9 (C(1)); 195.6 (C(3)).
A mixture of 4A and 4C. MS, m/z (Irel (%)): 167 [M + 1]+ (17),
166 [M]+ (100), 149 (13), 138 (31), 137 (32), 122 (29), 107 (32),
80 (30), 68 (31). Found (%): C, 65.15; H, 6.12. C9H10O3. Calcuꢀ
lated (%): C, 65.05; H, 6.07.
Reaction of coruscanone B (1) with dimethyl sulfate. Dry
K2CO3 (0.94 g, 0.005 mol) was added under argon to a solution
of coruscanone B (1) (0.15 g, 0.62 mmol) in anhydrous acetone
(30 mL). The mixture was refluxed for 5 min, freshly distilled
Me2SO4 (0.87 g, 7.0 mmol) was added dropwise, and reflux was
continued for an additional 30 min. The precipitate was filtered
off, the filtrate was evaporated to dryness, and the residue was
chromatographed on SiO2. Elution with hexane—acetone (20 : 1)
gave a ~1 : 1 mixture of (Z)ꢀ and (E)ꢀisomers of coruscanone A
(2) (0.123 g, 77%), which is fully identical with the sample charꢀ
acterized above.
Reaction of triketone 3 with dimethyl sulfate. A mixture of
triketone 3 (0.152 g, 1.0 mmol), freshly distilled Me2SO4 (1.06 g,
8.5 mmol), and dry K2CO3 (1.88 g, 0.01 mol) was refluxed in
anhydrous acetone (30 mL) for 40 min. The precipitate was
filtered off, the filtrate was evaporated to dryness, and the resiꢀ
due was chromatographed on SiO2. Elution with hexane—aceꢀ
tone (7 : 1) gave a ~3 : 2 mixture of (Z)ꢀ and (E)ꢀisomers of ether
4 (0.033 g, 20%), which is fully identical with the sample characꢀ
terized above.
This work was financially supported by the Rusꢀ
sian Academy of Sciences (Grant of the FarꢀEast Diꢀ
vision of the Russian Academy of Sciences 09ꢀIIIꢀAꢀ
19. C. Reichardt, Losungsmittel — Effekte in der organischen Cheꢀ
mie, Verlag Chemie, 1969.

90
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Shestak and Novikov
20. A. K. Kiang, H. H. Lee, K. Y. Sim, J. Chem. Soc., 1962,
11, 4338.
25. F. Ramirez, S. Dershowitz, J. Org. Chem., 1957, 22, 41.
26. S. F. Ingham, R. A. MassyꢀWestropp, G. D. Reynolds, Aust.
J. Chem., 1974, 27, 1477.
27. C. F. Ingham, R. A. MassyꢀWestropp, G. D. Reynolds, W. D.
Thorpe, Aust. J. Chem., 1975, 28, 2499.
21. H. H. Lee, C. H. Tan, J. Chem. Soc. (C), 1967, 17, 1583.
22. A. A. Akhrem, A. M. Moiseenkov, F. A. Lakhvich, A. I.
Poselenov, T. M. Ivanova, Izv. Akad. Nauk SSSR,
Ser. Khim., 1971, 371 [Bull. Acad. Sci. USSR, Div. Chem. Sci.
(Engl. Transl.), 1971, 20, 305].
28. M. Nilsson, Acta Chem. Scand., Ser. A, 1964, 18, 441.
23. A. A. Akhrem, A. M. Moiseenkov, F. A. Lakhvich, A. I.
Poselenov, Izv. Akad. Nauk SSSR, Ser. Khim., 1972, 143
[Bull. Acad. Sci. USSR, Div. Chem. Sci. (Engl. Transl.), 1972,
21, 128].
24. V. L. Novikov, O. P. Shestak, N. N. Balaneva, Ya. Ya.
Paulin´sh, G. B. Elyakov, Izv. Akad. Nauk Latv. SSR, Ser.
Khim., 1985, 6, 718 (in Russian).
Received August 7, 2009;
in revised form November 3, 2009