Electrochemical chlorination of physcion - An approach to naturally occurring chlorinated secondary metabolites of lichens

Article abstract of DOI:10.1002/hlca.201100011

The electrochemical chlorination of physcion (=1,8-dihydroxy-3-methoxy-6- methylanthracene-9,10-dione; 1) in AcOH and CH₂Cl₂ was investigated by cyclic voltammetry and prep.-scale electrolysis. This approach provided access to a number of diverse biologically and pharmacologically interesting chlorinated secondary metabolites of lichen. Unlike the only previous literature report on the 'classical' chlorination of physcion (1), which allowed the preparation of 4-chlorophyscion (2b), 4,5-dichlorophyscion (3b), and 2,4,5-trichlorophyscion (4), the present procedure also gave fragilin (=2-chlorophyscion; 2a) and 2,4-dichlorophyscion (3a), alongside the previously obtained 2b, 3b, and 4. All of these compounds, except for 2a, were isolated by column chromatography and medium-pressure liquid chromatography (MPLC) and characterized by spectral data. The preparative electrolysis with a 2F·mol^-1 charge consumption in AcOH and 10F·mol ^-1 in CH₂Cl₂ may have a practical synthetic utility, since the thus obtained product mixtures can be readily fractioned by column chromatography to afford pure 2b and 4, respectively. The regioselectivity of the reaction is explained by the resonance stabilization of the corresponding arenium cations - potential products of an electrophilic attack of a 'positive' Cl species on the physcion molecule. Copyright

Full text of DOI:10.1002/hlca.201100011

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Helvetica Chimica Acta – Vol. 94 (2011)
Electrochemical Chlorination of Physcion – An Approach to Naturally
Occurring Chlorinated Secondary Metabolites of Lichens
by Dragana Stevanovic´ a), Ivan Damljanovic´ a), Mirjana Vukic´evic´ b), Nedeljko Manojlovic´ b), Niko S.
Radulovic´*c), and Rastko D. Vukic´evic´*a)
a
´
) Department of Chemistry, Faculty of Science, University of Kragujevac, R. Domanovica 12,
34000 Kragujevac, Serbia (e-mail: vuk@kg.ac.rs)
) Department of Pharmacy, Faculty of Medicine, University of Kragujevac, S. Markovica 69,
b
´
34000 Kragujevac, Serbia
c
ˇ
ˇ
) Department of Chemistry, Faculty of Science and Mathematics, University of Nis, Visegradska 33,
ˇ
18000 Nis, Serbia (phone: þ 381-63-7582352; fax: þ 381-18-533014; e-mail: vangelis0703@yahoo.com)
The electrochemical chlorination of physcion (¼1,8-dihydroxy-3-methoxy-6-methylanthracene-
9,10-dione; 1) in AcOH and CH2Cl2 was investigated by cyclic voltammetry and prep.-scale electrolysis.
This approach provided access to a number of diverse biologically and pharmacologically interesting
chlorinated secondary metabolites of lichen. Unlike the only previous literature report on the ꢀclassicalꢁ
chlorination of physcion (1), which allowed the preparation of 4-chlorophyscion (2b), 4,5-dichlorophy-
scion (3b), and 2,4,5-trichlorophyscion (4), the present procedure also gave fragilin (¼2-chlorophyscion;
2a) and 2,4-dichlorophyscion (3a), alongside the previously obtained 2b, 3b, and 4. All of these
compounds, except for 2a, were isolated by column chromatography and medium-pressure liquid
chromatography (MPLC) and characterized by spectral data. The preparative electrolysis with a 2 F ·
molꢀ1 charge consumption in AcOH and 10 F · molꢀ1 in CH2Cl2 may have a practical synthetic utility,
since the thus obtained product mixtures can be readily fractioned by column chromatography to afford
pure 2b and 4, respectively. The regioselectivity of the reaction is explained by the resonance stabilization
of the corresponding arenium cations - potential products of an electrophilic attack of a ꢀpositiveꢁ Cl
species on the physcion molecule.
Introduction. – The scientific interest in secondary metabolites produced by plants
has, nowadays, increased due to an intense search for new drugs of plant origin. The
extensive research performed in this field made secondary metabolites an important
source of bioactive compounds. For example, miscellaneous antraquinone
(¼anthracene-9,10-dione) derivatives, such as physcion (often called parietin),
emodin, fallacinal, teloschistin, chrysophanol, xanthorin, etc., abound in lichens and
some plants [1], from which they can be easily isolated. In many cases, isolated single
compounds of this kind, as well as the whole plant extract possess bioactivity, so that a
plethora of research reports devoted to this problem can be found in the literature [2 –
9]. Halogenated antraquinones, like fragilin, 2-chloroemodin, etc., also appear among
secondary metabolites of some lichens, although as minor components [10][11].
A partial, selective transformation of a naturally occurring compound is very often
the best way to synthesize another one with a similar structure, that is, however, present
in less quantity or absent from the corresponding natural source. Even more, in some
cases, this is the only economically feasible way to synthesize compounds that could be
ꢂ 2011 Verlag Helvetica Chimica Acta AG, Zꢃrich

Helvetica Chimica Acta – Vol. 94 (2011)
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interesting for certain purposes. Thus, to obtain two of the above mentioned natural
chlorinated antraquinones, fragilin (¼2-chloro-1,8-dihydroxy-3-methoxy-6-methylan-
thracene-9,10-dione; 2a) and 2-chloroemodin (¼2-chloro-1,3,8-trihydroxy-6-methyl-
anthracene-9,10-dione), Sargent and co-worker [12] chlorinated physcion (¼1,8-
dihydroxy-3-methoxy-6-methylanthracene-9,10-dione; 1) isolated from Xanthoria
parietina (L.) Beltram, and then selectively dechlorinated the obtained trichloro
derivative. In continuation of our permanent interest in the electrochemical halogen-
ation of natural products or their derivatives [13 – 16], we decided to examine the
possibility of an electrochemical chlorination of physcion (1), the most widespread
anthraquinone derivative in lichens [4]. At least, two advantages of an electrochemical
approach compared with the classic one exist: i) it is much more appropriate to handle
a chloride (from which free Cl2 will be liberated through this process) than harmful
gaseous Cl2 stored in bottles under pressure and ii) the electrochemical method can
provide a much more precise Cl2-dosage control. The latter problem is not an
insignificant one, particularly when working with small amounts of (expensive)
substrates, and this is very often the case when studying certain natural products
(including those described in the present work). The preparation of a solution of Cl2 in
the corresponding solvent and determination of the exact concentration of ꢀactiveꢁ Cl2
by classical analytical methods is the usual way to overcome this problem. An
electrochemical method, however, allows for the addition (liberation) of free Cl2 into
the reaction mixture practically molecule by molecule. We now wish to report on our
first results obtained through both the cyclovoltametric measurements and the
preparative scale electrolysis of physcion (1) isolated from a lichen species of the
genus Xanthoria by a known method [12].
Results and Discussion. – The electrochemical chlorination of physcion (1) was
conceptualized as the electrolysis of a chloride in the presence of substrate 1 and the
appropriate system of solvent and electrolyte. Since the classical chlorination of 1
described in [12] has been performed in AcOH and CHCl3 as the solvents, we chose
Et4NCl in AcOH and CH2Cl2 as the electrolysis media (the use of CHCl3 as the solvent
in preparative-scale electrochemical experiments is not suitable because its salt
solutions do not provide reasonable electrical conductivity). However, we performed
several cyclovoltammetric experiments before the preparative electrolysis to examine
the electrochemical behavior of the chloride and physcion in these solvents with
Bu4N(ClO4) (TBAP) as the electrolyte. The substrate 1 and the chloride ions were first
analyzed separately, and then the reactivity of the species generated by the oxidation of
the chloride was evaluated by cyclovoltammetry of these ions in the presence of 1.
On the basis of preliminary measurements, we chose the 0.50 – 1.65 V potential
window for cyclovoltammetry in AcOH. As it can be seen (Fig. 1,b), physcion (1) is not
electroactive in this potential window at a Pt electrode in a 0.1m solution of Bu4N(ClO4)
in this solvent. The chloride ions of 5 · 10ꢀ3 m Et4NCl, on the other hand, exhibit one
oxidation wave on the forward potential sweep (1.416 V) and one reduction wave
(0.893 V) on the back potential sweep under the same conditions (Fig. 1,c). This redox
couple is due to the oxidation of the Clꢀ ion to elemental Cl2 by the forward potential
sweep, and the reduction of Cl2 to Clꢀ at the back potential sweep. The cyclic
voltammetry of the chloride Et4NCl in the presence of 1 (2.5 · 10ꢀ3 m) results in a

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Helvetica Chimica Acta – Vol. 94 (2011)
Fig. 1. Cyclic voltammetry of Et4NCl and physcion (1) in 0.1m Bu4N(ClO4) in AcOH by using a platinum-
disc electrode (2 mm diameter), at v ¼ 0.1 V sꢀ1: a) electrolyte Bu4N(ClO4), b) physcion (1), c) 5 mm
Et4NCl, d) 5 mm Et4NCl/2.5 mm physcion (1)
change of the voltammogram shape of these ions, decreasing remarkably the reduction
peak current (Fig. 1,d). We assume that this decrease is the consequence of the Cl2-
concentration decrease at the electrode surface and its vicinity due to its reaction with 1
(Scheme), compared with the experiments without the substrate.
The cyclic voltammetry of the chloride Et4NCl and 1 in 0.1m Bu4N(ClO4) in CH2Cl2
was similar to that performed in AcOH, but it was ꢀcleanerꢁ, i.e., the oxidation and
reduction peaks were sharper (at 1.200 and 0.780 V, resp., Fig. 2). Therefore, exactly
the same conclusions as in the previous case can be made by analyzing these results.
Having in mind the above-established facts, we decided to conduct the preparative
electrolysis of physcion (1) in solutions of Et4NCl in AcOH and CH2Cl2. First we
performed a constant-current electrolysis (30 mA) with a 2 F · molꢀ1 charge consump-
tion (the theoretically necessary amount for 1 mol-equiv. of Cl2, i.e., for the
monochlorination) in AcOH, using an undivided electrolytic cell supplied with a
cylindrical Pt foil (as the anode) and a spiral Cu wire (as the cathode). Because of the
low solubility of 1 in AcOH, this electrolysis was performed at 508. This resulted in a
mixture containing mainly the unconsumed substrate 1, followed by two products
(Table, Entry 1). The 1H-NMR spectra of this mixture in combination with the GC/MS
analysis allowed us to identify these products as fragilin (¼2-chlorophyscion; 2a) [11]
and 4-chlorophyscion (2b) [12] (Scheme). Apparently, a great part of the liberated Cl2
migrates during the electrolysis to the cathode undergoing the reduction there, causing
such a low current efficiency (33%). The mixture containing 1/2a/2b was submitted

Helvetica Chimica Acta – Vol. 94 (2011)
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Scheme. Electrochemical Chlorination of Physcion (1)
again to electrolysis under the same conditions consuming an additional 4 F molꢀ1
charge, which resulted in a mixture containing the monochlorinated 2a and 2b as the
main products (Entry 2).
Table 1. Electrochemical Chlorination of Physcion (1)
Entry Reaction conditions (solvent/cell/F · molꢀ1
)
Product distribution [%]a)
2a 2b 3a 3b
67.0 4.0 29.0
3.7 12.7 77.2 1.5
4.0 12.5 79.5
1
4
unidentified
1
AcOH/undivided/2
AcOH/undivided/6
AcOH/divided/2
AcOH/divided/4
AcOH/divided/6
AcOH/divided/10
CH2Cl2/undivided/2
CH2Cl2/undivided/6
CH2Cl2/divided/2
CH2Cl2/divided/4
CH2Cl2/divided/6
CH2Cl2/divided/10
–
–
4.1
4.0
–
–
–
–
0.8
–
2
3
4
5
6
7
8
9
–
–
–
–
96
–
3.6 33.5 11.0 19.5 18.7 13.7
–
–
–
4.3 14.2 39.3 21.4 20.8
3.7 13.3 21.6 22.8 38.6
4.0
–
–
–
–
–
–
5.0
17.4 59.8 2.0 15.8
30.5 9.1 56.4 3.5 < 1
< 1
7.2
5.9 9.4 10.8 15.5 23.3 35.1
63.5 15.8
10
11
12
–
–
–
14.5 39.0 15.4 16.5 7.4
–
–
–
–
a
1
) On the basis of H-NMR spectra.

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Helvetica Chimica Acta – Vol. 94 (2011)
Fig. 2. Cyclic voltammetry of Et4NCl and physcion (1) in 0.1m Bu4N(ClO4) in CH2Cl2 by using a
platinum-disc electrode (2 mm diameter), at v ¼ 0.2 V sꢀ1: a) electrolyte Bu4N(ClO4), b) physcion (1),
c) 5 mm Et4NCl, d) 5 mm Et4NCl/2.5 mm physcion (1)
However, the starting substrate 1 was not consumed completely although two
dichloro derivatives, 2,4- and 4,5-dichlorophyscion (3a and 3b, resp.), appeared as
additional reaction products (Entry 2). This prompted us to perform a constant-current
electrolysis of 1 in the same solvent/electrolyte system but in a divided electrolytic cell
(by a ceramic membrane; 20 mA). Thus, the reaction performed at 508, passing 2 F ·
molꢀ1 of charge, gave the monochlorinated derivatives 2a/2b in the ratio 13.6 :86.4,
followed by a much smaller amount of unchanged 1 and 4,5-dichlorophyscion (3b)
(Entry 3); therefore, the current efficiency of this reaction is 100%, regardless of the
fact that 1 was not completely consumed. We also found that, despite the low solubility
of 1 in AcOH, this reaction could be run at room temperature. Indeed, as the
electrolysis progressed, the starting suspension of 1 in AcOH became a clear solution,
apparently due to a higher solubility of the products (chlorinated physcions) in this
solvent than that of 1.
Electrolysis with a 4 F · molꢀ1 charge consumption in a divided electrolytic cell was
also conducted to examine the possibility of a direct dichlorination of physcion (1).
However, although the two dichlorophyscions 3a and 3b, and even 2,4,5-trichlorophy-
scion (4) appeared as the products of this reaction, 2b was still the most abundant
component of the resulting mixture (Entry 4). A prolonged time of the electrolysis
caused a decrease in the 2b abundance and an increase of the relative amounts of the
dichloro and trichloro derivatives 3a, 3b, and 4. For example, the electrolysis
accompanied by a passage of 6 F · molꢀ1 charge through the solution gave a mixture
containing traces (less than 0.05%) of 2a, 4.3% of 2b, 14.2% of 3a, 39.3% of 3b, 21.4%

Helvetica Chimica Acta – Vol. 94 (2011)
1411
of 4, and some unidentified products (Entry 5). However, even electrolysis with a
10 F · molꢀ1 charge consumption did not give the pure trichloro derivative 4 (Entry 6).
The reaction mixtures always contained considerable amounts of the dichloro
derivatives 3a and 3b. We were able to isolate four of the mentioned products as
pure compounds, i.e., 2b, 3a, 3b, and 4, by combining gravity column chromatography
1
and prep. MPLC. This and the fact that the H-NMR spectra of 2a, 2b, 3b, and 4 are
known [11][12] enabled us to perform more detailed analyses of the reaction mixtures.
Surprisingly, the electrochemical monochlorination in CH2Cl2 as the solvent, in
which physcion (1) is much more soluble than in AcOH, proceeded with a slightly lower
current efficiency and selectivity. Thus, the constant-current electrolysis of 1 in CH2Cl2
in an undivided cell (r.t.; 2 F · molꢀ1 charge consumption) resulted in a mixture
containing ca. 96% of the unchanged 1 and only ca. 4% of 4-chlorophyscion (2b)
(Entry 7). On the other hand, the electrolysis in a divided cell under the conditions for
monochlorination (2 F · molꢀ1 charge consumption) gave a mixture containing up to
30.5% of unchanged 1 (Entry 9). Similarly to the reaction conducted in AcOH, a
prolonged electrolysis led to mixtures containing several products. In addition, some
new products appeared, but neither the isolation of the pure compounds nor the
complete identification through a careful analysis of the 1H-NMR spectra was possible.
The electrolysis with a 10 F · molꢀ1 charge consumption, however, resulted in a mixture
containing 63.5% of the trichloro derivative 4, which was isolated by column
chromatography for the measurement of its spectral data. This is an additional
noteworthy difference between the chlorination in CH2Cl2 and AcOH.
Our results considerably differ from those of the only previous report on the
chlorination of physcion (1) [12], which deserves a short discussion. According to [12],
the monochlorination of 1 by Cl2 itself (1:1 molar ratio of the reactants) gave
compound 2b as the sole product. However, despite the fact that the reaction
conditions for monochlorination in our experiments differed, one could assume that the
regioselectivity of the monochlorination in both cases would be the same. Since 2b was
isolated by recrystallization in [12], the presence of the unchanged substrate 1 and of
fragilin (2a) might have been missed because these substances should have remained in
the mother liquor. On the other hand, under the conditions of monochlorination
(Table, Entries 3 and 9), the other two possible monochloro derivatives, 5- and 7-
chlorophyscion, did not form. We made sure that these latter monochloro derivatives
1
were absent by a careful analysis of the monosubstitution pattern in the H-NMR
spectra. The introduction of a Cl-atom into the physcion molecule or already
chlorinated physicon molecules does not change the chemical shifts of the remaining
protons to any significant extent but causes only small differences which, however,
allow to distinguish different di-, mono-, and nonchlorinated physcion (compare the
data of 3a in the Exper. Part and the literature data of 1, 2a, 2b, 3b, and 4 [4][11][12]).
We assume that the observed regioselectivity of the monochlorination of 1 is the
consequence of a somewhat different stabilization of the corresponding intermediary
ions (by the positive-charge delocalization) obtained after the initial attack of a
ꢀpositive chlorineꢁ species on physcion. Indeed, both of the ꢀouterꢁ benzene rings of 1
are equally activated by the OH groups and deactivated by the C¼O groups for an
electrophilic substitution, but the MeO-substituted benzene ring is rather more
activated than the Me-substituted one (the predomination of 2b over 2a, on the other

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Helvetica Chimica Acta – Vol. 94 (2011)
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hand, is steric in nature). As depicted in Fig. 3, the corresponding arenium ions
obtained on attack of 1 at the positions 2 and 4 (see AI–V and BI–V) possess one
important contributing resonance structure more (see AV and BV) than those obtained
by the attack at the positions 5 and 7 (see CI–IV and DI–IV).
In our experiments the regioselectivity of dichlorination is surely different from that
reported for the classical method [12]. Under all conditions permitting dichlorination
(electrolysis with 4 or more F · molꢀ1 charge consumption), we found both 2,4- (3a) and
4,5-dichlorophyscion (3b) in the reaction mixtures. The formation of 3a rather than 3c
illustrates in the best way how much the MeO-substituted benzene ring is more
susceptible to electrophilic attack than the Me-substituted one. Namely, even though
the MeO-substituted ring bearing the newly introduced Cl-atom at position 2 (see 2a)
should be deactivated to some extent for further electrophilic substitution on
dichlorination by another electrophilic attack, the second Cl-atom is bonded to this
ring and not to the unchlorinated one.
Yet, another explanation for the observed regioselectivity of chlorination may be
operational. In the case of phenol and 4-chlorophenol in neutral to acidic media, the
rate constant for chlorination is up to an order of magnitude higher for the already
chlorinated compound [17]. This is explained by the mechanistic consideration that the
chlorination of phenol and chlorophenols proceeds in neutral and alkaline media by the
reaction of hypochlorous acid with the phenolate or chlorophenolate [17]. Since
chlorinated phenols are more acidic than the parent phenols (and this is even more true
in the case of the unchlorinated Me-substituted ring of physcion), the concentration of
the true nucleophile in this reaction, the phenolate, is greater for the monochlorinated
phenols and hence this makes them more reactive in electrophilic aromatic
substitutions (a well known example [17] of this is the polyhalogenation of phenol
itself with less than 1 equiv. of a halogen available for reaction).
Conclusions. – Electrochemical chlorination of physcion (1) in AcOH and CH2Cl2
allowed access by avoiding ring synthesis to fragilin (2a), 4-chlorophyscion (2b), 2,4-
and 4,5-dichlorophyscions (3a and 3b, resp.), and trichlorophyscion 4. The electrolysis
with a 2 F · molꢀ1 charge consumption in AcOH and 10 F · molꢀ1 in CH2Cl2 may have a
practical synthetic utility, since the reaction mixtures obtained under these conditions
could readily be separated by column chromatography to afford pure 2b and 4,
respectively. The pure dichloro derivatives 3a and 3b were isolated by prep. MPLC.
Electrochemical chlorination of physcion (1) presents a good alternative to the classical
chlorination of this natural product with free Cl2 because it avoids the disadvantageous
use of gaseous Cl2 stored in the high-pressure cylinders. To the best of our knowledge,
there is no other rich source of chlorinated physcions, thus turning our electrochemical-
chlorination procedure into a useful access to these compounds, which will allow to
study their properties including their promising biological and pharmacological
activities.
This work was supported by the Ministry of Education and Science of the Republic of Serbia (grant
ˇ ´
´
172034). We are grateful to Vida ꢂuricic (Technician School ꢀNikola Teslaꢁ, Leposavic, Serbia) for
supplying us with generous amounts of the lichen Xanthoria elegans.

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Helvetica Chimica Acta – Vol. 94 (2011)
Experimental Part
General. The physcion (1) used in this study was isolated from a lichen species of the genus Xanthoria
by a known method [12]. All other chemicals were commercially available and used as received, except
for the solvents, which were purified by distillation. Bu4N(ClO4) was used as the supporting electrolyte in
the cyclic voltammetry experiments. Prep.-scale electrolyses: divided (by a ceramic membrane) or
undivided cell in an Autolab apparatus; cylindrical Pt foil (2.5 cm diameter) and Pt spiral (1 cm diameter)
as the anode and the cathode, resp. Column chromatographic (CC): silica gel 60 (SiO2; 230 – 400 mesh
ASTM; Merck). Prep. medium-pressure liquid chromatography (MPLC): pump module C-601 and
pump controller C-610, Work-21 pump (Bꢃchi, Switzerland); pre-packed column cartridges (40 ꢁ
75 mm; SiO2 60, particle size distribution 40 – 63 mm; Bꢃchi). TLC: SiO2 60 F254 (Merck) on Al plates,
layer thickness 0.2 mm. Cyclic voltammetry: at r.t. under Ar in a three-electrode cell; Autolab
potentiostat (PGSTAT 302N); working electrode Pt disk (2-mm diameter), counter electrode Pt wire,
and reference electrode. Ag wire. IR Spectra: PerkinꢀElmer FT-IR 31725-X spectrophotometer; ˜n in
cmꢀ1. NMR Spectra: Varian-Gemini (200 MHz) spectrometer; in CDCl3; d in ppm rel. to Me4Si as the
internal standard, J in Hz. EI-MS: mass selective detector HewlettꢀPackard (5975B) part of a GC/MS
system (70 eV); in m/z (rel. %). GC/MS: Hewlett-Packard 6890N gas chromatograph; fused-silica cap.
column DB-5MS (5% phenylmethylsiloxane, 30 m ꢁ 0.25 mm, film thickness 0.25 mm; Agilent Tech-
nologies, USA) and 5975B mass selective detector (from the same company); carrier gas He at 1.0 ml
minꢀ1
.
Prep. Electrolyses. The electrochemical cells (divided and undivided) were filled with AcOH or
CH2Cl2 (30 ml) containing Et4NCl (0.1m). Physcion (1; ca. 30 mg, ca. 0.1056 mmol) was then added (in
the anodic compartment if the divided cell was used). Electrolyses were performed at a constant current
(30 mA in the undivided cell and 20 mA in the divided one). Reactions were run until a charge of 2, 4, 6,
or 10 F (ca. 20.4, ca. 40.8, ca. 61.2, or ca. 101.9 C, resp.) was passed through the solns. (see Table). The
solvent was distilled off under reduced pressure from the crude reaction mixture obtained after the end of
the electrolysis, the residue extracted with Et2O, the Et2O phase washed with the sat. NaHCO3 soln.,
dried overnight (Na2SO4), and concentrated, and the residue separated by CC and MPLC and analyzed
by TLC, GC/MS, and NMR. The identification of the products was performed by combining the
1H-NMR and GC/MS data. Compounds 2a, 2b, 3b, and 4 (Scheme) are known, and their 1H-NMR data
were identical to those given in [11][12].
2,4-Dichlorophyscion (¼2,4-Dichloro-1,8-dihydroxy-3-methoxy-6-methylanthracene-9,10-dione;
3a). IR (KBr): 3414.8, 3138.7, 2953.75, 2924.6, 2853.8, 1731.8, 1681.9, 1635.2, 1602.2, 1542.2, 1485.6,
1456.9, 1392.8, 1369.9, 1348.0, 1305.5, 1266.0, 1244.9, 1212.9, 1144.0, 1115.9, 1034.0, 974.4, 912.6, 864.0,
822.2, 812.5, 792.8, 765.0, 756.4, 707.3, 624.2, 588.36, 560.5, 540.6, 478.5. 1H-NMR (200 MHz, CDCl3): 2.48
(s, Me); 4.04 (s, MeO); 7.11 (s, HꢀC(7)); 7.63 (s, HꢀC(5)); 11.68 (s, OH); 13.53 (s, OH). EI-MS: 354
(63.5), 352 (100.0, Mþ), 335 (2.6, [M ꢀ OH]þ), 317 (12.5, [M ꢀ Cl]þ), 245 (2.9), 162 (9.5).
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Received November 17, 2010