Stereoselective total syntheses of atrochrysone, torosachrysone and related 3,4-dihydroanthracen-1(2H)-ones

Article abstract of DOI:10.1039/b003053h

The total synthesis of the pre-anthraquinones atrochrysone 1 and torosachrysone 2 in both enantiomeric forms is described. The synthesis relies on the regioselective Tebbe methylenation of a chiral diester followed by an intramolecular enol ether acylation with N-triflyl-4-(dimethylamino)pyridinium triflate. The resulting 3-methoxycyclohex-2-enone 9 is condensed with suitable orsellinic acid derivatives to yield after deprotection the optically active 3,4-dihydroanthracen-1(2H)-ones 1 and 2. This flexible approach can be used for the synthesis of ¹³C-labelled compounds and should provide access to a series of analogues. The Royal Society of Chemistry 2000.

Full text of DOI:10.1039/b003053h

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Stereoselective total syntheses of atrochrysone, torosachrysone and
related 3,4-dihydroanthracen-1(2H)-ones
Michael Müller,† Kai Lamottke, Erich Löw, Eva Magor-Veenstra and Wolfgang Steglich*
1
Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstr. 5–13 (F),
D-81377 München, Germany
Received (in Cambridge, UK) 17th April 2000, Accepted 15th May 2000
Published on the Web 3rd July 2000
The total synthesis of the pre-anthraquinones atrochrysone 1 and torosachrysone 2 in both enantiomeric forms
is described. The synthesis relies on the regioselective Tebbe methylenation of a chiral diester followed by an
intramolecular enol ether acylation with N-triflyl-4-(dimethylamino)pyridinium triflate. The resulting 3-methoxy-
cyclohex-2-enone 9 is condensed with suitable orsellinic acid derivatives to yield after deprotection the optically
active 3,4-dihydroanthracen-1(2H)-ones 1 and 2. This flexible approach can be used for the synthesis of 13C-labelled
compounds and should provide access to a series of analogues.
The only stereoselective synthesis of a pre-anthraquinone of
Introduction
type A (Scheme 1) so far is that of (R)-torosachrysone 8-methyl
ether (R)-3. It was derived from (Ϫ)-quinic acid in 18 steps, thus
providing rigorous proof for the absolute configuration of this
pigment.14 In the present study, we describe a flexible enantio-
selective synthesis of atrochrysone 1 and torosachrysone 2
which can also be applied to other pre-anthraquinones.
Atrochrysone 1 and torosachrysone 2 can be considered as the
Results and discussion
Synthetic plan
The synthesis of pre-anthraquinones of type A presents
considerable difficulties due to the high tendency of these com-
pounds towards aromatisation. We considered Weinreb’s con-
vergent strategy15 as the most suitable for the synthesis of the
dihydroanthracenone nucleus since it should allow the conden-
sation of an orsellinic acid fragment B with an optically active
3-methoxycyclohexenone unit C under comparatively mild
conditions (Scheme 1). For the synthesis of the chiral building
block C the intramolecular cyclisation of a carboxylic acid
derivative D with a terminal methyl enol ether group appeared
attractive. We assumed that compounds of this type should be
accessible by regioselective Tebbe methylenation of a suitable
diester E carrying besides the methyl ester a sterically more
demanding ester group. Since both enantiomers of E can be
obtained by known methods16 this approach should allow the
preparation of the pre-anthraquinones A in both enantiomeric
forms.
biosynthetic precursors of octaketide derived anthraquinones
from fungi and higher plants. (R)-Atrochrysone has been dis-
covered in the toadstools Cortinarius atrovirens and C. odora-
tus,1,2 whereas the (S)-enantiomer of 1 occurs in the Australian
toadstool WAT 20 881.3 Dermocybe splendida produces (S)-
torosachrysone,2,4 whereas other Australian toadstools belong-
ing to Cortinarius and Dermocybe contain an unequal mixture
of the enantiomers of 2.5 (S)-Torosachrysone has been
obtained from Cassia torosa and other members of the
Fabaceae family,6–8 and the (R)-form from Araliorhamnus
vaginata.9 (S)-Torosachrysone 8-methyl ether (S)-3 is found in
several European Cortinarius and Tricholoma species.1,2
The monomers 1 and 2 serve as precursors in the biosynthesis
of a large number of dimeric pre-anthraquinones, which are
found in great variety in toadstools of the genus Cortinarius1,2
and in some higher plants.10 C- and O-prenylated derivatives of
atrochrysone form the vismione group of anthranoids11 which
is characteristic for several plants of the Guttiferae family.
Anthranoids of this type have been shown to display anti-
bacterial,6 antimalarial12 and insect antifeedant activity.13
Synthesis of fragment C
The stereoselective synthesis of fragment C starts from the
monomethyl ester 5 obtained in optically pure form by pig
liver esterase catalysed hydrolysis of the prochiral diester
417 (Scheme 2). Treatment of 5 with two equivalents of tert-
† Present address: Institut für Biotechnologie 2, Forschungszentrum
Jülich GmbH, D-52425 Jülich, Germany.
Scheme 1 Retrosynthesis of the pre-anthraquinones A.
DOI: 10.1039/b003053h
J. Chem. Soc., Perkin Trans. 1, 2000, 2483–2489
This journal is © The Royal Society of Chemistry 2000
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Scheme 2 Reagents and conditions: i, pig liver esterase, pH 8, 92%;
ii, TBDMS-OTf, lutidine, CH2Cl2, 0→rt, 86%; iii, Tebbe reagent,
THF, Ϫ78 ЊC, 30 min, then rt, 1 h, 61–85%; iv, aq. K2CO3, MeOH;
v, Tf2O, DMAP (each 10 equiv.), CH2Cl2, then (R)-8, Ϫ20 ЊC, 2 h, rt,
2 d, 40–80% over two steps.
Scheme 3 Reagents and conditions: i, (R)-1-(1Ј-naphthyl)ethanol,
DMAP, CH2Cl2, Ϫ60 ЊC, 5 d, then MeOH (4 equiv.), DCC, Ϫ40 ЊC, 2
h, rt, 24 h, 75%; ii, TBDMS-OTf, lutidine (80%); iii, Tebbe reagent,
THF, Ϫ50→Ϫ30 ЊC, 3 h, 66%; iv, 1 M KOH, EtOH, rt, 28 h; v, Tf2O,
DMAP (each 10 equiv.), CH2Cl2, then (S)-8, Ϫ20 ЊC, 2 h, rt, 2 d, 41%
over two steps.
butyldimethylsilyl (TBDMS) triflate 18 yielded the TBDMS
ester 6 with simultaneous protection of the tertiary hydroxy
group.
Synthesis of the dihydroanthracenones A
The TBDMS-protected (R)-torosachrysone 8-methyl ether 15a
was prepared in 25% yield by condensation of the lithiated
methylbenzoate 14a with 3-methoxycyclohexenone (R)-9.
(Scheme 4). The removal of the TBDMS group from 15a was
The diester 6 was treated with one equivalent of Tebbe
reagent.19 We were pleased to note that at Ϫ78 ЊC and on warm-
ing up to room temperature this reaction afforded only the
desired enol ether 7 by reaction of the organometallic reagent
with the less hindered methyl ester group. To our knowledge
this is the first example of a regioselective diester olefination.
Selective alkaline hydrolysis of the TBDMS ester with aqueous
potassium carbonate20 yielded the potassium salt (R)-8. The
intramolecular cyclisation of the carboxylate salt (R)-8 proved
to be difficult. Thus, conversion of (R)-8 into the corresponding
acid chloride by the mild method of Ghosez et al.21 yielded
none of the desired cyclohexenone (R)-9.22 Finally, the cyclis-
ation was achieved by the reaction of (R)-8 with N-triflyl-4-
(dimethylamino)pyridinium triflate. This reagent, easily formed
from triflic anhydride and DMAP,23 afforded the enantiomeric-
ally pure 3-methoxycyclohexenone (R)-9 in 40–80% yield. The
varying yields for the cyclisation step may be explained by the
differing quality of the potassium salt 8 from which water has
to be completely removed.
Scheme 4 Reagents and conditions: i, LDA, 14a, THF, Ϫ78 ЊC, then
(R)-9, 25%; ii, HF, CH3CN, 78%.
Although this five-step reaction sequence provides a short
and efficient entry to enantiomerically pure (R)-3-methoxy-
cyclohexenone, the method is limited to compounds of the
(R)-series. Access to both enantiomers, however, is provided by
the desymmetrisation of prochiral 3-hydroxy-3-methylpentane-
dioic anhydride (10) with (R)- or (S)-1-(1-naphthyl)ethanol,
respectively, in the presence of DMAP at Ϫ60 ЊC24 (Scheme 3).
To achieve high diastereoselectivity the reaction has to be run
for several days at this temperature. Subsequently, methanol
and DCC25 were added and the mixed ester (3S,1ЈR)-11 was
thereby obtained starting from (R)-1-(1-naphthyl)ethanol in
75% chemical yield with 86% de.26 In the same manner the
enantiomeric diester (3R,1ЈS)-11 (86% de) was prepared from
(S)-1-(1-naphthyl)ethanol. After protection of the tertiary
hydroxy group with the TBDMS residue, treatment of diester
12 with one equivalent of Tebbe reagent at low temperature
proceeded with high regioselectivity and afforded the desired
methyl enol ether 13, which was converted to cyclohexenone
(S)-9 (86% ee) with N-triflyl-DMAP triflate. Starting from
diester (3R,1ЈS)-11 the (R)-enantiomer of cyclohexenone 9 was
obtained by the same methodology.
best achieved with HF in acetonitrile.27 The resulting enantio-
merically pure (R)-torosachrysone 8-methyl ether 3 showed the
opposite optical rotation and CD curve to the (S)-compound
from Cortinarius splendens.2 All other analytical data were in
complete agreement.
For the synthesis of atrochrysone 1 and torosachrysone 2 a
phenol protecting group that can be removed under very mild
conditions had to be attached to the orsellinate fragment. We
selected the benzyloxymethyl (BOM) group28 and prepared
methyl 2,4-bis(benzyloxymethoxy)-6-methylbenzoate 14b and
2-benzyloxymethoxy-4-[13C]methoxy-6-methylbenzoate 14c*
by standard procedures. The 13C-labelled compound 14c* was
needed for the synthesis of both enantiomers of labelled
torosachrysone for biosynthetic studies.29
Condensation of the BOM-protected orsellinic acid
derivatives 14b and 14c* with 3-methoxycyclohexenone (R)-9
afforded the pre-anthraquinones (R)-15b and (R)-15c*, respec-
tively, in moderate to good yields (Scheme 5). The BOM groups
were smoothly removed by catalytic hydrogenation to give the
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(S)-3-Hydroxy-3-methylpentanedioic acid monomethyl ester 5
To a solution of dimethyl 3-hydroxy-3-methylpentanedioate (4)
(2.50 g, 13.1 mmol) in 1 M phosphate buffer (20 cm3, pH 8) was
added 1 mg of pig liver esterase (PLE, 1500 U). The pH was
kept within the range 7.5–8.0 by addition of aqueous 1 M
NaOH. The mixture was incubated for 24 h at 25 ЊC, after
which additional diester 4 (2.50 g) and PLE (1 mg) were added.
This was repeated for up to a total of 150 g (78.8 mmol) of
diester 4. The reaction mixture was stirred for an additional 2 d,
after which the pH was adjusted to 8.5 and the unreacted start-
ing material extracted with ethyl acetate (50 cm3). The aqueous
phase was adjusted to pH 2 and saturated with NaCl prior to
extraction with ethyl acetate (3 × 50 cm3). The combined
organic phases were dried over MgSO4 and concentrated to
afford 12.7 g (92%) of enantiomerically pure 5 as a colourless
oil; [α]D20 ϩ1.8 (c 1.0, CHCl3); νmax (NaCl)/cmϪ1 3500, 3010, 2985,
1720, 1435, 1405, 1375, 1345; δH (400 MHz) 1.4 (3H, s), 2.65
(1H, d, J 15.8 Hz), 2.67 (1H, d, J 15.5 Hz), 2.73 (1H, d, J 15.8
Hz), 2.74 (1H, d, J 15.5 Hz), 3.73 (3H, s); δC (100.6 MHz) 27.2,
44.3, 44.9, 51.9, 69.8, 172.5, 175.6; m/z (EI) 177 [Mϩ ϩ H,
0.5%], 143 (5), 117 (5), 43 (100) (Found Mϩ ϩ H: 177.0757.
Calc. for C7H13O5: 177.0764).
Scheme 5 Reagents and conditions: i, LDA, 14, THF, Ϫ78 ЊC, then (R)-
9; ii, H2, Pd/C; iii, HF, CH3CN; * = 13C label.
dihydroanthracenones (R)-16b and (R)-16c*, which were desi-
lylated with HF in acetonitrile to yield optically pure (R)-
atrochrysone (R)-1 and (R)-torosachrysone (R)-2*, respectively.
The use of (S)-9 instead of the (R)-enantiomer afforded (S)-1
and (S)-2*. Since the optical purity of the products depends on
that of the starting enone 9, the ee values of the (S)-compounds
were in the range of 86%. The spectroscopic data of the
synthetic pre-anthraquinones were identical with those of the
natural products.
Our new method allows the synthesis of both enantiomers of
pre-anthraquinones from a single starting material. It demon-
strates the use of a regioselective Tebbe reaction and the
potential of N-triflyl-4-(dimethylaminopyridinium) triflate for
effecting the intramolecular acylation of enol ethers. Work on
the synthesis of biologically active vismiones along these lines is
in progress.
tert-Butyldimethylsilyl methyl (R)-3-(tert-butyldimethylsilyl-
oxy)-3-methylpentanedioate 6
2,6-Lutidine (9.10 cm3, 78 mmol) and tert-butyldimethylsilyl
trifluoromethanesulfonate (15 cm3, 65.0 mmol) were added to
a solution of 5 (4.60 g, 26 mmol) in CH2Cl2 (25 cm3) at Ϫ10 ЊC.
The mixture was stirred for 2 h at rt, then hydrolysed with water
and extracted with ethyl acetate (3×). The combined organic
phases were washed with aqueous NH4Cl and brine, dried
(MgSO4) and concentrated. Column chromatography (15:1
light petroleum ether–EtOAc) afforded the product (9.05 g,
86%) as a colourless oil; bp 130 ЊC/4 × 10Ϫ2 Torr (bulb-to-bulb
distillation); [α]D25 Ϫ0.9 (c 1.0, CHCl3); νmax (NaCl)/cmϪ1 3490,
2870, 1730, 1710, 1465, 1355, 1340, 1250, 1200, 1150, 1100, 830;
δH (400 MHz) 0.10 (6H, s), 0.26 (6H, s), 0.83 (9H, s), 0.93 (9H,
s), 1.47 (3H, s), 2.68 (1H, d, J 15 Hz), 2.77 (2H, s), 2.85 (1H, d,
J 15 Hz), 3.64 (3H, s); δC (100.6 MHz) Ϫ4.8, Ϫ4.7, Ϫ2.2, Ϫ2.1,
17.6, 18.0, 25.6, 25.7, 28.5, 45.9, 48.0, 51.2, 73.1, 171.2, 171.3.
Experimental
General methods
The reactions were performed using oven-dried (130 ЊC)
glassware under an argon atmosphere. CH2Cl2 was distilled
from Sicapent (Merck) and THF from potassium immedi-
ately prior to use. Light petroleum ether (boiling range 40–
60 ЊC) and ethyl acetate were distilled through a glass column
at atmospheric pressure. Melting points and boiling points
Preparation of the Tebbe reagent
A solution of trimethylaluminium (48 mmol) in toluene (2 M,
24 cm3) was added to a stirred solution of dicyclopentadienylti-
tanium dichloride (5.98 g, 24 mmol) over 1 h. After the mixture
had been stirred for 72 h at rt, another portion of the AlMe3
solution (9.6 cm3) was added dropwise. After stirring for an
additional 48 h the solution was ready for use in the subsequent
steps. The Tebbe reagent is stable for 2 months under argon.
1
are uncorrected. H NMR and 13C NMR were recorded on
Bruker AMXR 300 and Varian VXR 400 S spectrometers in
CDCl3 as solvent with chemical shift values reported in ppm
relative to residual chloroform (δH = 7.26 or δC = 77.0) as
internal standard unless otherwise stated. Mass spectra were
determined at an ionising voltage of 70 eV and the spectral
data are tabulated as m/z. Optical rotations were measured on
tert-Butyldimethylsilyl (R)-3-(tert-butyldimethylsilyloxy)-5-
methoxy-3-methylhex-5-enoate 7
The Tebbe solution (20 cm3, 7 mmol) was slowly added at
Ϫ78 ЊC to a solution of diester 6 (2.02 g, 5.00 mmol) in THF
(10 cm3). The solution was warmed to rt and stirred for 3 h. The
mixture was quenched with 2 M NaOH (10 cm3), diluted with
diethyl ether (40 cm3) and stirred for 12 h at rt. After filtration
through Celite, the residue was rinsed with diethyl ether. The
filtrate was washed with aqueous NaHCO3 and brine, dried
(Na2SO4) and evaporated. The residue was chromatographed
(15:1 light petroleum ether-EtOAc) to yield 7 (1.23 g, 61%) as
a colourless oil; bp 130 ЊC/7 × 10Ϫ2 Torr (bulb-to-bulb distil-
lation); [α]D20 Ϫ2.4 (c 1.0, CHCl3); νmax (NaCl)/cmϪ1 2940, 2920,
2850, 1710, 1645, 1465, 1455, 1245, 1190, 1155, 1100, 830;
δH (400 MHz) 0.06 (6H, s), 0.23 (3H, s), 0.24 (3H, s), 0.82 (9H,
s), 0.91 (9H, s), 1.37 (3H, s), 2.38 (1H, d, J 13 Hz), 2.53 (2H, s),
2.56 (1H, d, J 13 Hz), 3.45 (3H, s), 3.93 (2H, s); δC (75.5 MHz)
Ϫ4.8, Ϫ2.0, 17.6, 18.2, 25.7, 25.9, 28.2, 47.9, 48.5, 54.5, 74.1,
a
Perkin-Elmer 241 polarimeter. Infrared spectra were
recorded using Perkin-Elmer 1420 and Bruker IFS 45 spec-
trometers. CD- and UV-spectra were recorded on an S. A.
Jobin Yvon CD-6-Dichrograph. Elemental analysis were
performed at the Microanalytical Laboratory of the Depart-
ment of Chemistry, LMU München. Unless otherwise noted,
flash chromatography was carried out on silica gel (Merck
Kieselgel 60 F254, particle size 0.040–0.063 mm). TLC was
performed on silica gel 60 F254 (Merck).
The known 4,30 1031 and methyl 2,4-dihydroxy-6-methyl-
benzoate32 were prepared by published procedures. (R)- and
(S)-1-(1-naphthyl)ethanol (>98% ee) were obtained as described
by Klibanov33 or purchased from Fluka. Compound 14a was
purchased from Lancaster, pig liver esterase (EC 3.1.1.1) from
Sigma.
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84.3, 161.3, 171.6; m/z (EI) 402 [Mϩ, 0.1%], 401 [Mϩ Ϫ H,
0.5%], 387 (0.5), 273 (2), 213 (5), 147 (28), 73 (100) (Found Mϩ:
402.2622. Calc. for C20H42O4Si2: 402.2650).
Methyl (R)-1-(1-naphthyl)ethyl (S)-3-(tert-butyldimethylsilyl-
oxy)-3-methylpentanedioate 12
To a solution of (3S,1ЈR)-11 (202 mg, 0.61 mmol) in CH2Cl2
(20 cm3) were added 2,6-lutidine (215 µl, 1.84 mmol) and
tert-butyldimethylsilyl trifluoromethanesulfonate (225 µl, 0.98
mmol) at Ϫ20 ЊC. The mixture was stirred for 2 h at rt, then
hydrolysed with water and extracted with ethyl acetate (2×).
The combined organic phases were washed with saturated
aqueous NaHCO3, aqueous NH4Cl and brine, dried (Na2SO4)
and concentrated. Column chromatography (10:1 light petrol-
eum ether–EtOAc) afforded the product (216 mg, 80%) as a
colourless oil (Found: C, 67.6; H, 8.1. Calc. for C22H30O5Si: C,
67.5; H, 8.2%); Rf 0.52 (3:1 light petroleum–EtOAc); [α]D25
ϩ15.5 (c 1.1, MeOH); νmax (KBr)/cmϪ1 2954, 2931, 2857, 1739,
1600, 1512, 1473, 1464, 1376, 1345, 1254, 1104; δH (300 MHz)
0.08 (6H, s), 0.76 (9H, s), 1.47 (3H, s), 1.70 (3H, d, J 6.6 Hz),
2.65–2.93 (4H, m), 3.63 (3H, s), 6.65 (1H, q, J 6.6 Hz), 7.43–
7.60 (4H, m), 7.79 (1H, d, J 8.3 Hz), 7.87 (1H, d, J 7.6 Hz), 8.07
(1H, d, J 8.1 Hz); δC (75.5 MHz) Ϫ2.2, 17.9, 21.8, 25.5, 28.4,
46.2, 46.6, 51.2, 69.3, 73.1, 123.1, 123.2, 125.3, 125.6, 126.2,
128.3, 128.9, 130.2, 133.8, 137.4, 170.0, 171.2; m/z (CI) 445
[Mϩ ϩ H, 5%], 391 (2), 291 (21), 233 (5), 197 (6), 155 (100).
(R)-5-(tert-Butyldimethylsilyloxy)-3-methoxy-5-methylcyclohex-
2-en-1-one (R)-9
A solution of enol ether 7 (700 mg, 1.72 mmol) in THF (3.5
cm3) was treated with K2CO3 (340 mg, dissolved in 13.5 cm3 1:3
water–methanol). After stirring for 2 h at rt, the solvent was
removed in vacuo and the remaining salt (R)-8 dried at 0.1 mbar
for 1 h.
The suspension, prepared by slowly adding trifluoro-
methanesulfonic anhydride (1.7 cm3, 10 mmol) to a solution of
DMAP (2.40 g, 20.0 mmol) in dry CH2Cl2 (80 cm3) at Ϫ20 ЊC
under argon, was transferred via a double-tipped needle into a
second flask containing (R)-8 at Ϫ20 ЊC. After stirring for 2 h,
the suspension was allowed to warm to rt, and stirring was
continued for 24 h. The mixture was poured into aqueous
NaHCO3, the organic phase dried (Na2SO4) and concentrated.
The residue was purified by column chromatography (2:1 light
petroleum ether–EtOAc) yielding (R)-9 (380 mg, 81%) as a
colourless oil; bp 75 ЊC/2 × 10Ϫ3 Torr (Found: C, 62.55, H 9.78;
Calc. for C14H26O3Si: C, 62.18, H, 9.69%); Rf 0.14 (3:1 light
petroleum–EtOAc); [α]D25 Ϫ38.7 (c 1.0, CHCl3); λmax/nm (MeOH)
224 (Erel 0.65), 251 (0.8); CD λ/nm (MeOH): 256 (∆εmax Ϫ1.26),
295 (0.18); νmax (NaCl film)/cmϪ1 2950, 2920, 2850, 1650, 1605,
1370, 1250, 1220, 1135, 1110, 1025, 835; δH (400 MHz) 0.01
(3H, s), 0.02 (3H, s), 0.73 (9H, s), 1.32 (3H, s), 2.33 (1H, d, J 16
Hz), 2.47 (1H, d, J 16 Hz), 2.47 (1H, d, J 17 Hz), 2.49 (1H, d,
J 17 Hz), 3.63 (3H, s), 5.33 (1H, s); δC (100.6 MHz) Ϫ2.5, Ϫ2.4,
17.9, 25.6, 29.2, 44.0, 51.9, 55.8, 73.4, 101.4, 175.8, 198.1; m/z
(EI) 269 [Mϩ Ϫ H, 0.3%], 255 (5), 215 (3), 214 (12), 213 (100),
195 (7), 181 (42), 171 (10), 139 (10), 89 (12) (Found Mϩ Ϫ H:
269.1573. Calc. for C14H25O3Si: 269.1587).
(R)-1-(1-Naphthyl)ethyl (S)-3-(tert-butyldimethylsilyloxy)-5-
methoxy-3-methylhex-5-enoate 13
The Tebbe reagent solution (7.00 cm3, 2.45 mmol) was slowly
added at Ϫ50 ЊC to a solution of diester 12 (683 mg, 1.54 mmol)
in THF (25 cm3). The mixture was then warmed to Ϫ30 ЊC and
stirred for 3 h. After the addition of 2 M NaOH (3 cm3, gas
evolution!) and dilution with diethyl ether (14 cm3), the mixture
was stirred for 12 h at rt. After filtration through Celite, the
residue was rinsed with diethyl ether. The combined filtrates
were washed with aqueous NaHCO3 and brine, dried (Na2SO4)
and evaporated in vacuo. The residue was chromatographed
(10:1 light petroleum ether–EtOAc) to yield 13 (450 mg, 66%)
as a colourless oil (Found: C, 70.7, H, 8.5; Calc. for C26H38O4Si:
C, 70.6, H, 8.6%); Rf 0.39 (10:1 light petroleum ether–EtOAc );
[α]D25 ϩ10.1 (c 1.7, MeOH); νmax (KBr)/cmϪ1 3051, 2953, 2930,
2855, 1737, 1655, 1599, 1253, 1155, 1066, 836, 800, 776; δH (300
MHz) 0.06 (3H, s), 0.09 (3H, s), 0.82 (9H, s), 1.42 (3H, s), 1.71
(3H, d, J 6.5 Hz), 2.39–2.82 (4H, m), 3.42 (3H, s), 3.92 (2H, s),
6.66 (1H, q, J 6.5 Hz), 7.44–7.63 (4H, m), 7.79 (1H, d, J 8.1 Hz),
7.86 (1H, d, J 7.8 Hz), 8.11 (1H, d, J 8.4 Hz); δC (75.5 MHz)
Ϫ2.1, Ϫ2.0, 18.1, 21.9, 25.8, 28.0, 47.0, 48.2, 54.5, 69.1, 74.2,
84.3, 123.3, 123.4, 125.3, 125.6, 126.2, 128.3, 128.8, 130.3,
133.8, 137.7, 161.0, 170.3.
Methyl (R)-1-(1-naphthyl)ethyl (S)-3-hydroxy-3-methylpentane-
dioate (3S,1ЈR)-11
To a solution of anhydride 10 (1.54 g, 10.7 mmol) and (R)-1-(1-
naphthyl)ethanol (2.00 g, 11.6 mmol) in dry acetone–CH2Cl2
1:1 (30 cm3) at Ϫ60 ЊC was added dropwise with stirring a
solution of DMAP (1.42 g, 11.6 mmol) in CH2Cl2 (10 cm3). The
suspension was kept for 5 d at this temperature.26 After warm-
ing to Ϫ40 ЊC, methanol (1.80 cm3, 44.5 mmol) and DCC (2.40
g, 11.6 mmol) in CH2Cl2 (10 cm3) were added, and the solution
was stirred for 2 h at Ϫ40 ЊC and for 24 h at rt. CH2Cl2 (10 cm3)
was added and the mixture filtered. The filtrate was dried
(Na2SO4) and concentrated and the residue purified by column
chromatography (3:1 light petroleum ether–EtOAc) to yield
(3S,1ЈR)-11 (2.65 g, 75%) as a colourless oil [14:1 mixture of
diastereomers by 1H NMR spectroscopic analysis of the methyl
ester signals, δ 3.67 (major), δ 3.64 (minor)] (Found: C, 69.3; H,
6.6. Calc. for C19H22O5: C, 69.1; H, 6.7%); [α]D25 ϩ15.4 (c 4.0,
CHCl3); νmax (KBr)/cmϪ1 2981, 1735, 1598, 1512, 1439, 1349,
1199, 1069, 1044; δH (300 MHz) 1.35 (3H, s), 1.73 (3H, d, J 6.5
Hz), 2.64–2.84 (4H, m), 3.67 (3H, s), 4.05 (1H, s), 6.69 (1H, q,
J 6.5 Hz), 7.44–7.58 (3H, m), 7.59 (1H, d, J 7.0 Hz), 7.81 (1H, d,
J 8.3 Hz), 7.88 (1H, d, J 8.5 Hz), 8.07 (1H, d, J 8.3 Hz); δC (75.5
MHz) 21.7, 27.3, 44.8, 45.0, 51.7, 69.7, 69.9, 122.9, 123.2, 125.3,
125.7, 126.4, 128.6, 128.9, 130.1, 133.8, 137.0, 171.3, 172.1;
m/z (EI) 330 [Mϩ, 22%], 170 (15), 155 (100) (Found Mϩ:
330.1501. Calc. for C19H22O5: 330.1467).
(S)-5-(tert-Butyldimethylsilyloxy)-3-methoxy-5-methylcyclohex-
2-en-1-one (S)-9
A solution of enol ether 13 (189 mg, 0.43 mmol) in 1 M
ethanolic KOH (1.00 cm3) was stirred for 28 h at rt. The solvent
was carefully removed in vacuo and the residual (S)-8 dried at
0.1 mbar for 3 h.
Trifluoromethanesulfonic anhydride (600 µl, 3.66 mmol) was
slowly added to a solution of DMAP (600 mg, 4.91 mmol) in
dry CH2Cl2 (100 cm3) at Ϫ20 ЊC under argon. The suspension
was transferred via a double-tipped needle into a second flask
containing the carboxylate (S)-8 at Ϫ50 ЊC. After stirring
for 2 h, the suspension was allowed to warm to rt and poured
into aqueous NaHCO3. Work-up as described for the (R)-
compound afforded (S)-9 (48 mg, 41%) as a colourless oil;
[α]D25 ϩ40.2 (c 1.0, CHCl3); CD λ/nm (MeOH) 256 (∆εmax 1.26),
295 (Ϫ0.17); all other spectral characteristics were identical
with those of the enantiomeric material (R)-9.
Methyl (S)-1-(1-naphthyl)ethyl (R)-3-hydroxy-3-methylpentane-
dioate (3R,1ЈS)-11
The above procedure was repeated with (S)-1-(1-naphthyl)-
ethanol yielding (3R,1ЈS)-11 as a colourless oil; [α]D25 Ϫ15.0
(c 4.0, CHCl3); its spectral characteristics were identical with
those of the enantiomer.
Methyl 2,4-bis(benzyloxymethoxy)-6-methylbenzoate 14b
Methanol (1.50 cm3) and sodium methoxide (81 mg, 1.50
mmol) were added to methyl 2-hydroxy-4-[13C]methoxy-6-
2486
J. Chem. Soc., Perkin Trans. 1, 2000, 2483–2489

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methylbenzoate (118 mg, 0.60 mmol), and the mixture was con-
centrated in vacuo. The residue was suspended in dry THF
(5 cm3), treated with triethylamine (600 µl, 4 mmol) and benzyl
chloromethyl ether (400 µl, 2.40 mmol) and stirred for 12 h at rt.
The reaction mixture was washed with aqueous NaHCO3 and
brine, dried (Na2SO4) and the solvent removed. Purification by
column chromatography (5:1 light petroleum ether–EtOAc)
yielded 14b (338 mg, 80%) as a colourless oil; δH (400 MHz)
2.29 (3H, s), 3.90 (3H, s), 4.69 (2H, s), 4.71 (2H, s), 5.25 (2H, s),
5.26 (2H, s), 6.60 (1H, d, J 2.3 Hz), 6.80 (1H, d, J 2.3 Hz), 7.28–
7.36 (10H, m); δC (100.6 MHz) 19.8, 52.1, 70.0, 70.1, 92.1, 92.6,
101.4, 111.0, 127.9, 127.9, 128.0, 128.1, 128.4, 128.5, 137.1,
137.1, 138.1, 155.5, 158.8, 168.5; m/z (EI) 422 [Mϩ, 4%], 392
(10), 362 (5), 181 (20), 91 (100) (Found Mϩ: 422.1731. Calc. for
C25H26O6: 422.1728).
hexenone 9 (219 mg, 800 µmol) was added. Stirring was con-
tinued at Ϫ70 ЊC for 15 min and the mixture allowed to warm to
rt within 30 min. After hydrolysis with saturated aqueous
NH4Cl (200 cm3), the organic layer was extracted with diethyl
ether (3 × 50 cm3). The combined organic phases were washed
with water and brine, and dried over MgSO4. The solvent was
removed and the residue purified by chromatography on silica
gel (2:1 light petroleum ether–EtOAc).
(R)-3-(tert-Butyldimethylsilyloxy)-9-hydroxy-6,8-dimethoxy-
3-methyl-3,4-dihydroanthracen-1(2H)-one 15a. From 2,4-
dimethoxy-6-methylbenzoate 14a and (R)-9 (>99% ee) in 25%
yield, light yellow oil; λmax/nm (MeOH) 227 (Erel 0.55), 268
(0.8), 313 (0.15), 388 (0.27); CD λ/nm (MeOH) 213 (∆εmax 0.9),
231 (Ϫ1.5), 254 (1.6), 280 (Ϫ0.32), 295 (0.45), 309 (0.35), 320
(0.75), 385 (Ϫ1.05); δH (400 MHz) 0.01 (3H, s), 0.06 (3H, s),
0.62 (9H, s), 1.41 (3H, s), 2.73 (1H, d, J 16.8 Hz), 2.83 (1H, dd,
J 16.8, 1.7 Hz), 2.98 (1H, d, J 16.1 Hz), 3.04 (1H, d, J 16.1 Hz),
3.90 (3H, s), 3.98 (3H, s), 6.42 (1H, d, J 2.2 Hz), 6.55 (1H, d,
J 2.2 Hz), 6.82 (1H, s), 15.04 (1H, s); m/z (EI) 416 [Mϩ, 27%],
359 (100), 341 (15), 317 (34), 285 (15) (Found Mϩ: 416.2019,
Calc. for C23H32O5Si: 416.2017).
Methyl 2-hydroxy-4-[13C]methoxy-6-methylbenzoate34
To a suspension of K2CO3 (453 mg, 3.28 mmol) in dry acetone
(3 cm3), a solution of methyl 2,4-dihydroxy-6-methylbenzoate
(300 mg, 1.65 mmol) and iodo[13C]methane (102 µl, 1.65 mmol)
in acetone (1.5 cm3) was added at rt. After heating the reaction
mixture for 3 h at reflux, the precipitate was dissolved in H2O.
The mixture was concentrated in vacuo and extracted with ethyl
acetate (3×). The combined organic layers were washed with
brine (2×), dried (Na2SO4) and the solvent removed in vacuo.
The crude material was purified by column chromatography
(8:1 light petroleum ether–EtOAc) to yield methyl 2-hydroxy-4-
[13C]methoxy-6-methylbenzoate (295 mg, 91%) as colourless
needles, mp 66 ЊC; Rf 0.42 (5:1 light petroleum ether–EtOAc);
νmax (KBr)/cmϪ1 3046, 2982, 2950, 1649, 1617, 1578, 1456, 1295,
1269, 1218, 1198, 1155, 1041, 816; δH (300 MHz) 2.49 (3H, s),
3.79 (3H, d, J 144 Hz), 3.92 (3H, s), 6.28 (1H, dd, J 2.6, 0.8 Hz),
6.32 (1H, d, J 2.6 Hz), 11.78 (1H, s); δC (75.5 MHz, CDCl3)
24.0, 51.5, 55.0 [13C], 98.5 (d, J 4.7), 105.0, 110.8 (d, J 3.5),
142.9, 163.7 (d, J 2.0), 165.4, 171.9; m/z (EI) 197 [Mϩ, 39%], 165
(100.0), 137 (35), 121 (12) (Found Mϩ: 197.0777. Calc. for
C913C1H12O4: 197.0768).
(R)-6,8-Bis(benzyloxymethoxy)-3-(tert-butyldimethylsilyl-
oxy)-9-hydroxy-3-methyl-3,4-dihydroanthracen-1(2H)-one (R)-
15b. From 14b and (R)-9 (>99% ee) in 50% yield, yellow oil; [α]D25
Ϫ2.4 (c 1.5, CHCl3); CD λ/nm (MeOH) 215 (∆εmax 2.28), 231
(Ϫ2.1), 267 (2.7), 282 (Ϫ0.23), 293 (0.43), 305 (0.25), 320 (0.6),
382 (Ϫ1.29); νmax (KBr)/cmϪ1 2955, 2929, 2860, 1624, 1583,
1381, 1171, 1061, 1023, 836; δH (400 MHz) 0.02 (3H, s), 0.09
(3H, s), 0.67 (9H, s), 1.43 (3H, s), 2.74 (1H, d, J 16.9 Hz), 2.84
(1H, dd, J 16.9, 1.7 Hz), 2.98 (1H, d, J 16.0 Hz), 3.05 (1H, d,
J 16.0 Hz), 4.75 (2H, s), 4.88 (2H, s), 5.37 (2H, s), 5.38 (2H, s),
6.86 (1H, s), 6.87 (1H, d, J 2.3 Hz), 6.94 (1H, d, J 2.3 Hz), 7.28–
7.41 (10H, m), 14.97 (1H, s); δC (100.6 MHz) Ϫ2.4, Ϫ2.2, 17.9,
25.5, 28.9, 44.6, 53.2, 70.3, 70.4, 73.5, 92.1, 93.6, 103.5, 104.0,
110.3, 117.1, 127.8, 128.0, 128.1, 128.1, 128.2, 128.4, 128.5,
137.0, 137.2, 137.3, 142.0, 158.3, 159.1, 165.2, 203.0; m/z (EI)
628 [Mϩ, 32%], 598 (28), 541 (30), 511 (26), 508 (19), 451 (16),
421 (33), 91 (100) (Found Mϩ: 628.2856. Calc. for C37H44O7Si:
628.2911).
Methyl 2-benzyloxymethoxy-4-[13C]methoxy-6-methylbenzoate
14c*
To methyl 2-hydroxy-4-[13C]methoxy-6-methylbenzoate (118
mg, 0.60 mmol) were added methanol (1.5 cm3) and sodium
methoxide (81 mg, 1.50 mmol), and the mixture was concen-
trated in vacuo. The residue was suspended in dry THF (5 cm3),
treated with triethylamine (120 µl, 0.80 mmol) and benzyl
chloromethyl ether (100 µl, 0.66 mmol) and stirred for 12 h at rt.
The reaction mixture was washed with aqueous NaHCO3 and
brine, dried (Na2SO4) and the solvent removed. Purification by
column chromatography (5:1 light petroleum ether–EtOAc)
yielded 14c* (162 mg, 85%) as a colourless oil; mp 19 ЊC; Rf 0.32
(5:1 light petroleum ether–EtOAc); νmax (KBr)/cmϪ1 3065,
3032, 2951, 1728, 1607, 1270, 1189, 1155, 1059, 740; δH (300
MHz) 2.29 (3H, s), 3.36 (3H, d, J 144 Hz), 3.88 (3H, s), 4.70
(2H, s), 5.25 (2H, s), 6.39 (1H, d, J 2.2 Hz), 6.62 (1H, d, J 2.2
Hz), 7.29–7.33 (5H, m); δC (75.5 MHz) 19.9, 51.9, 55.4 [13C],
70.0, 92.7, 99.3 (d, J 4 Hz), 108.9 (d, J 4 Hz), 117.5, 127.9,
128.1, 128.4, 137.1, 138.1, 155.8, 161.2, 168.5; m/z (EI) 317 [Mϩ,
5%], 287 (26), 255 (11), 228 (7), 165 (10), 91 (100) (Found Mϩ:
317.1347. Calc. for C1713C1H20O5: 317.1344).
(S)-6,8-Bis(benzyloxymethoxy)-3-(tert-butyldimethylsilyl-
oxy)-9-hydroxy-3-methyl-3,4-dihydroanthracen-1(2H)-one (S)-
15b. From 14b and (S)-9 (86% ee) in 35% yield, yellow oil; [α]D25
ϩ2.2 (c 1.4, CHCl3); CD λ/nm (MeOH) 215 (∆εmax Ϫ2.28), 231
(2.1), 267 (Ϫ2.7), 282 (2.3), 293 (Ϫ0.43), 305 (Ϫ0.25), 320
(Ϫ0.59), 382 (1.29); all other spectral data were identical with
those of the enantiomer (R)-15b.
(R)-8-Benzyloxymethoxy-3-(tert-butyldimethylsilyloxy)-9-
hydroxy-6-[13C]methoxy-3-methyl-3,4-dihydroanthracen-1(2H)-
one (R)-15c*. From 14c* and (R)-9 (>99% ee) in 36% yield,
light yellow oil; [α]D25 Ϫ4.0 (c 1.7, CHCl3); λmax/nm (MeOH) 225
(Erel 0.46), 268 (0.68), 313 (0.12), 383 (0.25); CD λ/nm (MeOH)
203 (∆εmax Ϫ3.19), 216 (0.98), 230 (Ϫ1.90), 261 (2.2), 281
(Ϫ0.6), 320 (0.82), 385 (Ϫ1.05); νmax (KBr)/cmϪ1 2956, 2930,
2900, 2860, 1616, 1583, 1375, 1165, 1064, 836; δH (400 MHz)
0.01 (3H, s), 0.08 (3H, s), 0.64 (9H, s), 1.44 (3H, s), 2.74 (1H, d,
J 16.9 Hz), 2.84 (1H, dd, J 16.9, 1.7 Hz), 2.99 (1H, d, J 16.0 Hz),
3.05 (1H, d, J 16.0 Hz), 3.87 (3H, d, J 144.3 Hz), 4.85 (2H, s),
5.45 (2H, s), 6.63 (1H, d, J 2.5 Hz), 6.75 (1H, d, J 2.5 Hz), 6.83
(1H, s), 7.28–7.39 (5H, m), 14.94 (1H, s); δC (100.6 MHz) Ϫ2.4,
Ϫ2.2, 17.9, 25.5, 28.9, 44.7, 53.2, 55.4 [13C], 70.4, 73.4, 93.4,
100.7 (d, J 4.4 Hz), 102.8 (d, J 3.8 Hz), 110.1, 116.8, 127.8,
128.1, 128.4, 137.2, 137.4, 141.7, 158.2, 161.6 (d, J 2.4 Hz),
165.2, 202.8; m/z (EI) 523 [Mϩ, 23%], 493 (38), 436 (100), 418
(12), 394 (25), 346 (35), 330 (32) (Found Mϩ: 523.2486. Calc. for
C2913C1H38O6Si: 523.2471).
General procedure for the condensation of the orsellinates 14 with
cyclohexenone 9
To a solution of diisopropylamine (220 µl, 1.72 mmol) in dry
THF (30 cm3) was added 2.5 M n-butyllithium in hexane (600
µl, 1.50 mmol) at 0 ЊC. The mixture was stirred for 10 min at
0 ЊC and then for 10 min at Ϫ78 ЊC. Within 30 s the orsellinate
14 (500 µmol) dissolved in dry THF (3 cm3) was added, which
produced a deep red solution. After 10 min of stirring, cyclo-
J. Chem. Soc., Perkin Trans. 1, 2000, 2483–2489
2487

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(S)-8-Benzyloxymethoxy-3-(tert-butyldimethylsilyloxy)-9-
hydroxy-6-[13C]methoxy-3-methyl-3,4-dihydroanthracen-1(2H)-
one (S)-15c*. From 14c* and (S)-9 (86% ee) in 46% yield, light
yellow oil; [α]D25 ϩ3.9 (c 1.7, CHCl3); CD λ/nm (MeOH) 203
(∆εmax 3.20), 216 (Ϫ1.0), 230 (1.9), 261 (Ϫ2.2), 281 (0.6), 320
(Ϫ0.8), 385 (1.0); all other spectral data were identical with
those of the enantiomer (R)-15c*.
of aqueous CaCl2 and ethyl acetate. The organic layer was
washed with water (2×), dried (MgSO4) and the solvent
removed in vacuo. Purification of the residue by column
chromatography on Sephadex LH 20 (Pharmacia) with
methanol as eluent yielded the deprotected pre-anthraquinones.
(R)-Torosachrysone 8-methyl ether (R)-3. From 15a in 70%
yield, yellow crystals; λmax/nm (MeOH) 225 (Erel 0.35), 269
(0.82), 320 (0.24), 332 (0.27), 365 (0.34); CD λ/nm (MeOH) 213
(∆εmax Ϫ1.92), 231 (0.26), 239 (Ϫ0.32), 253 (0.56), 267 (Ϫ0.11),
278 (Ϫ1.08), 293 (0.57), 302 (0.35), 322 (1.36), 385 (Ϫ0.20);
δH (400 MHz) 1.40 (3H, s), 2.79 (1H, d, J 17.5 Hz), 2.84 (1H, d,
J 17.5 Hz), 3.02 (1H, d, J 17.0 Hz), 3.06 (1H, d, J 17.0 Hz), 3.88
(3H, s), 3.96 (3H, s), 6.41 (1H, d, J 2.0 Hz), 6.53 (1H, d, J 2.0
Hz), 6.85 (1H, s), 15.1 (1H, s); m/z (EI) 302 [Mϩ, 100%], 284
(10), 269 (20), 245 (17), 244 (37), 229 (10), 226 (15) (Found Mϩ:
302.1154. Calc. for C17H18O5: 302.1110).
General procedure for the deprotection of the BOM derivatives
A flask containing a stirred solution of the BOM-protected
dihydroanthracenone 15 (50.0 µmol) in MeOH (10 cm3) was
degassed (4×) and refilled with argon. Then, 10% palladium on
charcoal (4.5 mg) was added and the atmosphere replaced with
hydrogen gas (4×). The solution was stirred for 12 h at 25 ЊC in
the dark. After replacing the hydrogen atmosphere with argon,
the suspension was passed through a short plug of Celite,
washed with MeOH, and concentrated in vacuo. Purification
was performed by column chromatography on Sephadex LH 20
(Pharmacia) with methanol as eluent.
(R)-Atrochrysone (R)-1. From (R)-16b in 70% yield, yellow
powder; λmax/nm (MeOH) 225 (Erel 0.56), 271 (0.8), 321 (0.14),
333 (0.13), 394 (0.24); CD λ/nm (MeOH) 251 (∆εmax 0.43), 254
(0.39), 258 (0.46), 264 (Ϫ0.29), 266 (Ϫ0.26), 276 (Ϫ1.68), 296
(0.89), 312 (0.53), 324 (0.75), 403 (Ϫ0.46); δH (400 MHz,
CDCl3 ϩ [2H6]acetone) 1.35 (3H, s), 2.71 (1H, d, J 17.3 Hz), 2.76
(1H, d, J 17.3 Hz), 2.94 (2H, br s), 4.02 (1H, br s), 6.36 (1H, d,
J 2.3 Hz), 6.46 (1H, d, J 2.3 Hz), 6.7 (1H, br s), 8.38 (1H, br s),
9.77 (1H, d, J 0.6 Hz), 16.2 (1H, d, J 0.6 Hz); m/z (EI) 274 [Mϩ,
100%], 256 (71), 232 (12), 216 (27), 213 (11), 190 (5) (Found
Mϩ: 274.0834. Calc. for C15H14O5: 274.0841).
(R)-3-(tert-Butyldimethylsilyloxy)-6,8,9-trihydroxy-3-methyl-
3,4-dihydroanthracen-1(2H)-one (R)-16b. From (R)-15b in 51%
yield, yellow crystals; mp 164–165 ЊC; [α]D25 Ϫ3.5 (c 0.5, CHCl3);
δH (300 MHz) 0.00 (3H, s), 0.07 (3H, s), 0.64 (9H, s), 1.43 (3H,
s), 2.73 (1H, d, J 17.0 Hz), 2.85 (1H, dd, J 17.0, 1.5 Hz), 2.96
(1H, d, J 15.8 Hz), 3.02 (1H, d, J 15.8 Hz), 5.43 (1H, br s), 6.41
(1H, d, J 2.2 Hz), 6.51 (1H, d, J 2.2 Hz), 6.77 (1H, s), 9.89 (1H,
s), 16.08 (1H, s); m/z (EI) 388 [Mϩ, 25%], 332 (22), 331 (100),
313 (28), 298 (5), 289 (30), 256 (8) (Found Mϩ: 388.1673. Calc.
for C21H28O5Si: 388.1706).
(S)-Atrochrysone (S)-1. From (S)-16b in 70% yield, yellow
powder; CD λ/nm (MeOH) 262 (∆εmax Ϫ0.57), 277 (0.75), 296
(Ϫ0.73), 310 (Ϫ0.56), 324 (Ϫ0.72), 395 (0.17); all other spectral
characteristics were identical with those of the enantiomer
(R)-1.
(S)-3-(tert-Butyldimethylsilyloxy)-6,8,9-trihydroxy-3-methyl-
3,4-dihydroanthracen-1(2H)-one (S)-16b. From (S)-15b in 51%
yield, yellow crystals; mp 164–165 ЊC; [α]D25 ϩ3.3 (c 0.6, CHCl3);
all other spectral characteristics were identical with those of the
enantiomer (R)-16b.
(R)-[methoxy-13C]Torosachrysone (R)-2*. From (R)-16c* in
75% yield, yellow crystals; λmax/nm (MeOH) 226 (Erel 0.45),
271.5 (0.85), 316 (0.13), 394 (0.22); CD λ/nm (MeOH) 213
(∆εmax Ϫ1.55), 231 (0.19), 238 (Ϫ0.15), 259 (0.86), 278 (Ϫ0.43),
294 (0.92), 309 (0.72), 322 (1.18), 413 (Ϫ0.56); νmax (KBr)/cmϪ1
2967, 2933, 1638, 1586, 1391, 1346, 1155; δH (400 MHz) 1.45
(3H, s), 1.79 (1H, br s), 2.84 (2H, m), 3.04 (2H, m), 3.88 (3H, d,
J 144.5 Hz), 6.48 (1H, d, J 2.2 Hz), 6.53 (1H, d, J 2.2 Hz), 6.86
(1H, br s), 9.79 (1H, s), 16.1 (1H, s); δC (100.6 MHz, [2H6]-
acetone) 29.3, 43.6, 51.4, 55.8 [13C], 70.8, 100.1, 101.3, 108.4,
109.4, 118.0, 138.2, 142.1, 160.4, 164.3, 166.3, 204.4; m/z (EI)
289 [Mϩ, 100%], 272 (9), 271 (49), 256 (5), 247 (13), 232 (15),
231 (25), 204 (7) (Found Mϩ: 289.1063. Calc. for C1513C1H16O5:
289.1031).
(R)-3-(tert-Butyldimethylsilyloxy)-8,9-dihydroxy-6-[13C]-
methoxy-3-methyl-3,4-dihydroanthracen-1(2H)-one (R)-16c*.
From (R)-15c* in 70% yield, light yellow crystals; mp 127 ЊC;
[α]D20 Ϫ4.5 (c 2.2, CHCl3); λmax/nm (MeOH) 209 (log ε 0.80), 225
(1.42), 240 (0.74), 270 (2.47), 296 (0.26), 314 (0.42), 339 (0.19),
392 (0.65); νmax (KBr)/cmϪ1 2956, 2931, 2856, 1639, 1585, 1155,
1023, 839; δH (300 MHz) 0.00 (3H, s), 0.07 (3H, s), 0.64 (9H, s),
1.43 (3H, s), 2.72 (1H, d, J 17.0 Hz), 2.83 (1H, dd, J 17.0, 1.5
Hz), 2.96 (1H, d, J 15.7 Hz), 3.02 (1H, d, J 15.7 Hz), 3.87 (3H,
d, J 144.4 Hz), 6.46 (1H, d, J 2.3 Hz), 6.52 (1H, d, J 2.3 Hz),
6.81 (1H, s), 9.79 (1H, s), 16.01 (1H, s); δC (100.6 MHz) Ϫ2.3,
Ϫ2.2, 17.9, 25.5, 29.1, 44.3, 52.4, 55.5 [13C], 73.7, 99.6 (d, J 4.9
Hz), 100.9 (d, J 3.9 Hz), 108.0, 108.6, 117.3, 136.5, 141.0, 159.7,
163.3 (d, J 2.0 Hz), 165.5, 202.8; m/z (EI) 403 [Mϩ, 32%], 347
(23), 346 (100), 328 (25), 304 (30) (Found Mϩ: 403.1876. Calc.
for C2113C1H30O5Si: 403.1896).
(S)-[methoxy-13C]Torosachrysone (S)-2*. From (S)-16c* in
75% yield, yellow crystals; mp 186 ЊC; [α]D20 ϩ7.1 (c 1.5, dioxane);
CD λ/nm (MeOH) 213 (∆εmax 1.55), 231 (Ϫ0.19), 238 (0.15), 259
(Ϫ0.86), 278 (0.43), 294 (Ϫ0.92), 309 (Ϫ0.72), 322 (Ϫ1.18), 413
(0.56); all other spectral characteristics were identical with
those of the enantiomeric material (R)-2*.
(S)-3-(tert-Butyldimethylsilyloxy)-8,9-dihydroxy-6-[13C]-
methoxy-3-methyl-3,4-dihydroanthracen-1(2H)-one (S)-16c*.
From (S)-15c* in 82% yield, light yellow oil; mp 127 ЊC; [α]D20
ϩ4.3 (c 2.2, CHCl3); CD λ/nm (MeOH) 214 (∆εmax Ϫ0.1), 231
(0.15), 261 (Ϫ0.39), 283 (Ϫ0.03), 300 (Ϫ0.12), 310 (Ϫ0.1), 321
(Ϫ0.15), 393 (0.21); all other spectral data were identical with
those of the enantiomer (R)-16c*.
Acknowledgements
This paper is dedicated to the memory of Professor Leslie
Crombie. We thank the Deutsche Forschungsgemeinschaft
(SFB 369) and the Fonds der Chemischen Industrie for
financial support. The skilful technical assistance of Mrs
Sabine Voß is gratefully acknowledged.
General procedure for the deprotection of the TBDMS
derivatives
A 10 cm3 flask charged with a solution of silyl ether 15a or 16
(50.0 µmol) in acetonitrile (3 cm3) was purged with argon.
Then, 4 drops of a 40% aqueous HF solution were added, and
the mixture was stirred for 2–3 h at 50 ЊC in the dark. The
solution was poured in a separating funnel containing a mixture
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