Synthetic approaches to the angucycline antibiotics. A route to C-glycosidic benz[a]anthraquinones

Article abstract of DOI:10.1071/CH99124

3-Deoxy-6′-hydroxy-13-norurdamycinone B (32a) and 3-deoxy-13-norurdamycinone B (32b) have been synthesized in eight steps from 5,8-dimethoxynaphthalen-1-ol (9) both in 28% overall yield. The key step in this approach is the boron trifluoride diethyl ether

Full text of DOI:10.1071/CH99124

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Volume 53, 2000
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Aust. J. Chem., 2000, 53, 15–24
Synthetic Approaches to the Angucycline Antibiotics.
A Route to C-Glycosidic Benz[a]anthraquinones
Fleur L. Andrews,A David S. Larsen A,B and Lesley LarsenA
A Department of Chemistry, University of Otago,
P.O. Box 56, Dunedin, New Zealand.
B Author to whom correspondence should be addressed.
3-Deoxy-6Ј-hydroxy-13-norurdamycinone B (32a) and 3-deoxy-13-norurdamycinone B (32b) have been synthe-
sized in eight steps from 5,8-dimethoxynaphthalen-1-ol (9) both in 28% overall yield. The key step in this approach
is the boron trifluoride diethyl etherate promoted ␤-C-glycosylations of (9) and 1,3,4,6-tetra-O-acetyl-2-deoxy- and
1,3,4-tri-O-acetyl-2-deoxy-D-arabino-hexopyranoses (13) and (19). The solvent, acetonitrile, was essential for the
success of these reactions. Acetylation of the C-glycosyl-5,8-dimethoxynaphthalen-1-ols (16) and (20) followed by
oxidation with ceric ammonium nitrate gave C-glycosyl-5-acetoxy-1,4-naphthoquinone derivatives (21) and (23)
in 63 and 49% overall yields from (9). Selective deacetylation of the C5 acetoxy groups of (21) and (23) was
achieved by treatment with boron trifluoride etherate in dichloromethane to give 3,4,6-tri-O-acetyl-2-deoxy- and
3,4-di-O-acetyl-2,6-dideoxy-␤-D-arabino-hexopyranosyl-5-hydroxy-1,4-naphthoquinones (24) and (25) respec-
tively. The tetra-O-acetyl diborate promoted Diels–Alder reactions of (24) and (25) with (±)-(E)-1-acetoxy-3-(2-
methoxyvinyl)cyclohex-2-ene (8) each gave a 1 : 1 mixture of diastereoisomeric cycloadducts which, upon
treatment with 1,8-diazabicyclo[5.4.0]undec-7-ene gave (1R*)-1-acetoxy-9-(3,4,6-tri-O-acetyl-2-deoxy-␤-D-
arabino-hexopyranosyl)- and (1R*)-1-acetoxy-9-(3,4-di-O-acetyl-2,6-dideoxy-␤-D-arabino-hexopyranosyl)-8-
hydroxy-1,2,3,4-tetrahydrobenz[a]anthracene-7,12-dione (30a) and (30b) respectively. Sequential deacetylation
and photochemical oxidation of (30a) and (30b) gave the targets (32a) and (32b) respectively.
Keywords. Diels–Alder; glycosylation; naphthoquinones; synthesis; urdamycinone.
Introduction
We felt that a simple extension of our initial approach to
(±)-rubiginone B1 (1) would provide a rapid method for the
construction of C-glycosylated benz[a]anthraquinones. It
was envisaged that the reaction of 6-C-glycosyl-5-hydroxy-
We have reported the syntheses of the angucyclinone
antibiotics rubiginone B1 (1) and B2 (2) albeit in racemic
forms, and a number of related analogues using the stereose-
lective Diels–Alder reaction of 5-hydroxynaphthoquinone
(3) and the diene (±)-(4) as the key synthetic step.1,2 An
extension to this work which utilized a monochiral Lewis
acid to promote an asymmetric Diels–Alder reaction culmi-
nated in the syntheses of (+)-emycin A (5) and (+)-ochromy-
cinone (6).3 As a natural progression of this chemistry our
attention has been directed to the syntheses of the more
complex C-glycosidic members of the angucycline family of
antibiotics. Representatives of this group include
vineomycin A1,4 saquayamycins A–D,5 and the urdamycins
A, C, D and G which all share the common aglycon
aquayamycin.6,7 Another member, urdamycin B, lacking the
angular hydroxy functionality at C 4a and C 12b gives the
aglycon urdamycinone B (7) on mild acid treatment.6
The syntheses of aryl C-glycosides have received a great
deal of attention in the past decade;8 however, there has been
relatively little work directed to C-glycosidic members of the
angucycline group. The only syntheses of C-glycosidic
benz[a]anthraquinones reported to date are that of urdamyci-
none B (7),9,10 its enantiomer [i.e. ent-(7)] using a
biomimetic approach11 and Suzuki’s synthesis of C10412 and
galtamycinone.13
Manuscript received 24 September 1999
© CSIRO 2000
10.1071/CH99124
0004-9425/00/010015

16
F. L. Andrews, D. S. Larsen and L. Larsen
1,4-naphthoquinones with a diene such as (8), followed by
an aromatization step, would provide analogues of urdamy-
cinone B (7). In a preliminary communication we have
reported the syntheses of several per-acetylated 6-C-glyco-
syl-5-acetoxy-1,4-naphthoquinones.14 In this paper we
describe their syntheses in detail, a selective deprotection
protocol to afford 6-C-glycosyl-5-hydroxy-1,4-naphtho-
quinones for use as C-glycosidic dienophiles, and the elabo-
ration of two to C-glycosidic benz[a]anthraquinone
analogues of urdamycinone B.
the yield of (14) to 82%. No trace of (10) was found.
Similarly, reaction of (13) and 2-naphthol in
dichloromethane at room temperature promoted by boron
trifluoride etherate gave the ␤-C-glycoside (14) in 83%
yield. The spectral data for (14) were consistent with the
structure and the assignment of anomeric configuration was
confirmed from the magnitude of the coupling constants,
J1Ј,2Јax and J1Ј,2Јeq of 12 and 2 Hz respectively, for the reso-
nance at ␦ 5.61 attributed to the anomeric proton. Once
again, reaction of the naphthol (9) under similar conditions
gave complex mixtures of products, none of which were
Results and Discussion
Our initial approach to the synthesis of the C-glycosidic
CD ring system of the angucycline antibiotics was based on
work reported by Kometani et al.15 who found that aryl O-
glycosides would undergo a boron trifluoride etherate pro-
moted rearrangement to the corresponding ␤-C-glycoside.
We felt that the most convenient method to access the
required O-glycosides was the triphenylphosphine hydro-
bromide (Ph3PHBr) catalysed addition of naphthol (9)16 to
readily accessible glycals.17 A retrosynthetic analysis
showing our approach to the initial target is given in Scheme
1. To this end a study of the Ph3PHBr catalysed reactions of
2-naphthol with tri-O-acetyl- and tri-O-benzyl-D-glucal was
undertaken. The reaction of the former gave the correspond-
ing O-glycoside (10) in low yield (15%) after a prolonged
reaction time. The poor yield of (10) was attributed to the
deactivating nature of the C 3 acetate group of tri-O-acetyl-
1
D-glucal. H n.m.r. analysis of the crude product from the
reaction of tri-O-benzyl-D-glucal indicated the successful
formation of the O-glycoside (11) as a mixture of anomers.
Unfortunately, (11) proved to be very unstable and was
unable to be isolated. This problem was overcome by treat-
ing a dichloromethane solution of the crude reaction product
with boron trifluoride etherate. This resulted in a smooth
rearrangement to the ␤-C-glycoside (12) in 72% for the two
steps. The structure of (12) was evident from the spectral
data. The i.r. spectrum exhibited a sharp absorption at 3354
cm–1 attributed to the hydroxy group, whilst a resonance at ␦
5.80 assigned to the anomeric proton, H 1Ј, with coupling
constants J1Ј,2Јax and J1Ј,2Јeq of 12 and 2 Hz respectively, con-
firmed the assignment of the ␤-anomeric configuration. With
the successful synthesis of a C-glycoside of 2-naphthol in
hand we applied the above two-step protocol to the CD ring
synthon of the benz[a]anthraquinone system. Unfortunately,
the Ph3PHBr catalysed addition of 5-,8-dimethoxynaph-
thalen-1-ol (9) to both tri-O-acetyl- and tri-O-benzyl-D-
glucal proved unsuccessful.
In an alternative strategy we employed the methodology
of Suzuki and coworkers18 who have developed a direct syn-
thetic route to ortho aryl C-glycosides by the Lewis acid pro-
moted reaction of 1-O-acetyl 2-deoxy sugars with phenols.
In a trial reaction, treatment of a dichloromethane solution of
2-naphthol and 1,3,4,6-tetra-O-acetyl-2-deoxy-D-glucopyra-
nose (13) at –78°C with tin(IV) chloride gave after warming
to –10°C the O-glycoside (10) and the ␤-C-glycoside (14) in
yields of 25 and 51% respectively. Allowing the reaction
mixture to warm from –78°C to room temperature increased

Approaches to the Angucycline Antibiotics
17
identified as the target compound. The use of the alternative
promoter, Cp2HfCl2–AgClO4,18 was also unsuccessful.
Allevi et al. reported the synthesis of carminic acid, the C-
glucosyl colorant of cochineal.19 They found that boron tri-
fluoride promoted C-glycosylation of activated aromatic
methyl ethers was facilitated by the use of glycosyl trifluo-
roacetate donors and acetonitrile as the reaction solvent.
Indeed, this proved to be the case in this study. In
dichloromethane the BF3·Et2O promoted C-glycosylation of
2-naphthol and 3,4,6-tetra-O-acetyl-2-deoxy-1-trifluo-
roacetyl-D-glucopyranose (15) (prepared in situ) gave the O-
glycoside (10) and the corresponding ␤-C-glycoside (14) in
13 and 63% yields respectively. When acetonitrile was used
as the solvent (14) was isolated as the sole product in 74%
yield. Our attention then turned to the angucycline CD ring
synthon (9). The BF3·Et2O promoted reaction of naphthol (9)
and donor (15) in acetonitrile gave the target aryl ␤-C-gly-
coside (16) in 79% yield. The analytical and spectral data
7.72 attributed to the aromatic protons H 6 , H 7, H 3 and H 4.
The anomeric proton, H 1Ј, resonated as a doublet of doublet
at ␦ 5.12 with coupling constants, J1Ј,2Јax and J1Ј,2Јeq , 11 and 2
Hz respectively, confirming the assignment of the anomeric
stereochemistry. An assumption that substitution had
occurred at the C 2 position, ortho to the hydroxy group, of
the naphthalene ring system was made by analogy to the
reactions of 2-naphthol described above. All other data sup-
ported the structural assignment. The reaction was investi-
gated further to determine whether the leaving group of the
glycosyl donor contributed to its success. The per-acetylated
donor (13) under the same reaction conditions gave an
improved yield (94%) of (16). With the success of this latter
reaction a range of different glycosyl donors were investi-
gated. Treatment of a mixture of naphthol (9) and a variety of
1-O-acetyl- and 1-O-trifluoroacetyl-2-deoxyglycopyranoses
in acetonitrile with boron trifluoride etherate were investi-
gated. The results are summarized in Table 1 and good yields
for C-glycosides (16), (18), (20) and ent-(20) were obtained.
In our hands all attempts to synthesize 1-O-acetyl-3,4,6-tri-
O-benzyl-2-deoxy-D-glucopyranose failed because of its
1
were consistent with the proposed structure, with the H
n.m.r. spectrum exhibiting a singlet at ␦ 9.76 assigned to the
hydroxyl proton and four doublets at ␦ 6.62, 6.68, 7.55 and
Table 1. Glycosylation of 5,8-dimethoxynaphthalen-1-ol (9)
Entry
Glycosyl donor
R2
Product
R2
Yield
(%)
Compound
R1
R3
Compound
R3
a
b
c
d
e
(15)
(13)
(17)
COCF3
Ac
COCF3
Ac
Ac
Ac
CH2Ph
Ac
Ac
OAc
OAc
OCH2Ph
H
(16)
(16)
(18)
Ac
Ac
CH2Ph
Ac
Ac
OAc
OAc
OCH2Ph
H
79
94
81
72
75
ent-(19)
(19)
ent-(20)
(20)
Ac
H
H
Table 2. Glycosylation of (9), and further reactions
Reagents and reaction conditions: (i) BF3·Et2O, room temp.; (ii) Ac2O, pyridine, 4-dimethylaminopyridine, room temp.; (iii) ceric
ammonium nitrate, H2O/MeCN
Entry
Glycosyl donor
R2
Product
R2
Yield
(%)A
Compound
R1
Ac
COCF3
Ac
R3
Compound
R3
f
(13)
(17)
ent-(19)
(19)
Ac
CH2Ph
Ac
OAc
OCH2Ph
(21)
(22)
ent-(23)
(23)
Ac
CH2Ph
Ac
OAc
OCH2Ph
H
H
63
53
52
49
g
h
i
H
H
Ac
Ac
Ac
A Isolated yield of product for the three steps.

18
F. L. Andrews, D. S. Larsen and L. Larsen
susceptibility to hydrolysis. Thus benzylated C-glycoside
(18) (entry c) was prepared from the corresponding trifluo-
roacetate (17) which was prepared in situ. Both the precursor
to naturally occurring C-glycosidic angucyclines, (20) and
its enantiomer ent-(20) (entries d and e), were obtained from
D- and L-olivose derivatives (19) and ent-(19) respectively.
It was evident that decomposition of the C-glycosides
(16), (18) and (20) was occurring to some extent during and
after the purification process. We believe that this con-
tributed to the decreased yields of (20) and its enantiomer. To
circumvent this problem the crude products from the C-gly-
cosylation were used in the next reactions in the sequence.
The reaction sequence and results are summarized in Table
2. Acetylation of the crude C-glycosides followed by oxida-
tion with cerium(IV) ammonium nitrate in aqueous acetoni-
trile gave the C-glycosidic quinones (21)–(23). The
acetylation of the aromatic hydroxy group was necessary to
prevent the formation of substituted naphthazarin species.20
To utilize the C-glycosidic naphthoquinones as
dienophiles in Lewis acid promoted Diels–Alder reactions a
selective deacetylation of the C 5 acetoxy group was
required. Unfortunately, attempted deacetylation of (21)
under standard hydrolytic conditions (protic acids, hydrox-
ide and methoxide) gave complex mixtures of products.
However, treatment with excess boron trifluoride etherate in
dichloromethane at ambient temperature resulted in a selec-
tive deacetylation of the aromatic acetoxy group to give the
hydroxynaphthoquinone (24) in 44% yield along with a 45%
recovery of the starting material (21). Recycling the starting
material three times gave 80% overall yield of the target
compound (24). The analytical and spectral data were con-
sistent with the proposed structure with deacetylation being
evident from the resonance of the hydrogen-bonded pheno-
1
lic proton at ␦ 12.29 in the H n.m.r. spectrum. An HMBC
experiment, showing three-bond correlations from the C 1
resonance to both those of H8 and H 3 (Fig. 1), between
those of the phenolic hydrogen and C 6, and between H 2Јax
and C 6, confirmed that C-glycosylation had occurred ortho
to the C 5 hydroxy group. Deacetylation of (23) proved much
more facile under the same reaction conditions and gave an
87% yield of dienophile (25) (shown in Scheme 2).
Scheme 2. Reagents and conditions: (i) (AcO)4B2O, CH2Cl2; (ii) 1,8-
diazabicyclo[5.4.0]undec-7-ene, CH2Cl2, air; (iii) NaOMe, MeOH; (iv)
h␯, O2, CH2Cl2–MeOH.
From the sequence developed for the synthesis of (±)-
rubiginone B1,1,2 the tetra-O-acetyl diborate promoted
Diels–Alder reaction of (24) and the diene (8) gave an
approximately 1 : 1 mixture of the cycloadducts (26a) and
(27a) in a 73% yield after chromatography (Scheme 2). The
ratio was estimated from the peak heights of the C 6
methoxyl resonances at ␦ 2.99 and 3.00 in the 1H n.m.r spec-
trum. The lack of facial selection exhibited by (24) in its
reaction with (8) is in contrast to the high selectivity shown
by the tetra-O-acetyl-␤-D-glucopyranoside (28) in its
Diels–Alder reactions reported by Stoodley.21,22 In a separate
reaction of (24) and (8) partial separation of the adducts was
achieved by fractional crystallization to give (27a) as white
crystals in 37% yield. All data were consistent with the pro-
posed structure and the resonances and splitting patterns for
the protons of the benz[a]anthracene nucleus in the 1H n.m.r.
spectrum closely resembled the related cycloadduct (29a)1
from earlier work, thus confirming the assignment of relative
stereochemistry at C 1, C 6, C 6a, C 12a and C 12b. The abso-
lute stereochemistry at these centres was tentatively assigned
by comparison of the signs of the specific rotation of (27a)
{[␣]D –161° in CH2Cl2} to that of (29b)3 {[␣]D +425° in
Fig. 1. HMBC correlations observed for (24).

Approaches to the Angucycline Antibiotics
19
CH2Cl2}. The regiochemical outcome of the tetra-O-acetyl
diborate promoted cycloaddition reactions of diene (8) and
5-hydroxy-1,4-naphthoquinone has been established previ-
ously.1,2 Because our target molecule contained no chiral
centres in the benz[a]anthracene moiety the mixture of
cycloadducts (26a) and (27a) was carried through the
remaining steps in the synthesis. Aromatization was effected
by treatment of a dichloromethane solution of (26a) and
(27a) with 1,8-diazabicyclo[5.4.0]undec-7-ene under an air
atmosphere to give the protected angucyclinones (30a) as a
1 : 1 mixture of stereoisomers in 90% yield. At this stage it
was envisaged that a photochemically induced oxidation by
irradiation of a dichloromethane solution of (30a) under an
oxygen atmosphere with a broad spectrum tungsten lamp
would give the ketone (31); however, this reaction proceeded
slowly giving only a 51% yield of the desired product. In
earlier work directed at the rubiginones we found that the
rate of oxidation of 1-acetoxybenz[a]anthraquinones was
much slower than that of their deacetylated counterparts.1,2
Deacetylation of (30a) with sodium methoxide in methanol
and subsequent irradiation of a methanol solution of the
intermediary gave our target molecule 3-deoxy-6Ј-hydroxy-
13-norurdamycinone B (32a) in 84% yield after purification
by reverse phase h.p.l.c. Compound (32a) analysed as a dihy-
drate and all data supported the structural assignment. The
signal at ␦ 198.4 in the 13C n.m.r. spectrum confirmed that
oxidation had been effected at the C 1 position.
diastereoisomers in 88% yield for the two steps.
Deacetylation followed by photochemical oxidation of the
C 1 hydroxy group gave 3-deoxy-13-norurdamycinone B
(32b) in 75% yield. Compound (32b) was appreciably more
soluble in deuterated chloroform than (32a), hence all n.m.r.
data were recorded in this solvent. Once again the 13C n.m.r
spectral data confirmed that oxidation at C 1 was successful.
In summary, we have developed a method for the synthe-
sis of C-glycosylbenz[a]anthraquinones from simple starting
materials. The key step in the synthesis is the BF3·Et2O pro-
moted C-glycosylation of 2-deoxy glycosyl acetates and 1-
hydroxy-5,8-dimethoxynaphthoquinone (9). The use of
acetonitrile as the solvent proved vital to the success of these
reactions. After acetylation of the products, oxidation was
affected with ceric ammonium nitrate, and selective deacety-
lation of the C 5 acetate gave naphthoquinones (24) and (25).
Reaction of each with the diene (8) gave stereoisomeric mix-
tures of cycloadducts which were readily transformed into
urdamycinone B analogues, (32a) and (32b) respectively.
The overall yields of both (32a) and (32b) for the seven-step
process were 28%.
Experimental
Melting points were measured on a Gallenkamp capillary melting
point apparatus and are uncorrected. Varian Gemini 200 and VXR300
spectrometers were used to obtain 1H (200 and 300 MHz) and 13C (50
1
and 75 MHz) n.m.r. spectra. All H n.m.r. spectral data were obtained
from solutions of the compound in (D)chloroform at 300 MHz, with the
residual chloroform (␦ 7.26) as internal reference unless otherwise
stated. Chemical shifts are reported as parts per million (ppm) using the
␦ scale. Coupling constants (J) are reported to ±0.5 Hz. Similarly, all
13C n.m.r. spectral data were obtained from (D)chloroform solutions of
the compound measured at 75 MHz unless otherwise stated. I.r. spectra
were recorded on a Perkin–Elmer 1600 Fourier-transform infrared
spectrophotometer. E.i. and f.a.b. mass spectra were recorded on a
Kratos MSORF mass spectrometer operating with an accelerating voltage
of 4 kV and an ionization energy of 70 eV. For f.a.b. mass spectrometry
m-nitrobenzyl alcohol was used as the matrix and xenon as the ionizing
gas. Optical rotation measurements were made with a Jasco DIP-1000
digital polarimeter. Elemental analyses were carried out by Dr R. G.
Cunninghame and associates at the Campbell Microanalytical
Laboratory, University of Otago, Dunedin, New Zealand. Thin-layer
chromatography (t.l.c.) was preformed on Merck silica gel DC Alurolle
Kieselgel 60F254 plates and were visualized under a u.v. lamp and/or
with a spray consisting of 5% w/v dodecamolybdophosphoric acid in
ethanol with subsequent heating. Flash column chromatography was
carried out on Merck Kieselgel 60 (230–400 mesh). All chromatogra-
phy solvents were reagent grade. Tetrahydrofuran was distilled from
sodium/benzophenone ketyl under nitrogen and dichloromethane was
distilled from P2O5. All other solvents and reagents were purified by the
methods outlined in ref. 23.
1-(3Ј,4Ј,6Ј-Tri-O-acetyl-2Ј-deoxy-␤-D-arabino-hexopyranosyl)-
naphthalen-2-ol (14) and 2-(3Ј,4Ј,6Ј-Tri-O-acetyl-2Ј-deoxy-␣-D-
arabino-hexopyranosyloxy)naphthalene (10)
Tin(IV) chloride (105 ␮l, 0.89 mmol) was added to a solution of 2-
naphthol (86 mg, 0.59 mmol) and 1,3,4,6-tetra-O-acetyl-2-deoxy-D-
arabino-hexopyranoside (13) (100 mg, 0.30 mmol) in dry
dichloromethane (6 ml) at –78°C. The cooling bath was removed and
the reaction mixture was slowly warmed to –10°C. The reaction was
quenched with water (5 ml) and the mixture extracted with
dichloromethane. The combined extracts were washed with water, dried
(MgSO4), and the solvent was removed under reduced pressure.
Purification of the residue by silica gel column chromatography
[dichloromethane/diethyl ether (1: 1) as eluent] gave, after crystalliza-
The dienophile possessing the naturally occurring C-gly-
cosyl unit of the angucycline antibiotics was subjected to the
above reaction sequence. The cycloaddition reaction of (25)
and diene (8) gave a 1: 1 mixture of the adducts (26b) and
(27b) which were directly used in the following aromatiza-
tion step. Treatment of the mixture of cycloadducts with 1,8-
diazabicyclo[5.4.0]undec-7-ene under an air atmosphere
gave the protected angucycline (30b) as a 1: 1 mixture of C 1

20
F. L. Andrews, D. S. Larsen and L. Larsen
Representative Procedures for the C-Glycosylation Reactions of
2-Naphthol
tion from diethyl ether, the ␣-O-glycoside (10) (31 mg, 25%) as white
crystals, m.p. 90°C (Found: C, 63.2; H, 5.9. C22H24O8 requires C, 63.5;
1
H, 5.8%). ␯max (neat)/cm–1 2973, 1736 (ester C=O), 1653, 1379. H
Glycosyl Trifluoroacetates as Donors
n.m.r. ␦ 1.97, 2.06, 2.07, each 3H, s, 3×OAc; 2.05, m, H 2Јax; 2.54, ddd,
J 1.5, 5.5 and 13 Hz, H 2Јeq; 3.99, dd, J 2 and 12 Hz, H 6Ј; 4.10, ddd, J
2, 5 and 10 Hz, H5Ј; 4.33, dd, J 5 and 12 Hz, H 6Ј; 5.13, t, J 10 Hz, H4Ј;
5.60, ddd, J 5.5, 10 and 11.5 Hz, H 3Ј; 5.83, d, J 2, H 1Ј; 7.20–7.52, 4H,
m, ArH; 7.72–7.84, 3H, m, ArH. 13C n.m.r. ␦ 20.7, 20.8, 21.1, 3×OAc;
35.8, C 2Ј; 62.1, C 6Ј; 68.7, C 5Ј; 68.9, 69.1, C 3Ј and C 4Ј; 95.4, C 1Ј;
110.5, 118.8, 124.4, 126.7, 127.2, 127.7, 129.6, 7×CH; 129.7; 134.3;
153.9, C 1; 170.0, 170.4, 170.7, 3×OAc. Another product was the C-
glycoside (14) (64 mg, 51%) also as white crystals from diethyl ether
and hexanes, m.p. 128°C (Found: C, 63.5; H, 6.0. C22H24O8 requires C,
Trifluoroacetic anhydride (27 ␮l, 0.19 mmol) was added to a stirred
solution of 3,4,6-tri-O-acetyl-2-deoxy-D-arabino-hexopyranose (50
mg, 0.17 mmol) in anhydrous dichloromethane (5 ml). After 1 h, 2-
naphthol (37 mg, 0.26 mmol) dissolved in dichloromethane (3 ml) was
added to the reaction mixture. BF3·Et2O (65 ␮l, 0.53 mmol) was added
slowly to the mixture and the reaction was stirred for 2.5 h before being
quenched with water (5 ml). The crude reaction mixture was extracted
with dichloromethane and washed with water. The organic layer was
dried (MgSO4) and removal of solvents under reduced pressure gave an
oily residue. Purification of the residue by silica gel column chro-
matography [ethyl acetate/hexanes (1 : 1) as eluent] gave the O-glyco-
side (10) (9 mg, 13%) as white crystals from diethyl ether and the
C-glycoside (14) (45 mg, 63%) also as white crystals from diethyl ether
and hexanes.Using acetonitrile as the solvent in the above procedure
gave only the C-glycoside (14) (53 mg, 74%).
63.5; H, 5.8%). ␯ (KBr)/cm–1 3365 (OH), 1740 (ester C=O), 1230.
max
1H n.m.r. ␦ 2.02, 2.11, 2.16, each 3H, s, 3×OAc; 2.18, m, H 2Јax; 2.50,
m, H 2Јeq; 3.93, m, H 5Ј; 4.20, dd, J 2 and 12 Hz, H 6Ј; 4.42, dd, J 5 and
12 Hz, H6Ј; 5.30, t, J 10 Hz, H 4Ј; 5.33, m, H 3Ј; 5.61, dd, J 2 and 12
Hz, H 1Ј; 7.12, d, J 9 Hz, H 3; 7.32, dt, J 1 and 8.5 Hz, H 6; 7.48, dd, J
1.5 and 9 Hz, H 4; 7.61–7.80, 3H, m, H5, 7 and 8; 8.49, s, OH. 13C
n.m.r. ␦ 20.8, 20.8, 21.0, 3×OAc; 35.7, C 2Ј; 61.7, C 6Ј; 68.5, C 5Ј; 71.5,
76.0, 76.7, C 1Ј, C 3Ј and C 4Ј; 113.8, C 1; 120.0, 120.5, 123.2, 127.1,
Ar CH; 128.8; 129.0, 130.3, Ar CH; 153.9, C 12; 169.8, 170.4, 170.8,
3×OCOCH3.
Glycosyl Acetates as Donors
BF3·OEt2 (43 ␮l, 0.35 mmol) was added to a stirred solution of 2-
naphthol (26 mg, 0.18 mmol) and 1,3,4,6-tetra-O-acetyl-2-deoxy-D-
glucopyranoside (13) (50 mg, 0.15 mmol) in anhydrous acetonitrile (5
ml). The mixture was stirred for 2.5 h then quenched with water (5 ml).
Workup and purification by silica gel column chromatography [ethyl
acetate/hexanes (1: 1) as eluent] gave C-glycoside (14) (52 mg, 83%)
as white crystals from diethyl ether and hexanes.
Ph3PHBr Catalysed Additions of Glycals to 2-Naphthol
(a) 2-(3Ј,4Ј,6Ј-Tri-O-acetyl-2Ј-deoxy-␣-D-arabino-
hexopyranosyloxy)naphthalene (10)
Synthesis of C-Glycosides (16), (18), (20) and ent-(20)
2-Naphthol (79 mg, 0.55 mmol) was added to a stirred solution of
tri-O-acetyl-D-glucal (100 mg, 0.37 mmol) and triphenylphosphine
hydrobromide (6 mg, 0.02 mmol) in anhydrous dichloromethane (15
ml). The mixture was stirred for 2 days at room temperature. The
solvent was removed under reduced pressure and purification by silica
gel column chromatography [ethyl acetate/hexanes (1: 1) as eluent]
gave the title compound (10) (23 mg, 15%) as white crystals from
diethyl ether and hexanes, m.p. 91°C.
(a) 2-(3Ј,4Ј,6Ј-Tri-O-acetyl-2Ј-deoxy-␤-D-arabino-hexopyranosyl)-
5,8-dimethoxynaphthalen-1-ol (16)
Method 1. Trifluoroacetic anhydride (45 ␮l, 0.32 mmol) was added
to a stirred solution of 3,4,6-tri-O-acetyl-2-deoxy-D-glucopyranose (63
mg, 0.22 mmol) and anhydrous acetonitrile (5 ml). After 1 h, 5,8-
dimethoxynaphthalen-1-ol (9) (40 mg, 0.20 mmol) dissolved in acetoni-
trile (3 ml) was added to the reaction mixture. BF3·Et2O (73 ␮l, 0.59
mmol) was added to the mixture and the reaction was stirred for 20 min
then quenched with water (5 ml). The reaction mixture was extracted
with dichloromethane and washed with water. The extracts were dried
(MgSO4) and removal of solvents under reduced pressure gave an oily
residue. Purification by silica gel column chromatography
[dichloromethane/diethyl ether (9 :1) as eluent] gave a clear oil which
crystallized from diethyl ether and hexanes to give (16) (74 mg, 79%) as
white crystals, m.p. 199°C, [␣]2D1 17.3° (c, 0.20 in CH2Cl2) (Found: C,
60.4; H, 5.7. C24H28O10 requires C, 60.5; H, 5.9%). ␯max (KBr)/cm–1 3345
(OH), 1735 (ester C=O), 1391. 1H n.m.r. ␦ 1.77, ddd, J 11, 11 and 13 Hz,
H2Јax; 2.01, 2.07, 2.10, each 3H, s, 3×OAc; 2.52, ddd, J 2, 5 and 13 Hz,
H2Јeq; 3.84, ddd, J 2, 5 and 10 Hz, H5Ј; 3.93, 4.01, each 3H, s, 2×OCH3;
4.18, dd, J 2 and 12 Hz, H6Ј; 4.35, dd, J 5 and 12 Hz, H6Ј; 5.12, dd, J 2
and 11 Hz, H 1Ј; 5.14, t, J 10 Hz, H 4Ј; 5.25, ddd, J 5, 10 and 11 Hz, H3Ј;
6.62, d, J 8 Hz, H7; 6.68, d, J 8 Hz, H6; 7.55, d, J 8 Hz, H4; 7.72, d, J 8
Hz, H3; 9.76, s, OH. 13C n.m.r. ␦ 20.9, 21.0, 21.1, 3×OAc; 36.8, C 2Ј;
55.8, 56.5, 2×OCH3; 63.1, C6Ј; 69.8, C4Ј; 71.9, C1Ј; 72.6, C3Ј; 76.2,
C5Ј; 103.1, C3; 103.8, C4; 113.2, C6; 115.2; 122.2; 124.4, C 7; 127.7,
C2; 150.6, C1; 150.2, 150.3, C 4 and C8; 170.1, 170.5, 171.0,
3×OCOCH3. m/z (f.a.b.) 476 (M+, 58%), 417 (13), 136 (100).
(b) 1-(3Ј,4Ј,6Ј-Tri-O-benzyl-2Ј-deoxy-␤-D-arabino-hexopyranosyl)-
naphthalen-2-ol (12)
2-Naphthol (52 mg, 0.36 mmol) was added to a stirred solution of
tri-O-benzyl-D-glucal (100 mg, 0.24 mmol) and triphenylphosphine
hydrobromide (4 mg, 0.01 mmol) in anhydrous dichloromethane (15
ml). The mixture was stirred overnight at room temperature. The
solvent was removed under reduced pressure to give the O-glycoside
(11) (␣/␤ ratio 2 : 1) as an impure product. Data for the ␣-anomer: 1H
n.m.r. (200 MHz, CDCl3) ␦ inter alia 1.95, ddd, J 3, 12 and 13 Hz,
H2Јax; 2.55, ddd, J 1.5, 5 and 13 Hz, H 2Јeq; 3.43–3.96, 4H, m, H 3Ј,
H4Ј and H2 6Ј; 4.28, ddd, J 5, 8.5 and 11 Hz, H 5Ј; 4.40–4.82, 5H, m, 5
of CH2Ph; 4.95, d, J 11.5 Hz, 1 of CH2Ph; 5.80, dd, J 1.5 and 3 Hz, H 1Ј.
Data for the ␤-anomer:1H n.m.r. (200 MHz, CDCl3) ␦ inter alia 4.74,
dd, J 3 and 9 Hz, H 1Ј.
BF3·OEt2 (150 ␮l, 1.2 mmol) was added to a stirred solution of the
residue in dichloromethane (30 ml), stirred for 1.2 h at room tempera-
ture, then quenched with water (5 ml). The mixture was extracted with
dichloromethane, washed with water and the extracts were dried
(MgSO4). Removal of solvent under reduced pressure and purification
by silica gel column chromatography [dichloromethane/hexanes (9 : 1)
as eluent] gave the C-glycoside (12) (97 mg, 72%) as a clear oil
Method 2. BF3·Et2O (123 ␮l, 0.98 mmol) was added dropwise to
a stirred solution of 5,8-dimethoxynaphthalen-1-ol (9) (100 mg, 0.49
mmol) and 1,3,4,6-tetra-O-acetyl-2-deoxy-D-arabino-hexopyranose
(13) (179 mg, 0.54 mmol) in anhydrous acetonitrile (10 ml). The
mixture was stirred for 15 min at room temperature then quenched with
water (5 ml). Workup and purification as for method 1 gave the title C-
glycoside (16) (219 mg, 94%) as white crystals.
(Found: C, 79.0; H, 6.7. C37H36O5 requires C, 79.3; H, 6.5%). ␯
max
(neat)/cm–1 3354 (OH), 2971, 1653, 1379. 1H n.m.r. ␦ 2.00, ddd, J 12,
12 and 14 Hz, H 2Јax; 2.48, ddd, J 2, 4 and 14 Hz, H 2Јeq; 3.63–3.92,
5H, m, H 3Ј, H 4Ј, H 5Ј, H2 6Ј; 4.44–4.71, 5H, m, 5 of CH2Ph; 4.96, d,
J 11 Hz, 1 of CH2Ph; 5.46, dd, J 2 and 12, H 1Ј; 7.04–7.80, 21H, m,
ArH and Ph. 13C n.m.r. ␦ inter alia 36.1, C 2Ј; 68.1, C 6Ј; 71.4, 73.5,
75.4, CH2Ph; 75.64, C 1Ј; 77.3, 79.0, 80.4, C 3Ј, C 4Ј and C 5Ј; 130.7,
C 1; 138.0, 138.3, 138.4, ipso Ph; 154.0, C 2. m/z (f.a.b.) 560 (M+, 2%),
452 (1), 91 (100).
(b) 2-(3Ј,4Ј,6Ј-Tri-O-benzyl-2Ј-deoxy-␤-D-arabino-hexopyranosyl)-
5,8-dimethoxynaphthalen-1-ol (18)
When method 1 for the preparation of (16) was used, 3,4,6-tri-O-
benzyl-2-deoxy-D-arabino-hexopyranose (255 mg, 0.59 mmol) and (9)

Approaches to the Angucycline Antibiotics
21
(100 mg, 0.49 mmol) gave the title compound (18) (246 mg, 81%) as a
clear oil after purification by silica gel column chromatography
(dichloromethane as eluent), [␣]2D5 33.3° (c, 0.27 in CH2Cl2) (Found:
mixture was stirred for 30 min. Water (200 ml) was added and the
product was extracted with dichloromethane. The extracts were washed
with 0.1 M hydrochloric acid, saturated aqueous sodium hydrogen car-
bonate, and water. After drying (MgSO4) the solvent was removed, and
purification of the residue by silica gel column chromatography
(dichloromethane as eluent) gave a pale yellow oil. Crystallization from
diethyl ether and hexanes gave the title compound (21) (151 mg, 63%)
as pale yellow crystals. m.p. 177°C, [␣]2D1 18.6° (c, 0.16 in CH2Cl2)
M+•, 620.2788. C39H40O7 requires M+•, 620.2774). ␯
(neat)/cm–1
max
3384 (OH), 3056, 3002, 2934, 2836, 1643, 1600, 1686, 1419. 1H n.m.r.
␦ inter alia 1.63, ddd, J 11, 11 and 13 Hz, H 2Јax; 2.59, ddd, J 2, 5 and
13 Hz, H 2Јeq; 3.65-4.00, 5H, m, H3Ј, H 4Ј, H 5Ј and H2 6Ј; 3.99, 4.01,
each 3H, s, OCH3; 4.60–4.78, 5H, m, 5 of CH2Ph; 4.98, d, J 11 Hz, 1 of
CH2Ph; 5.01, dd, J 2 and 11 Hz, H 1Ј; 6.61, d, J 8 Hz, H 7; 6.68, d, J 8
Hz, H6; 7.20–7.43, 15H, m, Ph; 7.65, d, J 8 Hz, H 4; 7.74, d, J 8 Hz,
H3; 9.76, s, OH. 13C n.m.r. ␦ inter alia 37.4, C 2Ј; 55.7, 56.4, 2×OCH3;
69.7, C 6Ј; 71.1, C 1Ј; 71.8, 73.4, 75.0, 3×CH2Ph; 78.5, 79.5, 81.4, C 3Ј,
C 4Ј and C 5Ј; 102.8, C 3; 103.6, C 4; 113.2, C 6; 115.1; 123.7; 124.8,
C 7; 127.4–128.3, Ph; 138.6, 138.7, 138.7, ipso Ph; 149.6, 150.0, 150.2,
C 5, C 8 and C 1. m/z (f.a.b.) 620 (M+, 27%), 91 (100).
(Found: C, 59.0; H, 4.9. C24H24O11 requires C, 59.0; H, 5.0%). ␯
max
(KBr)/cm–1 1774 (ester C=O), 1733 (C=O), 1372. 1H n.m.r. ␦
1.61–1.73, 2H, m, H2 2Ј; 2.00, 2.05, 2.08, 2.48 each 3H, s, 4×OAc; 3.77,
ddd, J 2, 5 and 10 Hz, H5Ј; 4.13, dd, J 2 and 12 Hz, H6Ј; 4.12, dd, J 5
and 12 Hz, H6Ј; 4.67–4.83, br s, H1Ј; 5.05, t, J 10 Hz H4Ј; 5.15, ddd,
J 5, 10 and 11 Hz, H3Ј; 6.81, d, J 8 Hz, H 3; 6.91, d, J 8 Hz, H2; 7.94,
d, J 8 Hz, H 8; 8.05, d, J 8 Hz, H 7. 13C n.m.r. ␦ 20.8, 20.8, 20.9, 21.1;
4×OAc; 37.0, C 2Ј; 63.7, C 6Ј; 69.0, C 4Ј; 71.9; C 1Ј; 72.0, C 3Ј; 76.5,
C 5Ј; 122.8; 125.1, C 7; 132.3, C 8; 132.7; 137.4, C 2; 140.0, C 3; 140.5,
C 6; 145.8, C 5; 169.9, 170.4, 170.8, 4×OAc; 183.7, 184.0, C 1 and C 4.
m/z (f.a.b.) 489 (MH+, 28%), 429 (9), 154 (100).
(c) 2-(3Ј,4Ј-Di-O-acetyl-2Ј,6Ј-dideoxy-␤-L-arabino-hexopyranosyl)-
5,8-dimethoxynaphthalen-1-ol ent-(20)
When method 2 for the preparation of (16) was used, the naphthol
(9) (100 mg, 0.49 mmol) and 1,3,4-tri-O-acetyl-2,6-dideoxy-L-arabino-
hexopyranose ent-(19) (179 mg, 0.65 mmol) gave the title compound,
ent-(20) (150 mg, 72%), as white crystals after purification by silica gel
column chromatography (dichloromethane as eluent) and crystalliza-
tion from diethyl ether and hexanes, m.p. 176°C, [␣]2D5 –29.9° (c, 0.19
in CH2Cl2) (Found: C, 62.8; H, 6.3. C22H26O8 requires C, 63.1; H,
6.3%). ␯max (KBr)/cm–1 3346 (OH), 1734 (ester C=O), 1391. 1H n.m.r.
␦ 1.31, d, J 6, Hz, H3 6Ј; 1.75, apparent q, J 12, 11.5 and 11.5 Hz, H2Јax;
2.01, 2.10, s, 2×OAc; 2.49, ddd, J 2, 5 and 12 Hz, H 2Јeq; 3.70, dq, J 9.5
and 6 Hz, H 5Ј; 3.93, 4.01, each 3H, s, 2×OCH3; 4.88, t, J 9.5 Hz, H4Ј;
5.10, dd, J 2 and 11.5 Hz, H 1Ј; 5.21, ddd, J 9.5, 9.5 and 11.5 Hz, H3Ј;
6.62, d, J 8.5 Hz, H 6; 6.68, d, J 8.5 Hz, H 7; 7.56, d, J 8.5 Hz, H4; 7.72,
d, J 8.5 Hz, H 3; 9.75, s, OH. 13C n.m.r. ␦ 18.2, C 6Ј; 21.0, 21.2, 2×OAc;
37.2, C 2Ј; 55.8, 55.5, 2×OCH3; 71.5, C 4Ј; 72.6, C 1Ј; 74.4, C 3Ј; 75.1,
C 5Ј; 103.0, C 3; 103.7, C 4; 113.2, C 6; 115.2; 122.6; 124.6, C 7; 127.7,
C 2; 150.1, 150.2, 150.3, C 1, C 5 and C 7; 170.4, 170.5, 2×OCOCH3.
m/z (f.a.b.) 418 (M+, 100%), 359 (9).
(b) 5-Acetoxy-6-(3Ј,4Ј,6Ј-tri-O-benzyl-2Ј-deoxy-␤-D-arabino-
hexopyranosyl)naphthalene-1,4-dione (22)
Trifluoroacetic anhydride (172 ␮l, 1.22 mmol) was added to a
stirred solution of 3,4,6-tri-O-benzyl-2-deoxy-D-arabino-hexopyra-
nose (255 mg, 0.59 mmol) in anhydrous acetonitrile (5 ml). After
1 h, 5,8-dimethoxynaphalen-1-ol (9) (100 mg, 0.49 mmol) dissolved in
acetonitrile (5 ml) was added and the resulting mixture was treated as
for the preparation of (21) above. Purification of the residue by silica
gel column chromatography (dichloromethane as eluent) gave the title
compound (22) (164 mg, 53%) as a pale yellow oil, [␣]2D5 13.6° (c, 0.27
in CH2Cl2). ␯(neat)/cm–1 2924, 2836, 1774 (ester C=O), 1667 (C=O),
1364. 1H n.m.r. ␦ 1.51–1.70, m, H 2Јax; 2.38, s, OAc; 3.53–4.83, 5H, m,
H3Ј, H4Ј, H5Јand H2 6Ј; 4.53–4.73, 6H, m, 5 of CH2Ph and H1Ј; 4.95,
d, J 11 Hz, 1 of CH2Ph; 6.82, d, J 8 Hz, H 3; 6.91, d, J 8 Hz, H2;
7.23–7.43, 15H, m, Ph; 7.99, d, J 8 Hz, H8; 8.05, d, J 8 Hz, H7. 13C
n.m.r. ␦ 21.1, OAc; 37.7, C 2Ј; 69.4, C 6Ј; 71.4, C 1Ј; 72.2, 73.5, 75.1,
CH2Ph; 78.0; 79.6; 80.5; 122.8; 125.0, C 7; 127.7–128.6, Ph; 129.7;
137.3, C 2; 138.2, 138.6, 138.4, ipso Ph; 140.0, C 3; 142.0, C 6; 145.8,
C 5; 184.0, 184.2, C 1 and C 4. m/z (f.a.b.) 632 (M+, 1%), 541 (2), 350
(8), 91 (100).
(d) 2-(3Ј,4Ј-Di-O-acetyl-2Ј,6Ј-dideoxy-␤-D-arabino-hexopyranosyl)-
5,8-dimethoxynaphthalen-1-ol (20)
When method 2 for the preparation of (16) was used, the naphthol
(9) (100 mg, 0.49 mmol) and 1,3,4-tri-O-acetyl-2,6-dideoxy-D-
arabino-hexopyranose (19) (179 mg, 0.65 mmol) gave the title com-
pound, (20) (156 mg, 75%), as white crystals after purification by silica
gel column chromatography (dichloromethane as eluent) and crystal-
lization from diethyl ether and hexanes, m.p. 177°C, [␣]2D0 29.4° (c, 0.06
in CH2Cl2) (Found: C, 63.2; H, 6.3. C22H26O8 requires C, 63.1; H,
6.3%). All other data were identical to those of ent-(20).
(c) 5-Acetoxy-6-(3Ј,4Ј-di-O-acetyl-2Ј,6Ј-dideoxy-␤-L-arabino-
hexopyranosyl)naphthalene-1,4-dione ent-(23)
In the procedure outlined for the preparation of (21), reaction of (9)
(100 mg, 0.49 mmol) and 1,3,4-tri-O-acetyl-2,6-dideoxy-L-arabino-
hexopyranose ent-(19) (179 mg, 0.65 mmol) gave after purification of
the residue by silica gel column chromatography (dichloromethane as
eluent) a pale yellow oil. Crystallization from diethyl ether and hexanes
gave the title compound ent-(23) (110 mg, 52%) as pale yellow crystals,
m.p. 149°C, [␣]2D0 –23.2° (c, 0.10 in CH2Cl2) (Found: C, 61.6; H, 5.0.
C22H22O9 requires C, 61.4; H, 5.2%). ␯max (KBr)/cm–1 2937, 1735 (ester
C=O), 1640 (C=O), 1370. 1H n.m.r. ␦ 1.30, d, J 6 Hz, H3 6Ј; 1.66, q, J
11.5 Hz, H2Јax; 2.02, 2.08, 2.50, each 3H, s, 3×OAc; 3.66, dq, J 9.5 and
6 Hz, H5Ј; 4.73, br s, H 1Ј; 4.86, t, J 9.5 Hz, H4Ј; 5.12, ddd, J 9.5, 9.5
and 11.5 Hz, H 3Ј; 6.83, d, J 10.5 Hz, H 3; 6.93, d, J 10.5 Hz, H2; 7.98,
d, J 8 Hz, H8; 8.06, d, J 8 Hz, H7. 13C n.m.r. ␦ 18.0, C 6Ј; 21.1, 21.1,
21.9, 3×OAc; 37.4, C 2Ј; 71.7, C 1Ј; 71.9, C 3Ј; 74.2, C 4Ј; 74.7, C 5Ј;
122.8; 125.1, C 7; 132.4, C 8; 132.7; 137.3, C 2; 140.0, C 3; 141.1, C 6;
145.9, C 5; 170.1, 170.1, 170.4, 3×OCOCH3; 183.7, 184.1, C1 and
Synthesis of Quinones (21)–(23) and ent-(23)
(a) 5-Acetoxy-6-(3Ј,4Ј,6Ј-tri-O-acetyl-2Ј-deoxy-␤-D-arabino-
hexopyranosyl)naphthalene-1,4-dione (21)
BF3·Et2O (123 ␮l, 0.98 mmol) was added to a stirred solution of 5,8-
dimethoxynaphthalen-1-ol (9) (100 mg, 0.49 mmol) and 1,3,4,6-tetra-
O-acetyl-2-deoxy-D-arabino-hexopyranose (13) (179 mg, 0.54 mmol)
in anhydrous acetonitrile (10 ml). The mixture was stirred for 15 min at
room temperature then quenched with water (5 ml). The reaction
mixture was extracted with dichloromethane and washed with water.
The combined extracts were dried (MgSO4) and removal of the solvent
under reduced pressure gave an oily residue. Pyridine (2 ml) was added
to a cooled solution (0°C) of the residue in acetic anhydride (2 ml), and
stirred overnight. The crude reaction mixture was then poured into
C4. m/z (f.a.b.) 432 (MH2 , 11%), 431 (MH+, 13), 390 (35), 307 (43),
+
269 (31), 154 (100), 136 (98).
(d) 5-Acetoxy-6-(3Ј,4Ј-di-O-acetyl-2Ј,6Ј-dideoxy-␤-D-arabino-
hexopyranosyl)naphthalene-1,4-dione (23)
0.1
M aqueous hydrochloric acid (200 ml) and extracted with
dichloromethane (3×50 ml). The extracts were washed with dilute
hydrochloric acid, saturated aqueous sodium hydrogen carbonate and
finally water. The organic solution was dried (MgSO4) and removal of
the solvent under reduced pressure gave a brown residue. Ceric ammo-
nium nitrate (524 mg, 0.98 mmol) dissolved in water (3 ml) was added
dropwise to a solution of the residue in acetonitrile (5 ml) and the
In the procedure outlined for the preparation of (21), reaction of (9)
(100 mg, 0.49 mmol) and 1,3,4-tri-O-acetyl-2,6-dideoxy-D-arabino-
hexopyranose (19) (179 mg, 0.65 mmol) gave, after purification of the
residue by silica gel column chromatography (dichloromethane as
eluent), a pale yellow oil. Crystallization from diethyl ether and hexanes

22
F. L. Andrews, D. S. Larsen and L. Larsen
gave the title compound (23) (103 mg, 49%) as pale yellow crystals,
m.p. 148°C, [␣]2D0 23.9° (c, 0.14 in CH2Cl2) (Found: C, 61.1; H, 5.0.
C22H22O9 requires C, 61.4; H, 5.2%). All other data were identical to
those of ent-(23).
Crystallization from diethyl ether and hexanes gave (27a) (53 mg, 37%)
as white crystals, m.p. 207°C, [␣]1D9 –161.3° (c, 0.15 in CH2Cl2) (Found:
C, 61.8; H, 5.9. C33H38O13 requires C, 61.7; H, 6.0%). ␯max (KBr)/cm–1
3449 (OH), 2928, 1740 (ester C=O), 1636 (C=O). 1H n.m.r. ␦
1.20–1.40, m, H2ax; 1.60–1.82, 3H, m, H3ax, H3eq and H 2Јax; 1.91,
2.01, 2.07, 2.09, each 3H, s, 4×OAc; 2.20–2.50, 4H, m, H4ax, H2eq,
H4eq and H12b; 2.58, ddd, J 2, 5 and 13 Hz, H2Јeq; 3.00, s, OCH3; 3.18,
t, J 5 Hz, H6a; 3.48, t, J 5 Hz, H12a ; 3.80, ddd, J 2, 5 and 10 Hz, H5Ј;
4.03, 1H, br t, J 5 Hz, H6; 4.16, dd, J 2 and 12 Hz, H6Ј; 4.30, dd, J 5
and 12 Hz, H6Ј; 4.97, dd, J 2 and 12 Hz, H1Ј; 5.08, t, J 10 Hz, H4Ј;
5.21, ddd, J 5, 10 and 12 Hz, H 3Ј; 5.76, dt, J 5 and 2.5 Hz, H5; 5.85,
dt, J 4.5 and 11 Hz, H1; 7.37, d, J 8 Hz, H11; 7.75, d, J 8 Hz, H10;
12.31, s, OH. 13C n.m.r. ␦ 20.9, 20.9, 21.0, 21.2, 4×OAc; 22.1, C 3; 31.8,
C 2; 33.6, C 4; 36.5, C 2Ј; 43.6, C 12b; 43.8, C 12a; 54.1, C 6a; 56.6,
OCH3; 62.9, C 6Ј; 69.5, C 4Ј; 71.2, C 1Ј; 72.2, C 3Ј; 73.1, C 1; 73.3, C 6;
76.3, C 5Ј; 116.7, C 11; 118.3; 118.7, C 5; 133.4, C 10; 138.8; 141.3,
C 9; 157.5, C 8; 170.0, 170.2, 170.4, 170.9, 4×OCOCH3; 195.1, C 12;
204.9, C 7. m/z (f.a.b.) 643 (MH+, 9%), 583 (20), 551 (44), 286 (78) 137
(100).
Removal of the mother liquors of the filtrate gave mainly the
(1S,6S,6aR,12aR,12bS) isomer (26a) as an impure brown syrup. 1H
n.m.r. ␦ inter alia 1.16–1.36, m, H 2ax; 1.57–1.80, 3H, m, H2 3 and
H2Јax; 1.94, 2.01, 2.07, 2.09, each 3H, s, 4×OAc; 2.16–2.48, 4H, m,
H2 4, H2eq and H 12b; 2.59, ddd, J 2, 5 and 13 Hz, H 2Јeq; 2.99, s, OCH3;
3.29, t, J 5 Hz, H 6a; 3.49, t, J 5 Hz, H 12a; 3.80, ddd, J 2, 5 and 10 Hz,
H5Ј; 4.00, br t, J 5 Hz, H6; 4.16, dd, J 2 and 12 Hz, H6Ј; 4.30, dd, J 5
and 12 Hz, H6Ј; 4.97, dd, J 2 and 12 Hz, H 1Ј; 5.08, t, J 10 Hz, H4Ј;
5.23, ddd, J 5, 10 and 12 Hz, H3Ј; 5.76, dt, J 5 and 2.5 Hz, H5; 5.87,
dt, J 4.5 and 11 Hz, H1; 7.40, d, J 8 Hz, H11; 7.77, d, J 8 Hz, H10;
12.31, s, OH.
Synthesis of Hydroxy Quinones (24) and (25)
5-Hydroxy-6-(3Ј,4Ј,6Ј-tri-O-acetyl-2Ј-deoxy-␤-D-arabino-hexopyran-
osyl)naphthalene-1,4-dione (24)
BF3·OEt2 (0.386 ml, 3.07 mmol) was added to a solution of acetate
(21) (300 mg, 0.62 mmol) in anhydrous dichloromethane (300 ml) and
the mixture was stirred at room temperature for 10 h. The mixture was
then poured into water and extracted with dichloromethane (2×150 ml).
The extracts were washed with hydrochloric acid (0.1 M), saturated
aqueous sodium hydrogen solution and water. The extracts were dried
(MgSO4); removal of the solvents under reduced pressure and purifica-
tion of the crude material by silica gel column chromatography
[dichloromethane/diethyl ether (95: 5) as eluent] gave (24) as a orange
oil and the starting material (21) (135 mg, 45%). Crystallization of (24)
from diethyl ether and hexanes gave the title compound (24) (121 mg,
46%) as yellow crystals. The reaction was repeated three times with the
recovered starting material each time, to give (24) (220 mg, 80%), m.p.
181°C, [␣]1D8 45.2° (c, 0.1 in CH2Cl2) (Found: C, 58.9; H, 5.1. C22H22O10
requires C, 59.2; H, 5.0). ␯max (KBr)/cm–1 3452 (OH), 1754, 1735, 1433.
1H n.m.r. ␦ 1.60, ddd, J 11, 11 and 13 Hz, H2Јax; 2.02, 2.08, 2.10, each
3H, s, 3×OAc; 2.64, ddd, J 2, 5 and 13 Hz, H 2Јeq; 3.82, ddd, J 2, 5 and
10 Hz, H 5Ј; 4.18, dd, J 2 and 12 Hz, H 6Ј; 4.35, dd, J 5 and 12 Hz,
H6Ј; 4.98, dd, J 2 and 11 Hz, H 1Ј; 5.08, t, J 9.5 Hz, H 4Ј; 5.24, ddd, J
5, 10 and 11 Hz, H3Ј; 6.95, 2H, s, H2 and H 3; 7.65, d, J 8 Hz, H 8;
7.85, d, J 8 Hz, H 7; 12.29, s, OH. 13C n.m.r. ␦ 20.8, 20.9, 21.0, 3×OAc
; 36.5, C 2Ј; 62.7, C 6Ј; 69.3, C 4Ј; 71.4, C 1Ј; 71.9, C 3Ј; 76.3, C 5Ј;
119.2, C 2; 125.1; 130.8; 133.1, C 3; 138.6, C 8; 139.7, C 7; 140.0, C 6;
157.6, C 5; 170.0, 170.3, 170.8, 3×OCOCH3; 184.1, C 1; 190.6, C 4.
m/z (f.a.b.) 447 (MH+, 20%), 387 (6), 327 (8), 267 (26), 136 (100).
(1R*)-1-Acetoxy-8-hydroxy-9-(3Ј,4Ј,6Ј-tri-O-acetyl-2Ј-deoxy-␤-D-
arabino-hexopyranosyl)-1,2,3,4-tetrahydrobenz[a]anthracene-7,12-
dione (30a)
6-(3Ј,4Ј-Di-O-acetyl-2Ј,6Ј-dideoxy-␤-D-arabino-hexopyranosyl)-5-
hydroxynaphthalene-1,4-dione (25)
A mixture of tetra-O-acetyl diborate (92 mg, 0.34 mmol) and naph-
thoquinone (24) (100 mg, 0.22 mmol) in dichloromethane (8 ml) was
stirred at 0°C for 5 min. (±)-(E)-1-Acetoxy-3-(2-methoxyvinyl)cyclo-
hex-2-ene (8) (66 mg, 0.34 mmol) was added and the mixture was
stirred for a further 15 min. The mixture was poured into water (100 ml)
and extracted with dichloromethane (3×30 ml). The extracts were
washed with water and dried (MgSO4). Removal of the solvent under
reduced pressure and purification of the crude product by silica gel
column chromatography [dichloromethane/diethyl ether (4: 1) as
eluent] gave a 1: 1 mixture of diastereoisomers (26a) and (27a) (103
mg, 73%) as a pale oil. The mixture of cycloadducts was dissolved in
dichloromethane (10 ml), 1,8-diazabicyclo[5.4.0]undec-7-ene (48 ␮l,
0.32 mmol) was added and the mixture stirred at room temperature
under an air atmosphere for 1.5 h. The reaction mixture was slowly
added to hydrochloric acid (0.05 M, 50 ml) and extracted with
dichloromethane (3×20 ml). The organic extracts were dried (MgSO4)
and the residue was purified by silica gel column chromatography
[dichloromethane/diethyl ether (9: 1) as eluent] to give the title com-
pound (30a) [88 mg, 90%, 66% overall from (24)] as a bright yellow oil
and as a 1: 1 mixture of diastereoisomers (Found: MH+•, 609.19720.
Acetate (23) (100 mg, 0.23 mmol) was deacetylated according to the
procedure described above for (21) to give, after purification by silica
gel column chromatography [dichloromethane/diethyl ether (9: 1) as
eluent] and crystallization from diethyl ether and hexanes, the title com-
pound (25) (78 mg, 87%) as orange crystals, m.p. 151°C; [␣]1D8 35.0°
(c, 0.10 in CH2Cl2) (Found: C, 61.9; H, 5.2. C20H20O8 requires C, 61.9;
H, 5.2%). ␯max (KBr)/cm–1 3453 (OH), 1736 (ester C=O), 1668, 1640
(C=O), 1433. 1H n.m.r. ␦ 1.30, 3H, d, J 6.5 Hz, H3 6Ј; 1.57, ddd, J 11,
11 and 12.5 Hz, H 2Јax; 2.02, 2.09, each 3H, s, 2×OAc; 2.61, ddd, J 2, 5
and 12.5 Hz, H2Јeq; 3.70, dq, J 10 and 6.5 Hz, H5Ј; 4.85, t, J 10 Hz,
H4Ј; 4.96, dd, J 2 and 11.5 Hz, H 1Ј; 5.20, ddd, J 5, 10 and 11.5 Hz,
H3Ј; 6.95, 2H, s, H 2 and H 3; 7.65, d, J 8 Hz, H 7; 7.87, d, J 8 Hz, H8;
12.28, s, OH. 13C n.m.r. ␦ 18.1, C 6Ј; 20.9, 21.0, 2×OAc; 36.9, C 2Ј;
71.1, C1Ј; 72.0, C 3Ј; 74.5, C 4Ј; 74.6, C 5Ј; 114.5; 119.2, C 2; 130.7;
133.2, C 3; 136.9, C 6; 138.6, C 2; 139.8, C 3; 157.7, C 5; 170.3, 170.4,
2×OAc ; 184.1, C 1; 190.6, C 4. m/z (f.a.b.) 389 (MH+, 18%), 329 (7),
269 (16), 154 (100).
C32H34O12 requires 609.19721). ␯ (neat)/cm–1 3450 (OH), 2916,
max
Benz[a]anthraquinones
1
2848, 1734 (ester C=O), 1670 (C=O), 1634 (C=C), 1236. H n.m.r. ␦
(1R,6R,6aS,12aS,12bR)-1-Acetoxy-8-hydroxy-6-methoxy-
9-(3Ј,4Ј,6Ј-tri-O-acetyl-2Ј-deoxy-␤-D-arabino-hexopyranosyl)-
1,2,3,4,6,6a,12a,12b-octahydrobenz[a]anthracene-7,12-dione (27a)
inter alia 1.55–1.80, m, H 2Јax, 1.80–2.00, 3H, m, H 2ax, H2 4; 2.02,
2.03, 2.05, 2.10, each 3H, s, 4×OAc; 2.22–2.40, m, H2eq; 2.63, ddd, J
2, 5 and 12.5 Hz, H2Јeq; 2.82–3.15, 2H, m, H2 3; 3.82, m, H5Ј; 4.18, dd,
J 2 and 12 Hz, H 6Ј; 4.34, dd, J 5 and 12 Hz, H6Ј; 5.00, dd, J 2 and 12
Hz, H1Ј; 5.09, t, J 10 Hz, H4Ј; 5.25, ddd, J 5, 10 and 12 Hz, H3Ј; 6.77,
br t, J 3.5 Hz, H1; 7.54, d, J 8 Hz, H5; 7.77, d, J 8 Hz, H11; 7.87, d, J
A mixture of tetra-O-acetyl diborate (92 mg, 0.34 mmol) and naph-
thoquinone (24) (100 mg, 0.22 mmol) in dichloromethane (8 ml) was
stirred at 0°C for 5 min. (±)-(E)-1-Acetoxy-3-(2-methoxyvinyl)cyclo-
hex-2-ene1,2 (8) (66 mg, 0.34 mmol) was added and the mixture was
stirred for a further 15 min. The mixture poured into water (100 ml) and
extracted with dichloromethane (3×30 ml). The extracts were washed
with water and dried (MgSO4). Removal of the solvent under reduced
pressure and purification of the crude product by silica gel column
chromatography [dichloromethane/diethyl ether (4: 1) as eluent] gave a
1 : 1 mixture of diastereoisomers (26a) and (27a) as a pale oil.
8 Hz, H10; 8.29, d, J 8 Hz, H6; 12.80 and 12.81, each 0.5H, s, OH. 13
C
n.m.r. ␦ inter alia 16.9 (peak split), C 4; 20.9, 20.9, 21.0, 21.1, 4×OAc;
28.6 (peak split), C 2; 31.1, C 3; 36.6, C 2Ј; 62.9, C 6Ј; 67.1, C 1; 69.5,
C 4Ј; 71.5, C 1Ј; 72.1, C 3Ј; 76.4, C 5Ј; 114.8; 119.8, C 11; 127.2, C 6;
132.2; 133.4, C 10; 133.4; 134.0; 134.9; 135.3, C 5; 136.1, 147.4, C 9;
157.9, C 8; 170.0, 170.2, 170.3, 170.9, 4×OCOCH3; 183.7 (peak split),
C 12; 188.6, C 7.

Approaches to the Angucycline Antibiotics
23
(1R*)-1-Acetoxy-9-(3Ј,4Ј-di-O-acetyl-2Ј,6Ј-dideoxy-␤-D-arabino-
hexopyranosyl)-8-hydroxy-1,2,3,4-tetrahydrobenz[a]anthracene-
7,12-dione (30b)
11.5 Hz, H2Јax; 2.41, 2H, apparent p, J 7 Hz, H2 3; 2.65, ddd, J 2, 5 and
13 Hz, H 2Јeq; 3.07, 2H, apparent t, J 7 Hz, H2 4; 3.17, 2H, apparent t, J
6 Hz, H2 2; 3.57–3.65, 2H, m, H4Ј and H5Ј; 3.95, ddd, J 5, 8 and 11.5
Hz, H 3Ј; 4.00, dd, J 5 and 12 Hz, H 6Ј; 4.15, dd, J 2 and 12 Hz, H6Ј;
5.14, dd, J 2 and 11 Hz, H 1Ј;7.81, d, J 8 Hz, H 5; 7.89, d, J 8 Hz, H10;
8.22, dd, J 1 and 8 Hz, H6; 8.51, d, J 8Hz, H11. 13C n.m.r. (75 MHz,
CD3SOCD3) ␦ 22.4, C 3; 29.1 C 2, C 4; 61.3, C 6Ј; 70.6, C 1Ј; 71.5, C 4Ј;
72.0; C 5Ј; 81.3, C 3Ј; 114.8; 118.5, C 10; 128.3, C 6; 133.0; 133.3;
133.4, C 5; 133.6, C 11; 135.1; 136.3; 136.9; 151.9, C 9; 157.3, C 8;
182.2, C 12; 187.4, C 7; 198.4, C 1.
The benzanthraquinone (30b) was prepared from the naphtho-
quinone (25) (36 mg, 0.09 mmol) and (±)-(E)-1-acetoxy-3-(2-
methoxyvinyl)cyclohex-2-ene (8) (70 mg, 0.36 mmol) according to the
procedure for the preparation of (30a). The reaction afforded the title
compound (30b) (38 mg, 87%) as a yellow solid after purification by
silica gel column chromatography [dichloromethane/diethyl ether
(4: 1) as eluent], m.p. 215°C (Found: C, 65.5; H, 5.6. C30H30O10
requires C, 65.5; H, 5.5%). ␯max (KBr)/cm–1 1745 (ester C=O), 1242. 1H
n.m.r. ␦ 1.28, d, J 6 Hz, H3 6Ј; 1.50–1.63, m. H 2Јax; 1.80–1.95, 3H, m;
1.99, 2.01, 2.07, each 3H, s, 3×OAc; 2.27–2.38, 1H, m, H2; 2.59, ddd,
J 2, 6 and 13 Hz, H2Јeq; 2.82–3.10, m, H2 4; 3.68, dq, J 10 and 6 Hz,
H5Ј; 4.84, t, J 10 Hz, H 4Ј; 4.96, dd, J 2 and 11 Hz, H1Ј; 5.19, ddd, J 5,
10 and 11 Hz, H 3Ј; 6.77, br s, H1; 7.56, d, J 8 Hz, H 5; 7.76, dd, J 2 and
9-(2Ј,6Ј-Dideoxy-␤-D-arabino-hexopyranosyl)-8-hydroxy-1,2,3,4-
tetrahydrobenz[a]anthracene-1,7,12-trione (32b)
Using the procedure as for the preparation of (32a), the dione (30b)
(38 mg, 0.07 mmol) gave the title compound (32b) (22 mg, 76%) as
yellow crystals after purification by reverse phase silica gel column
chromatography [methanol/water (7: 3) as eluent] and crystallization
from dichloromethane and diethyl ethers, m.p. dec. >190°C, [␣]1D9
199.5° (c, 0.22 in MeOH) (Found: M+•, 422.13624. C24H22O7 requires
M+•, 422.13655). ␯max (KBr)/cm–1 3415 (OH), 2925, 1699 (C=O), 1670
8 Hz; H11; 7.85, d, J 8 Hz, H 10; 8.28, d, J 8 Hz, H 6; 12.78, s, OH. 13
C
n.m.r. ␦ 16.9; 16.9; 18.1, C 6Ј; 21.0, 21.1, 21.1, 3×OAc; 28.7; 31.1;
36.9; 67.2; 71.1; 72.1; 74.5; 74.7; 114.8; 119.8; 127.2; 132.3; 133.5;
133.5; 133.9; 135.3; 135.6; 136.1; 147.3; 158.0; 170.3 and 170.4,
3×OCOCH3; 183.8, C 12; 188.7, C 7. m/z (f.a.b.) 550 (M+, 5%), 507
(12), 492 (12), 60 (100).
1
and 1628 (quinone C=O), 1280. H n.m.r. ␦ 1.42, d, J, 6 Hz, H3 6Ј;
1.46–1.60, m, 2×OH, H 2Јax; 2.17–2.28, m, H2 3; 2.52, ddd, J 2, 5 and
13 Hz, H 2Јeq;; 2.88–2.96, 4H, m, H2 2 and H2 4; 3.22, t, J 9 Hz, H4Ј;
3.52, dq, J 9 and 6 Hz, H5Ј; 3.85, ddd, J 5, 9 and 11 Hz, H 3Ј; 4.94, dd,
J 2 and 11 Hz, H1Ј; 7.56, d, J 8 Hz, H5; 7.72, d, J 8 Hz, H10; 7.91, d,
J 8 Hz, H11; 8.29, d, J 8 Hz, H6; 12.72, s, 8-OH. 13C n.m.r. ␦ 18.2,
C 6Ј; 22.7, C 3; 30.1, C 4; 39.1, C 2; 39.5, C 2Ј; 71.3, C 11; 76.0, C 5Ј;
78.1, C 4Ј; 114.9; 119.8, C 5; 128.9, C 11; 132.8, C 10; 133.6; 133.8,
C 6; 135.9, C 12a; 137.0, C 9; 151.6, C 4a; 158.4, C 8; 182.8, C 12;
188.0, C 7; 199.4, C 1.
8-Hydroxy-9-(3Ј,4Ј,6Ј-tri-O-acetyl-2Ј-deoxy-␤-D-arabino-hexopyran-
osyl)-1,2,3,4-tetrahydrobenz[a]anthracene-1,7,12-trione (31)
A solution of (30a) (60 mg, 0.11 mmol) in dichloromethane (50 ml)
was placed under an atmosphere of oxygen and irradiated with a broad
spectrum tungsten filament lamp (150 W) for 5 days. Concentration of
the solution under reduced pressure gave a yellow oil which was puri-
fied by silica gel column chromatography (dichloromethane as eluent)
to give an orange oil. Crystallization from diethyl ether and hexanes
gave (31) (29 mg, 51%) as orange crystals, m.p. 214°C, [␣]2D1 20.6o (c,
0.27 in CH2Cl2) (Found: C, 63.5; H, 5.1. C30H28O11 requires C, 63.8; H,
Acknowledgments
The authors wish to thank the University of Otago for
financial support. We also thank Mrs M. Dick and Mr R. M.
McAllister for microanalyses, Mr B. Clark (University of
Canterbury) for the measurement of mass spectra, and Dr M.
Thomas and Mr R. Coulbeck for assistance in acquiring
n.m.r. spectra.
5.0%). ␯ (KBr)/cm–1 3445 (OH), 2950, 1742 (ester C=O), 1670
max
(C=O), 1252. 1H n.m.r. ␦ 1.61, ddd, J 11, 11 and 13 Hz, H2Јax; 2.00,
2.06, 2.09, each 3H, s, 3×OAc; 2.20, 2H, m, H2 3; 2.64, ddd, J 2, 5 and
13 Hz, H2Јeq; 2.90, 4H, m, H2 2, H2 4; 3.81, ddd, J 2, 5 and 10 Hz, H5Ј;
4.17, dd, J 2 and 12.5 Hz, H6Ј; 4.33, dd, J 5 and 12.5 Hz, H 6Ј; 4.98, dd,
J 2 and 11 Hz, H 1Ј; 5.07, t, J 10 Hz, H 4Ј; 5.24, ddd, J 5, 10 and 11 Hz,
H3Ј; 7.55, d, J 8 Hz, H 5; 7.70, d, J 8 Hz, H 10; 7.85, d, J 8 Hz, H11;
8.30, d, J 8 Hz, H 6; 12.68, s, OH. 13C n.m.r. ␦ 20.9, 20.9, 21.0, 3×OAc;
22.7, C 3; 30.1, C 2; 36.6, C 2Ј; 39.2, C 4; 62.9, C 6Ј; 69.5, C 4Ј; 71.6,
C 1Ј; 72.1, C 3Ј; 76.4, C 5Ј; 115.0; 119.7, C 10; 128.9, C 6; 132.9, C 5;
133.5; 133.7, C 11; 134.0; 135.4; 135.9; 137.2; 151.7, C 9; 158.3, C 8;
170.0, 170.4, 170.9, OCOCH3; 182.6, C 12; 187.9, C 7; 199.2, C 1. m/z
(e.i.) 564 (M+, 5%), 384 (49) 169 (100), 69 (98).
References
1
Larsen, D. S., and O’Shea, M. D., Tetrahedron Lett., 1993, 34, 3769,
1373.
2
Larsen, D. S., and O’Shea, M. D., J. Chem. Soc., Perkin Trans. 1,
1995, 1019.
3
Larsen, D. S., O’Shea, M. D., and Brooker, S., Chem. Commun.,
1996, 203.
9-(2Ј-Deoxy-␤-D-arabino-hexopyranosyl)-8-hydroxy-1,2,3,4-
tetrahydrobenz[a]anthracene-1,7,12-trione (32a)
4
Ohta, K., Mizuta, E., Okazaki, H., and Kishi, T., Chem. Pharm.
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Uchida, T., Imoto, M., Watanabe, Y., Miura, K., Dobashi, T.,
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5
A solution of (30a) (80 mg, 0.14 mmol) in tetrahydrofuran (5 ml)
was added to a cooled solution (0°C) of sodium methoxide in methanol
(10 ml) [generated by the addition of sodium hydride (324 mg, 1.35
mmol)] and stirred at room temperature for 2 h. The reaction mixture
was poured into 0.1 M aqueous HCl (50 ml) and extracted with
dichloromethane (3×30 ml). The combined extracts were dried
(MgSO4) and the solvent was removed under reduced pressure. The
residue was dissolved in dichloromethane (20 ml) and methanol (2 ml).
The resultant solution was placed under an atmosphere of oxygen and
irradiated with a broad spectrum tungsten filament lamp (150 W)
overnight. Concentration of the solution under reduced pressure gave a
yellow oil which was purified by silica gel column chromatography
[dichloromethane/methanol (95: 5) as eluent] and by reverse phase
h.p.l.c. [methanol/water (70 : 30) as eluent] to give the title compound
(32a) (49 mg, 84%) as a yellow solid, m.p. 201°C, [␣]2D1 128.2° (c, 0.17
in MeOH) (Found: C, 60.6; H, 5.3%. MH+•, 439.13929. C24H22O8.2H2O
6
7
8
9
10
11
Yamaguchi, M., Okuma, T., Horiguchi, A., Ikeura, C., and Minami,
T., J. Org. Chem., 1992, 57, 1647.
Matsumoto, T., Sohma, T., Yamaguchi, H., Kurata, S., and Suzuki,
requires, 60.7; H, 5.5%. MH+•, 439.13955). ␯ (KBr)/cm–1 3404
12
max
(OH), 2930, 1700 (ketone C=O), 1670 and 1630 (quinone C=O), 1280.
K., Synlett, 1995, 263; Matsumoto, T., Sohma, T., Yamaguchi, H.,
Kurata, S., and Suzuki, K., Tetrahedron, 1995, 51, 7347.
1H n.m.r. (300 MHz, CD3OD, referenced to ␦ 3.50) ␦ 1.60, dt, J 13 and

24
F. L. Andrews, D. S. Larsen and L. Larsen
13
14
Bingham, S., Muir, M., and Tyman, J., J. Chem. Soc., Chem.
Commun., 1991, 1319; Allevi, P., Anastasia, M., Bingham, S.,
Ciuffreda, P., Fiecchi, A., Cighetti, G., Muir, M., Scala, A., and
Tyman, J., J. Chem. Soc., Perkin Trans. 1, 1998, 575.
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