A novel short-step synthesis of new xanthenedione derivatives from the cyclization of 3-cinnamoyl-2-styrylchromones

Article abstract of DOI:10.1055/s-0030-1261172

Novel (E)-3-aryl-4-benzylidene-8-hydroxy-3,4-dihydro-1H-xanthene-1,9(2H)- diones are prepared by the cyclization of (E,E)-3-cinnamoyl-5-hydroxy-2- styrylchromones efficiently catalyzed with boron tribromide. The (E,E)-3-cinnamoyl-5-hydroxy-2-styrylchromon

Full text of DOI:10.1055/s-0030-1261172

LETTER
2005
A Novel Short-Step Synthesis of New Xanthenedione Derivatives from the
Cyclization of 3-Cinnamoyl-2-styrylchromones
New
Synthesis of
X
a
nthen
a
odione De
n
rivatives a C. G. A. Pinto,a Ana M. L. Seca,a,b Stéphanie B. Leal,a Artur M. S. Silva,*a José A. S. Cavaleiroa
a
Department of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal
Fax +351(234)370084; E-mail: artur.silva@ua.pt; E-mail: diana@ua.pt
b
DCTD, University of Azores, 9501-801 Ponta Delgada, Azores
Received 13 June 2011
such as antinorovirus,12 anti-inflammatory,13 and
antioxidant14 activities.
Abstract: Novel (E)-3-aryl-4-benzylidene-8-hydroxy-3,4-dihydro-
1H-xanthene-1,9(2H)-diones are prepared by the cyclization of
(E,E)-3-cinnamoyl-5-hydroxy-2-styrylchromones efficiently cata-
lyzed with boron tribromide. The (E,E)-3-cinnamoyl-5-hydroxy-2-
styrylchromones are obtained from the Baker–Venkataraman rear-
rangement of (E,E)-2-acetyl-1,3-phenylene bis(3-phenylacrylate),
which is greatly improved under microwave irradiation.
Following our interest in the synthesis of biologically
active compounds, especially polyhydroxy-2-styryl-
chromones, a program aimed at the synthesis of (E,E)-3-
cinnamoyl-5-hydroxy-2-styrylchromones 8 was initiated
(Scheme 1).
Key words: xanthenediones, 3-cinnamoyl-5-hydroxy-2-styrylchro-
mones, microwave irradiation, cyclization, boron tribromide
HO
O
OH
HO
O
O
OH
O
O
Xanthones are a class of secondary metabolites widely oc-
curring in higher plant families such as Guttiferae and
Gentianaceae.1 The growing interest in this class of com-
pounds is associated with the important pharmacological
properties demonstrated by both natural and synthetic
derivatives, such as anti-inflammatory,2 antitumour,3 and
antioxidant activities.4 To the best of our knowledge, xan-
thenedione derivatives are scarce in nature; so far four
xanthene-2,9-dione derivatives have been found, garcin-
ianones A (1) and B (2), isolated from Garcinia multiflo-
ra,5 allanxanthone C (3a), isolated from Allanblackia
monticola Staner L. C.,6 and 1,2-dihydro-3,6,8-trihy-
droxy-1,1-diisoprenyl-5-(1,1-dimethylprop-2-enyl)xanthen-
2,9-dione (3b), isolated from Hypericum erectum
(Figure 1).7 Allanxanthone C (3a) demonstrated moderate
activity against two strains of Plasmodium falciparum.6
References to synthetic xanthenediones are more fre-
quent, however, the common type of substitution pattern
OH
O
OH
1
2
R2
O
HO
R1
O
OH
O
O
O
OH
O
3a R1 = CH2CH=C(Me)2, R2 = H
3b R1 = H, R2 = C(Me)2CH=C(Me)2
4
O
R1
is
the
9-aryl-3,4,5,6,7,9-hexahydro-1H-xanthene-
O
5
O
1,8(2H)-dione (4, Figure 1).8 Xanthene-1,9(2H)-diones
have not been found in nature and synthetic derivatives
also seem to be scarce, only 3,4-dihydro-1H-xanthene-
1,9(2H)-dione (5, Figure 1) has been described.9
R3
R1
R3
R4
O
O
6a R1 = OH, R2 = Me, R3, R4 = OMe
6b R1 = OH, R2 = Me, R3 = OMe, R4 = H
6c R1, R2, R3, R4 = H
2-Styrylchromones are also a scarce group of naturally oc-
curring compounds, only three derivatives have been iso-
R2
OH
lated
[hormothamnione
(6a)
and
desmeth-
Figure 1 Naturally occurring xanthenediones and (E)-2-styrylchro-
mones
oxyhormothamnione (6b), from the marine blue green
alga Chrysophaeum taylori,10 and (E)-5-hydroxy-2-
styrylchromone (6c), from the rhizomes of Imperata cy-
lindrical (Figure 1)].11 Even so, 2-styrylchromone deriva-
tives are associated with important biological properties,
Knowing the importance of the catechol moiety to im-
prove the antioxidant activity of 2-styrylchromones,15 it
was decided to synthesize (E,E)-3-(3,4-dihydroxycin-
namoyl)-5-hydroxy-2-(3,4-dihydroxystyryl)chromone. In
order to achieve this we firstly obtained the corresponding
methoxy derivative 8g. Its synthesis could be accom-
plished in a two-step approach as previously reported16 or
SYNLETT 2011, No. 14, pp 2005–2008
Advanced online publication: 10.08.2011
DOI: 10.1055/s-0030-1261172; Art ID: D18311ST
© Georg Thieme Verlag Stuttgart · New York
x
x
.x
x
.2
0
1
1

2006
D. C. G. A. Pinto et al.
LETTER
R2
R3
R2
R3
5'
R3
R1
4'
3'
6'
O
b
O
O
R1
R2
5''
R3
2'
R1
5
8
O
a
R3
R2
3
2
O
2
3
4''
3''
4
6''
6
7
i) BBr3, r.t.
ii) H2O, r.t.
7
6
MW
K2CO3, py
a'
9
4
R2
R1
O
O
1
8
2''
R1
5
b'
OH
O
O
OH
O
O
8
9
for compounds 7 and 8:
a) R1, R2, R3 = H
9a R1, R2, R3 = H
R1
R2
b) R1, R2 = H, R3 = Me
c) R1, R2 = H, R3 = OMe
d) R1, R2 = H, R3 = Cl
e) R1 = OMe, R2, R3 = H
f) R1 = Cl, R2, R3 = H
g) R1 = H, R2, R3 = OMe
9b R1, R2 = H, R3 = Me
9c R1, R2 = H, R3 = OH
9d R1, R2 = H, R3 = Cl
9e R1 = OH, R2, R3 = H
9f R1 = Cl, R2, R3 = H
9g R1 = H, R2, R3 = OH
R3
7
Scheme 1
in one-pot sequence as recently described.17 Our choice, 8d and 8f, which were obtained in good yields (over
due to the less expensive reagents and shorter reaction 60%). These results, together with the fact that all at-
time, was the two-step approach (bisesterification of the tempts to obtain nitro derivatives failed, indicate that
appropriate 2¢-hydroxyacetophenone with cinnamoyl withdrawing groups do not favor the Baker–Venkata-
chloride derivatives followed by the Baker–Venkata- raman rearrangement.24
raman rearrangement of the formed diester),16 in combi-
The next step in our strategy was the cyclization of (E,E)-
3-cinnamoyl-5-hydroxy-2-styrylchromones 8 with boron
nation with a great improvement achieved by using
microwave irradiation.18 This methodology was success-
tribromide as Lewis acid catalyst. After three hours at
fully employed for the rearrangement of (E,E)-2-acetyl-
room temperature the starting material 8a was completely
1,3-phenylene bis(3-phenylacrylate) (7g) leading to
consumed, and (E)-4-benzylidene-8-hydroxy-3-phenyl-
(E,E)-3-cinnamoyl-5-hydroxy-2-styrylchromone (8g) in
3,4-dihydro-1H-xanthene-1,9(2H)-dione (9a) was ob-
good yield (86%, Scheme 1).19,20 Next, cleavage of the
tained in good yield (66%). The scope of this reaction was
methoxy group with boron tribromide was attempted, but
investigated and it was demonstrated that, in the case of
mixtures of compounds bearing methoxy and hydroxy
8d and 8f, eight hours were needed to complete the reac-
tion and in the case of 8c and 8e one-pot cyclization and
groups were obtained. Therefore, we decided to extend
the reaction time and after 22 hours, cleavage of the meth-
oxy group was complete and a pure yellow solid was ob-
demethylation occurred furnishing hydroxy derivatives 9c
and 9e in moderate yields (over 40%).21
tained. NMR analysis indicated that the expected
The described cyclization reaction presumably proceeds
demethylation occurred but the compound obtained was
by the activation of (E,E)-3-cinnamoyl-5-hydroxy-2-
(E)-4-(3,4-dihydroxy-benzylidene)-8-hydroxy-3-(3,4-di-
styrylchromones 8a–g through a chelation with BBr3 (in-
hydroxyphenyl)-3,4-dihydro-1H-xanthene-1,9(2H)-dione
termediate A), which promotes the subsequent cyclization
and deprotonation reactions (intermediate B and C). Fi-
nally, the treatment with water performs the cleavage of
(9g, 81%). This result means that there was the expected
deprotection together with an unprecedented cyclization
of (E,E)-3-(3,4-dimethoxycinnamoyl)-5-hydroxy-2-(3,4-
the oxygen–boron bond to give the desired compounds
dimethoxystyryl)chromone (8g, Scheme 1).21 This sur-
(Scheme 2).25
prising result and the reported important biological appli-
cations for similar derivatives prompted us to study this
synthetic methodology. We herein report an efficient and
concise synthetic route for (E)-3-aryl-4-benzylidene-8-
hydroxy-3,4-dihydro-1H-xanthene-1,9(2H)-diones 9a–g
(Scheme 1).22,23
The stereochemical assignment of compounds 9a–g was
based on the analysis of 1H–1H coupling constants and of
the NOESY spectra (Figure 2). Taking into account that
there are no NOE between the benzylidene proton with
those of the 3-phenyl ring or with H-3, but there is a small
NOE between H-5 and the benzylidene proton and be-
tween H-3 and the aromatic protons of the benzylidene
group, we conclude that the benzylidene double bond of
compounds 9a–g has the E-configuration.
The use of (E,E)-3-cinnamoyl-5-hydroxy-2-styryl-
chromones 8a–g as starting materials is very attractive
due to the fact that their reactivity has never been reported
and we could also study the scope of the Baker–Venkata-
raman rearrangement of (E,E)-2-acetyl-1,3-phenylene
bis(3-phenylacrylates) 7a–g under microwave irradia-
tion.19 This strategy proved to be excellent since almost all
compounds were obtained in very good yields (over 80%)
and in less than 20 minutes reaction time. Furthermore,
purification procedures were needed only for derivatives
In summary, we have established a successful methodol-
ogy to perform the Baker–Venkataraman rearrangement
of (E,E)-2-acetyl-1,3-phenylene bis(3-phenylacrylates)
into the corresponding (E,E)-3-cinnamoyl-5-hydroxy-2-
styrylchromones. The beneficial effect of using micro-
Synlett 2011, No. 14, 2005–2008 © Thieme Stuttgart · New York

LETTER
New Synthesis of Xanthenodione Derivatives
2007
(7) An, T. Y.; Hu, L. H.; Chen, Z. L. Chin. Chem. Lett. 2002, 13,
623.
Ar
H
Ar
O
O
Ar
(8) (a) Brito-Arias, M.; Tapia-Albarrán, M.; Padilla-Martínez,
I.; Martínez-Martínez, F.; Espinosa, G.; Molins, E.;
Espinosa, E. J. Chem. Crystallogr. 1999, 29, 759.
(b) Karthikeyan, G.; Pandurangan, A. J. Mol. Catal. A:
Chem. 2009, 311, 36. (c) Pore, D. M.; Shaikh, T. S.; Patil, N.
G.; Dongare, S. B.; Desai, U. V. Synth. Commun. 2010, 40,
2215.
O
Ar
OH
O
OH
O
O
B
Br2
B
Br3
A
B
(9) Gabbutt, C. D.; Hepworth, J. D.; Urquhart, M. W. J.; Miguel,
L. M. V. J. Chem. Soc., Perkin Trans. 1 1997, 1819.
(10) (a) Gerwick, W. H.; Lopez, A.; Van Duyne, G. D.; Clardy,
J.; Ortiz, W.; Baez, A. Tetrahedron Lett. 1986, 27, 1979.
(b) Gerwick, W. H. J. Nat. Prod. 1989, 52, 252.
(11) Yoon, J. S.; Lee, M. K.; Sung, S. H.; Kim, Y. C. J. Nat. Prod.
2006, 69, 290.
Ar
Ar
O
O
Ar
O
O
Ar
H2O
OH
O
OH
O
(12) Rocha-Pereira, J.; Cunha, R.; Pinto, D. C. G. A.; Silva, A. M.
S.; Nascimento, M. S. J. Bioorg. Med. Chem. 2010, 18, 4195.
(13) Gomes, A.; Fernandes, E.; Silva, A. M. S.; Pinto, D. C. G.
A.; Santos, C. M. M.; Cavaleiro, J. A. S.; Lima, J. L. F. C.
Biochem. Pharmacol. 2009, 78, 171.
9
C
B
Br2
Scheme 2
(14) Gomes, A.; Neuwirth, O.; Freitas, M.; Couto, D.; Ribeiro,
D.; Figueiredo, A. G. P. R.; Silva, A. M. S.; Seixas, R. S. G.
R.; Pinto, D. C. G. A.; Tomé, A. C.; Cavaleiro, J. A. S.;
Fernandes, E.; Lima, J. L. F. C. Bioorg. Med. Chem. 2009,
17, 7218.
(15) Gomes, A.; Fernandes, E.; Garcia, M. B. Q.; Silva, A. M. S.;
Pinto, D. C. G. A.; Santos, C. M. M.; Cavaleiro, J. A. S.;
Lima, J. L. F. C. Bioorg. Med. Chem. 2008, 16, 7939.
(16) Pinto, D. C. G. A.; Silva, A. M. S.; Cavaleiro, J. A. S. New
J. Chem. 2000, 24, 85.
R
R
H
H
5
H
O
J3-2cis = 5.0 – 6.5 Hz
J3-2trans = 2.2 – 3.2 Hz
J2trans-2cis = 14.8 – 15.5 Hz
4
3
Hcis
Htrans
OH
O
O
Figure 2 Main NOE and J values of 9
(17) Königs, P.; Neumann, O.; Kataeva, O.; Schnakenburg, G.;
Waldvogel, S. Eur. J. Org. Chem. 2010, 6417.
(18) Pinto, D. C. G. A.; Silva, A. M. S.; Cavaleiro, J. A. S. Synlett
2007, 1897.
wave irradiation was the shortening of the reaction time
from 1 hour to 17 minutes. We have also developed a nov-
el efficient synthesis of (E)-3-aryl-4-benzylidene-8-
hydroxy-3,4-dihydro-1H-xanthene-1,9(2H)-diones. Good
yields of the novel products and experimental simplicity
are the main advantages of this method.
(19) Optimized Experimental Procedure
A two-necked flask equipped with a magnetic stirring bar,
fibre-optic temperature control, and reflux condenser was
charged with a mixture of the appropriate (E,E)-2-acetyl-
1,3-phenylene bis(3-phenylacrylate) 7a–g (1 mmol) and
anhyd K2CO3 (28 mg, 2 mmol) in anhyd pyridine (10 mL)
and was then irradiated in an Ethos SYNTH microwave
(Milestone Inc.) at constant power of 400 W for 17 min.
After this period the reaction mixture was poured onto a
mixture of ice (10 g) and H2O (20 mL), and the pH was
adjusted to 2 with dilute HCl. The so-formed solids (E,E)-3-
cinnamoyl-5-hydroxy-2-styrylchromones 8a–gwerefiltered
off. In the case of compounds 8d and 8f a column
chromatography purification, using CH2Cl2 as eluent, was
necessary; 8a, 378 mg, 96%; 8b, 409 mg, 97%; 8c, 445 mg,
98%; 8d, 301 mg, 65%; 8e, 422 mg, 93%; 8f, 287 mg, 62%;
8g, 443 mg, 86%.
Acknowledgment
Thanks are due to the University of Aveiro, to Fundação para a
Ciência e a Tecnologia (FCT) and FEDER for funding the Organic
Chemistry Research Unit. We are also grateful to the Portuguese
National NMR Network (RNRMN) supported with funds from
FCT.
References and Notes
(1) (a) Roberts, J. C. Chem. Rev. 1961, 38, 591. (b) Gales, L.;
Damas, A. M. Curr. Med. Chem. 2005, 12, 2499.
(2) Park, H. H.; Park, Y.-D.; Han, J.-M.; Im, K.-R.; Lee, B. W.;
Jeong, I. Y.; Jeong, T.-S.; Lee, W. S. Bioorg. Med. Chem.
Lett. 2006, 16, 5580.
(3) (a) Shadid, K. A.; Shaari, K.; Abas, F.; Israf, D. A.; Hamzah,
A. S.; Syakroni, N.; Saha, K.; Lajis, N. Hj. Phytochemistry
2007, 68, 2537. (b) Ee, G. C. L.; Daud, S.; Izzaddin, S. A.;
Rahmani, M. J. Asian Nat. Prod. Res. 2008, 10, 475.
(4) Suvarnakuta, P.; Chaweerungrat, C.; Devahastin, S. Food
Chem. 2011, 125, 240.
(5) Chiang, Y.-M.; Kuo, Y.-H.; Oota, S.; Fukuyama, Y. J. Nat.
Prod. 2003, 66, 1070.
(6) Azebaze, A. G. B.; Meyer, M.; Valentin, A.; Nguemfo, E. L.;
Fomum, Z. T.; Nkengfack, A. E. Chem. Pharm. Bull. 2006,
54, 111.
(20) Physical Data of 5-Hydroxy-3¢,4¢-dimethoxy-3-(3,4-
dimethoxycinnamoyl)-2-styrylchromone (8g)
Mp 208–211 °C. 1H NMR (300.13 MHz, CDCl3): d = 3.93
(s, 4 × 3 H, 3¢,4¢,3¢¢,4¢¢-OCH3), 6.84 (dd, 1 H, J = 0.7, 8.2
Hz, H-6), 6.88 (d, 1 H, J = 8.3 Hz, H-5¢¢), 6.89 (d, 1 H,
J = 8.3 Hz, H-5¢), 6.90 (d, 1 H, J = 15.8 Hz, H-a), 7.02 (dd,
1 H, J = 0.7, 8.2 Hz, H-8), 7.07 (d, 1 H, J = 1.8 Hz, H-2¢),
7.10 (d, 1 H, J = 15.8 Hz, H-a¢), 7.13 (d, 1 H, J = 1.8 Hz,
H-2¢¢), 7.20 (dd, 2 H, J = 1.8, 8.3 Hz, H-6¢,6¢¢), 7.59 (t, 1 H,
J = 8.2 Hz, H-7), 7.62 (d, 1 H, J = 15.8 Hz, H-b¢), 7.75 (d, 1
H, J = 15.8 Hz, H-b), 12.50 (s, 1 H, 5-OH) ppm. 13C NMR
(75.47 MHz, CDCl3): d = 56.0 (3¢,4¢,3¢¢,4¢¢-OCH3), 106.7
(C-8), 109.9 and 110.1 (C-2¢ and/or C-2¢¢), 110.5 (C-10),
111.0 and 111.1 (C-5¢ and/or C-5¢¢), 111.8 (C-6), 115.1 (C-
a), 120.3 (C-3), 123.1 (C-6¢), 123.8 (C-6¢¢), 125.4 (C-a¢),
Synlett 2011, No. 14, 2005–2008 © Thieme Stuttgart · New York

2008
D. C. G. A. Pinto et al.
LETTER
127.3 (C-1¢¢), 127.8 (C-1¢), 135.8 (C-7), 140.7 (C-b), 145.3
(C-b¢), 149.2 and 149.3 (C-3¢ and/or C-3¢¢), 151.5 and 151.7
(C-4¢ and/or C-4¢¢), 155.4 (C-9), 161.0 (C-5), 162.6 (C-2),
181.6 (C-4), 190.9 (C=O) ppm. MS (ESI+): m/z (%) = 515
(60) [M + H]+, 537 (100) [M + Na]+, 553 (45) [M + K]+.
HRMS (EI): m/z calcd for [C30H26O8]+: 514.1628; found:
514.1639.
(C-1¢), 132.7 (C-2¢¢,6¢¢), 136.4 (C-6), 139.4 (C-7¢¢), 154.6 (C-
4b), 156.5 (C-4¢), 160.0 (C-4¢¢), 160.6 (C-8), 169.9 (C-4a),
179.8 (C-9), 191.8 (C-1) ppm. MS (ESI+): m/z (%) = 427
(15) [M + H]+, 449 (100) [M + Na]+, 465 (10) [M + K]+.
HRMS (EI): m/z calcd for [C26H18O6]+: 426.1103; found:
426.1116.
(23) Physical Data of (E)-4-(4-Chlorobenzylidene)-3-(4-
chlorophenyl)-8-hydroxy-3,4-dihydro-1H-xanthene-1,9
(2H)-dione (9d)
(21) Optimized Experimental Procedure
A CH2Cl2 solution of BBr3 (2 mmol) was slowly added to a
solution of the appropriate (E,E)-3-cinnamoyl-5-hydroxy-2-
styrylchromone 8a–g (0.4 mmol) in anhyd CH2Cl2 (20 mL)
at low temperature (–78 °C). After the addition, the cooling
system was removed, and the reaction mixture was stirred at
r.t. for 3 h (8 h for 8d and 8f and 22 h for 8g). Then, H2O
(80 mL) was added, and the resulting reaction mixture was
stirred at r.t. for 3–4 h. The mixture was extracted with
CHCl3 (3 × 80 mL) and the combined extracts evaporated
and purified by TLC, using CH2Cl2 as eluent (except in the
case of compound 9g which was filtered off): 9a, 99 mg,
63%; 9b, 150 mg, 89%; 9c, 118 mg, 69%; 9d, 95 mg, 51%;
9e, 70 mg, 41%; 9f, 69 mg, 37%; 9g, 148 mg, 81%.
(22) Physical Data of (E)-8-Hydroxy-4-(4-hydroxy-
benzylidene)-3-(4-hydroxyphenyl)-3,4-dihydro-1H-
xanthene-1,9 (2H)-dione (9c)
Mp 110–113 °C. 1H NMR (300.13 MHz, CDCl3): d = 3.05
(dd, 1 H, J = 2.5, 15.5 Hz, H-2trans), 3.15 (dd, 1 H, J = 5.6,
15.5 Hz, H-2cis), 4.68 (dd, 1 H, J = 2.5, 5.6 Hz, H-3), 6.84
(dd, 1 H, J = 0.6, 8.4 Hz, H-7), 7.02 (dd, 1 H, J = 0.6, 8.4 Hz,
H-5), 7.19 (br d, 2 H, J = 8.4 Hz, H-2¢,6¢), 7.26 (d, 2 H,
J = 8.6 Hz, H-2¢¢,6¢¢), 7.30 (br d, 2 H, J = 8.4 Hz, H-3¢,5¢),
7.37 (d, 2 H, J = 8.6 Hz, H-3¢¢,5¢¢), 7.59 (t, 1 H, J = 8.4 Hz,
H-6), 8.06 (s, 1 H, H-7¢¢), 12.54 (s, 1 H, 8-OH) ppm. 13
C
NMR (75.47 MHz, CDCl3): d = 39.8 (C-3), 45.5 (C-2),
106.8 (C-5), 111.0 (C-8a), 112. 9 (C-7), 113.6 (C-9a), 128.3
(C-2¢,6¢), 129.3 (C-3¢¢,5¢¢), 129.6 (C-3¢,5¢), 129.7 (C-4),
130.7 (C-2¢¢,6¢¢), 132.4 (C-1¢¢), 133.7 (C-4¢), 136.2 (C-6 and
C-4¢¢), 137.9 (C-7¢¢), 138.3 (C-1¢), 154.7 (C-4b), 161.7 (C-8),
168.7 (C-4a), 180.0 (C-9), 190.7 (C-1) ppm. MS (ESI+):
m/z (%) = 463 (70) [(M + H)+, 35Cl], 465 (40) [(M + H)+,
35Cl37Cl], 467 (7) [(M + H)+, 37Cl], 485 (75) [(M + Na)+,
35Cl], 487 (45) [(M + Na)+, 35Cl37Cl], 489 (8) [(M + Na)+,
37Cl], 501 (15) [(M + K)+, 35Cl], 503 (10) [(M + K)+,
35Cl37Cl], 505 (2) [(M + K)+, 37Cl]. Anal. Calcd (%) for
C26H16Cl2O4·0.5H2O (456.32): C, 66.12; H, 3.63. Found: C,
66.05; H, 3.58. HRMS (EI): m/z calcd for [C26H1635Cl2O4]+:
462.0426; found: 462.0406; m/z calcd for [C26H1635Cl37ClO4]+:
464.0396; found: 464.0374; m/z calcd for [C26H1637Cl2O4]+:
466.0367; found: 466.0384.
Mp 319–320 °C. 1H NMR (300.13 MHz, DMSO-d6):
d = 2.69 (dd, 1 H, J = 2.2, 14.8 Hz, H-2trans), 3.23 (dd, 1 H,
J = 5.9, 14.8 Hz, H-2cis), 4.66 (dd, 1 H, J = 2.2, 5.9 Hz, H-3),
6.72 (br d, 2 H, J = 8.6 Hz, H-3¢,5¢), 6.83 (d, 2 H, J = 8.7 Hz,
H-3¢¢,5¢¢), 6.84 (dd, 1 H, J = 0.9, 8.3 Hz, H-7), 7.12 (br d, 2
H, J = 8.6 Hz, H-2¢,6¢), 7.29 (dd, 1 H, J = 0.9, 8.3 Hz, H-5),
7.37 (d, 2 H, J = 8.7 Hz, H-2¢¢,6¢¢), 7.72 (t, 1 H, J = 8.3 Hz,
H-6), 8.18 (s, 1 H, H-7¢¢), 9.57 (s, 1 H, 4¢-OH), 10.50 (s, 1 H,
4¢¢-OH), 12.71 (s, 1 H, 8-OH) ppm. 13C NMR (75.47 MHz,
DMSO-d6): d = 39.2 (C-3), 46.4 (C-2), 107.7 (C-5), 110.4
(C-8a), 111. 9 (C-7), 112.5 (C-9a), 116.0 (C-3¢¢,5¢¢), 115.9
(C-3¢,5¢), 125.2 (C-1¢¢), 125.7 (C-4), 128.1 (C-2¢,6¢), 130.8
(24) (a) Baker, W. J. Chem. Soc. 1933, 1381. (b) Gualati, K. C.;
Venkataraman, K. J. Chem. Soc. 1933, 942.
(25) Bellur, E.; Langer, P. J. Org. Chem. 2005, 70, 3819.
Synlett 2011, No. 14, 2005–2008 © Thieme Stuttgart · New York

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