A novel and efficient route for the synthesis of hydroxylated 2,3-diarylxanthones

Article abstract of DOI:10.1055/s-2007-990900

A novel, efficient and general route for the synthesis of hydroxylated 2,3-diarylxanthones is described. 3-Bromo-2-styryl-chromone, the key intermediate of this synthesis, is obtained by a Baker-Venkataraman rearrangement of the appropriate 2′-cinnamoylox

Full text of DOI:10.1055/s-2007-990900

LETTER
3113
A Novel and Efficient Route for the Synthesis of Hydroxylated
2,3-Diarylxanthones
Efficient
R
oute fo
l
r
the
S
e
ynthesis of
m
H
ydroxylated 2,3-
D
e
iarylxanth
n
ones tina M. M. Santos,a,b Artur M. S. Silva,*b José A. S. Cavaleirob
a
Department of Agro-Industries, Escola Superior Agrária de Bragança, Campus de Santa Apolónia, 5301855 Bragança, Portugal
Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810193 Aveiro, Portugal
Fax +351(23)4370084; E-mail: artur.silva@ua.pt
b
Received 27 July 2007
our previous work on the synthesis of xanthones, using the
3-bromo-2-methylchromone13 as key intermediate was
not effective in the synthesis of 2-aryl-3-(3,4-dihydroxy-
phenyl)xanthone derivatives, since the condensation of 3-
Abstract: A novel, efficient and general route for the synthesis of
hydroxylated 2,3-diarylxanthones is described. 3-Bromo-2-styryl-
chromone, the key intermediate of this synthesis, is obtained by a
Baker–Venkataraman rearrangement of the appropriate 2¢-cin-
namoyloxyacetophenone, followed by a one-pot reaction with bromo-2-methylchromone with 3,4-dioxygenatedbenzal-
phenyltrimethylammonium tribromide. The Heck reaction of these
dehydes does not occur. To circumvent these difficulties
bromochromones with substituted styrenes gives methoxylated 2,3-
we have developed a general method for the synthesis of
diarylxanthones. The cleavage of the methyl groups with BBr3
hydroxylated 2,3-diarylxanthones, starting from 2¢-hy-
gives the desired hydroxylated 2,3-diarylxanthones.
droxyacetophenone (1) and cinnamic acid derivatives 2a–
Key words: hydroxylated diarylxanthones, 3-bromo-2-styryl-
c (Schemes 1– 3), for further evaluation of the antioxidant
chromones, phenyltrimethylammonium tribromide, Heck reaction,
demethylation
activity.
The first part of the new synthetic route considers the
preparation of 3-bromo-2-styrylchromones 5a–c by a
three-step sequence depicted in Scheme 1. It started by the
cinnamoylation of 2¢-hydroxyacetophenone (1) with com-
Xanthones are a class of oxygenated heterocyclic com-
pounds widely occurring as secondary metabolites in
some higher plant families, fungi and lichens.1 These nat-
ural derivatives can exhibit numerous substitutions at dif-
ferent positions of their skeleton: methoxy, hydroxyl and
glycosyl groups being the most frequently occurring
ones.2
mercially available cinnamoyl chloride (2a) or with the in
situ prepared acid chlorides from cinnamic acids 2b,c and
phosphoryl chloride, affording the corresponding 2¢-cin-
namoyloxyacetophenones 3a–c. The second step consist-
ed of the cinnamoyl group transposition from the 2¢-
position to the 2-position of the acetophenone moiety,
which is known as the Baker–Venkataraman rearrange-
ment.14 It was performed by treatment of 3a–c with potas-
sium hydroxide in DMSO to afford 5-aryl-3-hydroxy-1-
(2-hydroxyphenyl)-2,4-pentadiene-1-ones 4a–c, in good
yields (73–95%). The last step consisted of a novel one-
pot synthesis, involving bromination and cyclization reac-
tions, giving rise to the desired 3-bromo-2-styryl-
chromones 5a–c (53–67%).15,16 The a-ketone
bromination was selectively carried out with phenyltri-
methylammonium tribromide (PTT),17 while the cyclode-
hydration of the obtained brominated compounds
occurred probably due the acidic conditions originating
during the bromination reaction.
The pharmacological properties of both natural and syn-
thetic xanthone derivatives have been extensively report-
ed in the literature;3 they include antiallergic,4 antifungal,5
anti-inflammatory,6 antimalarial7 and antitumour
activities8 and this reveals the growing interest in this type
of compounds.
One of the most promising properties of xanthones is re-
lated to their application as antioxidant agents.9 The aro-
matic character and the presence of hydroxyl groups and/
or cathecol moieties at certain positions of the xanthone
core are requirements for a strong antioxidant activity.10 It
is worth mentioning that there are already two formula-
tions in the market containing oxygenated and prenylated
xanthones, as antioxidants.11
The Heck cross-coupling reaction is one of the most pow-
erful and efficient methods for carbon–carbon bond for-
mation and consists of a palladium-catalyzed reaction
involving olefins and vinyl or aryl halides.18 In the present
study, 3-bromo-2-styrylchromones 5a–c were used as vi-
nyl halides and styrenes 6a–c as olefins (Scheme 2).19 Op-
timization studies were performed to determine the
influence of bases, phosphines, palladium catalysts, tem-
perature and reaction time on the coupling reaction. The
best results were obtained with one equivalent of triethy-
lamine as base, 0.1 equivalent of triphenylphosphine and
5 mol% of tetrakis(triphenylphosphine)palladium(0) as
Taking into consideration the referred structural charac-
teristics for a high antioxidant activity, we developed a
novel route for the synthesis of hydroxylated 2,3-diaryl-
xanthones. The classical methods widely described for the
synthesis of xanthones (e.g. Friedel–Crafts acylation,
Fries rearrangement or Ullmann condensation)12 do not
allow the synthesis of our target compounds. Moreover,
SYNLETT 2007, No. 20, pp 3113–3116
x
x
.x
x
.2
0
0
7
Advanced online publication: 21.11.2007
DOI: 10.1055/s-2007-990900; Art ID: D23507ST
© Georg Thieme Verlag Stuttgart · New York

3114
C. M. M. Santos et al.
LETTER
R1
R2
OH
5
XOC
R2
R1
a R1 = R2 = H
b R1 = OMe, R2 = H
c R1 = R2 = OMe
O
O
R4
R3
O
O
(i)
2a–c
R2
R1
1
6
O
O
a R3 = R4 = H
b R3 = OMe, R4 = H
c R3 = R4 = OMe
a R1 = R2 = H
Br
b R
1 = OMe, R2 = H
5a–c
6a–c
c R1 = R2 = OMe
(i)
R1
R2
3a–c
(ii)
R1
R1
OH
O
R2
R1
H
H
(iii)
O
O
O
O
R2
R4
R2
R4
H
Br
5a–c
OH
4a–c
O
O
diketone form
R3
R3
7a–i
8a–i
Scheme 1 Reagents and conditions: (i) (a) X = Cl, anhyd pyridine,
r.t., 2 h; (b) X = OH, POCl3, anhyd pyridine, 60 ºC, 2 h; (ii) DMSO,
KOH, r.t., 2 h; (iii) PTT, THF, r.t., 12 h.
Scheme 2 Reagents and conditions: (i) NMP, Et3N, PPh3,
Pd(PPh3)4.
R5
R1
catalyst. Under these conditions the desired 2,3-diaryl-
xanthones 7a–i20 and the semioxidized intermediates 2,3-
diaryl-3,4-dihydroxanthones 8a–i21 were obtained
(Scheme 2, Table 1). The formation mechanism of xan-
thones 7a–i and 8a–i is similar to those presented in our
previous work.13
O
O
O
O
(i)
R6
R8
R2
R4
R7
R3
7b–i
9b–i
R1, R2, R3, R4 = H, OMe
R5, R6, R7, R8 = H, OH
Demethylation of 2,3-diarylxanthones 7b–i was achieved
by their treatment with boron tribromide22 in anhydrous
dichloromethane (Scheme 3).23 The hydroxylated 2,3-di-
arylxanthones 9b–i24 were obtained in good yields (70–
94%).
Scheme 3 Reagents and conditions: (i) (a) anhyd CH2Cl2, BBr3,
–78 °C to r.t.
The main features in the 1H NMR spectra of 3-bromo-2-
styrylchromones 5a–c are the doublets corresponding to
the resonances of the two vinylic protons H-a and H-b in
the trans configuration (3JHa–Hb = 15.8–16.0 Hz). The res-
onances assigned to H-b (d = 7.66–7.73 ppm) and C-b
(d = 139.3–139.6 ppm) appears at higher frequency val-
ues than those of H-a (d = 7.33–7.51 ppm) and C-a (d =
116.7–119.2 ppm), due to the mesomeric deshielding ef-
fect of the carbonyl group. An important characteristic of
the 1H NMR spectra of 2,3-diarylxanthones 7a–i and 9b–
i are the singlets corresponding to the resonances of H-1
(d = 7.98–8.39 ppm) and H-4 (d = 7.50–7.65 ppm). H-1
appears at higher frequency values due to the anisotropic
All the synthesized compounds have been characterized
1
by NMR, MS and elemental analysis. In the H NMR
spectra of 5-aryl-3-hydroxy-1-(2-hydroxyaryl)-2,4-penta-
dien-1-ones 4a–c it is possible to observe the presence of
two singlets at d = 12.23–12.28 ppm and d = 14.65–14.75
ppm, which are due to the resonances of protons involved
in hydrogen bonds. One can conclude that the compounds
4a–c exist in enolic forms, as shown in Scheme 1, and the
former signals correspond to the resonances of the phenol-
ic protons whereas the latter ones are due to the 3-OH pro-
tons.
Table 1 Heck Reaction of 3-Bromo-2-styrylchromones 5a–c with Styrenes 6a–c
Compd 7/8
R1
R2
R3
R4
Temp.
160 °C
160 °C
160 °C
reflux
reflux
reflux
reflux
reflux
reflux
Time (h)
Yield of 7 (%) Yield of 8 (%)
a
b
c
d
e
f
H
H
H
H
9
3
54
66
44
60
46
21
62
46
55
9
14
6
H
H
OMe
OMe
H
H
H
H
OMe
H
12
9
OMe
OMe
OMe
OMe
OMe
OMe
H
11
11
4
H
OMe
OMe
H
H
3
H
OMe
H
3
g
h
i
OMe
OMe
OMe
9
3
OMe
OMe
H
6
21
6
OMe
9
Synlett 2007, No. 20, 3113–3116 © Thieme Stuttgart · New York

LETTER
Efficient Route for the Synthesis of Hydroxylated 2,3-Diarylxanthones
3115
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and mesomeric deshielding effect of the carbonyl group.
The assignment of proton H-1 was also confirmed by the
connectivity found in the HMBC spectrum between the
singlet at higher frequency value and the carbonyl carbon.
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1
In the H NMR spectra of 2,3-diarylxanthones 7b–i one
can observe the singlets corresponding to the resonances
of the methoxy protons (d = 3.52–3.90 ppm) whereas in
the 2,3-diarylxanthones 9b–i these signals are absent and
the singlets corresponding to the hydroxyl protons appear
at higher frequency values (d = 8.94–9.67 ppm). HMBC
and NOESY spectra were used for the structure assign-
ment of 2,3-diaryl-3,4-dihydroxanthones 8a–i, similarly
to the procedure described in our previous work.13
In summary, a novel, efficient and general route for the
synthesis of 2,3-diarylxanthones 7a–i was developed. 3-
Bromo-2-styrylchromones 5a–c, the key intermediates in
this synthetic process, were obtained by a novel one pot-
reaction of 5-aryl-3-hydroxy-1-(2-hydroxyphenyl)-2,4-
pentadien-1-ones 4a–c with PTT. The Heck reaction of 3-
bromo-2-styrylchromones 5a–c with styrenes 6a–c led to
the formation of methoxylated 2,3-diarylxanthones 7a–i
and 2,3-diaryl-3,4-dihydroxanthones 8a–i in a one-pot re-
action. The final step consists of the cleavage of the meth-
yl groups of 7b–i to afford the desired hydroxylated and
polyhydroxylated 2,3-diarylxanthones 9b–i.
(13) Santos, C. M. M.; Silva, A. M. S.; Cavaleiro, J. A. S. Synlett
2005, 3095.
(14) (a) Mahal, H. S.; Venkataraman, K. J. Chem. Soc. 1934,
1767. (b) Baker, W. J. Chem. Soc. 1933, 1381.
(15) Typical Experimental Procedure:
Acknowledgment
Thanks are due to the University of Aveiro, FCT and FEDER for
funding the Organic Chemistry Research Unit and the project
POCI/QUI/59284/2004. One of us (C.M.M. Santos) is also grateful
to PRODEP 5.3 for financial support.
Phenyltrimethylammonium tribromide (PTT; 2.1 g, 5.5
mmol) was added to a THF (60 mL) solution of the
appropriate 5-aryl-3-hydroxy-1-(2-hydroxyphenyl)-2,4-
pentadien-1-ones 4a–c (5 mmol). The reaction mixture was
stirred and allowed to stand at r.t. for 12 h. After that period,
the solution was poured into ice (50 g) and H2O (80 mL),
stirred for 20 min and the yellow solid was removed by
filtration. The residue was taken in CHCl3 (50 mL) and
washed with H2O (3 × 50 mL). The organic layer was
collected, the solvent was evaporated to dryness and the
residue was purified by silica gel column chromatography
using CH2Cl2 as eluent. The solvent was evaporated and the
residue was recrystallized from EtOH to give the 3-bromo-
2-styrylchromones 5a–c in good yields (5a: 67%; 5b: 53%;
5c: 64%).
References and Notes
(1) (a) Hostettman, K.; Hostettman, M. In Methods in Plant
Biochemistry, Plant Phenolics, Vol. 1; Dey, P. M.; Harbone,
J. B., Eds.; Academic Press: London, 1989, 493.
(b) Bennett, G. J.; Lee, H.-H. Phytochemistry 1989, 28, 967.
(c) Gales, L.; Damas, A. M. Curr. Med. Chem. 2005, 12,
2499.
(2) (a) Vieira, L. M. M.; Kijjoa, A. Curr. Med. Chem. 2005, 12,
2413. (b) Roberts, J. C. Chem. Rev. 1961, 591.
(3) Pinto, M. M. M.; Sousa, M. E.; Nascimento, M. S. J. Curr.
Med. Chem. 2005, 12, 2517.
(4) (a) Dube, M.; Zunker, K.; Neidhart, S.; Carle, R.; Steinhart,
H.; Paschke, A. J. Agric. Food Chem. 2004, 52, 3938.
(b) Pfister, J. R.; Ferraresi, R. W.; Harrison, I. T.; Rooks, W.
H.; Freid, J. H. J. Med. Chem. 1978, 21, 669.
(5) (a) Abdel-Lateff, A.; Klemke, C.; König, G. M.; Wright, A.
D. J. Nat. Prod. 2003, 66, 706. (b) Fukai, T.; Yonekawa,
M.; Hou, A.-J.; Nomura, T.; Sun, H.-D.; Uno, J. J. Nat. Prod.
2003, 66, 1118. (c) Mackeen, M. M.; Ali, A. M.; Lajis, N.
H.; Kawazu, K.; Hassan, Z.; Amran, M.; Habsah, M.; Mooi,
L. Y.; Mohamed, S. M. J. Ethanopharmacol. 2000, 72, 395.
(6) (a) 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. (b) Lin, C. N.; Chung, M. I.;
Liou, S. J.; Lee, T. H.; Wang, J. P. J. Pharm. Pharmacol.
1996, 48, 532.
(16) Physical Data of 3-Bromo-3¢,4¢-dimethoxy-2-styryl-
chromone (5c): mp 187–189 ºC. 1H NMR (300.13 MHz,
CDCl3): d = 3.95 (s, 3 H, 4¢-OMe), 3.98 (s, 3 H, 3¢-OMe),
6.92 (d, J = 8.3 Hz, 1 H, H-5¢), 7.14 (d, J = 2.0 Hz, 1 H, H-
2¢), 7.24 (dd, J = 2.0, 8.3 Hz, 1 H, H-6¢), 7.33 (d, J = 15.8 Hz,
1 H, H-a), 7.41 (ddd, J = 0.8, 7.7, 7.8 Hz, 1 H, H-6), 7.53 (d,
J = 7.9 Hz, 1 H, H-8), 7.66 (d, J = 15.8 Hz, 1 H, H-b), 7.70
(ddd, J = 1.6, 7.7, 7.9 Hz, 1 H, H-7), 8.23 (dd, J = 1.6, 7.8
Hz, 1 H, H-5). 13C NMR (75.47 MHz, CDCl3): d = 55.96,
55.99 (3¢-OMe, 4¢-OMe), 109.0 (C-3), 109.6 (C-2¢), 111.1
(C-5¢), 116.9 (C-a), 117.4 (C-8), 122.1 (C-10), 122.6 (C-6¢),
125.3 (C-6), 126.4 (C-5), 127.9 (C-1¢), 133.9 (C-7), 139.6
(C-b), 149.3 (C-3¢), 151.2 (C-4¢), 154.9 (C-9), 158.7 (C-2),
172.7 (C-4). MS (ESI+): m/z (%) = 387 (19) ([M + H]+, 79Br),
389 (20) ([M + H]+, 81Br), 409 (9) ([M + Na]+, 79Br), 411 (9)
([M + Na]+, 81Br), 425 (4) ([M + K]+, 79Br), 427 (4) ([M +
K]+, 81Br), 795 (7) ([2 × M + Na]+, 79Br), 797 (15) ([2 × M +
Na]+, 81Br). Anal. Calcd for C19H15BrO4: C, 58.93; H, 3.90.
Found: C, 58.53; H, 3.84.
(7) (a) Riscoe, M.; Kelly, J. X.; Winter, R. Curr. Med. Chem.
2005, 12, 2539. (b) Portela, C.; Afonso, C. M. M.; Pinto, M.
Synlett 2007, No. 20, 3113–3116 © Thieme Stuttgart · New York

3116
C. M. M. Santos et al.
LETTER
(17) Fougerousse, A.; Gonzalez, E.; Brouillard, R. J. Org. Chem.
2000, 65, 583.
(18) (a) Trzeciak, A. M.; Ziółkoeski, J. J. Coord. Chem. Rev.
2007, 251, 1281. (b) Nicolaou, K. C.; Bulger, P. G.; Sarlah,
D. Angew. Chem. Int. Ed. 2005, 44, 4442. (c) Farina, V.
Adv. Synth. Catal. 2004, 346, 1553.
(19) Typical Experimental Procedure: To a mixture of the
appropriate 3-bromo-2-styrylchromones 5a–c (0.4 mmol),
triphenylphosphine (10.5 mg, 0.04 mmol),
1.3, 8.8 Hz, 1 H, H-3), 6.71 (d, J = 8.1 Hz, 1 H, H-5¢¢), 6.81–
6.86 (m, 2 H, H-2¢¢, H-6¢¢), 6.83 (d, J = 8.9 Hz, 2 H, H-3¢, H-
5¢), 7.36 (d, J = 8.0 Hz, 2 H, H-5), 7.38 (ddd, J = 1.4, 7.6, 7.7
Hz, 1 H, H-7), 7.44 (s, 1 H, H-1), 7.44 (d, J = 8.9 Hz, 2 H,
H-2¢, H-6¢), 7.60 (ddd, J = 1.6, 7.7, 8.0 Hz, 1 H, H-6), 8.28
(dd, J = 1.6, 7.6 Hz, 1 H, H-8). 13C NMR (75.47 MHz,
CDCl3): d = 36.8 (C-4), 41.4 (C-3), 55.3, 55.75, 55.80 (4¢-
OMe, 3¢¢-OMe, 4¢¢-OMe), 110.4 (C-2¢¢), 111.4 (C-5¢¢), 113.9
(C-3¢, C-5¢), 114.8 (C-1), 116.9 (C-9a), 118.0 (C-5), 119.2
(C-6¢¢), 123.8 (C-8a), 125.0 (C-7), 126.2 (C-8), 126.9 (C-2¢,
C-6¢), 131.7 (C-1¢), 132.9 (C-6), 133.1 (C-1¢¢), 135.3 (C-2),
148.0 (C-4¢¢), 149.1 (C-3¢¢), 155.9 (C-4b), 159.2 (C-4¢),
162.2 (C-4a), 174.2 (C-9). MS (EI): m/z (%) = 440 (13)
[M+·], 439 (26), 438 (100), 423 (13), 497 (14), 391 (7), 380
(7), 363 (7). HRMS (EI): m/z calcd for C28H24O5: 440.1624;
found: 440.1624.
tetrakis(triphenylphosphine)palladium(0) (23.1 mg, 0.02
mmol) and triethylamine (55.8 mL, 0.4 mmol) in N-methyl-
2-pyrrolidinone (6 mL) was added the appropriate styrene
6a–c (2 mmol for styrene 6a and 0.8 mmol for styrenes
6b,c). The reaction mixture was stirred under different
conditions of time and temperature according to the
substituents in the compounds (Table 1). Then, the mixture
was poured into H2O (20 mL) and ice (10 g) and extracted
with Et2O (4 × 25 mL) and dried over anhyd Na2SO4. The
residue was evaporated, taken in CH2Cl2 (15 mL) and
purified by TLC (eluent: CH2Cl2–light petroleum, 7:3). Two
spots were collected in each case: the major one, having
higher Rf value, consisted of 2,3-diarylxanthones 7a–i and
the minor one, with lower Rf value, consisted of 2,3-diaryl-
3,4-dihydroxanthones 8a–i. The 2,3-diarylxanthones 7a–i
were recrystallized from EtOH in yields presented in
Table 1.
(22) (a) Punna, S.; Meunier, U. H.; Finn, M. G. Org. Lett. 2004,
6, 2777. (b) Nordvik, T.; Brinker, U. H. J. Org. Chem. 2003,
68, 9394.
(23) Typical Experimental Procedure: A solution of the
appropriate 2,3-diarylxanthones 7b–i in freshly distilled
CH2Cl2 (3 mL) was cooled to – 78 °C under nitrogen. A
solution of BBr3 in 0.1 M CH2Cl2 (2.5 equiv for each methyl
group to be cleaved) was gradually added. The reaction
mixture was stirred at r.t. for a period of time according to
the substituents in the compounds (1 h for each group to be
cleaved). After that period, the solution was poured into H2O
(20 mL) and vigorously stirred until the formation of a
yellow precipitate. The solid was washed abundantly with
H2O (4 × 50 mL) and then with light petroleum (4 × 20 mL)
to afford the hydroxylated 2,3-diarylxanthones 9b–i in good
yields (9b: 72%; 9c: 80%; 9d: 82%; 9e: 94%; 9f: 80%; 9g:
80%; 9h: 94%; 9i: 70%).
(24) Physical Data of 2-(4-Hydroxyphenyl)-3-(3,4-dihy-
droxyphenyl)xanthone (9h): mp 277–279 °C. 1H NMR
(300.13 MHz, DMSO-d6): d = 6.50 (dd, J = 2.0, 8.1 Hz, 1 H,
H-6¢¢), 6.62 (d, J = 2.0 Hz, 1 H, H-2¢¢), 6.67 (d, J = 8.1 Hz, 1
H, H-5¢¢), 6.70 (d, J = 8.4 Hz, 2 H, H-3¢, H-5¢), 6.99 (d, J =
8.4 Hz, 2 H, H-2¢, H-6¢), 7.50 (dd, J = 7.6, 7.7 Hz, 1 H, H-7),
7.52 (s, 1 H, H-4), 7.68 (d, J = 8.1 Hz, 1 H, H-5), 7.89 (ddd,
J = 1.5, 7.6, 8.1 Hz, 1 H, H-6), 8.01 (s, 1 H, H-1), 8.22 (dd,
J = 1.5, 7.7 Hz, 1 H, H-8), 8.97 (s, 1 H, 4¢¢-OH), 9.15 (s, 1 H,
3¢¢-OH), 9.51 (s, 1 H, 4¢-OH). 13C NMR (75.47 MHz,
DMSO-d6): d = 115.1 (C-3¢, C-5¢), 115.5 (C-5¢¢), 116.9 (C-
2¢¢), 118.3 (C-5), 118.9 (C-4), 119.6 (C-9a), 120.8 (C-6¢¢),
121.3 (C-8a), 124.4 (C-7), 126.1 (C-8), 127.0 (C-1), 130.5
(C-1¢, C-2¢, C-6¢), 130.7 (C-1¢¢), 135.5 (C-6), 136.6 (C-2),
145.0 (C-3¢¢), 145.3 (C-4¢¢), 147.7 (C-3), 154.4 (C-4a), 155.8
(C-4b), 156.4 (C-4¢), 175.7 (C-9). MS (EI): m/z (%) = 396
(100) [M+·], 395 (6), 380 (7), 379 (11), 349 (8), 98 (10), 97
(10), 83 (10). HRMS (EI): m/z calcd for C25H16O5:
396.0998; found: 396.0996.
(20) Physical Data of 2-(4-Methoxyphenyl)-3-(3,4-dimeth-
oxyphenyl)xanthone (7h): mp 148–150 °C. 1H NMR
(300.13 MHz, CDCl3): d = 3.60 (s, 3 H, 4¢¢-OMe), 3.80 (s, 3
H, 4¢-OMe), 3.90 (s, 3 H, 3¢¢-OMe), 6.61 (d, J = 2.0 Hz, 1 H,
H-2¢¢), 6.81 (d, J = 8.8 Hz, 2 H, H-3¢, H-5¢), 6.83 (d, J = 8.0
Hz, 1 H, H-5¢¢), 6.90 (dd, J = 2.0, 8.0 Hz, 1 H, H-6¢¢), 7.11
(d, J = 8.8 Hz, 2 H, H-2¢, H-6¢), 7.40 (ddd, J = 0.9, 7.7, 7.8
Hz, 1 H, H-7), 7.52 (dd, J = 0.9, 8.1 Hz, 1 H, H-5), 7.56 (s,
1 H, H-4), 7.75 (ddd, J = 1.7, 7.7, 8.1 Hz, 1 H, H-6), 8.33 (s,
1 H, H-1), 8.37 (dd, J = 1.7, 7.8 Hz, 1 H, H-8). 13C NMR
(75.47 MHz, CDCl3): d = 55.2 (4¢-OMe), 55.6 (4¢¢-OMe),
55.8 (3¢¢-OMe), 110.7 (C-5¢¢), 113.2 (C-2¢¢), 113.6 (C-3¢, C-
5¢), 118.0 (C-5), 119.0 (C-4), 120.4 (C-9a), 121.9 (C-8a, C-
6¢), 123.9 (C-7), 126.7 (C-8), 128.1 (C-1), 130.9 (C-2¢, C-6¢),
132.4, 132.5 (C-1¢, C-1¢¢), 134.7 (C-6), 136.6 (C-2), 147.3
(C-3), 148.2, 148.5 (C-3¢¢, C-4¢¢), 155.1 (C-4a), 156.3 (C-
4b), 158.6 (C-4¢), 177.0 (C-9). MS (EI): m/z (%) = 438 (100)
[M+·], 423 (11), 407 (14), 380 (8), 363 (8), 309 (8), 308 (31),
307 (25), 293 (14), 292 (12), 291 (12), 277 (10), 250 (7), 222
(6), 188 (24), 151 (8), 102 (9), 86 (8), 84 (11). Anal. Calcd
for C28H22O5: C, 76.70, H, 5.06. Found: C, 76.41; H, 5.42.
(21) Physical Data of 2-(4-Methoxyphenyl)-3-(3,4-dimeth-
oxyphenyl)-3,4-dihydroxanthone (8h): yellow oil. 1H
NMR (300.13 MHz, CDCl3): d = 2.98 (dd, J = 1.3, 17.2 Hz,
1 H, H-4trans), 3.62 (dd, J = 8.8, 17.2 Hz, 1 H, H-4cis), 3.76 (s,
3 H, 3¢¢-OMe), 3.79 (s, 6 H, 4¢-OMe, 4¢¢-OMe), 4.22 (dd, J =
Synlett 2007, No. 20, 3113–3116 © Thieme Stuttgart · New York

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