Synthesis and reactivity of 5,8-dihydroxythioflavanone derivatives

Article abstract of DOI:10.1021/jo980586w

The synthesis of substituted chalcones, thioflavanones, and thioflavones hydroxylated in both A and B rings is described. Acetoquinone (1) was transformed into 2,5-dihydroxy-6-(p-methoxybenzylmercapto)acetophenone (2) and subsequently into its 2,5-dimethoxy (3) and 2,5-dibenzyloxy (4) derivatives. Compounds 3 and 4 were condensed with suitable benzaldehydes to give chalcones 5-10. The thiol group of the chalcones was deprotected by a cleavage of the p-methoxybenzyl protecting group using a new, mild method (silver nitrate in boiling ethanol, 2 h), and the products were cyclized to thioflavanones (15-20). Dehydrogenation of the thioflavanones gave related thioflavones (25-27). Deprotection of methoxy and benzyloxy groups is also described.

Full text of DOI:10.1021/jo980586w

J . Org. Chem. 1999, 64, 359-364
359
Syn th esis a n d Rea ctivity of 5,8-Dih yd r oxyth iofla va n on e
Der iva tives
Marek T. Konieczny,*,† Barbara Horowska,† Antoni Kunikowski,† J erzy Konopa,†
Konstanty Wierzba,‡ Yuji Yamada,‡ and Tetsuji Asao‡
Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdansk, 80-952
Gdansk, Poland, and Taiho Pharmaceutical Company, Hanno Research Center, Yaoroshi, Hanno-city,
Saitama 357, J apan
Received March 31, 1998
The synthesis of substituted chalcones, thioflavanones, and thioflavones hydroxylated in both A
and B rings is described. Acetoquinone (1) was transformed into 2,5-dihydroxy-6-(p-methoxyben-
zylmercapto)acetophenone (2) and subsequently into its 2,5-dimethoxy (3) and 2,5-dibenzyloxy (4)
derivatives. Compounds 3 and 4 were condensed with suitable benzaldehydes to give chalcones
5-10. The thiol group of the chalcones was deprotected by a cleavage of the p-methoxybenzyl
protecting group using a new, mild method (silver nitrate in boiling ethanol, 2 h), and the products
were cyclized to thioflavanones (15-20). Dehydrogenation of the thioflavanones gave related
thioflavones (25-27). Deprotection of methoxy and benzyloxy groups is also described.
Ta ble 1. Ch a lcon es F or m ed in th e Rea ction of
Acetop h en on e Der iva tives 3 a n d 4 w ith Su bstitu ted
Ben za ld eh yd es
Constant interest in the synthesis of polyhydroxylated
flavonoids stems from their diverse biological activity,
including antimicrobial, mutagenic, cytotoxic, and anti-
oxidant properties.1-3 Thioflavonoids4 constitute a still
unexplored source of interesting analogues of biologically
active flavonoids. It seems that the compounds do not
attract much attention because of the inaccessibility of
suitable starting materials, as substituted derivatives of
thiophenol are scarce. Compounds which ultimately
would result in the synthesis of flavonoids hydroxylated
similarly as in natural flavonoids, in both A and B rings,
are of special interest.
compd
OR1
OR2
OR3
OR4
yield, %
5
6
7
8
9
2′-OBn
2′-OBn
2′-OBn
2′-OBn
2′-OMe
2′-OMe
5′-OBn
5′-OBn
5′-OBn
5′-OBn
5′-OMe
5′-OMe
3-OBn
2-OBn
2-OBn
3-OMe
3-OBn
3-OMe
4-OBn
4-OBn
3-OBn
4-OMe
4-OBn
4-OMe
90
51
86
73
45
66
10
Ta ble 2. P r ep a r ed Th iofla va n on e Der iva tives
While looking for a method of synthesis of thiofla-
vanones hydroxylated in both rings, attention was paid
to the procedure published by Taylor and Dean,5 who
prepared thioflavanones by acid-catalyzed deprotection-
cyclization of suitable 2′-methoxybenzylmercaptochal-
cones. On the basis of this concept, a synthesis starting
from acetoquinone (1) was proposed, and even though the
direct application of Taylor’s method failed, its major
modification resulted in a new procedure which led to
the preparation of the desired compounds. Reaction of
acetoquinone6 (1) with 4-methoxy-R-toluenethiol led to
the key intermediate 2 (Scheme 1). The liquid product
was identified by NMR only and transformed directly into
its methyl (3) or benzyl (4) derivatives. Protected deriva-
tives 3 and 4 were condensed under phase transfer
conditions with suitable benzaldehydes to give chalcones
5-10 (Scheme 2, Table 1). Attempted cyclization of the
compd
OR1
OR2
OR3
OR4
yield, %
50
61
41
15
16
17
18
19
20
21
22
23
24
5-OMe
5-OBn
5-OBn
5-OBn
5-OBn
5-OMe
5-OH
5-OH
5-OH
5-OH
8-OMe
8-OBn
8-OBn
8-OBn
8-OBn
8-OMe
8-OH
8-OH
8-OH
8-OMe
3′-OMe
3′-OBn
2′-OBn
2′-OBn
3′-OMe
3′-OBn
3′-OH
2′-OH
2′-OH
3′-OH
4′-OMe
4′-OBn
4′-OBn
3′-OBn
4′-OMe
4′-OBn
4′-OH
4′-OH
3′-OH
4′-OH
26
30
33
30a, 0b, 59c
28d
23d
11d
Deprotection method: aAlCl3-dimethylaniline from 16; b AlCl3-
dimethylaniline from 20; c boron trifluoride-dimethyl sulfide from
d
20; AlCl3-dimethylaniline from 17, 18, and 20, respectively.
† Technical University of Gdansk.
Sch em e 1
‡ Taiho Pharmaceutical Co.
(1) Flavonoids: Advances in Research, Harborne, J . B., Ed.; Chap-
man & Hall: London, 1993.
(2) Pathak, D.; Pathak, K.; Singla, A. K. Fitoterapia 1991, 62, 371-
389.
(3) Cushman, M.; Nagarathnam, D. J . Nat. Prod. 1991, 54, 1656-
1660 and references therein.
(4) Balint, J .; Bognar, R.; Rakosi, M. In Organic Sulfur Chemistry;
Bernardi, F., Csizmadia, I. G., Mangini, A., Eds.; Elsevier: Amsterdam,
1985; pp 660-706.
(5) Taylor, A. W.; Dean, D. K. Tetrahedron Lett. 1988, 29, 1845-
1848.
(6) Kloetzel, M. C.; Dayton, R. P.; Abadir, B. Y. J . Org. Chem. 1955,
20, 38-48.
chalcones to corresponding thioflavanones using both
formic and trifluoroacetic acid5 failed. Complicated mix-
tures of products were obtained, and even though NMR
10.1021/jo980586w CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/06/1999

360 J . Org. Chem., Vol. 64, No. 2, 1999
Konieczny et al.
Sch em e 2
Sch em e 4
Sch em e 3
Ta ble 3. P r ep a r ed Th iofla von e Der iva tives
compd
OR1
OR2
OR3
OR4
yield, %
25
26
27
12
28
29
30
5-OBn
5-OBn
5-OBn
5-OMe
5-OH
8-OBn
8-OBn
8-OBn
8-OMe
8-OH
3′-OBn
2′-OBn
2′-OBn
3′-OMe
3′-OH
4′-OBn
4′-OBn
3′-OBn
4′-OMe
4′-OH
55
62
64
18
30
16
19
5-OH
5-OH
8-OH
8-OH
2′-OH
2′-OH
4′-OH
3′-OH
give compound 14. NMR spectrum of the compound was
identical to that of 11, but IR fingerprint regions of both
compounds were different. Elemental analysis was done
only for the analogous benzyl derivative from chalcone 5
and suggested that one silver cation is still present in
the molecule. Cyclization of compound 14 to 15 was
attempted using trifluoroacetic and formic acids, but the
best results were achieved with p-toluenesulfonic acid in
methylene chloride solution. The complex 11 treated with
p-toluenesulfonic acid also gave thioflavanone 15, but the
reaction was not as clean as that starting from 14.
Chalcones 5-9 were transformed into related thiofla-
vanones using the same procedure (Table 2, compounds
16-20).
The obtained thioflavanones were deprotected using
several methods. Catalytic hydrogenation of compound
16 over palladium on charcoal did not take place, most
probably due to catalyst poisoning by the sulfur atom.
Reaction of 16 with boron trifluoride-methyl sulfide
complex gave a mixture of products which could not be
separated. Synthesis of tetrahydroxyflavanone 21 was
finally achieved using an aluminum chloride-dimethyl-
aniline mixture. For dimethoxy dibenzyl derivative 20,
reaction with aluminum chloride complex gave a multi-
component mixture from which monomethoxy derivative
24 was isolated with a low yield, and deprotection with
boron trifluoride-methyl sulfide complex cleanly gave
tetrahydroxy derivative 21. The obtained hydroxy deriva-
tives of thioflavanones are listed in Table 2.
spectra proved that the mixtures contained the desired
cyclic system, the compounds could not be isolated in pure
form. It seems that observed side products were formed
by deprotection of the hydroxy group in position 2′ of
chalcones 5-10 and eventual cyclization through the
hydroxyl to flavanones. Under these circumstances, the
literature5 procedure was abandoned, and a method
depending on separation of the deprotection and cycliza-
tion steps was examined.
Typical procedures7 for cleavage of p-methoxybenzyl
thioethers use trifluoroacetic acid or a mixture of tri-
fluoroacetic acid with mercury acetate and were not
suitable for our purpose. It is known,8 however, that some
aryl alkyl thioethers can be cleaved by electrophilic metal
ions such as Hg2+ or Ag+. Mercury salts are likely to
metalate phenols9 even at room temperature, and for this
reason, silver salts were chosen as the most promising
to cleave S-p-methoxybenzyl thioethers 5-10. Several
attempts failed, but a three-step procedure presented in
Scheme 3 gave satisfactory results. Reflux of chalcone
10 with an alcoholic solution of silver nitrate gave yellow
precipitate 11. NMR spectrum of the product demon-
strated that the p-methoxybenzyl protecting group had
been cleaved, and elemental analysis suggested strongly
that the product contained two silver ions and a nitrate
anion. Structure of the complex 11 was not studied
further. Ethanolic filtrate and solutions from washing of
11 with ethanol were separated by chromatography to
give thioflavone 12 and ethyl p-methoxybenzyl ether (13).
Formation of the ether 13 proved that the p-methoxy-
benzyl cation formed by cleavage of thioether is quenched
by solvent. It was supposed that silver cations could be
removed from 11 by reaction with bromine anion.
A suspension of 11 in an ethyl acetate-water mixture
was stirred with cetyltrimethylammonium bromide to
The above mentioned formation of side product 12
suggested that thioflavanones could be relatively easily
dehydrogenated to thioflavones. The transformation was
achieved, with preparatively satisfactory yields, using
2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as de-
hydrogenating agent,10 (Scheme 4). The obtained com-
pounds (25-27) are listed, along with the products of
their deprotection (28-30), in Table 3.
Thioflavonoids can be oxidized to related 1,1-dioxides,4
and indeed both thioflavanone 16 and thioflavone 25
reacted smoothly with m-chloroperbenzoic acid to give
dioxides 31 and 32. Deprotection of the compounds by
(7) Greene, T.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; Wiley: New York, 1991; p 281.
(8) Satchell, D. P. N. Chem. Soc. Rev. 1977, 345-371.
(9) Wardell, J . L. In Comprehensive Organometallic Chemistry;
Wilkinson, G., Stone, F. G. A., Eds.; Pergamon Press: Oxford, 1982;
Vol. 2, p 874.
(10) Shanker, Ch. G.; Mallaiah, B. V.; Srimannarayana, G. Synthesis
1983, 310 - 311.

5,8-Dihydroxythioflavanone Derivatives
J . Org. Chem., Vol. 64, No. 2, 1999 361
2,5-Dih ydr oxy-6-(p-m eth oxyben zylm er capto)acetoph e-
n on e (2). Acetoquinone6 (1) (300 mg, 2 mmol) was added to a
solution of p-methoxy-R-toluenethiol (0.7 mL, 4.2 mmol) in
ethanol (4 mL). The solution was stirred at room temperature
for 30 min and evaporated, and the residue was separated on
a silica gel column in chloroform to give the product 2 as a
yellow oil (550 mg, 90%): NMR (200 MHz, CDCl3) δ 10.9 (bs),
7.12 (d, 1 H, J ) 9.1 Hz), 6.97 (d, 1 H, J ) 9.1 Hz), 6.87 (d, 2
H, J ) 8.8 Hz), 6.75 (d, 2 H, J ) 8.8 Hz), 3.78 (s, 3 H), 3.75 (s,
2 H), 2.71 (s, 3 H).
Sch em e 5
2,5-Dim eth oxy-6-(p-m eth oxyben zylm er capto)acetoph e-
n on e (3). A mixture of 2,5-dihydroxy-6-(p-methoxybenzyl-
mercapto)acetophenone (2) (550 mg, 1.8 mmol), dimethyl
sulfate (0.45 mL, 4.8 mmol), and anhydrous potassium carbon-
ate (830 mg, 6 mmol) in acetone (10 mL) was refluxed with
stirring for 30 min. The solvent was evaporated, and the
residue was treated with water (20 mL) and extracted with
chloroform (90 mL). The extract was washed with water (3 ×
20 mL), 1 N HCl (1 × 20 mL), saturated sodium bicarbonate
(1 × 20 mL), water (2 × 20 mL), and brine (1 × 20 mL) and
dried (MgSO4). The solution was evaporated and purified on
a short silica gel column in chloroform to give 3 as an oil (540
mg, 90%): NMR (200 MHz, CDCl3) δ 6.7-7.1 (m, 6 H), 3.96 (s,
3 H), 3.85 (s, 3 H), 3.75 (s, 3 H), 3.74 (s, 2 H), 2.17 (s, 3 H).
2,5-Diben zyloxy-6-(p-m eth oxyben zylm er ca p to)a ceto-
p h en on e (4). A mixture of 2,5-dihydroxy-6-(p-methoxyben-
zylmercapto)acetophenone (2) (550 mg, 1.8 mmol), benzyl
bromide (0.52 mL, 4.3 mmol), and anhydrous potassium
carbonate (650 mg, 4.7 mmol) in acetone (15 mL) was refluxed
with stirring for 1.5 h. The solvent was evaporated, and the
residue was treated with water (20 mL) and extracted with
chloroform (90 mL). The extract was washed with water (3 ×
20 mL), 1 N HCl (1 × 20 mL), saturated sodium bicarbonate
(1 × 20 mL), water (2 × 20 mL), and brine (1 × 20 mL) and
dried (MgSO4). The solution was evaporated, and the residue
was washed with methanol and recrystallized from the same
solvent to give 576 mg (66%) of white crystals, mp 115-117
°C. Anal. Calcd for C30H28O4S: C, 74.35; H, 5.82; S, 6.62.
Found: C, 74.15; H, 5.73; S, 6.55. NMR (200 MHz, CDCl3) δ
7.2-7.5 (m, 10 H), 6.94 (d, 2 H, J ) 8.8 Hz), 6.78 (s, 2 H), 6.65
(d, 2 H, J ) 8.8 Hz), 5.04 (s, 2 H), 4.98 (s, 2 H), 3.94 (s, 2 H),
3.68 (s, 3 H), 2.14 (s, 3 H).
Sch em e 6
Gen er a l P r oced u r e for Con d en sa tion of Ben za ld e-
h yd es w ith 6-(p-Meth oxyben zylm er ca p to)a cetop h en on e
Der iva tives (3 or 4) u n d er P h a se Tr a n sfer Con d ition s.
A mixture of suitable 6-(p-methoxybenzylmercapto)acetophe-
none (0.9 mmol), substituted benzaldehyde (1.35 mmol), and
tetrabutylammonium chloride (64 mg, 0.2 mmol) in methylene
chloride (4 mL) and 50% potassium hydroxide (4 mL) was
stirred at room temperature for 50-70 h. The solution was
diluted with methylene chloride (80 mL); washed with water
(3 × 50 mL), 1 N HCl (1 × 20 mL), water (1 × 20 mL),
saturated sodium bicarbonate (1 × 20 mL), water (2 × 20 mL),
and brine (1 × 20 mL); dried (MgSO4); and evaporated. The
residue was purified either on a silica gel column or by
crystallization.
2′,3,4,5′-Tet r a ben zyloxy-6′-(p -m et h oxyb en zylm er ca p -
to)ch a lcon e (5). The residue after evaporation of solvent
solidified upon the addition of methanol. It was filtered and
recrystallized from chloroform-methanol, yield 90%, mp 159-
161 °C. Anal. Calcd for C51H44O6S: C, 78.03; H, 5.65; S, 4.08.
Found: C, 77.89; H, 5.56; S, 3.87. NMR (200 MHz, CDCl3) δ
6.78-7.54 (m, 28 H), 6.66 (d, 1 H, J ) 15.5 Hz), 6.54 (d, 2 H,
J ) 8.6 Hz), 5.17 (s, 2 H), 5.13 (s, 2 H), 5.07 (s, 2 H), 4.97 (s,
2 H), 3.94 (s, 2 H), 3.57 (s, 3 H).
catalytic hydrogenation and by aluminum chloride-
dimethylaniline gave hydroxy derivatives 33 and 34,
respectively. (Scheme 5). Another interesting transfor-
mation occurred during an attempted reaction of thiofla-
vanone 16 with benzaldehyde under strongly alkaline
conditions; instead of the expected ring-functionalized
compound 35, methylene chloride substituted chalcone
36 was formed (Scheme 6). Compound 36 seemed to be
stable under the reaction conditions, and neither products
of hydrolysis of the R-halogenoalkyl sulfide function nor
products formed via a carbene intermediate were ob-
served.11
The described transformations and the easily modified
starting material (quinone) make the synthesis of many
new analogues of thioflavonoids possible. The reported
methods allow the synthesis of compounds hydroxylated
in both A and B rings, which seems to be important for
biological activity of flavonoids.
2,2′,4,5′-Tet r a ben zyloxy-6′-(p-m et h oxyb en zylm er ca p -
to)ch a lcon e (6). The residue after evaporation of solvent was
separated on a silica gel column in chloroform-ethyl acetate
50:1 solution and recrystallized from ethanol, yield 51%, mp
119-120 °C. Anal. Calcd for C51H44O6S: C, 78.03; H, 5.65; S,
4.08. Found: C, 77.69; H, 5.67; S, 3.95. NMR (200 MHz, CDCl3)
δ 6.45-7.55 (m, 31 H), 5.08 (s, 2 H), 5.07 (s, 2 H), 4.97 (s, 2
H), 4.89 (s, 2 H), 3.93 (s, 2 H), 3.57 (s, 3H).
Exp er im en ta l Section
Gen er a l. All materials were used as obtained from com-
mercial sources. TLC was performed using silica gel 60 F254
plates with visualization by UV. Melting points were deter-
mined in an open capillary apparatus and are uncorrected.
2,2′,3,5′-Tet r a ben zyloxy-6′-(p-m et h oxyb en zylm er ca p -
to)ch a lcon e (7). The residue after evaporation of solvent was
(11) Boche, G.; Schneider, D. R. Tetrahedron Lett. 1975, 4247-4248.

362 J . Org. Chem., Vol. 64, No. 2, 1999
Konieczny et al.
separated on a silica gel column in chloroform to give an oil,
yield 86%. Anal. Calcd for C51H44O6S: C, 78.04; H, 5.65; S,
4.08. Found: C, 78.15; H, 5.71; S, 3.87. NMR (200 MHz, CDCl3)
δ 6.75-7.6 (m, 30 H), 6.57 (d, 1 H, J ) 8.7 Hz), 5.12 (s, 2 H),
5.07 (s, 2 H), 4.87 (s, 2 H), 4.81 (s, 2 H), 3.94 (s, 2 H), 3.62 (s,
3 H).
2′,5′-Diben zyloxy-3,4-d im eth oxy-6′-(p-m eth oxyben zyl-
m er ca p to)ch a lcon e (8). The residue after evaporation of
solvent solidified upon the addition of methanol. It was filtered
and recrystallized from methanol, yield 73%, mp 117-118 °C.
Anal. Calcd for C39H36O6S: C, 74.03; H, 5.74; S, 5.07. Found:
C, 74.28; H, 5.70; S, 5.00. NMR (200 MHz, CDCl3) δ 6.55-
7.55 (m, 21 H), 5.10 (s, 2 H), 5.01 (s, 2 H), 3.99 (s, 2 H), 3.91
(s, 3 H), 3.90 (s, 3 H), 3.64 (s, 3 H).
Complex 14 (110 mg, 0.22 mmol) was added to a solution of
p-toluenesulfonic acid (80 mg, 0.46 mmol) in methylene
chloride (5 mL); the mixture was stirred at room temperature
for 30 min. The formed suspension was diluted with methylene
chloride to 50 mL; washed with water (5 × 20 mL), NaHCO3
(2 × 20 mL), and water (2 × 20 mL); dried (MgSO4); and
evaporated. The residue was separated on a silica gel column
in chloroform to give 3′,4′,5,8-tetr a m eth oxyth iofla va n on e
(15) (40 mg, 50%). The compound was recrystallized from
toluene-methanol, mp 134-135 °C. Anal. Calcd for
C
19H20O5S: C, 63.31; H, 5.59. Found: C, 63.41; H, 5.50. NMR
(500 MHz, CDCl3) δ 7.00 (dd, 1 H, J 1 ) 8.3 Hz, J 2 ) 2.4 Hz),
6.97 (d, 1 H, J ) 8.7 Hz), 6.97 (d, 1 H, J ) 2.4 Hz), 6.87 (d, 1
H, J ) 8.3 Hz), 6.73 (d, 1 H, J ) 8.7 Hz), 4.60 (dd, 1 H, J 1
)
3,4-d iben zyloxy-2′,5′-d im eth oxy-6′-(p-m eth oxyben zyl-
m er ca p to)ch a lcon e (9). The residue after evaporation of
solvent was purified on a silica gel column in chloroform and
recrystallized from ethanol, yield 45%, mp 92-94 °C. Anal.
Calcd for C39H36O6S: C, 74.03; H, 5.74; S, 5.07. Found: C,
73.95; H, 5.75; S, 4.95. NMR (200 MHz, CDCl3) δ 6.55-7.55
(m, 21 H), 5.19 (s, 2 H), 5.16 (s, 2 H), 3.95 (s, 2 H), 3.86 (s, 3
H), 3.70 (s, 3 H), 3.62 (s, 3 H).
13.7 Hz, J 2 ) 3.0 Hz), 3.92 (s, 3 H), 3.911 (s, 3 H), 3.908 (s, 3
H), 3.89 (s, 3 H), 3.35 (dd, 1 H, J 1 ) 13.7 Hz, J 2 ) 15.1 Hz),
3.14 (dd, 1 H, J 1 ) 15.1 Hz, J 2 ) 3.0 Hz).
Gen er a l P r oced u r e for Syn th esis of Th iofla va n on e
Der iva tives (16-20). The method essentially follows the
three-step procedure described above for methoxy derivative
15: (step 1) 2 h of reflux with silver nitrate in ethanol; (step
2) 30 min of stirring at room temperature with cetyltrimethyl-
ammonium bromide in an ethyl acetate-water solution; and
(step 3) 30 min of stirring at room temperature with p-
toluenesulfonic acid in methylene chloride. The yields are given
in Table 2 and were calculated for the whole process, starting
from chalcones.
2′,3,4,5′-Tetr a m eth oxy-6′-(p-m eth oxyben zylm er ca p to)-
ch a lcon e (10). The residue after evaporation of solvent was
purified on a silica gel column in chloroform. The obtained oil
solidified under the influence of methanol. The product was
recrystallized from chloroform-methanol, yield 66%, mp 158-
160 °C. Anal. Calcd for C27H28O6S‚0.5 H2O: C, 66.24; H, 5.97.
Found: C, 66.18; H, 5.75. NMR (200 MHz, CDCl3) δ 6.55-
7.05 (m, 10 H), 6.67 (d, 1 H, J ) 16.1 Hz), 3.91 (s, 2 H), 3.85
(s, 3 H), 3.84 (s, 3 H), 3.80 (s, 3 H), 3.66 (s, 3 H), 3.61 (s, 3 H).
Step w ise Syn th esis of 3′,4′,5,8-Tetr a m eth oxyth iofla -
va n on e (15) by Dep r otection u sin g Silver Nitr a te a n d
Cycliza tion by p-Tolu en esu lfon ic Acid . A suspension of
2′,3,4,5′-tetramethoxy-6′-(p-methoxybenzylmercapto)chal-
cone (10) (960 mg, 2 mmol) and silver nitrate (1360 mg, 4
mmol) in 90% ethanol (50 mL) was refluxed for 2 h. The
solution was cooled and filtered, and the precipitate was
washed with ethanol (4 × 10 mL) and water (4 × 10 mL) to
give a yellow solid of silver complex 11 (660 mg, 52%), mp >205
°C. Anal. Calcd for C19H19O8SNAg2: C, 35.81; H, 3.00; S, 5.03;
N, 2.20. Found: C, 36.22; H, 2.96; S, 4.94; N, 2.20. NMR (200
MHz, DMSO-d6) δ 7.21 (bs, 1 H), 7.10 (d, 1 H, J ) 16.0 Hz),
7.00 (bd, 1 H, J ) 8.4 Hz), 6.88 (d, 1 H, J ) 16.0 Hz), 6.80 (m,
3 H), 3.73 (s, 3 H), 3.70 (s, 3 H), 3.61 (s, 3 H), 3.52 (s, 3 H); IR
(Nujol, cm-1) 1700, 1620, 1595, 1515, 1320, 1290, 1180, 1160,
1130, 1065, 1040, 840, 820.
Collected filtrates were diluted with water and extracted
with chloroform (200 mL). The organic layer was washed with
water (3 × 100 mL) and brine (3 × 50 mL), dried (MgSO4),
and evaporated. The residue was separated on a silica gel
column in chloroform to give eth yl p-m eth oxyben zyl eth er
(13) (250 mg, 75%): NMR (200 MHz, CDCl3) δ 7.27 (d, 2 H,
J ) 8.7 Hz), 6.88 (d, 2 H, J ) 8.7 Hz), 4.44 (s, 2 H), 3.80 (s, 3
H), 3.50 (q, 2 H, J ) 7 Hz), 1.23 (t, 3 H, J ) 7 Hz). A second
fraction contained 3′,4′,5,8-tetr a m eth oxyth iofla von e (12)
(130 mg, 18%). The compound was recrystallized from ethanol,
mp 204-205 °C. Anal. Calcd for C19H18O5S: C, 63.67; H, 5.06;
S, 8.95. Found: C, 63.56; H, 5.12; S, 8.78. NMR (500 MHz,
CDCl3) δ 7.88 (s, 1 H), 7.40 (dd, 1 H, J 1 ) 8.3 Hz, J 2 ) 2.4
Hz), 7.29 (H-2′, under CHCl3), 7.04 (d, 1 H, J ) 8.8 Hz), 6.99
(d, 1 H, J ) 8.3 Hz), 6.72 (d, 1 H, J ) 8.8 Hz), 4.02 (s, 3 H),
3.99 (s, 3 H), 3.98 (s, 3 H), 3.97 (s, 3 H).
3′,4′,5,8-Tetr a ben zyloxyth iofla va n on e (16). Purification
method, recrystallization from toluene, mp 168-169 °C. Anal.
Calcd for C43H36O5S: C, 77.68; H, 5.46; S, 4.82. Found: C,
78.16; H, 5.70; S, 4.31. NMR (500 MHz, CDCl3) δ 7.15-7.6
(m, 20 H), 7.06 (d, 1 H, J ) 2 Hz), 6.97 (dd, 1 H, J 1 ) 8.3 Hz,
J 2 ) 2 Hz), 6.96 (d, 1 H, J ) 8.8 Hz), 6.94 (d, 1 H, J ) 8.3 Hz),
6.72 (d, 1 H, J ) 8.8 Hz), 5.19 (s, 4 H), 5.16 (d, 2 H, J ) 11.7
Hz,), 5.11 (s, 2 H), 4.55 (dd, 1 H, J 1 ) 13.7 Hz, J 2 ) 2.7 Hz),
3.27 (dd, 1 H, J 1 ) 15.1 Hz, J 2 ) 13.7 Hz), 3.08 (dd, 1 H, J 1
15.1 Hz, J 2 ) 2.7 Hz).
)
2′,4′,5,8-Tetr a ben zyloxyth iofla va n on e (17). Purification
method, recrystallization toluene-methanol, mp 186-188 °C.
Anal. Calcd for C43H36O5S: C, 77.68; H, 5.46. Found: C, 77.10;
H, 5.10. NMR (200 MHz, CDCl3) δ 7.22-7.60 (m, 21 H), 6.92
(d, 1 H, J ) 9.0 Hz), 6.67 (d, 1 H, J ) 9.0 Hz), 6.57 (m, 2 H),
5.14 (dd, partly under next peak, 1 H, J 1 ) 3.4 Hz), 5.13 (s, 2
H), 5.09 (s, 2 H), 5.07 (s, 2 H), 5.02 (s, 2 H), 3.32 (dd, 1 H, J 1
) 12.4 Hz, J 2 ) 15.1 Hz), 3.07 (dd, 1 H, J 1 ) 15.1 Hz, J 2 ) 3.4
Hz).
2′,3′,5,8-Tetr a ben zyloxyth iofla va n on e (18). Purification
method, silica gel column in chloroform, followed by recrys-
tallization from benzene-methanol, mp 106-107 °C. Anal.
Calcd for C43H36O5S: C, 77.68; H, 5.46; S, 4.82. Found: C,
77.78; H, 5.43; S, 4.59. NMR (200 MHz, CDCl3) δ 6.96-7.6
(m, 23 H), 6.92 (d, 1 H, J ) 9 Hz), 6.69 (d, 1 H, J ) 9 Hz), 5.15
(s, 2 H), 5.13 (s, 2 H), 5.10 (m, 3 H), 5.06 (s, 2 H), 3.25 (dd, 1
H, J 1 ) 15.4 Hz, J 2 ) 13.3 Hz), 2.87 (dd, 1 H, J 1 ) 15.4 Hz, J 2
) 3.1 Hz).
5,8-Diben zyloxy-3′,4′-d im eth oxyth iofla va n on e (19). Pu-
rification method, silica gel column in chloroform, followed by
recrystallization toluene-methanol, mp 149-151 °C. Anal.
Calcd for C31H28O5S: C, 72.63; H, 5.51; S, 6.26. Found: C,
72.30; H, 5.47; S, 6.13. NMR (200 MHz, CDCl3) δ 6.9-7.6 (m,
13 H), 6.83 (d, 1 H, J ) 8.1 Hz), 6.67 (d, 1 H, J ) 9 Hz), 5.05
(two d, 2 H), 5.03 (s, 2 H), 4.56 (dd, 1 H, J 1 ) 13.4 Hz, J 2 ) 3.0
Hz), 3.87 (s, 3 H), 3.86 (s, 3 H), 3.31 (dd, 1 H, J 1 ) 15.0 Hz, J 2
) 13.4 Hz), 3.08 (dd, 1 H, J 1 ) 15.0 Hz, J 2 ) 3.0 Hz).
3′,4′-Diben zyloxy-5,8-d im eth oxyth iofla va n on e (20). Pu-
rification method, silica gel column in chloroform, followed by
recrystallization toluene-methanol, mp 118-120 °C. Anal.
Calcd for C31H28O5S: C, 72.63; H, 5.51; S, 6.26. Found: C,
72.86; H, 5.51; S, 6.18. NMR (200 MHz, CDCl3) δ 6.8-7.5 (m,
14 H), 6.69 (d, 1 H, J ) 9.1 Hz), 5.15 (s, 4 H), 4.51 (dd, 1 H, J 1
) 13.2 Hz, J 2 ) 3.3 Hz), 3.87 (s, 3 H), 3.85 (s, 3 H), 3.23 (dd,
1 H, J 1 ) 15.0 Hz, J 2 ) 13.2 Hz), 3.04 (dd, 1 H, J 1 ) 15.0 Hz,
J 2 ) 3.3 Hz).
A suspension of silver complex 11 (150 mg, 0.23 mmol) and
cetyltrimethylammonium bromide (470 mg) in ethyl acetate
(50 mL) and water (20 mL) was stirred at room temperature
for 30 min. The organic layer was separated, diluted with ethyl
acetate to 100 mL, washed with water (5 × 30 mL) and brine
(4 × 30 mL), dried (MgSO4), and evaporated. The obtained
yellow solid was washed with methanol to give complex 14
(50 mg, 43%): NMR (200 MHz, DMSO) δ 7.20 (bs, 1 H), 7.09
(d, 1 H, J ) 16.0 Hz), 6.96 (bd, 1 H, J ) 8.4 Hz), 6.86 (d, 1 H,
J ) 16.0 Hz), 6.78 (m, 3 H), 3.73 (s, 3 H), 3.70 (s, 3 H), 3.61 (s,
3 H), 3.50 (s, 3 H); IR (Nujol, cm-1) 1700, 1640, 1580, 1515,
1275, 1180, 1160, 1065, 1055, 830.
Dep r otection of Th iofla va n on es w ith Alu m in u m Ch lo-
r id e-Dim eth yla n ilin e Com p lex. A suitable derivative of

5,8-Dihydroxythioflavanone Derivatives
J . Org. Chem., Vol. 64, No. 2, 1999 363
thioflavanone (16-18,20) (1.5 mmol) and N,N-dimethylaniline
(1.1 mL, 9 mmol) were dissolved in dry methylene chloride
(40 mL) and cooled to 0 °C, and aluminum chloride (1.6 g, 12
mmol) was added. The mixture was stirred at room temper-
ature for 1-4 h under argon. The mixture was concentrated
by half, poured into ice-cooled 5% HCl (50 mL) and extracted
with ethyl acetate (100 mL). The organic layer was washed
with water (2 × 30 mL), dried, and evaporated. The residue
was purified on a silica gel column or recrystallized.
(d, 1 H, J ) 8.9 Hz), 7.03 (d, 1 H, J ) 8.3 Hz), 6.96 (d, 1 H, J
) 8.9 Hz), 5.26 (s, 2 H), 5.25 (s, 4 H), 5.23 (s, 2 H).
2′,4′,5,8-Tet r a ben zyloxyt h iofla von e (26). Purified by
silica gel column in chloroform, yield 62%, mp 158-160 °C.
Anal. Calcd for C43H34O5S: C, 77.92; H, 5.17; Found: C, 77.28;
H, 4.71. NMR (200 MHz, CDCl3) δ 7.2-7.8 (m, 22 H), 7.15 (d,
1 H, J ) 8.9 Hz), 6.93 (s, 1 H), 6.91 (d, 1 H, J ) 2.4 Hz), 6.78
(dd, 1 H, J 1 ) 8.6 Hz, J 2 ) 2.4 Hz), 5.31 (s, 2 H), 5.26 (s, 2 H),
5.20 (s, 4 H).
3′,4′,5,8-Tetr a h yd r oxyth iofla va n on e (21). Column eluted
with chloroform-methanol solution 20:1, followed by recrys-
tallization from acetone-chloroform, yield 30%, mp 214-222
°C. Anal. Calcd for C15H12O5S: C, 59.20; H, 3.98; S, 10.54.
Found: C, 58.75; H, 3.84; S, 10.19. NMR (200 MHz, acetone)
δ 12.3 (s, 1 H), 8.1 (bs, 3 H), 7.08 (d, 1 H, J ) 8.8 Hz), 7.01 (d,
1 H, J ) 1.8 Hz), 6.86 (m, 2 H), 6.55 (d, 1 H, J ) 8.8 Hz), 4.64
(dd, 1 H, J 1 ) 13.2 Hz, J 2 ) 2.8 Hz), 3.40 (dd, 1 H, J 1 ) 13.2
Hz, J 2 ) 16.5 Hz), 3.06 (dd, 1 H, J 1 ) 16.5 Hz, J 2 ) 2.8 Hz).
2′,4′,5,8-Tetr a h yd r oxyth iofla va n on e (22). Column eluted
with chloroform: methanol solution 100:1, followed by precipi-
tation from acetone with chloroform, yield 28%, mp 267 °C,
decomp. Anal. Calcd for C15H12O5S: C, 59.20; H, 3.98. Found:
C, 59.06; H, 4.27. NMR (200 MHz, acetone) δ 12.3 (s, 1 H),
8.73 (s, 1 H), 8.44 (s, 1 H), 8.39 (s, 1 H), 7.28 (d, 1 H, J ) 8.3
Hz), 7.07 (d, 1 H, J ) 8.8 Hz), 6.54 (d, 1 H, J ) 8.8 Hz), 6.47
(d, 1 H, J ) 2.4 Hz), 6.40 (dd, 1 H, J 1 ) 8.3 Hz, J 2 ) 2.4 H),
2′,3′,5,8-Tet r a ben zyloxyt h iofla von e (27). Purified by
silica gel column in chloroform, followed by recrystallization
from benzene-methanol, yield 64%, mp 130-131 °C. Anal.
Calcd for C43H34O5S: C, 77.92; H, 5.17; Found: C, 77.81; H,
4.98. NMR (200 MHz, CDCl3) δ 6.96-7.7 (m, 25 H), 6.92 (d, 1
H, J ) 8.9 Hz), 5.21 (s, 2 H), 5.17 (s, 2 H), 5.16 (s, 2 H), 5.03
(s, 2 H).
Dep r otection of Th iofla von es (25-27) w ith Alu m in u m
Ch lor id e-Dim eth yla n ilin e Com p lex. A suitable derivative
of thioflavone (1 mmol) and N,N-dimethylaniline (1.5 mL, 12
mmol) were dissolved in dry methylene chloride (60 mL) and
cooled to 0 °C, and aluminum chloride (2.4 g, 18 mol) was
added. The mixture was stirred at room temperature for 1-4
h under argon. The mixture was concentrated by half, poured
into ice- cooled 5% HCl (50 mL), and extracted with ethyl
acetate (100 mL). The organic layer was washed with water
(2 × 30 mL), dried, and evaporated. The residue was purified
on a silica gel column or recrystallized.
3′,4′,5,8-Tetr a h yd r oxyth iofla von e (28). The crude prod-
uct was purified by multiple recrystallization from acetone-
chloroform-hexane, yield 30%, mp 293 °C, decomp. Anal.
Calcd for C15H10O5S: C, 59.59; H, 3.33. Found: C, 59.47; H,
3.50. NMR (200 MHz, CD3COCD3) δ 13.53 (s, 1 H), 9.3 (bs, 1
H), 8.7 (bs, 1 H), 8.5 (bs, 1 H), 7.34 (d, 1 H, J ) 2.3 Hz), 7.27
(dd, 1 H, J 1 ) 8.3 Hz, J 2 ) 2.3 Hz), 7.22 (d, 1 H, J ) 8.8 Hz),
7.02 (d, 1 H, J ) 8.3 Hz), 7.02 (s, 1 H), 6.79 (d, 1 H, J ) 8.8
Hz).
5.00 (dd, 1 H, J 1 ) 13.1 Hz, J 2 ) 3.0 Hz), 3.48 (dd, 1 H, J 1
)
16.5 Hz, J 2 ) 13.1 Hz), 3.01 (dd, 1 H, J 1 ) 16.5 Hz, J 2 ) 3.0
Hz).
2′,3′,5,8-Tetr a h yd r oxyth iofla va n on e (23). Column eluted
with chloroform: methanol 20:1, followed by recrystallization
from methanol - benzene - cyclohexane mixture, yield 23%,
mp 232-233 °C. Anal. Calcd for C15H12O5S: C, 59.20; H, 3.98;
Found: C, 59.28; H, 3.92. NMR (200 MHz, acetone) δ 12.3 (s,
1 H), 8.69 (s, 1 H), 8.48 (s, 1 H), 7.77 (s, 1 H), 7.08 (d, 1 H, J
) 8.8 Hz), 6.99 (dd, 1 H, J 1 ) 9.4 Hz, J 2 ) 1.6 Hz), 6.85 (dd,
1 H, J 1 ) 7.9 Hz, J 2 ) 1.6 Hz), 6.73 (t, 1 H, J ) 7.7 Hz), 6.56
(d, 1 H, J ) 8.8 Hz), 5.13 (dd, 1 H, J 1 ) 12.5 Hz, J 2 ) 3.0 Hz),
2′,4′,5,8-Tetr a h yd r oxyth iofla von e (29). The crude prod-
uct was purified by multiple recrystallization from methanol-
chloroform, yield 16%, mp >300 °C decomp. Anal. Calcd for
3.49 (dd, 1 H, J 1 ) 16.5 Hz, J 2 ) 12.5 Hz), 3.09 (dd, 1 H, J 1
16.5 Hz, J 2 ) 3.0 Hz).
)
C
15H10O5S: C, 59.59; H, 3.33. Found: C, 59.32; H, 3.25. NMR
3′,4′,5-tr ih yd r oxy-8-m eth oxyth iofla va n on e (24). Col-
umn eluted with chloroform: methanol 100:1, product washed
with chloroform, yield 11%, mp 178-180 °C. Anal. Calcd for
(200 MHz, CD3COCD3) δ 13.6 (s, 1 H), 9.2 (bs, 2 H), 9.0 (bs, 1
H), 7.43 (d, 1 H, J ) 8.4 Hz), 7.18 (d, 1 H, J ) 8.8 Hz), 7.17 (s,
1 H), 6.77 (d, 1 H, J ) 8.8 Hz), 6.60 (d, 1 H, J ) 2.3 Hz), 6.55
(dd, 1 H, J 1 ) 8.4 Hz, J 2 ) 2.3 Hz).
C
16H14O5S: C, 60.36; H, 4.43. Found: 60.17; H, 4.42. NMR
(200 MHz, acetone) δ 12.3 (s, 1 H), 8.10 (s, 1 H), 8.07 (s, 1 H),
7.23 (d, 1 H, J ) 9.0 Hz), 7.00 (s, 1 H), 6.85 (s, 2 H), 6.65 (d,
1 H, J ) 9.0 Hz), 4.65 (dd, 1 H, J 1 ) 13.4 Hz, J 2 ) 2.9 Hz),
3.83 (s, 3 H), 3.41 (dd, 1 H, J 1 ) 16.5 Hz, J 2 ) 13.4 Hz), 3.05
(dd, 1 H, J 1 ) 16.5 Hz, J 2 ) 2.9 Hz).
2′,3′,5,8-Tetr a h yd r oxyth iofla von e (30). The crude prod-
uct was purified by silica gel column in chloroform: methanol
50:1, followed by recrystallization from methanol-benzene,
yield 19%, mp >260 °C. Anal. Calcd for C15H10O5S: C, 59.59;
H, 3.33. Found: C, 59.51; H, 3.05. NMR (500 MHz, CD3COCD3)
δ 13.52 (s, 1 H), 9.24 (bs, 1 H), 8.96 (bs, 1 H), 8.16 (bs, 1 H),
7.25 (d, 1 H, J ) 8.8 Hz), 7.18 (s, 1 H), 7.07 (d, 2 H, J ) 8.3
Hz), 6.90 (t, 1 H, J ) 7.8 Hz), 6.83 (d, 1 H, J ) 8.8 Hz).
Syn th esis of 3′,4′,5,8-Tetr a ben zyloxyth iofla va n on e-1,1-
d ioxid e (31). A solution of 3′,4′,5,8-tetrabenzyloxythiofla-
vanone (16) (665 mg, 1 mmol) and m-chloroperbenzoic acid
(520 mg, 2.4 mmol) in methylene chloride (15 mL) was stirred
at room temperature for 1 h. The mixture was diluted with
methylene chloride to 100 mL; washed with sodium bicarbon-
ate (3 × 40 mL), water (3 × 40 mL), and brine (1 × 40 mL);
dried (MgSO4), and evaporated. The residue was purified on
a silica gel column in chloroform and washed with ethanol to
give 31, yield 524 mg (75%), mp 78-80 °C. Anal. Calcd for
Depr otection of 3′,4′-Diben zyloxy-5,8-dim eth oxyth iofla-
va n on e (20) w it h Bor on Tr iflu or id e-Met h yl Su lfid e
Com p lex. A boron trifluoride-methyl sulfide complex solution
in methylene chloride (8 mmol) was added to a stirred solution
of 20 (0.25 mmol) in methylene chloride (2 mL), and the
mixture was stirred at room temperature for 2 h. The solution
was quenched with water (5 mL), diluted with ethyl acetate
(50 mL), washed with water (4 × 20 mL) and brine (1 × 20
mL), and dried over MgSO4. The crude product was purified
on a silica gel column in chloroform - methanol 10:1 solution
to give 3′,4′,5,8-tetr a h yd r oxyth iofla va n on e (21), yield 59%.
Analytical data of the product were identical with those for
product obtained from tetrabenzyl derivative 16 by deprotec-
tion with aluminum chloride (see above).
C
43H36O7S: C, 74.12; H, 5.21; S, 4.60. Found: C, 73.93; H, 5.19;
Syn th esis of P r otected Der iva tives of Th iofla von es
(25-27) by Deh yd r ogen a tion of Th iofla va n on es (16-18).
A suitable thioflavanone (0.4 mmol) and DDQ (109 mg, 0.48
mmol) in dry toluene (5 mL) were refluxed with stirring for 2
h. The reaction mixture was diluted with chloroform (20 mL)
and filtered. The filtrate was evaporated to dryness, and the
residue was separated on a silica gel column.
3′,4′,5,8-Tetr a ben zyloxyth iofla von e (25). Column eluted
with chloroform, product recrystallized from toluene-metha-
nol, yield 55%, mp 98-99 °C. Anal. Calcd for C43H34O5S: C,
77.92; H, 5.17; S, 4.84. Found: C, 77.63; H, 5.11; S, 4.78. NMR
(500 MHz, CDCl3) δ 7.3-7.7 (m, 22 H), 7.14 (bs, 1 H), 7.09
S, 4.53. NMR (200 MHz, CDCl3) δ 6.9-7.6 (m, 25 H), 5.2 (m,
8 H), 4.73 (dd, 1 H, J 1 ) 13.9 Hz, J 2 ) 2.7 Hz), 3.79 (dd, 1 H,
J 1 ) 15.5 Hz, J 2 ) 13.9 Hz), 3.08 (dd, 1 H, J 1 ) 15.5 Hz, J 2
2.7 Hz).
)
Syn th esis of 3′,4′,5,8-tetr a ben zyloxyth iofla von e-1,1-
d ioxid e (32). A solution of 3′,4′,5,8-tetrabenzyloxythioflavone
(25) (320 mg, 0.5 mmol) and m-chloroperbenzoic acid (260 mg,
1.2 mmol) in methylene chloride (20 mL) was stirred at room
temperature for 24 h. Additional m-chloroperbenzoic acid (100
mg) was added, and the stirring was continued for 10 h. The
mixture was diluted with methylene chloride to 100 mL;
washed with sodium bicarbonate (3 × 40 mL), water (3 × 40

364 J . Org. Chem., Vol. 64, No. 2, 1999
Konieczny et al.
mL), and brine (1 × 40 mL); dried (MgSO4); and evaporated.
The residue was recrystallized twice from benzene-methanol
to give 320 mg (99%) of product, mp 99-100 °C. Anal. Calcd
for C43H34O7S: C, 74.33; H, 4.93; S, 4.61. Found: C, 74.56; H,
5.12; S, 4.42. NMR (200 MHz, CDCl3) δ 7.14-7.58 (m, 24 H),
7.00 (d, 1 H, J ) 8.5 Hz), 6.59 (s, 1 H), 5.31 (s, 2 H), 5.23 (s, 2
H), 5.21 (s, 2 H), 5.18 (s, 2 H).
methanol- cyclohexane, yield 55 mg (55%), mp 270 °C. Anal.
Calcd for C15H10O7S: C, 53.89; H, 3.01. Found: C, 53.37; H,
2.82. NMR (200 MHz, acetone) δ 12.6 (s, 1 H), 9.0 (bs, 3 H),
7.58 (d, 1 H, J ) 2.3 Hz), 7.47 (d, 1 H, J ) 9.2 Hz), 7.44 (dd,
1 H, J 1 ) 8.5 Hz, J 2 ) 2.3 Hz), 7.22 (d, 1 H, J ) 9.2 Hz), 7.00
(d, 1 H, J ) 8.5 Hz), 6.80 (s, 1 H).
Attem p ted Rea ction of 3′,4′,5,8-Tetr a ben zyloxyth iofla -
va n on e (16) w ith Ben za ld eh yd e. A suspension of 3′,4′,5,8-
tetrabenzyloxythioflavanone (16) (332 mg, 0.5 mmol), benzal-
dehyde (0.076 mL, 0.75 mmol), and tetrabutylammonium
bromide (50 mg) in methylene chloride (4 mL) and 50%
potassium hydroxide (4 mL) was stirred for 1.5 h. Methylene
chloride (100 mL) was added, and the organic layer was
separated; washed with water (2 × 20 mL), 1 N HCl (2 × 20
mL), water (4 × 20 mL), and brine (1 × 50 mL); and dried
(MgSO4). Evaporation of solvent gave a residue which was
washed with methanol to give the crude product (310 mg,
77%). The crude product was purified on a silica gel column
in methylene chloride-hexane 5:1 solution and recrystallized
from acetone-methanol to give 2′,3,4,5′-tetr a ben zyloxy-6′-
ch lor om eth ylm er ca p toch a lcon e (36), yield 180 mg (45%),
mp 144-146 °C. Anal. Calcd for C44H37O5SCl: C, 74.09; H,
5.23; S, 4.50. Found: C, 73.96; H, 4.98, S, 4.36. NMR (500
MHz, CDCl3) δ 7.24-7.5 (m, 20 H), 7.22 (d, 1 H, J ) 16.1 Hz),
7.16 (d, 1 H, J ) 1.7 Hz), 7.05 (dd, 1 H, J 1 ) 8.3 Hz, J 2 ) 1.7
Hz), 6.96 (s, 2 H), 6.92 (d, 1 H, J ) 8.3 Hz), 6.86 (d, 1 H, J )
16.1 Hz), 5.22 (s, 2 H), 5.17 (s, 2 H), 5.16 (s, 2 H), 5.05 (s, 2 H),
4.99 (s, 2 H).
Syn th esis of 3′,4′,5,8-Tetr a h yd r oxyth iofla va n on e-1,1-
d ioxid e (33). A solution of 3′,4′,5,8-tetrabenzyloxythiofla-
vanone-1,1-dioxide (31) (116 mg, 0.17 mmol) in ethyl acetate
(10 mL) was hydrogenated over 5% palladium on charcoal at
room temperature for 1 h. The catalyst was filtered off, the
solution was evaporated, and the residue was purified on a
silica gel column in chloroform-methanol 5:1 solution. The
product was washed with chloroform, yield 33 mg (59%), mp
225-227 °C. Anal. Calcd for C15H12O7S: C, 53.57; H, 3.60; S,
9.53. Found: C, 53.41; H, 3.53; S, 9.60. NMR (200 MHz, CD3-
COCD3) δ 12.41 (s, 1 H), 8.8 (bs, 1 H), 8.3 (bs, 2 H), 7.38 (d, 1
H, J ) 9.3 Hz), 7.26 (d, 1 H, J ) 9.3 Hz), 7.05 (s, 1 H), 6.92 (s,
2 H), 5.30 (dd, 1 H, J 1 ) 12.9 Hz, J 2 ) 3.3 Hz), 3.97 (dd, 1 H,
J 1 ) 18.0 Hz, J 2 ) 12.9 Hz), 3.34 (dd, 1 H, J 1 ) 18.0 Hz, J 2
3.3 Hz).
)
Syn t h esis of 3′,4′,5,8-Tet r a h yd r oxyt h iofla von e-1,1-
d ioxid e (34). To a solution of 3′,4′,5,8-tetrabenzyloxythiofla-
vone-1,1-dioxide (32) (200 mg, 0.29 mmol) and N,N-dimethyl-
aniline (0.4 mL, 3 mmol) in methylene chloride (10 mL) was
added aluminum chloride (220 mg, 1.65 mmol) at 0 °C, under
argon. The solution was stirred at room temperature for 1.5
h, cooled, and quenched with 2 N HCl. Ethyl acetate (60 mL)
was added, and the solution was washed with water (3 × 30
mL) and brine (2 × 30 mL), and dried (MgSO4). Evaporation
gave a product which was purified on a silica gel column in
chloroform: methanol 50:1 and recrystallized from benzene-
Ack n ow led gm en t. The authors wish to thank Taiho
Pharmaceutical Company, J apan for financial support.
J O980586W