Effective conversion of three diacetyl-C-(β-D-glycopyranosyl) phloroglucinols to spiroketal derivatives by refluxing in water

Article abstract of DOI:10.1080/07328300802030811

Refluxing of diacetylphloroglucinol C-β-D-gluco-, -galacto-, and -allopyranosides in water for 1 d gave two kinds of spiroketal derivatives in total yields of 77%, 74%, and 64%, respectively. The structure and stereochemistry of the six new spiro(benzofuran-[2H]pyran and -[2H]furan) derived from galactoside and alloside were verified by NMR analysis. The production ratios of the spiro derivatives were measured by HPLC analysis at regular time intervals. Since the majority of spiro(benzofuran-[2H]furan) were produced after 8 to 12 h of refluxing and most spiro(benzofuran-[2H]pyran) produced after 2 d of refluxing, it is assumed that formation of spirofuran and spiropyran is a kinetic- and thermodynamic-controlled reaction, respectively. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/07328300802030811

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Effective Conversion of Three
Diacetyl‐C‐(β‐D‐Glycopyranosyl)
Phloroglucinols to Spiroketal Derivatives by
Refluxing in Water
Shingo Sato a , Masahiro Miura a , Takashi Sekito a & Toshihiro Kumazawa a
a Graduate School of Science and Engineering , Yamagata University ,
Yonezawa‐shi, Yamagata, Japan
Published online: 28 May 2008.
To cite this article: Shingo Sato , Masahiro Miura , Takashi Sekito & Toshihiro Kumazawa (2008) Effective
Conversion of Three Diacetyl‐C‐(β‐D‐Glycopyranosyl) Phloroglucinols to Spiroketal Derivatives by Refluxing in
Water, Journal of Carbohydrate Chemistry, 27:2, 86-102, DOI: 10.1080/07328300802030811
To link to this article: http://dx.doi.org/10.1080/07328300802030811
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Journal of Carbohydrate Chemistry, 27:86–102, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0732-8303 print 1532-2327 online
DOI: 10.1080/07328300802030811
Effective Conversion
of Three Diacetyl-C-(b-D-
Glycopyranosyl)
Phloroglucinols to
Spiroketal Derivatives by
Refluxing in Water
Shingo Sato, Masahiro Miura, Takashi Sekito,
and Toshihiro Kumazawa
Graduate School of Science and Engineering, Yamagata University, Yonezawa-shi,
Yamagata, Japan
Refluxing of diacetylphloroglucinol C-b-D-gluco-, -galacto-, and -allopyranosides in
water for 1 d gave two kinds of spiroketal derivatives in total yields of 77%, 74%, and
64%, respectively. The structure and stereochemistry of the six new spiro(benzofuran-
[2H]pyran and -[2H]furan) derived from galactoside and alloside were verified by
NMR analysis. The production ratios of the spiro derivatives were measured by
HPLC analysis at regular time intervals. Since the majority of spiro(benzofuran-
[2H]furan) were produced after 8 to 12 h of refluxing and most spiro(benzofuran-
[2H]pyran) produced after 2 d of refluxing, it is assumed that formation of spirofuran
and spiropyran is a kinetic- and thermodynamic-controlled reaction, respectively.
Keywords Diacetylphloroglucinol C-b-D-glycopyranoside, Spiro(benzofuran-[2H] furan),
Spiro(benzofuran-[2H]pyran), Kinetic-controlled product, Thermodynamic-
controlled product
INTRODUCTION
Recently, two novel kinds of flavone C-glycosides have been isolated from plants.
Based on their structures, these compounds may form by a dehydration reaction
between the ortho-hydroxyl group of the phenol moiety and the 2-hydroxyl group
Received August 25, 2007; accepted November 19, 2007.
Address correspondence to Shingo Sato, Graduate School of Science and Engineering,
Yamagata University, 4-3-16 Jonan, Yonezawa-shi, Yamagata 992-8510, Japan.
E-mail: shingo-s@yz.yamagata-u.ac.jp
86

Conversion to Spiroketal Derivatives
87
of the C-glycosyl moiety, followed by ring closure of the sugar moiety. One of these
novel flavone C-glycosides, which has been extracted from oolong tea in trace
amounts, shows potent anti-inflammatory activity, while its precursor, flavone
6-C-b-D-glucopyranoside (isovitexin), does not (Figs. 1 and 2).[1]
The other compound is composed of four trace constituents, pinnatifides A
to D, which have been isolated from plants used in Chinese folk medicine. This
compound contains novel flavone C-glycosides, including a spiro(benzofuran-
[2H]furan) structure, which also seems to result from ketalization via a 1,2-
hydride shift of the sugar moiety followed by ring closure with dehydration
(Fig. 3).[2] Unfortunately, because only small amounts of these novel flavones
have been isolated, the biological activity of these compounds is yet to be
determined. On the other hand, chalcone C-glycoside, including a spiro(benzo-
furan-[2H]pyran), has been isolated as an acid-hydrolysate of chalcone C-b-D-
glucopyranoside (Fig. 4).[3]
To the best our knowledge only a few reports describing the isomerization
of polyphenol C-glycosides by internal-dehydration with 1,2-hydride shift have
been published. The resistance to acid-hydrolysis of a C-glycoside differs from
that of the corresponding O-glycoside. In addition, since the C-C bond of a C-
glycoside is not cleaved in cells, the biological activity of a C-glycoside[4]
occasionally differs from that of the O-glycoside and its aglycone. Furthermore,
since the C-C bond cannot be cleaved by heat treatment, it can be assumed that
this dehydrated isomerization occurs in flavonoid C-glycosides. However,
synthesis of this novel polyphenol C-glycoside has been reported only for
the above-mentioned flavone C-glycoside[1] and not for spiro-type polyphenol
C-glycosides, except for bis-spiro fructodisaccharides.[5]
In a previous study, phloroacetophenone C-glucopyranoside and C-galacto-
pyranoside (1 and 3) were successfully converted to the corresponding spiro(-
benzofuran-[2H]pyran) derivatives (2 and 4) by refluxing in water in the
presence of p-tolunensulfonic acid (p-TsOH) (Sch. 1, equations (1) and (2)).[6]
Recently, diacetylphloroglucinol C-b-D-glucopyranoside (5) also was con-
verted to the spiro(benzofuran-[2H]furan) derivative (7), in 9.8% yield, by
refluxing in water without any catalysts (Sch. 2).[7]
Figure 1: Naturally occuring flavone C-glycosides.

S. Sato et al.
88
Figure 2: Novel flavone C-glycoside.
Following up on these studies, this paper describes the conversion of diace-
tylphloroglucinol C-b-D-glucopyranoside (5), -galactopyranoside (8), and -allo-
pyranoside (9) to the corresponding spiro derivatives, especially spirofuran
compound. In addition, the product ratio during the reaction was measured
at regular intervals by HPLC analysis and the effective production of the
desired spiro(benzofuran-[2H]furan) or spiro(benzofuran-[2H]pyran) was
explored. And the mechanism for conversion reaction to these spiro derivatives
was considered.
RESULTS AND DISCUSSION
Diacetylphloroglucinol C-b-D-glycopyranosides (5, 8, and 9) were synthesized
by direct C-glycosylation of diacetylphloroglucinol with the unprotected
sugars in the low yields of 32%, 25%, and 6.4%, respectively. Although most
Figure 3: Naturally occuring novel flavone C-glycosides having a spiro-structure.

Conversion to Spiroketal Derivatives
89
Figure 4: Novel chalcone C-glycosides having a spiro-structure.
of the starting materials were recovered under these reaction conditions, small
amounts of some spiro derivatives were yielded with the desired C-glycosides.
The reaction yields were low because of the relatively low reactivity of diace-
tylphloroglucinol (Sch. 3).[8] C-Glycosylation of diacetylphloroglucinol with
D-galactose gave C-b-D-galactofuranoside (10) along with C-b-D-galactopyra-
noside (8) in the ratio of 8:10 ¼ 14:1. A mixture of compounds 8 and 10 was
used in the next conversion reaction.
Next, each of the C-glycopyranosides was refluxed in water without cata-
lysts until the substrate nearly disappeared; durations ranged from overnight
to 1 d. Twenty-four-hour refluxing of 5 followed by acetylation [Ac2O/pyridine/
4-dimethylaminopyridine (DMAP)] and separation by silica gel column chrom-
atography gave a pyran-type spiro derivative (6) and a furan-type spiro deriva-
tive (7) in 49% and 28% yields, respectively (Sch. 4). Twenty-one-hour refluxing
of a mixture of 8 and 10 followed by acetylation gave a pyran-type spiro deriva-
tive (11) in 70% yield and a furan-type spiro derivative (12) in 4% yield (Sch. 5).
Sixteen-hour refluxing of 9 also gave furan-type spiro derivatives 13 and 14 in
35% and 25% yield, respectively (Sch. 6, equation (1)). Additional 34-h
Scheme 1: Conversion reaction of phloroacetophenone C-b-D-glucopyranoside and
-galactopyranside (1 and 3) in refluxing water in the presence of catalytic amounts of p-TsOH.

S. Sato et al.
90
Scheme 2: Conversion reaction of diacetylphloroglucinol C-b-D-glucopyranoside (5) in
refluxing water.
refluxing of 9 also gave furan-type spiro derivatives 13 and 14 in 23% and 15%
yield, in addition to pyran-type spiro derivatives 15 and 16 in 19% and 6.4%
yield, respectively (Sch. 6, equation (2)).
Structures of the spiro derivatives were elucidated by 1H and 13C NMR spec-
troscopy. Furthermore, the stereochemistry of the spiro-quaternary carbon was
1
determined by NOESY measurement.[6,7] The characteristic differences in H
NMR spectra between spiropyran- and spirofuran-type compounds (see
Table 1) were as follows: (a) a chemical shift of H-50 in spiropyran was observed
at lower field (d 5.14–5.47 ppm) and chemical shifts of H-60ab in spirofuran at
lower field (H-60a: d 4.24–4.43 ppm, H-60b: d 4.15–4.29 ppm), and (b) two methyl-
ene protons at C-10 in spiropyran were observed as one singlet peak or as two
doublet peaks in close proximity; however, the two methylene protons in spiro-
furan were observed as two distinct pairs of doublet peaks. Stereochemistry of
the spiro-quaternary carbon of each spiropyran- and spirofuran-type compounds
Scheme 3: Synthesis of three diacetylphloroglucinol C-b-D-glycopyranosieds.

Conversion to Spiroketal Derivatives
91
Scheme 4: Conversion reaction of diacetylphloroglucimol C-b-D-glucopyranoside (5) to
spiro-compound.
Scheme 5: Conversion reaction of diacetylphloroglucinol C-b-D-glactopyranosides (8 and
10) to spiro-compound.
Scheme 6: Conversion reaction of diacetylphloroglucinol C-b-D-allopyranoside (9) to spiro-
compound.
(11, 12, 13, 14, 15, and 16), which were isolated for the first time in the present
study, was elucidated by NOESY measurement (Figs. 5, 6, and 7).
The stereochemistry of the quaternary carbon of the spiro(benzofuran-
[2H]pyran) (11) formed from galactosides (8 and 10) was determined to be R
from the NOE correlation between an acetyl-methyl group and H-40, and
5
an acetyl-methyl group and H-60b. In addition, the pyran moiety was a C2
form of the H-50 axial from J5 6 b ¼ 10 Hz. The stereochemistry of the other
0
0

Table 1: 1H NMR data for O-acetylated spiro-compounds.
Compound no.
13
Chemical
shifts (ppm)
6
7
11
12
14
15
16
H-1a
H-1b
H-30
3.14
3.13
5.63
5.30
5.47
4.18
3.92
2.05
2.07
2.11
2.26
2.27
2.42
2.62
3.38
3.25
5.59
5.44
4.36
4.43
4.21
2.05
2.06
2.07
2.26
2.27
2.42
2.61
3.05
3.39
3.13
5.64
5.75
4.65
4.24
4.21
2.08
2.11
2.15
2.27
2.29
2.42
2.54
3.31
3.24
5.24
5.35
4.49
4.34
4.29
2.08
2.11
2.13
2.27
2.29
2.43
2.63
3.33
3.16
5.57
5.53
4.45
4.36
4.15
2.06
2.08
2.14
2.18
2.24
2.28
2.40
3.08
3.02
5.17
5.75
5.14
4.15
3.80
2.04
2.04
2.15
2.26
2.29
2.42
2.74
3.16
3.10
5.46
5.44
5.28
4.22
4.01
2.03
2.16
2.21
2.27
2.28
2.42
2.58
5.59
5.41
5.33
4.06
3.76
2.02
2.08
2.22
2.27
2.28
2.42
2.63
H-40
H-50
H-60a
H-60b
OAc ꢀ 3
ArOAc
Ac
J value (Hz)
1a,b
17.0
10.5
3.5
1.5
2.0
17.0
7.0
6.0
4.0
7.5
—
3.2
10.4
5.7
10.3
11.7
17.3
4.7
5.5
4.7
7.5
17.1
6.6
6.6
3.2
4.1
17.3
4.6
7.2
3.5
6.0
16.8
3.4
3.2
11.0
5.3
16.8
3.6
3.6
2.1
2.0
30,40
40,50
50,60a
50,60b
60a,b
13.0
12.0
11.8
12.2
12.2
11.0
13.4
30,60b 1.1
30,50 1.0

Conversion to Spiroketal Derivatives
93
Figure 5: The NOESY correlation of spiro-compounds (10 and 11) synthesized from
galactoside.
spiro(benzofuran-[2H]furan) (12) was R based on the NOE correlation between
an acetyl-methyl group and H-30 (Fig. 5). The stereochemistry of the two spiro
(benzofuran-[2H]furan) (13 and 14) derived from alloside was determined to be
R and S, respectively, from NOE correlations between H-30 and H-10ab for 13,
between H-30 and an acetyl-methyl group, and H-30 and H-60ab for 14 (Fig. 6).
The stereochemistry of the two spiro(benzofuran-[2H]pyran) (15 and 16)
derived from alloside was determined to be R and S, respectively, because of
NOE correlations between H-30 and H-10ab, H-60a and an acetyl-methyl group
for 15, between an acetyl-methyl group and H-6’a, an acetyl-methyl group and
H-40, H-30 and H-10ab for 16. The pyran moiety conformations for 15 and 16
5
2
0
0
were assumed to be C2 and C5, respectively, for 15, J5 6 a ¼ 11 Hz and there
was an NOE correlation between H-60b and H-50. For 16, J5 6 ab ¼ 2.1 and
0
0
2.0 Hz and there was an NOE correlation between H-60a and H-40.

S. Sato et al.
94
Figure 6: The NOESY correlation of spirofuran compounds (13 and 14) synyhesized from
alloside.
Next, the product ratios were measured at regular time intervals by HPLC.
For HPLC analysis, small amounts of hydroxy-free spiro compounds (60, 70, 110,
120, 130, 140, 150, and 160) were prepared by each de-O-acetylation of acetates
[NaOMe and then Dowex (Hþ) resin treatment]. HPLC analysis of the
product ratio at regular time intervals during the 90-h refluxing reaction of 5
in water showed that the production of spiro(benzofuran-[2H]furan) (70) was
maximal (ratio ¼ 33%) after 8 h and gradually reduced. In contrast, the pro-
duction of spiro(benzofuran-[2H]pyran) (60) gradually increased after 8 h and
reached the maximum (ratio ¼ 78%) after 48 h. HPLC analysis of the
product ratio for a 90-h reflux reaction in water of a mixture of 8 and 10
showed results similar to those obtained for 5. The production of spiro(benzo-
furan-[2H]furan) (120) was maximal after 8 h (ratio ¼ 12%). The production
of spiro(benzofuran-[2H]pyran) (110) reached the maximum after 90 h and
the product ratio was 70%. Reactions of both glucoside and galactoside gave
either an R- or an S-diastereomer of spiropyran- and spirofuran-type com-
pounds, respectively. Similarly, HPLC analysis of the product ratio of 9
showed different results from those of 5 and a mixture of 8 and 10 as follows:
both spiropyran- and spirofuran-type compounds were composed of a

Conversion to Spiroketal Derivatives
95
Figure 7: The NOESY correlation of spiropyran compounds (15 and 16) synthesized from
alloside.
mixture of R- and S-diastereomers. Productions of the spirofuran-type com-
pounds 130 and 140 were maximal after 12 h (production ratios ¼ 38% and
30% for 130 and 140, respectively). Productions of the spiropyran-type com-
pounds 150 and 160 reached maximum values after 48 h (production
ratios ¼ 27% and 11%, for 150 and 160, respectively) (Figures 8, 9, and 10).
Figure 8: Conversion ratio at time intervals on the reflux reaction of diacetylphloroglucinol
C-b-D-glucopyranoside (5) in water.

S. Sato et al.
96
Figure 9: Conversion ratio at time intervals on the reflux reaction of diacetylphloroglucinol
C-b-D-galactopyranosides (8 and 10) in water.
A possible mechanism for ketalization of the phloroglucinol C-glycopyrano-
sides is as follows (Sch. 7): (i) phloroglucinol C-b-glycopyranoside causes the
pinacol-typed 1,2-hydride shift via a quinone methide form to afford a ring-
opened ketose, (ii) an ortho-hydroxyl group of the phloroglucinol moiety
attacks the ketose to afford a benzodihydrofuran, and (iii) dehydration from
the benzodihydrofuran resulting from subsequent attacking of a 6-hydroxyl
(a) or a 5-hydroxyl (b) group produces a spiropyran or a spirofuran derivative.
¨
This reaction was catalyzed by Bronsted acid such as a p-TsOH or Lewis acid
such as a scandium(III) trifluoromethanesulfonate [Sc(OTf)3]; however, in
that case it yielded many products. Use of alcohol or dioxane in place of
water as a solvent yielded also many products. Just a simple reaction, 8- to
10-h refluxing in water of diacetylphloroglucinol C-glycoside produced
mainly the corresponding spirofuran derivatives, and over 2-d refluxing
mainly the corresponding spiropyran derivatives. On the other hand, the
Figure 10: Conversion ratio at time intervals on the reflux reaction of diacetylphloroglucinol
C-b-D-allopyranoside (9) in water.

Conversion to Spiroketal Derivatives
97
Scheme 7: Possible mechanism for the spiroketalization of polyphenol C-glycoside.
conversion reaction of mono-acetylphloroglucinol C-glycopyranoside produced
only the spiropyran derivative in the yield of 30% or 35% (Sch. 1).[6]
CONCLUSION
A conversion reaction of three diacetylphloroglucinol C-b-D-glycopyranosides
by refluxing in water was carried out and the conversion ratios of the resulting
spiro derivatives were determined by HPLC analysis at regular time intervals.
In each reaction, the production of spirofuran-type compound reached to
maximal after 8 to 10 h, while that of spiropyran-type compound took over
2 d. The results of this study demonstrate that spirofuran is a kinetic-
controlled product and spiropyran is a thermodynamic-controlled product. It
was found that two kinds of spiro compounds can be selectively prepared by
refluxing time. It was assumed that the formation of two kinds of spiro com-
pounds is caused by internal ketalization via pinacol-type rearrangement of
a hydride ion. However, it is obscure that the conversion reaction of galacto-
sides 8 and 10 or alloside 9 formed preferentially R-spiropyran and R-spiro-
furan but that of glucoside 5 only S-diastereomers.[5c] Naturally occurring
products, pinnatifinosides A and B are R-spirofuran compounds derived from
glucoside, and pinnatifinosides C and D are S- and R-spirofuran compounds
derived from alloside. We here had S-spirofuran (7) derived from glucoside
and R- and S-spirofurans (13 and 14) derived from alloside in hand. Further
studies will attempt the total synthesis of pinnatifinosides A to D based on
the results of the present study.
EXPERIMENT
Water used in this study was purified by distillation of deionized water using a
Yamato Auto Still model WO-41 instrument. Reactions were monitored by TLC

S. Sato et al.
98
on 0.25-mm silica gel F254 plates (E. Merck) using UV light, and either a 5%
ethanolic solution of ferric chloride or a 7% ethanolic solution of phosphomolyb-
dic acid with heat to visualize the bands. For separation and purification, flash
column chromatography was performed on silica gel (230–400 meshes, Fuji-
Silysia Co. Ltd., BW-300). Melting points were determined on an AS ONE
ATM-01 melting point apparatus and were not corrected. Optical rotations
were recorded on a JASCO DIP-370 polarimeter. IR spectra were recorded on
a Horiba FT-720 IR spectrometer in the form of KBr disks. NMR spectra
were recorded on a Varian Inova 500 spectrometer using Me4Si as the
internal standard. Mass spectral data were obtained by fast-atom bombard-
ment (FAB) using glycerol or m-nitrobenzylalcohol (NBA) as the matrix on a
JEOL JMS-AX505HA instrument. Elemental analyses were performed on a
Perkin-Elmer PE 2400 II instrument. HPLC was performed on a Hitachi
L-7100 and L-4200H system using the following conditions: column: GL
Sciences Inc., Inertsil ODS-3 column (4.6 ꢀ 250 mm); solvent: MeOH-H2O-
AcOH ¼ 60:38:2; flow rate: 1 mL/min; wavelength: UV254 nm.
Diacetylphloroglucinol C-b-D-galactopyranoside
and -furanoside (8 and 10)
A solution of diacetylphloroglucinol (500 mg, 2.38 mmol), D-galactose
(857 mg, 4.76 mmol), and Sc(OTf)3 (234 mg, 0.476 mmol) in CH3CN-H2O (2:1
10 mL) was stirred at 708C in an oil bath for 1 d. After the reaction mixture
was evaporated to remove CH3CN, 100 mL of water was added and the result-
ing solution was absorbed to a Diaion-CHP20P gel (50 mL) column, washed
with 200 mL of water, and eluted with acetone-water (200 mL 1:1) and
acetone-MeOH (200 mL 1:1). The eluate was evaporated to dryness. The
residue including the desired products and unreacted diacetylphloroglucinol
was separated by silica gel column chromatography (10:1 CHCl3-MeOH) to
give a mixture of 8 and 10 (255 mg, 28.8%, 8:10 ¼ 14:1). Pure 10 was
afforded by recrystallization from MeOH, and the filtrate was separated by
silica gel column chromatography with toluene-AcOEt-AcOH (5:2:0.2) and
recrystallized from EtOH to give pure 8.
Data for 8—Colorless prism. mp 137–1388C (EtOH). [a]2D1 þ104 (c 0.98,
1
MeOH). IR (KBr) n 3396, 2931, 1620, 1427, 1365, and 1288 cm21. H NMR
(DMSO-d6) d 2.63 (3H, s, CH3), 3.76 (1H, t, J 9.4 Hz, H-20), 4.74 (1H, d,
J 9.6 Hz, H-10), 16.3 (1H, br.s, OH). 13C NMR (DMSO-d6) d (galactose moiety)
60.6 (C-60), 68.3, 69.7, 73.9, 74.0, 79.4, (diaetylphloroglucinol moiety) 32.7
(COCH3 ꢀ 2), 103.4 (C-3,5), 104.1 (C-1), 166.7 (C-2,6), 170.2 (C-4), 204.6
(COCH3 ꢀ 2). FAB-MS (glycerol, m/z) 373 (M þ H)þ. Anal. Calcd for
C16H20O10: C, 51.61; H, 5.41. Found: C, 51.59; H, 5.45.
Data for 10—Colorless prism. mp 1668C (MeOH). [a]2D1 2 132 (c 0.98,
1
MeOH). IR (KBr) n 3429, 2935, 1624, 1431, 1300, and 1066 cm21. H NMR

Conversion to Spiroketal Derivatives
99
(DMSO-d6, at 80oC) d 2.63 (3H, s, COCH3), 3.90 (1H, t, J 3.3 Hz, OH), 4.01 (1H,
d, J 3.2 Hz, OH), 4.07 (1H, d, J 1.7 Hz, OH), 5.35 (1H, J 3.2 Hz, H-10), 16.1 (1H,
br.s, OH). 13C NMR (DMSO-d6) d (galactose moiety) 62.8 (C-60), 70.3, 77.4, 78.3,
80.0, 85.8, (diacetylphloroglucinol moiety) 32.6 and 32.7 (COCH3 ꢀ 2), 98.9 (C-
3,5), 103.1 (C-1), 167.3 (C-2,6), 170.1 (C-4), 203.9 (COCH3 ꢀ 2). FAB-MS
(glycerol, m/z) 373 (M þ H)þ. Anal. Calcd for C16H20O10: C, 51.61; H, 5.41.
Found: C, 51.44; H, 5.33.
Diacetylphloroglucinol C-b-D-allopyranoside (9)
A solution of diacetylphloroglucinol (500 mg, 2.38 mmol), D-galactose
(857 mg, 4.76 mmol) and Sc(OTf)3 (245 mg, 0.498 mmol) in CH3CN-H2O (2:1
10 mL) was refluxed with stirring in an oil bath for 66 h. The reaction
mixture was separated and purified in the same manner as the described
above for the galactosides (8 and 10) to give 9 (55.4 mg, 6.25%) as colorless
prisms.
Colorless prism. mp 166–1678C (EtOH). [a]2D1 þ49.1 (c 0.293, MeOH). IR
1
(KBr) n 3496, 3407, 3103, 2929, 1606, 1371, and 1278 cm21. H NMR d 2.65
(3H, s, CH3), 5.16 (1H, d, J 10.0 Hz, H-10), 12.9 (1H, br.s, OH), 16.3 (1H, br.s,
13
OH). C NMR (DMSO-d6) d (allose moiety) 59.3 (C-60), 65.9, 69.6, 70.0, 71.1,
76.2, (diacetylphloroglucinol moiety) 32.7 (COCH3 ꢀ 2), 102.9 (C-3,5), 103.5
(C-1), 167.2 (C-2,6), 170.1 (C-4), 204.0 (COCH3 ꢀ 2). FAB_MS (glycerol, m/z)
373 (M þ H)þ. Anal. Calcd for C16H20O10: C, 51.61; H, 5.41. Found: C, 50.39;
H, 5.55.
Conversion Reaction of Glycoside to Spiro Derivatives
A mixture of 8 and 10 (14:1, 100 mg) was dissolved in 100 mL of water and
the resulting solution was refluxed for 1 d. The reaction mixture was evaporated
to dryness. The residue was dissolved in pyridine (2 mL) and Ac2O (4 mL), and
DMAP (5 mg) was added to the mixture. After stirring at rt for 1 d, the reaction
mixture was poured into ice-cold water (50 mL) and extracted with AcOEt
three times. The organic layers were combined, washed with water and saturated
NaCl solution, dried with anhydrous Na2SO4, and then evaporated to dryness.
The residue was separated and purified by silica gel column chromatography
(3:1–1:1 hexane-AcOEt) to give 11 and 12. Conversion reaction of glucoside 5
and alloside 9 and succeeding workups were carried out in the same manner as
the described above for the galactosides, respectively.
(2R,30S,40S,50R)-304,40,50,6-Pentakis-acetoxy-5,7-diacetyl-30,40,50,60-
tetrahydrospiro[benzofuran-2(3H),20-[2H]pyran] (11)
Colorless prism. mp 2018C (MeOH). [a]2D1 þ66.7 (c 1.025, CHCl3). IR (KBr) n
2993, 2941, 1778, 1751, 1697, 1622, 1431, and 1371 cm21 13C NMR (CDCl3) d
.

S. Sato et al.
100
20.6, 20.7, 20.7, 20.8, 20.9, and 167.1, 168.9, 169.7, 169.7, 170.0 (OAc ꢀ 5), 36.7
(C-10), 62.0 (C-60), 65.3, 69.1, 70.0, 111.5 (C-20), (aromatic moiety) 114.9,
117.5, 123.6, 145.9, 146.9, 158.0, 31.3 and 32.0 (ArCOCH3 ꢀ 2), 195.1 and
197.2 (ArCOCH3 ꢀ 2). FAB-MS (NBA, m/z) 565 (M þ H)þ. Anal. Calcd for
C26H28O14: C, 55.32; H, 5.00. Found: C, 55.44; H, 5.05.
(2R,30S,40S,50R)-30,4,40,6,60-Pentakis-acetoxy-5,7-diacetyl-50-
acetoxymethylspiro[benzofuran-2(3H),20-(2H)furan] (12)
Colorless amorphous solid. [a]D21 þ76.0 (c 0.995, CHCl3). IR (KBr) n 3004,
2941, 1772, 1750, 1697, 1618, 1431, and 1373 cm21 13C NMR (CDCl3) d 20.3,
.
20.4, 20.7, 20.8, 21.0, and 167.3, 168.9, 168.9, 169.3, 170.5 (OAc ꢀ 5), 33.6 (C-
10), 62.3 (C-60), 70.9, 74.8, 76.5, 114.4 (C-20), (aromatic moiety) 117.6, 118.5,
123.0, 145.7, 146.8, 158.0, 31.4 and 31.9 (ArCOCH3 ꢀ 2), 195.5 and 197.3
(ArCOCH3 ꢀ 2). FAB_MS (NBA, m/z) 565 (M þ H)þ. Anal. Calcd for
C26H28O14: C, 55.32; H, 5.00. Found: C, 55.30; H, 5.29.
(2R,30R,40R,50R)-3,4,40,6,60-Pentakis-acetoxy-5,7-diacetyl-50-
acetoxymethylspiro[benzofuran-2(3H),20-(2H)furan] (13)
Colorless amorphous solid. [a]D21 –54.6 (c 1.065, CHCl3). IR (KBr) n 3004,
2941, 1776, 1751, 1697, 1622, 1431, and 1373 cm21 13C NMR (CDCl3) d 34.1
.
(C-10), 63.3 (C-60), 69.7, 72.3, 82.4, 113.8 (C-20), 20.4, 20.6, 20.7, 20.8, 21.0,
167.2, 169.0, 169.7, 17.0, 170.3 (OAc ꢀ 5), (aromatic moiety) 31.4 and 31.7,
195.3 and 197.4 (ArCOCH3 ꢀ 2), 116.3, 117.5, 122.9, 145.8, 147.0, 159.2.
FAB-MS (NBA, m/z) 565 (M þ H)þ. Anal. Calcd for C26H28O14: C, 55.32; H,
5.00. Found: C, 55.27; H, 5.14.
(2S,30R,40R,50R)-3,4,40,6,60-Pentakis-acetoxy-5,7-diacetyl-50-
acetoxymethylspiro[benzofuran-2(3H),20-(2H)furan] (14)
Colorless amorphous solid. [a]D21 þ84.6 (c 0.475, CHCl3). IR (KBr) n 2941,
1775, 1749, 1697, 1621, 1436, and 1371 cm21 13C NMR (CDCl3) d 33.5 (C-10),
.
63.7 (C-60), 71.1, 74.5, 79.3, 114.4 (C-20), 20.4, 20.5, 20.7, 20.7, 21.0, 167.2,
168.9, 169.1, 169.4, 170.4 (OAc ꢀ 5), (aromatic moiety) 31.4 and 32.0, 195.3
and 197.3 (ArCOCH3 ꢀ 2), 117.3, 119.0, 123.1, 145.7, 146.9, 157.8. FAB-MS
(NBA, m/z) 565 (M þ H)þ. Anal. Calcd for C26H28O14: C, 55.32; H, 5.00.
Found: C, 55.27; H, 5.07.
(2R,30R,40R,50R)-3,4,40,50,6-Pentakis-acetoxy-5,7-diacetyl[benzofuran-2(3H),
20-(2H)pyran] (15)
Colorless amorphous solid. [a]2D1 þ110 (c 1.045, CHCl3). IR (KBr) n 2981,
2956, 1778, 1758, 1691, 1618, 1434, and 1371 cm21 13C NMR (CDCl3) d 36.7
.
(C-10), 58.7 (C-60), 67.0, 67.8, 65.1, 110.0 (C-20), 20.5 (ꢀ2), 20.6, 20.8, 20.9,
167.1, 169.0, 169.3, 169.7, 170.1 (OAc ꢀ 5), (aromatic moiety) 31.3 and 31.9,
195.3 and 197.3 (ArCOCH3 ꢀ 2), 114.3, 117.5, 123.4, 145.9, 146.9, 159.5.

Conversion to Spiroketal Derivatives
101
FAB-MS (NBA, m/z) 565 (M þ H)þ. Anal. Calcd for C26H28O14: C, 55.32; H,
5.00. Found: C, 55.23; H, 4.80.
(2S,30R,40R,50R)-3,4,40,50,6-Pentakis-acetoxy-5,7-diacetyl[benzofuran-2(3H),
20-(2H)pyran] (16)
Colorless prism (from EtOAc). mp 1438C. [a]2D1 –92.5 (c 0.990, CHCl3). IR
(KBr) n 3020, 2940, 1774, 1751, 1697, 1617, 1430, and 1373 cm21 13C NMR
.
(CDCl3) d 36.9 (C-10), 63.9 (C-60), 65.5, 65.7, 68.2, 112.1 (C-20), 20.6, 20.7 (ꢀ2),
20.9 (ꢀ2), 167.2, 168.9, 169.4, 169.7, 170.1 (OAc ꢀ 5), (aromatic moiety) 31.3
and 31.9, 195.0 and 197.3 (ArCOCH3 ꢀ2), 115.0, 117.7, 123.5, 145.9, 146.8,
158.1. FAB-MS (NBA, m/z) 565 (M þ H)þ. Anal. Calcd for C26H28O14: C,
55.32; H, 5.00. Found: C, 55.14; H, 4.80.
HPLC Analysis
Each sample for HPLC analysis was prepared by de-O-acetylation in the
scale of several milligrams. Retention time (min) of each sample shows as
follows: (glucosides) 5: 7.03, 60: 7.72, 70: 11.42. (galactosides) 8: 7.42, 10:
10.88, 110: 14.91, 120: 13.00. (allosides) 9: 7.96, 130: 11.72, 140: 10.20, 150:
17.19, 160: 16.44.
ACKNOWLEDGMENT
The authors wish to thank Mr. Hiroya Masukawa and Mr. Yuki Takaoka for
their technical assistance.
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