Practical β-stereoselective O-glycosylation of phenols with penta-O-acetyl-β-D-glucopyranose

Full text of DOI:10.1081/CAR-100106933

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PRACTICAL β-STEREOSELECTIVE O-GLYCOSYLATION
OF PHENOLS WITH PENTA-O-ACETYL-β-D-
GLUCOPYRANOSE
Yeon Soo Lee a , Eun Suk Rho a , Yong Ki Min a , Bum Tae Kim a & Ki Ho Kim b
a Korea Research Institute of Chemical Technology, Yusong-ku, Taejon, 305-343, Korea
b Bioland Ltd., 39-4 Songjeong-ri, Byongchon-myun, Chonan-city, Chungcheongnam-do,
330-860, Korea
Version of record first published: 19 Aug 2006.
To cite this article: Yeon Soo Lee, Eun Suk Rho, Yong Ki Min, Bum Tae Kim & Ki Ho Kim (2001): PRACTICAL β-
STEREOSELECTIVE O-GLYCOSYLATION OF PHENOLS WITH PENTA-O-ACETYL-β-D-GLUCOPYRANOSE, Journal of Carbohydrate
Chemistry, 20:6, 503-506
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J. CARBOHYDRATE CHEMISTRY, 20(6), 503–506 (2001)
COMMUNICATION
PRACTICAL ꢀ-STEREOSELECTIVE
O-GLYCOSYLATION OF PHENOLS WITH
PENTA-O-ACETYL-ꢀ-D-GLUCOPYRANOSE
Yeon Soo Lee,1,* Eun Suk Rho,1 Yong Ki Min,1 Bum Tae Kim,1
and Ki Ho Kim2
1Korea Research Institute of Chemical Technology, Yusong-ku,
Taejon, 305-343, Korea
2Bioland Ltd. 39-4 Songjeong-ri, Byongchon-myun, Chonan-city,
Chungcheongnam-do, 330-860, Korea
O-Glycosylation of phenol derivatives is an important synthetic method for
natural products containing carbohydrate molecules.1 Although various O-glyco-
sylation methods have been studied in order to improve stereoselectivity and yield
by changing the leaving groups, catalysts and solvents, previous methods are not
always satisfactory in terms of ease and practicality.1–7 Recently Oyama et al. re-
ported the glycosylation of phenols with 2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyra-
nosyl fluoride in the presence of BF3ꢁOEt2 and hindered base in order to achieve
high ꢂ-stereoselectivity.7,8 However, it is not easy to obtain the starting glycosy-
lating reagent, 2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyranosyl fluoride.8
Compared to other leaving groups, an acetoxy group can be a very convenient
anomeric leaving group in glycosylation reactions. For example penta-O-acetyl-ꢂ-
D-glucopyranose can be prepared more easily than other glucosyl donors. We have
therefore tried to develop a new ꢂ-stereoselective O-glucosylation of phenols by
using penta-O-acetyl-ꢂ-D-glucopyranose. The results of our glycosylation experi-
ments of phenol are shown in Table 1.
It is well known that the glycosylation of phenols with penta-O-acetyl-ꢂ-D-
glucopyranose gives phenyl ꢂ-glucosides as major products, due to the neigh-
bouring group effect of the 2-O-acetyl group. A serious drawback of the method
is conversion to some extent of the kinetically stable phenyl ꢂ-glucoside 3b into
the thermodynamically stable ꢀ-anomer 3a during the glycosylation reaction (en-
try 1).9 However, glycosylation of phenol with penta-O-acetyl-ꢂ-D-glucose in the
presence of BF3ꢁEt2O and organic base results in both high yield and high ꢂ-
503
Copyright © 2001 by Marcel Dekker, Inc.
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LEE ET AL.
Table 1. Glycosylation of Phenol with Penta-O-acetyl-ꢂ-D-glucopyranose
BF3ꢁOEt2
base
(eq)
rxn time
(h)
yielda
(%)
ratiob
(3a/3b)
(eq)
1
2
3
4
5
6
7
8
9
2.5
2.5
2.5
2.5
2.5
2.5
2.5
1.5
1.5
4
0
5.5
3
3
5
5.5
7
72
89
92
89
91
88
87
72
87
80
92
18/82
7/93
2/98
4/96
3/97
3/97
3/97
1/99
2/98
2/98
9/91
TEA (0.1)
TEA (0.5)
TMGc (0.5)
2,6-lutidine (0.5)
DTBMPd (0.5)
TEA (1)
TEA (1)
TEA (0.5)
TEA (2)
5
11
5.5
2
10
11
10
TEA (1)
0.5
a: isolated yield. b: isolated ratio. c: 1,1,3,3-tetramethylguanidine. d: 2,6-di-tert-butyl-4-methylpyri-
dine.
stereoselectivity compared to glycosylation without organic base as shown in
Table 1.
Glycosylation of phenol in the presence of 2.5 equivalents of BF3ꢁEt2O and
0.5 equivalent of triethylamine to penta-O-acetyl-ꢂ-D-glucopyranose gave the
highest yield and excellent ꢂ-stereoselectivity (entry 3). The addtion of more than
0.5 equivalent of triethylamine decreased the reaction rate and the yield, but still
gave high ꢂ-stereoselectivity (entry 7). It is reported that base can abstract the pro-
ton quickly from the adduct intermediate cation7 of phenol in the glycosylation of
phenols with 2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyranosyl fluoride, and prevent iso-
merization of the ꢂ-isomer to the ꢀ-anomer.
We have also examined the glycosylation of several substituted phenols with
penta-O-acetyl-ꢂ-D-glucopyranose (Table 2). As shown in Table 2, the glycosy-
lation of phenols substituted with an electron withdrawing group retarded the re-
action rate (2h-2j). The reaction rate was also affected by the location of sub-
stituent, the order of reaction rate being; ortho ꢃ meta ꢃ para, irrespective of
substituent structure.
By taking advantage of this method, we have synthesized arbutin,10 a widely
used natural whitening agent. Deacetylation11 of phenyl-ꢂ-glucoside 4b with
sodium methoxide in methanol affords arbutin as shown in the scheme below.

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505
Table 2. Glycosylation of Several Phenols with Penta-O-acetyl-ꢂ-D-glucopyranose
2
R
rxn time (h)
yield (%)a
product ratio (ꢀ/ꢂ)b
a
b
c
d
e
f
g
h
i
H
3
24
7
92
92
91
90
86
88
91
75
86
91
83
3a/3bꢄ2/98
4a/4bꢄ2/98
5a/5bꢄ1/99
6a/6bꢄ2/98
7a/7bꢄ1/99
8a/8bꢄ2/98
9a/9bꢄ2/98
10a/10bꢄ2/98
11a/11bꢄ1/99
12a/12bꢄ2/98
13a/13bꢄ2/98
4-CH3COO
4-Cl
4-MeO
2-Br
3-Br
4-Br
2-NO2 c
3-NO2
4-NO2
3-C6H5
8
27
10
6
120
92
41
3
j
k
a: The yields were isolated b: The ratios of ꢀ/ꢂ were determined by gas chromatography.
c: 5 equivalents of BF3ꢁOEt2 and 1 equivalent of TEA were used.
Scheme.
EXPERIMENTAL
A typical procedure for the glucosylation is as follows: to a mixture of penta-
O-acetyl-ꢂ-D-glucopyranose (10 mmol) and phenol derivative (15 mmol) under a
nitrogen atomosphere, was added triethylamine (5 mmol) in methylene chloride
(20 mL) and then BF3ꢁOEt2 (25 mmol) in methylene chloride (5 mL) over 30 min.
The reaction mixture was then kept stirring for the time shown in Table 2. Satu-
rated aqueous sodium bicarbonate (20 mL) was added to the reaction mixture, and
the reaction mixture was then extracted with ethyl acetate (30 mL ꢅ 2). The or-
ganic layer was dried over magnesium sulfate and the filtrate was concentrated in
a vacuum evaporator. The residue was chromatographed on silica gel to give the
phenyl glucoside product.

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LEE ET AL.
ACKNOWLEDGMENT
The authors are grateful to the Ministry of Commerce, Industry and Energy
of Korea for financial support of this work.
REFERENCES
1. Toshima, K.; Tatsuta, K. Recent Progress in O-Glycosylation Methods and Its Ap-
plication to Natural Products Synthesis. Chem. Rev. 1993, 93, 1503–1531.
2. Matsumoto, T.; Katsuki, M.; Suzuki, K. Rapid O-Glycosidation of Phenols with Gly-
cosidyl Fluoride by using the Combinational Activator, Cp2HfCl2-AgClO4. Chem.
Lett. 1989, 437–440.
3. Smits, E.; Engberts, Jan B. F. N.; Kellogg, Richard M.; van Doren, Henk A. Reliable
Method for the Synthesis of Aryl ꢂ-D-glucopyranosides, Using Boron Trifluoride-Di-
ethyl Ether as Catalyst. J. Chem. Soc., Perkin Trans.1 1996, 2873–2877.
4. Li, Z-J.; Cai, L-N.; Cai, M-S. Studies on Glycosides X. An Alternate Method for
Highly Stereoselective Synthesis of Alkyl-ꢂ-d-Glucopyranosides. Synth. Commun.,
1992, 22, 2121–2124.
5. Clerici, F.; Gelmi, M. L.; Mottadelli, S. Glycosides. Part 1. New Synthesis of 1,2-
trans-O-acetyl Glycosides, via Tributyltin Phenoxides. J. Chem. Soc., Perkin Trans.1
1994, 985–988.
6. Oyama, K-I.; Kondo, T., Highly Efficient ꢂ-Glucosylation of the Acidic Hydroxyl
Groups, Phenol and Carboxylic Acid with a Peracetylated Glucosyl Fluoride Using a
Combination of BF3ꢁEt2O and DTBMP as a Promoter. Synlett. 1999, 1627–1629.
7. Yamaguchi, M.; Horiguchi, A.; Fukuda, A.; Minami, T. Novel Synthesis of Aryl
2,3,4,6-Tetra-O-Acetyl-d-glucopyranosides. J. Chem. Soc., Perkin Trans.1 1990
1079–1082.
8. Shimizu, M.; Togo, H.; Yokoyama, M. Chemistry of Glucosyl Fluoride. Synthesis,
1998, 799–822.
9. It was also proved in our experiments that phenyl-ꢂ-glucoside (3a) was not isomer-
ized to phenyl-ꢀ-glucoside (3b) in the presence of BF3ꢁEt2O (2.5 eq) and triethylamine
(0.5 eq) in methylene chloride, but 50% of phenyl-ꢂ-glucoside was isomerized to
phenyl-ꢀ-glucoside in the presence of only BF3ꢁEt2O (2.5 eq) within 10 h at rt.
10. Maeda, K.; Fukuda, M. Arbutin: Mechanism of Its Depigmenting Action in
Melanocyte Culture. J. Pharmacol. Exp. Ther. 1996, 276, 765–769.
11. Hirokai, T.; Shigeru, I. A Process for the Preparation of Arbutin and Analogs as
Drugs. Kokai Tokkyo Koho JP., 87,226,974, Oct 05, 1987.; Chem. Abstr. 1988, 109,
6894k.
Received March 30, 2001
Accepted May 31, 2001

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