Convenient construction of a variety of glycosidic linkages using a universal glucosyl donor

Article abstract of DOI:10.1016/j.tetlet.2005.08.109

This letter deals with the concept of constructing four types (cis-α, trans-α, cis-β, and trans-β) of glycosidic linkages using a universal glucosyl donor. The selectively protected universal glucosyl donor 8 was synthesized in 36% yield from d-glucose (eight steps). The donor 8 undergoes glycosidation with a primary carbohydrate alcohol 7 to give disaccharide 9 having a 1,2-cis-α-glycosidic linkage in 90% yield. The construction of the corresponding 1,2-trans-α-glycosidic linkage was performed in 68% yield (three steps) from 9. A similar glycosidation of the 2-O-(N- phenylcarbamoyl)-glucosyl donor 6 derived from 8 with 7 gave disaccharide 11 having a 1,2-trans-β-glycosidic linkage in 75% yield. The construction of the corresponding 1,2-cis-β-linkage was performed in 53% yield (three steps) from 11.

Full text of DOI:10.1016/j.tetlet.2005.08.109

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 7411–7414
Convenient construction of a variety of glycosidic linkages using
a universal glucosyl donor
Ken-ichi Sato,* Shoji Akai, Koudai Sakai, Masaru Kojima,
Hideshige Murakami and Tetsuya Idoji
Laboratory of Organic Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1, Rokkakubashi, Kanagawa-ku,
Yokohama 221-8686, Japan
Received 7 July 2005; revised 3 August 2005; accepted 19 August 2005
Available online 9 September 2005
Abstract—This letter deals with the concept of constructing four types (cis-a, trans-a, cis-b, and trans-b) of glycosidic linkages using
a universal glucosyl donor. The selectively protected universal glucosyl donor 8 was synthesized in 36% yield from D-glucose (eight
steps). The donor 8 undergoes glycosidation with a primary carbohydrate alcohol 7 to give disaccharide 9 having a 1,2-cis-a-glyco-
sidic linkage in 90% yield. The construction of the corresponding 1,2-trans-a-glycosidic linkage was performed in 68% yield (three
steps) from 9. A similar glycosidation of the 2-O-(N-phenylcarbamoyl)-glucosyl donor 6 derived from 8 with 7 gave disaccharide 11
having a 1,2-trans-b-glycosidic linkage in 75% yield. The construction of the corresponding 1,2-cis-b-linkage was performed in 53%
yield (three steps) from 11.
Ó 2005 Elsevier Ltd. All rights reserved.
The simple, efficient and selective synthesis of oligosac-
charides is one of the central problems in carbohydrate
chemistry.1 The so-called Koenigs–Knorr glycosidation2
has been an essential synthesis for a very long time.
Recently, many studies have been devoted to searching
for the Ônon-Koenigs–KnorrÕ activation of the anomeric
center. The trichloroacetimidate glycosidation3 has been
frequently used for the practical and selective syntheses
of complex oligosaccharides and glycoconjugates. Thio-
glycosides are also attracting attention on donors along
this line4 and for these stabilities. Usually, the anomeric
and steric effects, as well as the neighboring group par-
ticipation, result in the stereocontrolled glycosidation,
for example, 1,2-trans-a, and -b-linkages are effectively
achieved by the neighboring group (such as acyloxy)
participation at C-2.5 Contrary to the 1,2-trans-a-link-
age, construction of a 1,2-cis-b-linkage is not easy6 by
the effects mentioned above. Therefore, we have been
developing an indirect method for constructing the
1,2-cis-b-linkage including a SN2 displacement reaction
at C-27 of the suitably protected glycosyl donor for
synthesizing the naturally occurring oligosaccharides.
In these syntheses, the appropriate donor and reaction
conditions are selected for each purpose.
In this letter, we describe the concept of constructing
four different types of glycosidic linkages by the use of
a multipurpose glucosyl donor. Our concept consists of
the neighboring group participation of the N-phenyl-
carbamoyl (Car) group and SN2 displacement reaction
at C-2. Thus, the Car group, stable from pH 1 to
pH 12, has not been used for the protection of the
hydroxyl group, because of the difficulties with its un-
masking procedure. However, our research group has
developed a novel unmasking procedure8 without affect-
ing the acyl, silyl, methoxymethyl, benzylidene acetal,
and isopropylidene acetal protecting groups. At this
stage, the Car group is of a particular value for the syn-
thesis of complex oligosaccharides, which necessitates
the delicate chemical differentiation of a variety of pro-
tecting groups under mild conditions. On the other hand,
Nakagawa et al. reported that the stereoselective
a-glycosidation with a donor having 6-O-Car9 suggested
that the stereoselectivity is at least partly controlled by
the neighboring group participation of the Car group
at C-6. We have now examined the ability of the neigh-
boring group participation of Car group at C-2 and
C-6 for the first time. The results of the glycosidation
are shown in Table 1.
Keywords: Carbohydrates; Oligosaccharide synthesis; Glycosidation.
*
Corresponding author. Tel.: +81 45 481 5661x3853; fax: +81 45 413
9770; e-mail: satouk01@kanagawa-u.ac.jp
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.08.109

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K. Sato et al. / Tetrahedron Letters 46 (2005) 7411–7414
Table 1. Glycosidation of donors 1–6 with acceptor 7
OR1
O
OH
O
Product yield (%)a
a/bb
BnO
BnO
BzO
Entry
Donor: R1, R2
+
SEt
BzO
10: 97
20: 90
30: 93
40: 98
50: 93
60: 87
4:1
6:1
6:1
1:8
1:8
1:6
R2O
BzO
1
2
3
4
5
6
1: Bn, Bn
2: Bz, Bn
3: Car, Bz
4: Bn, Bz
5: Bn, Car
6: Bz, Car
OMe
7 (1.0 equiv.)
1—6 (1.0 equiv.)
OR1
O
NIS (1.5 equiv.)
TfOH (0.3 equiv.)
BnO
BnO
O
R2O
BzO
BzO
O
a Based on donors 1–6.
b Determined by 1H NMR spectrum.
CH2Cl2, _20 oC
BzO
OMe
1'−6'
Scheme 1. Glycosidation of donors 1–6 with acceptor 7.
Donors 1–6 and acceptor 7 were synthesized in the usual
manner. The ability of the neighboring group participa-
tion of Car at O-6 was newly examined and compared
with that of Car at O-2 for the reaction of donors 1–6
with acceptor 7 (Scheme 1 and Table 1). The reaction
of 1 and 7 in the presence of N-iodosuccinimide (NIS)
and trifluoromethanesulfonic acid (TfOH) in dichloro-
methane at ꢀ20 °C gave the corresponding disaccharide
10 (a/b = 4:1) in 97% yield. The ratios of a/b were deter-
responding disaccharide 20 (a/b = 6:1) and 30 (a/b = 6:1)
in good yields, respectively. In entry 1, the stereoselectiv-
ity seems to be mainly controlled by the anomeric effect.
In entries 2 and 3, the ratio of the cis-a disaccharide in-
creased compared with that of entry 1. These results sug-
gest that the contribution of a certain neighboring group
participation of the Car group at O-6 is the same as the
benzoyl (Bz) group. Under similar reaction conditions,
the reaction of 4 and 5 gave the corresponding disaccha-
1
mined by H NMR spectra in this study. Under similar
reaction conditions, the reaction of 2 and 3 gave the cor-
OBz
O
BnO
BnO
OBz
O
HO
BzO
MOMO
O
a)
O
BnO
BnO
cis - α
+
O
SEt
BzO
BzO
y. 90%
BzO
BzO
MOMO
OMe
BzO
8
7
9
OMe
3 steps
y. 68%
b)
BzO AcO
y. 93%
c)
O
BnO
BnO
trans -
α
O
O
BzO
BzO
BzO
OMe
10
OBz
O
BnO
BnO
BzO
AcO
SEt
O
HO
BnO
BnO
O
cis -
β
O
BzO
BzO
BzO
OMe
12
d)
y. 92%
3 steps
y. 53 %
e)
OBz
O
OBz
O
HO
BzO
BnO
BnO
O
trans -
β
O
BnO
BnO
+
CarO
BzO
SEt
BzO
y. 75%
O
CarO
BzO
OMe
BzO
7
6
BzO
OMe
11 (6'β)
Scheme 2. Reagents and conditions: (a) NIS, TfOH/CH2Cl2, ꢀ20 °C; (b) [i] 70% AcOH aq; [ii] Tf2O, Py/CH2Cl2; [iii] CsOAc, 18-crown-6/toluene,
ultrasonication; (c) 70% AcOH aq; (d) PhNCO/Py; (e) [i] n-Bu4NNO2, Ac2O, Py, 0–40 °C; [ii] Tf2O, Py/CH2Cl2; [iii] CsOAc, 18-crown-6/toluene.

K. Sato et al. / Tetrahedron Letters 46 (2005) 7411–7414
7413
ride 40 (a/b = 1:8) and 50 (a/b = 1:8) in good yields,
respectively. The result of entry 5 also shows that the
contribution of a certain neighboring group participa-
tion of the Car group at O-2 seems to be the same as
the Bz group (entry 4). The result of entry 6 suggests
that the neighboring group participation at the O-6 Bz
group reduces the b selectivity caused by that of the
O-2 Car group.
may be useful for the synthesis of a variety of
oligosaccharides.
Acknowledgements
This work was partially supported by a ÔHigh-Tech
Research Center ProjectÕ from the Ministry of Educa-
tion, Science, Sports and Culture, Japan. The authors
thank Professor Nakagawa, for helpful discussions.
Considering these results, a universal glucosyl donor
8 was designed and synthesized in 36% yield from D-
glucose in the usual manner.10 Especially, the 2-O pro-
tecting group is to be distinguished from the other
protecting groups by considering its selective deprotec-
tion. Our concept for constructing four types of glyco-
sidic linkages using 8 was examined as shown in
Scheme 2. The reaction of acceptor 7 and donor 8 in
the presence of molecular sieves 4A in dichloromethane,
NIS (1.5 equiv) then TfOH (0.3 equiv) at ꢀ20 °C gave
the corresponding cis-a disaccharide 9.11 The ratio of
a/b was 15:1. The deprotection of the methoxymethyl
(MOM) group of disaccharide 9 in 70% aq acetic acid
solution gave the corresponding 2-OH cis-a disaccharide
quantitatively. Then, trifluoromethanesulfonation of 2-
OH derivative with trifluoromethanesulfonic anhydride
(1.5 equiv) and pyridine (5.0 equiv) and subsequently
SN2 reaction with cesium acetate (2.0 equiv) and 18-
crown-6 ether (2.0 equiv) gave trans-a disaccharide
1011 in 73% yield.7 The total yield of the reaction from
9 into 10 was 68% (three steps).
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2005.08.109.
References and notes
1. For reviews, see (a) Paulsen, H. Angew. Chem., Int. Ed.
Engl. 1982, 21, 155–224; (b) Schmidt, R. R. Angew. Chem.,
Int. Ed. Engl. 1986, 25, 212–235; (c) Toshima, K.; Tatsuta,
K. Chem. Rev. 1993, 93, 1503–1531; (d) Boons, G. J.
Tetrahedron 1996, 52, 1095–1121; (e) Davis, Benjamin G.
J. Chem. Soc., Perkin Trans. 1 2000, 2137–2160.
2. (a) Koenigs, W.; Knorr, E. Berichte der Deutschen
Chemischen Gesellschaft 1901, 34, 957–981; (b) Fischer,
E.; Armstrong, E. F. Berichte der Deutschen Chemischen
Gesellschaft 1901, 34, 2885–2900.
3. Schmidt, R. R.; Michael, J. Angew. Chem., Int. Ed. Engl.
1980, 19, 731–732.
4. For short reviews, see (a) Fugedi, P.; Garegg, P. J.; Loehn,
H.; Norberg, T. J. Glycoconjugate 1987, 4, 97–108; (b)
Sinay, P. Pure Appl. Chem. 1991, 63, 519–528.
5. Hashimoto, S.; Honda, T.; Ikegami, S. J. Chem. Soc.,
Chem. Commun. 1989, 685–687.
6. (a) Paulsen, H.; Lebuhn, R. Ann. Chem. 1983, 1047; (b)
Nagai, H.; Matsumura, S.; Toshima, K. Carbohydr. Res.
2003, 338, 1531–1534; For a recent review, see (c) Ennis,
Seth C.; Osborn, Helen M. I. In Carbohydrates; Osborn,
Helen M. I., Ed.; Elsevier Science Ltd.: Oxford, UK, 2003,
pp 239–276.
7. (a) Sato, K.; Yoshitomo, A. Chem. Lett. 1995, 39–40; (b)
Sato, K.; Yoshitomo, A.; Takai, Y. Bull. Chem. Soc. Jpn.
1997, 70, 885–890.
8. Akai, S.; Nishino, N.; Iwata, Y.; Hiyama, J.; Kawashima,
E.; Sato, K.; Ishido, Y. Tetrahedron Lett. 1998, 39, 5583–
5586.
9. Nakagwa, T.; Ishimaru, Y.; Ikegawa, H.; Ogihara, J.;
Kobayashi, N.; Nakamura, S.; Kubo, K.; Masuno, K.
Yokohama-shiritsu Daigaku Ronso, Natural Science Series
1998, 49, 7–14.
10. For experimental procedure and their physical data, see
Supplementary data at doi:10.1016/j.tetlet.2005.08.109.
11. 1H NMR (500 MHz, CDCl3) of compound 9, 10, 11, and
12.
The other donor 6 producing a b-linkage was synthe-
sized from 8 in two steps as follows.10 The hydrolysis
of 8 in 70% aq acetic acid gave the corresponding 2-
OH derivative in 93% yield. The reaction of the 2-OH
derivative with phenylisocyanate (1.5 equiv) in pyridine
gave the corresponding 2-O-Car derivative 6 in 92%
yield.10 For a similar treatment of the reaction of 7 with
8, the reaction of donor 7 and acceptor 6 gave the cor-
responding trans-b disaccharide 11 (60b),11 which was
purified on a column of silica gel, in 75% yield.10 The
a/b ratio was 1:6. The deprotection of the Car group
of 11 with tetra-n-butylammonium nitrite (4.0 equiv)
and acetic anhydride (1.5, 1.2, and 1.0 equiv) in pyri-
dine8 gave the corresponding 2-OH trans-b disaccharide
in 73% yield. In a similar reaction of 9 into 10, the 2-OH
trans-b disaccharide was quantitatively converted into
the corresponding 2-O-trifluoromethanesulfonate, and
subsequently SN2 reaction with cesium acetate
(2.0 equiv) and 18-crown-6 ether (2.0 equiv) gave cis-b
disaccharide 1211 in 73% yield.7,10 The total yield of
the reaction from 11 into 12 was 53% (three steps).
Compound 9: d 7.99–7.23 (30H, m, PhH), 6.13 (1H, dd,
In this letter, an example is described for constructing
four types of glycosidic linkages using a stable donor
(2-O-MOM or 2-O-Car), which can be synthesized in a
large quantity and stored for a long time. The MOM
group acts like the ether-type protecting group, which
is easily cleaved. The convenient interconversion be-
tween the MOM and the Car groups without affecting
the other protecting groups seems to have wide applica-
tions, for example, introducing an N3 group or deoxyna-
tion at C-2.7 Therefore, we consider that this concept
J2 ,3 = 9.8 Hz, J3 ,4 = 9.5 Hz, H-30), 5.63 (1H, dd,
0
0
0
0
J4 ,5 = 10.7 Hz, H-40), 5.22 (1H, dd, J1 ,2 = 3.7 Hz, H-
20), 5.21 (1H, d, H-10), 5.02 (1H, d, J1,2 = 3.7 Hz, H-1),
5.02, 4.86 (2H, each d, JAB = 11.0 Hz, Ph–CH2–), 4.91,
4.60 (2H, each d, JAB = 10.7 Hz, Ph–CH2–), 4.46 (1H, dd,
0
0
0
0
0
J5 ,6a = 2.1 Hz, J6a,6b = 12.2 Hz, H-6a), 4.35 (1H, dd,
0
0
J5,6b = 11.6 Hz, H-6b), 4.25 (1H, ddd, J5 ,6a = 6.4 Hz,
J5 ,6b = 2.1 Hz, H-50), 3.96 (1H, ddd, J4,5 = 10.1 Hz, H-5),
0
0
3.92 (1H, dd, J6a ,6b = 11.6 Hz, H-6a0), 3.82 (1H, dd,
0
0
J2,3 = 9.2 Hz, J3,4 = 8.9 Hz, H-3), 3.67–3.75 (2H, m, H-2,

7414
K. Sato et al. / Tetrahedron Letters 46 (2005) 7411–7414
H-6b0), 3.58 (1H, dd, H-4), 3.44 (3H, s, –OCH3), 2.60 (1H,
br s, –OH).
Ph–CH2–), 4.82, 4.77 (2H, each d, JAB = 11.3 Hz, Ph–
CH2–), 4.54 (1H, dd, J5,6a = 2.1 Hz, J6a,6b = 11.9 Hz, H-
6a), 4.43 (1H, dd, J5,6b = 4.3 Hz, H-6b), 4.39 (1H, d, H-1),
Compound 10: d 8.02–7.23 (30H, m, PhH), 6.14 (1H,
dd, J2 ,3 = 9.8 Hz, J3 ,4 = 9.8 Hz, H-30), 5.75 (1H, dd,
J1,2 = 0.9 Hz, J2,3 = 2.7 Hz, H-2), 5.39 (1H, dd,
4.21 (1H, ddd, J5 ,6a = 1.8 Hz, J5,6b = 5.2 Hz, H-6a0),
0
0
0
0
0
0
0
4.17 (1H, dd, J6a ,6b = 10.9 Hz, H-6a0) , 3.79 (1H, dd,
J3,4 = 8.9 Hz, J4,5 = 8.9 Hz, H-4), 3.71 (1H, dd, H-3), 3.61
(1H, ddd, H-5), 3.59 (1H, dd, H-6b0), 3.27 (3H, s, –OCH3).
0
0
J4 ,5 = 9.8 Hz, H-40), 5.23 (1H, dd, J1 ,2 = 3.7 Hz, H-20),
5.20 (1H, d, H-10), 4.91, 4.59 (2H, each d, JAB = 10.7 Hz,
Ph–CH2–), 4.79, 4.57 (2H, each d, JAB = 11.0 Hz, Ph–
CH2–), 4.63 (1H, d, H-1), 4.59 (1H, dd, J5,6a = 2.1 Hz,
J6a,6b = 11.6 Hz, H-6a), 4.44 (1H, dd, J5,6b = 5.5 Hz, H-
0
0
0
0
Compound 12: d 8.05–7.27 (30H, m, PhH), 6.12 (1H,
0
0
0
0
0
dd, J2 ,3 = 9.6 Hz, J3 ,4 = 9.6 Hz, H-3 ), 5.61 (1H, dd,
J1,2 = 0.8 Hz, J2,3 = 1.1 Hz, H-2), 5.43 (1H, dd,
6b), 4.24 (1H, ddd, J5 ,6a = 1.8 Hz, J5 ,6b = 7.6 Hz H-50),
J4 ,5 = 9.6 Hz, H-40), 5.23 (1H, dd, J1 ,2 = 3.5 Hz, H-20),
5.18 (1H, d, H-10), 4.98, 4.72 (2H, each d, JAB = 10.9 Hz,
Ph–CH2–), 4.85, 4.66 (2H, each d, JAB = 11.0 Hz, Ph–
CH2–), 4.63 (1H, d, H-1) 4.61 (1H, dd, J5,6a = 4.8 Hz,
0
0
0
0
0
0
0
0
4.07 (1H, dd, J6a ,6b = 11.3 Hz, H-6a0), 3.82 (1H, dd,
J3,4 = 9.2 Hz J4,5 = 9.5 Hz, H-4), 3.73 (1H, dd, H-3), 3.69
(1H, dd, H-6b0), 3.61 (1H, ddd, H-5), 3.43 (3H, s,
–OCH3),2.19 (3H, s, –OCOCH3).
0
0
J6a,6b = 12.1 Hz, H-6a), 4.41 (1H, dd, J5,6b = 9.8 Hz, H-
0
0
0
0
0
Compound 11: d 8.00–7.05 (36H, m, PhH, –NH–), 6.05
6b), 4.18 (1H, ddd, J5 ,6a = 3.6 Hz, J5 ,6b = 7.6 Hz, H-5 ),
(1H, dd, J2 ,3 = 9.5 Hz, J3 ,4 = 9.5 Hz, H-30), 5.49 (1H,
4.07 (1H, dd, J6a ,6b = 11.8 Hz, H-6a0), 3.79 (1H, dd,
J3,4 = 9.2 Hz, J4,5 = 9.2 Hz, H-4), 3.74 (1H, dd, H-3), 3.70
(1H, dd, H-6b0), 3.63 (1H, ddd, H-5), 3.44 (3H, s, –OCH3),
2.23 (3H, s, –OCOCH3).
0
0
0
0
0
0
dd, J4 ,5 = 9.8 Hz, H-40), 5.13 (1H, dd, J1 ,2 = 3.0 Hz, H-
20), 5.10 (1H, d, H-10), 5.01 (1H, dd, J1,2 = 7.9 Hz,
J2,3 = 9.5 Hz, H-2), 4.86, 4.59 (2H, each d, JAB = 10.7 Hz,
0
0
0
0