Efficient glycosylation using ods adsorption method based on the affinity of long alkoxybenzyl glycoside

Article abstract of DOI:10.1055/S-2008-1077948

p-Oleyloxybenzyl (POB) glycoside, selectively removable with TMSOTf, was developed as a protecting group for the glycosyl acceptor. Activation of the trichloroacetimidate was efficiently accomplished using 20 mol% of Cu(OTf) ₂. Purification of the resulting glycoside was rapidly and efficiently accomplished by an ODS adsorption method based on the significant affinity of long alkyl chains and the ODS. The procedure is particularly useful for convergent oligosaccharide synthesis.

Full text of DOI:10.1055/S-2008-1077948

LETTER
1981
Efficient Glycosylation Using ODS Adsorption Method Based on the Affinity
of Long Alkoxybenzyl Glycoside
Efficient
Glycosyl
i
ation U
r
sing O
D
o
S
A
dsorption
s
M
ethod hi Imagawa,* Atsushi Kinoshita, Hirofumi Yamamoto, Kosuke Namba, Mugio Nishizawa*
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan
Fax +81(88)6553051; E-mail: mugi@ph.bunri-u.ac.jp
Received 30 April 2008
OBn
AcO
Abstract: p-Oleyloxybenzyl (POB) glycoside, selectively remov-
able with TMSOTf, was developed as a protecting group for the gly-
cosyl acceptor. Activation of the trichloroacetimidate was
efficiently accomplished using 20 mol% of Cu(OTf)2. Purification
of the resulting glycoside was rapidly and efficiently accomplished
by an ODS adsorption method based on the significant affinity of
long alkyl chains and the ODS. The procedure is particularly useful
for convergent oligosaccharide synthesis.
O
BnO
AcO
O
NH
CCl3
(1.2 equiv)
2
OR
OBn
O
–20 °C
AcO
BnO
AcO
OR
OH
CH2Cl2–toluene
(1:1)
O
1a–d
3a–d
Key words: glycosylations, glycosides, octadecylsilane, p-oleyl-
oxybenzyl ether, ODS adsorption
a: R = C6H13, b: R = C12H25, c: R = (CH2)7CH=CH(CH2)8CH3 d: R = C18H37
C6H13 OC6H13
O
O
In recent years, the significance of sugar-chain engineer-
ing has grown rapidly based on an understanding of the
importance of oligosaccharides in numerous biological
events such as cell-to-cell interaction, recognition, in-
flammation, and viral infection.1 Solid-supported oli-
gosaccharide synthesis is one of the methods potentially
useful in providing oligosaccharides at a practical level,
and a variety of procedures have already been devel-
oped.2,3 Recently, several methodologies incorporating
the advantages of both solid- and liquid-phase syntheses,
such as the capture-release strategy, and fluorous and ion-
ic liquid tag methods have been reported.4,5 In 2005,
Rademann and co-workers introduced a novel hydropho-
bically assisted switching-phase method (HASP) for oli-
gosaccharide synthesis based upon the affinity of a
specially designed double-chain anchor with ODS (octa-
decylsilane).6a They carried out the glycosylation in the
solution phase and following purification on the solid
phase, the product, which adsorbed on ODS, was easily
released by washing with CH2Cl2 for the next glycosyla-
tion in the solution phase. However, the hydrophobic an-
chor on the anomeric position is a benzyl ether derivative,
and so can be removed only by catalytic hydrogenation
(or Birch reduction). Thus the deprotection must be car-
ried out at the final step in the oligosaccharide synthesis
since in most cases common benzyl protecting groups are
incorporated. Consequently, this method is not appropri-
ate for the synthesis of the building blocks of a convergent
strategy. Herein we describe selectively removable p-ole-
yloxybenzyl (POB) glycosides, which are useful both as
the anomeric protection for glycosylation in the liquid
phase, and also for the subsequent purification by ODS
4
Scheme 1 Synthesis of p-alkoxybenzyl glycosides
adsorption method, and will be very useful for convergent
oligosaccharide synthesis.7
First we examined the glycosylation of D-mannosyl
trichloroacetimidate 2 with p-hexyloxybenzyl alcohol
(1a) to find the most suitable catalyst (Scheme 1).8 Both
TMSOTf and BF3·OEt2 resulted in decomposition afford-
ing a complex mixture including bisbenzyl ether 4
(Table 1, entry 1 and 2). Although AgOTf did not act as
catalyst, Zn(OTf)2 afforded the glycoside 3a in a quantita-
tive yield with complete a-selectivity after 12 hours in
CH2Cl2–toluene (1:1) at –20 °C (entries 3 and 4). The re-
action using Cu(OTf)2 (20 mol%) was completed within
15 minutes to give 3a in quantitative yield also with com-
plete a-selectivity (entry 5).9 The CuOTf–benzene com-
plex was also a good catalyst giving 3a within one hour
(entry 6). Glycosides 3b and 3c were also obtained by us-
ing Cu(OTf)2 in excellent yields with complete a-selectiv-
ity (entries 7, 8). However, the glycoside 3d was not
obtained due to the poor solubility of 1d under standard
conditions (CH2Cl2–toluene, –20 °C, entry 9).
Next we investigated the purification of glycosides by
ODS adsorption. Although the alkyl chain C6H13 of 3a as
well as C12H25 of 3b were not long enough to adsorb on an
ODS column when eluted with MeCN, the glycoside 3c
was efficiently adsorbed on ODS by elution with MeCN.
The adsorbed 3c was cleanly recovered by elution with
CH2Cl2. When the crude glycosylation product is trans-
ferred to the column of ODS, polar byproducts originated
from the excess glycosyl donor should selectively wash
out by elution with MeCN. Following elution with
CH2Cl2, the desired glycoside should be released effi-
ciently. Therefore, we decided to employ POB (p-oleyl-
SYNLETT 2008, No. 13, pp 1981–1984
x
x
.x
x
.2
0
0
8
Advanced online publication: 15.07.2008
DOI: 10.1055/s-2008-1077948; Art ID: U04508ST
© Georg Thieme Verlag Stuttgart · New York

1982
H. Imagawa et al.
LETTER
OAc
O
Table 1 Preparation of p-Alkoxybenzyl Glycosides
BnO
BnO
BnO
Entry Benzyl Catalysta
alcohol
Time (h) Product Yield (a/b)
OAc
O
BnO
BnO
BnO
O
OBn
O
HO
BnO
HO
a
b
c
OBn
O
3c
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1b
1c
1d
TMSOTf
BF3·OEt2
AgOTf
0.25
0.25
12
3a
3a
3a
3a
3a
3a
3b
3c
3d
Trace (–)
Trace (–)
0 (–)
BnO
O
OPOB
6
8
OPOB
OAc
BnO
BnO
BnO
OAc
O
O
BnO
BnO
BnO
Zn(OTf)2
Cu(OTf)2
12
99 (100:0)b
99 (100:0)b
99 (100:0)b
98 (100:0)b
97 (100:0)b
0 (–)
OAc
O
BnO
BnO
BnO
O
0.25
O
NH
OBn
O
BnO
O
CuOTf–benzene 1
OH
CCl3
9
7
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
0.25
Scheme 2 Synthesis of trisaccharide 9. Reagents and conditions: a,
(i) NaOMe, MeOH, r.t., 1 h; (ii) ODS adsorption, 92%; b, (i)
Cu(OTf)2 (20 mol%), 7 (3.5 equiv), CH2Cl2, r.t., 12 h; (ii) ODS ad-
sorption, 95%; c, TMSOTf (1.5 equiv), wet toluene, 0 °C, 5 min,
72%.
0.25
0.25
a The amount of 20 mol% was used.
b b-Isomer was not detected by 13C NMR.
OAc
BnO
O
BnO
BnO
oxybenzyl) 1c as the protecting group for the anomeric
centers due to its high affinity for ODS.
a
b
OAc
O
9
BnO
BnO
BnO
O
OBn
O
In 2000, Eckhardt and co-workers reported the structure
of Clostridium botulinum C2 toxin ligand 5 by analyzing
the C2 toxin sensitivity of Chinese hamster ovary (CHO)
cell mutants, which are deficient in specific sugar
chains.10 As segments of the N-linked oligosaccharide 5
would be useful in determining which parts of the sugar
chain are essential for binding the C2 toxin, we tried to ap-
ply the present method to prepare a variety of segments of
5 (Figure 1).
BnO
O
10
O
NH
CCl3
TBSO
HO
O
OPOB
BnO
OAc
O
BnO
TrocHN
BnO
BnO
Initially, the glycosyl acceptor 6 was prepared by the
treatment of glycoside 3c with NaOMe in MeOH. The
glycosylation of 6 with an excess of 7 in CH2Cl2 was car-
ried out using Cu(OTf)2 (20 mol%) at 0 °C to give trisac-
charide 8 in 95% yield with complete a-selectivity.12 The
impurities originating from the excess trichloroacetimi-
date 7 were efficiently and quickly removed by passing
through an ODS column using MeCN, and trisaccharide 8
was obtained following elution with CH2Cl2.11 The result-
ing 8 was pure enough to be used in the next reaction.12
The p-oleyloxybenzyl group of 8 was selectively cleaved
by treatment with 1.5 equivalents of TMSOTf in wet (H2O
sat.) toluene at 0 °C for 5 minutes giving rise to 9 in 72%
11
OAc
O
BnO
BnO
BnO
O
OBn
O
BnO
O
OTBS
O
12
O
BnO
OPOB
TrocHN
Scheme 3 Synthesis of tetrasaccharide 12. Reagents and conditi-
ons: a, CCl3CN (5 equiv), DBU (0.2 equiv), CH2Cl2, 0 °C, 3 h, 92%;
b, (i) Cu(OTf)2 (20 mol%), 11 (2 equiv), CH2Cl2, 0 °C, 4 h; (ii) ODS
adsorption, 92%.
HO
HO
HO
O
O
HO
HO
HO
AcHN
HO
HO
HO
O
O
O
O
AcHN
HO
HO
O
OH
O
OH
O
OH
HO
HO
HO
O
HO
O
O
O
HO
O
O
HO
NHAsn
AcHN
AcHN
5
Figure 1 Structure of Clostridium botulinus C2 toxin ligand
Synlett 2008, No. 13, 1981–1984 © Thieme Stuttgart · New York

LETTER
Efficient Glycosylation Using ODS Adsorption Method
1983
AcO
AcO
AcO
O
Ph
O
O
O
O
BnO
+
11
Cu(OTf)2
TrocHN
BnO
TrocHN
O
NH
(20 mol%)
+
6
O
(1.5 equiv)
18
BnO
CH2Cl2–toluene
0 °C, 15 min
CCl3
BnO
55%
O
NH
CCl3
Cu(OTf)2
O
Ph
(20 mol%)
TBSO
O
BnO
O
13
O
O
AcO
AcO
BnO
OPOB
CH2Cl2
r.t., 1 h
98%
O
O
TrocHN
TrocHN
AcO
AcO
AcO
AcO
TrocHN
BnO
19
O
AcO
AcO
AcO
O
O
O
BnO
TrocHN
BnO
BnO
BnO
BnO
+
6
TrocHN
O
NH
CCl3
O
OBn
O
(3 equiv)
AcO
AcO
AcO
20
O
O
O
BnO
O
Cu(OTf)2
14
TrocHN
BnO
OBn
O
AcO
AcO
AcO
OPOB
(20 mol%)
O
O
Scheme 4 Synthesis of pentasaccharide 14
CH2Cl2
r.t., 12 h
TrocHN
OPOB
99%
21
CCl3
OH
O
Ph
O
Scheme 6 Synthesis of glucosamine derivatives 19 and 21
O
O
O
NH
O
BnO
BnO
+
OPOB
TrocHN
O
TrocHN
16
OBn
OBn
BnO
based on the intense affinity of easily available long alkyl-
chain protecting groups with ODS. Furthermore we syn-
thesized segments of Clostridium botulinum C2 toxin
ligand and demonstrated the usefulness of the present pro-
cedure for the construction of oligosaccharides in a con-
vergent synthetic strategy.
15
O
O
OBn
O
Cu(OTf)2
(20 mol%)
OBn
BnO
CH2Cl2–toluene
(1:1)
O
Ph
O
BnO
O
O
BnO
0 °C, 2 h
OPOB
TrocHN
TrocHN
Acknowledgment
(α/β 100:0)
17
100%
This study was financially supported by a Grant-in-Aid from the
Ministry of Education, Culture, Sports, Science, and Technology of
the Japanese Government and a grant for the collaborative research
of Tokushima Bunri University.
Scheme 5 Synthesis of a-core fucose-containing trisaccharide 17
yield (Scheme 2).13 The alcohol 9 was converted to 10 by
treatment with CCl3CN and DBU, and the glycosylation
of 10 with 11 (Troc = 2,2,2-trichloroethoxycarbonyl) af-
forded a tetrasaccharide 12 in 92% yield with excellent a-
selectivity (Scheme 3).14 Purification of 12 was also effi-
ciently achieved using the ODS adsorption method.
References and Notes
(1) (a) Varki, A.; Cummings, R.; Esko, J.; Freeze, H.; Hart, G.;
Marth, J. Essentials of Glycobiology; Cold Spring Harbor
Laboratory Press: New York, 1999. (b) Dwek, R. A.;
Butters, T. A. Chem. Rev. 2002, 102, 283.
(2) (a) Frechet, J. M.; Schuerch, C. J. Am. Chem. Soc. 1971, 93,
492. (b) Danishefsky, S. J.; McClure, K. F.; Randolph, J. T.;
Ruggeri, R. B. Science 1993, 260, 1307. (c) Seeberger, P.
H.; Haase, W.-C. Chem. Rev. 2000, 100, 4349.
In contrast, the reaction of diol 6 with trichloroacetimidate
13 catalyzed by Cu(OTf)2 afforded a mixture of stereoiso-
mers of a pentasaccharide after quick purification by the
ODS adsorption method. After further purification of the
mixture by normal-phase HPLC, a,a-isomer 14 was ob-
tained in 55% yield (Scheme 4).
(3) Recent reports of solid-supported glycosylations: (a) Liang,
R.; Yan, L.; Loebach, J.; Ge, M.; Uozumi, Y.; Sekanina, K.;
Horan, N.; Gildersleeve, J.; Thompson, C.; Smith, A.;
Biswas, K.; Still, W. C.; Kahne, D. Science 1996, 274, 1520.
(b) Nicolaou, K. C.; Watanabe, N.; Li, J.; Pastor, J.;
Winssinger, N. Angew. Chem. Int. Ed. 1998, 37, 1559.
(c) Andrade, R. B.; Plante, O. J.; Melean, L. G.; Seeberger,
P. H. Org. Lett. 1999, 1, 1811. (d) Hummel, G.; Hindsgaul,
O. Angew. Chem. Int. Ed. 1999, 38, 1782. (e) Roussel, F.;
Knerr, L.; Grathwohl, M.; Schmidt, R. R. Org. Lett. 2000, 2,
3043. (f) Plante, O. J.; Palmacci, E. R.; Seeberger, P. H.
Science 2001, 291, 1523. (g) Lam, S. N.; Gervay-Hague, J.
Carbohydr. Res. 2002, 337, 1953. (h) Wu, X.; Grathwohl,
M.; Schmidt, R. R. Angew. Chem. Int. Ed. 2002, 41, 4489.
(i) Mogemark, M.; Elofsson, M.; Kihlberg, J. J. Org. Chem.
2003, 68, 7281. (j) Ratner, D. M.; Swanson, E. R.;
The synthesis of the core fucose-containing segment 17
was successfully achieved by the glycosylation of 15 with
16 giving a-isomer 17 in a quantitative yield.12 No trace of
the b-isomer was detected by 13C NMR after purification
by the ODS adsorption method (Scheme 5). Chitobiose
derivative 19 and trisaccharide segment 21 were also ob-
tained in 98% and 99% yield, respectively, by using this
methodology (Scheme 6).12,15
Therefore, we have developed an efficient glycosylation–
purification procedure using an ODS adsorption method
Synlett 2008, No. 13, 1981–1984 © Thieme Stuttgart · New York

1984
H. Imagawa et al.
LETTER
the mixture was stirred for 20 min. To this was added a
Seeberger, P. H. Org. Lett. 2003, 5, 4717. (k) Mogemark,
M.; Gustafsson, L.; Bengtsson, C.; Elofsson, M.; Kihlberg,
J. Org. Lett. 2004, 6, 4885. (l) Love, K. R.; Seeberger, P. H.
Angew. Chem. Int. Ed. 2004, 43, 602. (m) Jaunzems, J.;
Kashin, D.; Schönberger, A.; Kirschning, A. Eur. J. Org.
Chem. 2004, 3435. (n) Ako, T.; Daikoku, S.; Ohtsuka, I.;
Kato, R.; Kanie, O. Chem. Asian J. 2006, 1, 798. (o) Kanie,
O.; Ohtsuka, I.; Ako, T.; Daikoku, S.; Kanie, Y.; Kato, R.
Angew. Chem. Int. Ed. 2006, 45, 3851. (p) Jonke, S.; Liu,
K.-g.; Schmidt, R. R. Chem. Eur. J. 2006, 12, 1274.
(q) Matsushita, T.; Hinou, H.; Fumoto, M.; Kurogochi, M.;
Fujitani, N.; Shimizu, H.; Nishimura, S.-I. J. Org. Chem.
2006, 71, 3051. (r) Doi, T.; Kinbara, A.; Inoue, H.;
solution of trichloroacetimidate 7 (936 mg, 1.47 mmol) in
CH2Cl2 (3 mL) using a syringe drive over a period of 1 h, and
the mixture was stirred for 12 h at the same temperature. The
reaction was terminated by the addition of Et3N (720 mg,
7.12 mmol). Insoluble material was removed by passing
through a cotton Celite pad, and the filtrate was concentrated
under reduced pressure. The resulting material was
dissolved in MeCN (100 mL) and adsorbed onto an ODS
column (20 g), and the polar byproducts were eluted with
MeCN (100 mL). Trisaccharide 8 (666 mg, 95% yield) was
recovered by the elution with CH2Cl2.
Compound 8: [a]D22 +41.5 (c 1.9, CHCl3). FT-IR (neat):
3087, 3062, 3004, 2925, 2855, 1951, 1878, 1809, 1745,
1611, 1585, 1511, 1496, 1454, 1368, 1285, 1237, 1132,
1101, 1050, 1026, 981, 913, 840, 736, 699, 604 cm–1. 1H
NMR (400 MHz, CDCl3): d = 0.89 (3 H, t, J = 6.8 Hz), 1.27–
1.46 (22 H, m), 1.74–1.81 (2 H, m), 2.01–2.07 (4 H, m), 2.09
(3 H, s), 2.17 (3 H, s), 3.61–3.70 (3 H, m), 3.73–3.78 (2 H,
m), 3.82–3.95 (11 H, m), 3.99 (1 H, dd, J = 9.2, 3.2 Hz), 4.03
(1 H, dd, J = 9.2, 3.2 Hz), 4.19 (1 H, dd, J = 9.6, 3.2 Hz),
4.31 (1 H, d, J = 11.6 Hz), 4.41–4.70 (12 H, m), 4.54 (1 H,
d, J = 11.6 Hz), 4.76 (1 H, d, J = 11.2 Hz), 4.83 (1 H, d,
J = 1.6 Hz), 4.88 (2 H, dd, J = 10.8, 3.2 Hz), 4.98 (1 H, d,
J = 2.0 Hz), 5.20 (1 H, d, J = 1.6 Hz), 5.33–5.41 (2 H, m),
5.50–5.52 (2 H, m), 6.75–6.78 (2 H, m), 7.12–7.35 (42 H,
m). 13C NMR (100 MHz, CDCl3): d = 14.4 (q), 21.3 (q), 21.5
(q), 22.3 (t), 26.3 (t), 27.4 (t), 29.5–30.0 (many t), 32.2 (t),
32.9 (t), 66.7 (t), 68.2 (t), 68.7 (d, 2 C), 68.9 (t), 69.0 (d), 69.2
(t), 71.5 (d), 71.6 (d, 2 C), 72.0 (t), 72.4 (d), 72.4 (t), 73.6 (t),
73.6 (t), 74.4 (d), 74.5 (d), 75.2 (t), 75.3 (d), 75.4 (t), 77.5 (d),
77.8 (d), 77.9 (d), 78.3 (d), 79.0 (d), 95.7 (d), 98.2 (d), 99.9
(d), 114.6 (d), 127.7–130.2 (many d), 138.0 (s), 138.1 (s),
138.1 (s), 138.3 (s), 138.5 (s), 138.5 (s), 138.8 (s), 138.9 (s),
159.0 (s), 170.4 (s), 170.6 (s). MS (FAB, m-NBA): m/z =
1689 [M + Na]+. HRMS (FAB): m/z calcd for C103H124O19Na
[M + Na]+: 1687.8635; found: 1687.8654.
Takahashi, T. Chem. Asian J. 2007, 2, 188. (s) Manabe, S.;
Ueki, A.; Ito, Y. Chem. Commun. 2007, 3673.
(4) (a) Ando, H.; Manabe, S.; Nakahara, Y.; Ito, Y. Angew.
Chem. Int. Ed. 2001, 40, 4725. (b) Egusa, K.; Kusumoto, S.;
Fukase, K. Synlett 2001, 777. (c) Ito, Y.; Manabe, S. Chem.
Eur. J. 2002, 8, 3077. (d) Egusa, K.; Kusumoto, S.; Fukase,
K. Eur. J. Org. Chem. 2003, 3435. (e) Hanashima, S.;
Manabe, S.; Ito, Y. Synlett 2003, 979. (f) MacCoss, R. N.;
Brennan, P. E.; Ley, S. V. Org. Biomol. Chem. 2003, 1,
2029. (g) Hanashima, S.; Manabe, S.; Inamori, K.-I.;
Taniguchi, N.; Ito, Y. Angew. Chem. Int. Ed. 2004, 43,
5674. (h) Komba, S.; Kitaoka, M.; Kasumi, T. Eur. J. Org.
Chem. 2005, 5313. (i) Fukase, K.; Takashina, M.; Hori, Y.;
Tanaka, D.; Tanaka, K.; Kusumoto, S. Synlett 2005, 2342.
(j) Hanashima, S.; Manabe, S.; Ito, Y. Angew. Chem. Int. Ed.
2005, 44, 4218. (k) Wu, J.; Guo, Z. J. Org. Chem. 2006, 71,
7067.
(5) The glycosylations using fluorous tags: (a) Curran, D. P.;
Ferritto, R.; Hua, Y. Tetrahedron Lett. 1998, 39, 4937.
(b) Goto, K.; Miura, T.; Mizuno, M.; Takaki, H.; Imai, N.;
Murakami, Y.; Inazu, T. Synlett 2004, 2221. (c) Jing, Y.;
Huang, X. Tetrahedron Lett. 2004, 45, 4615. (d) Miura, T.;
Inazu, T. Tetrahedron Lett. 2003, 44, 1819. (e) Manzoni,
L.; Castelli, R. Org. Lett. 2004, 6, 4195. (f) Mizuno, M.;
Matsumoto, H.; Goto, K.; Hamasaki, K. Tetrahedron Lett.
2006, 47, 8831. (g) The glycosylation using ionic tag:
Kojima, M.; Nakamura, Y.; Takeuchi, S. Tetrahedron Lett.
2007, 48, 4431. (h) Pathak, A. K.; Yerneni, C. K.; Young,
Z.; Pathak, V. Org. Lett. 2008, 10, 145.
(6) (a) Bauer, J.; Rademann, J. J. Am. Chem. Soc. 2005, 127,
7296. (b) An affinity of polyethylene glycol linker with
silica gel was used for purification of glycoside. See: Jiang,
L.; Hartley, R. C.; Chan, T.-H. Chem. Commun. 1996, 2193.
(7) The synthesis of rhamnoside by using p-dodecyloxybenzyl
ether as a protection of an alcohol at C-2 was reported. See:
Pozsgay, V. Org. Lett. 1999, 1, 477.
(8) Critchley, P.; Clarkson, G. J. Org. Biomol. Chem. 2003, 1,
4148.
(9) The Cu(OTf)2-prompted glycosylation in benzotrifluoride
was reported. See: Yamada, H.; Hayashi, T. Carbohydr. Res.
2002, 337, 581.
(12) No other products were detected in the 13C NMR spectrum
of the saccharide.
(13) In the reaction using 2-acetylated trichloroacetimidate as
glycosyl donor, an ortho ester such as 22 was produced as an
intermediate. By continuing treatment with Cu(OTf)2 (12 h),
the ortho ester was transformed to the desired glycoside
(Figure 2).
OR
O
BnO
BnO
BnO
O
O
22
Figure 2
(14) The anomeric stereochemistry of 12 was determined from
the coupling constants JCH for anomeric carbons (164 Hz).
Although the b-isomer was separable using HPLC, it was not
possible to determine the stereochemistry by NMR
(10) Eckhardt, M.; Barth, H.; Blöcker, D.; Aktories, K. J. Biol.
Chem. 2000, 275, 2328.
(11) Synthesis of Trisaccharide 8 Using an ODS Adsorption
Method – General Procedure
spectroscopy due to insufficient sample. However, as the
high-resolution mass spectrum suggested the structure of a
tetrasaccharide, we concluded the stereochemistry is b.
(15) Compound 16 was prepared in 96% yield from the
disaccharide 19 by treatment with HF·pyridine.
To a stirred suspension of Cu(OTf)2 (30 mg, 0.084 mmol)
and 4 Å MS (powder, 50 mg) in anhyd CH2Cl2 (3 mL) was
added a solution of diol 6 (300 mg, 0.42 mmol) at r.t., and
Synlett 2008, No. 13, 1981–1984 © Thieme Stuttgart · New York