Efficient synthesis of core 2 class glycosyl amino acids by one-pot glycosylation approach

Article abstract of DOI:10.1016/j.tetlet.2003.12.042

We describe the one-pot synthesis of core 2 class branched oligosaccharides initiated by chemo-selective glycosylation of silyl ether. Glycosylation of 6-O-silyl-4-benzyl-2-azido-thiogalactoside with glycosyl fluoride provided selectively 6-glycosylated thioglycoside without both O-glycosylation at the 3 position and S-glycosylation. Subsequent coupling of galactosyl fluoride and amino acids afforded the protected branched oligosaccharides in good yields.

Full text of DOI:10.1016/j.tetlet.2003.12.042

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 1433–1436
Efficient synthesis of core 2 class glycosyl amino acids by one-pot
glycosylation approachq
Hiroshi Tanaka, Masaatsu Adachi and Takashi Takahashi*
Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, 2-12-1 Ookayama,
Meguro, Tokyo 152-8552, Japan
Received 20 October 2003; revised 5 December 2003; accepted 10 December 2003
Abstract—We describe the one-pot synthesis of core 2 class branched oligosaccharides initiated by chemo-selective glycosylation of
silyl ether. Glycosylation of 6-O-silyl-4-benzyl-2-azido-thiogalactoside with glycosyl fluoride provided selectively 6-glycosylated
thioglycoside without both O-glycosylation at the 3 position and S-glycosylation. Subsequent coupling of galactosyl fluoride and
amino acids afforded the protected branched oligosaccharides in good yields.
ꢀ 2003 Elsevier Ltd. All rights reserved.
Glycoconjugatges on cell surface such as glycoproteins
play important roles in biological events.1 Ligation of
the proteins with several saccharides modulate their
biological functions. However, it is relatively difficult to
elucidate the structure–activity relationships of individ-
ual glycoforms as most of the glycoproteins isolated
form cultured cells contain several different glycoforms.
library. Most of the methodologies are based on
sequential activation of glycosyl donors to provide lin-
ear oligosaccharides. Few approaches involve regio-
selective glycosylation in the sequential glycosylation
HO
O
HO
O
HO
AcHN
OH
Galb(1 fi 3)-[GlcNAcb(1 fi 6)]-GalNAca(1 fi 3)-Ser and
-Thr (1a and 1b) are contained in mucin type glyco-
proteins, and are named core 2 class glycosyl amino
acids (Scheme 1).2 Various di-branched N-acetyl galac-
tosaminyl derivatives at their 3 and/or 6 positions are
found in related glycoproteins. To elucidate the bio-
logical functions of the oligosaccharides, as well as the
glycoproteins, chemical tools composed of the corre-
sponding glycosyl amino acids are effective.3;4 Therefore,
an effective methodology for the synthesis of galacto-
samine derivatives varying not only in the branching
saccharides but also in the amino acids, is required.
HO
HO
HO
O
O
O
NH2
O
AcHN
HO
O
OH
1a : R1 = H
1b : R1 = Me
R1
i
AcO
AcO
AcO
O
X
TrocHN
OSiR2
2a : X = β-F
3
BnO
One-pot sequential glycosylation5–8 is one of the most
effective solution-phase methodologies not only for the
high speed synthesis of a target oligosaccharide but also
for the combinatorial synthesis of an oligosaccharide
2b : X = α-OC(=NH)CCl3
O
SPh
HO
N3
iii
ii
NHFmoc
OBn
OBn
O
BnO
BnO
3a : R2 = Me
3b : R2 = Et
HO
Y
O
R1
BzO
5a : R1 = H
Keywords: Glycosyl amino acids; One-pot glycosylation; Glycopep-
tides; Glycosyl fluorides; Oligosaccharide.
q Supplementary data associated with this article can be found, in the
online version, at doi:10.1016/j.tetlet.2003.12.042
* Corresponding author. E-mail: ttak@apc.titech.ac.jp
4 : Y =β-F
5b : R1 = Me
Scheme 1. Strategy for the one-pot synthesis of core 2 class amino
acids 1.
0040-4039/$ - see front matter ꢀ 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.12.042

1434
H. Tanaka et al. / Tetrahedron Letters 45 (2004) 1433–1436
process, and are effective for the synthesis of various
branched oligosaccharides.9 We have already reported a
combinatorial one-pot synthesis of linear and branched
trisaccharide libraries containing 3,6 branched gluco-
sides and mannosides.9b The success of the one-pot
synthesis of the branched oligosaccharides depends lar-
gely on the selectivity of the regio-selective glycosyl-
ation. However, the difference of the reactivity of the 3,6
di-hydroxyl groups of galactoside is not enough to
selectively glycosylate at 6 position due to an axial ori-
entated C4 hydroxyl group. Therefore, the one-pot
synthesis of 3,6 branched galactosides have not been
successful. Herein we describes the one-pot synthesis of
core 2 class amino acids 1a and 1b involving chemo-
selective glycosylation of silyl ether at 6 position of
galactoside.
Reductive cleavage of the acetal, followed by deprotec-
tion of silyl ether provided diol 8 in 62% yield in two
steps. Treatment of 8 with TMSCl or TESCl under basic
conditions selectively afforded mono-silyl ether 3a and
3b in 95% and 92% yields, respectively.
Glycosylation of thioglycosides 3 using glycosyl fluoride
2a13c;d with several activating reagents was examined
(Table 1and Scheme 2). An equivalent of BF 3ÆOEt2 was
found to be an effective reagent for glycosylation of
trimethyl ether 3a to give disaccharide 9 in excellent
yield (97%) (entry 1). Treatment of 2a and 3a with cat-
alytic amounts of BF3ÆOEt2 provided disaccharide 9
(66% yield) along with formation of small amounts of
trisaccharide 10 (2% yield) (entry 2). Glycosylation of
the triethylsilyl ether 3b under the same reaction con-
ditions afforded disaccharide 9 in reduced yield (74%)
(entry 3). When diol 8 was used as a glycosyl acceptor
for glycosyl fluoride 2a, significant amounts of thiogly-
coside 11 and trisaccharide 10 were generated (entry 4).
Glycosidation of glycosyl imidate 2b13b with diol 3 in the
presence of a catalytic amount of BF3ÆOEt2 at )78 °C
resulted in the yield of disaccharide 9 in 70% yield along
with thioglycoside 11 in 12% yield (entry 5). Thiogly-
coside 11 was generated via S-glycosylation, which is
often observed in the chemo-selective glycosylation of
thioglycosides with more disarmed donors.14 These
results indicate that the combination of trimethylsilyl
ether and a stoichometric amount of BF3ÆOEt2 is
essential for the chemo- and regio-selective glycosylation
with glycosyl fluoride 2a. Boron trifluoride complex with
the trimethylsilyl ether would make it more nucleophilic
to provide disaccharide 9 without both undesired O- and
S-glycosylations.
Strategy for the one-pot synthesis of 1a and 1b is shown
in Scheme 1. 6-O-Silyl protected 2-azido thiogalacto-
sides 3 was designed as a key intermediate. The silyl
ether would promote selective introduction of glycosyl
fluoride at the 6 position.10 The 2-azido substituent of
thioglycoside 3 could be effective for the formation of
the a-glycosidic linkage to amino acids.11 The one-pot
synthesis would be initiated by (i) chemo-selective
glycosylation of the silyl ether in the thiogalactosides 3
with glucosamine 2. Subsequent (ii) glycosylation of the
remaining hydroxyl group at 3 position with galactoside
4, followed by (iii) coupling with amino acids 5 provides
protected glycosyl amino acids. On the basis of our re-
ported branched one-pot glycosylation, there is a dif-
ferent pathways for the coupling of the two fragments 4
and 5 (iii fi ii). However, the coupling sequence involves
regio-selective glycosylation of the secondary hydroxyl
group of threonine 5b in the presence of the remaining
C3 secondary hydroxyl group.
The one-pot synthesis of glycosyl amino acids 1a and 1b
is illustrated in Scheme 3. Chemo-selective glycosylation
of 3a with 2a in the presence of BF3ÆOEt2, followed by
sequential coupling of the remaining secondary hydro-
xyl groups of 9 with glycosyl fluoride 4 in the presence of
Preparation of thiogalactosamine 3a and 3b is shown in
Scheme 2. 2-Azido-thioglycoside 612 was converted to
3,6-benzylidene derivative 7 by three steps in 86% yield.
Ph
OR1
BnO
OAc
AcO
a, b, c
d, e
O
O
O
O
AcO
SPh
HO
O
SPh
TBSO
SPh
N3
N3
N3
8 : R1 = H
3a : R1 = SiMe3
3a : R1 = SiEt3
g
6
f
7
AcO
AcO
AcO
TrocHN
BnO
O
Table 1
CH2Cl2
AcO
AcO
AcO
O
O
+
SPh
TrocHN
O
R2O
SPh
11
N3
9 : R2 = H
10 : R2 =
AcO
AcO
AcO
TrocHN
O
Scheme 2. Reagents and conditions: (a) NaOMe, MeOH; (b) PhCH(OMe)2, CSA, DMF, 80 °C; (c) TBSCl, imidazole, DMF, 86% in three steps; (d)
BH3ÆTHF, Bu2BOTf; (e) 40% aq HF, CH3CN, 62% in two steps; (f) TMSCl, Et3N, CH2Cl2, 95%; (g) TESCl, Et3N, CH2Cl2, 92%.

H. Tanaka et al. / Tetrahedron Letters 45 (2004) 1433–1436
Table 1. Chemo-selective glycosylation of 3a, 3b and 8 with 2
1435
Entry
Donor (equiv)a
Acceptor
BF3ÆEt2O
(equiv)b
Temperature
(°C)
Yield of 9
(%)
Yield of 10
(%)
Yield of 11
(%)
1
2
3
4
5
2a (1.40)
2a (1.40)
2a (1.40)
2a (1.10)
2b (1.10)
3a
3a
3b
8
1.00
0.50
1.00
1.00
0.05
0
0
97
66
74
48
70
––
––
2
2
0
9
12
Trace
12
12
0
8
)78
Trace
a Based on the acceptor 3a, 3b or 8.
b Based on the donor 2a or 2b.
solid-supported piperazine,18 to provide the corre-
sponding amines 15a-a and 15b-a in 82% and 93% yields.
Hydrogenolysis of the benzyl ethers and ester, followed
by hydrolysis of the benzoate provided the fully depro-
tected core 2 trisaccharides 1a and 1b in 96% and 93%
yields, respectively. Their analytical data (1H and 13C
NMR, MS) were identical with those previously re-
ported.3a;b
AcO
AcO
AcO
O
O
2a
TrocHN
a
b
BnO
BnO
BnO
OBn
O
+
8
O
3a
O
SPh
N3
BzO
12
AcO
AcO
AcO
In conclusion, we have demonstrated an effective one-
pot synthesis of the core 2 class branched glycosyl amino
acids 1a and 1b initiated by chemo-selective glycosyl-
ation of the trimethylsilyl ether of 4a with glycosyl
fluoride 2a in the presence of BF3ÆEt2O. Boron trifluo-
ride complex with the trimethylsilyl ether would enhance
the nucleophilicity of the silyl ether. This methodology
would be effective for the synthesis of branched oligo-
saccharide libraries.
O
Y
O
c
f, g
1a and 1b
BnO
BnO
OBn
O
O
X
O
BnO
NHZ
O
BzO
O
OBn
R1
a : R1 = H
b : R1 = Me
13 : X = N3, Y = NHTroc, Z = Fmoc
14 : X = Y = NHAc, Z = Fmoc
15 : X= Y = NHAc, Z = H
d
e
Supporting information available. Experimental proce-
dures for synthesis and full characterization for all
compounds.
Scheme 3. Reagents and conditions: (a) 2a (1.40 equiv), 3a
(1.00 equiv), BF3ÆOEt2 (2.25 equiv), CH2Cl2, MS4A, 0 °C; (b)
4
(1.45 equiv), ZrCp2Cl2, AgOTf, 0 °C; (c) 5a or 5b (1.50 equiv), NIS,
TfOH, )50 °C, toluene–CH2Cl2 (1:1), 75% for 13a, and 68% for 13b in
one-pot three steps; (d) Zn dust, THF, AcOH, Ac2O, 0 °C, 87% for
14a-a, and 89% for 14b-a; (e) piperazinomethyl polystylene, THF, rt,
82% for 15a-a and 93% for 15b-a; (f) Pd(OH)2, THF, MeOH, H2O; (g)
0.1N NaOH, MeOH, rt, 96% for 1a and 93% for 1b in two steps.
Acknowledgements
This work was supported by a Grand-in-Aid for Scien-
tific Research on Priority Area (S) from the Ministry of
Education, Culture, Sports, Science and Technology
(Grant-in-Aid No. 14103013). We also thank Mr.
Tamotsu Yamamoto (Asahi Chemical Industry Co.,
Ltd.) for mass spectral analysis.
ZrCp2Cl2/AgOTf15 provided 12. Subsequent glycosida-
tion of thioglycoside 12 with amino acids 5a and 5b by
NIS/TfOH16 in toluene–CH2Cl2 (1:1) provided the
amino acids 13a and 13b in 75% (a=b ¼ 63=37) and 68%
(a=b ¼ 60=40) yields, respectively.17 Further examina-
tion of the a-selective glycosidation of 12 using several
solvents and additives unfortunately did not result in
better reaction conditions applicable to the one-pot
three-step reaction. Separation of the a=b mixture of 13a
and 13b was performed by preparative thin layer chro-
matography for 13a and by column chromatography on
silica gel for 13b to give the corresponding pure isomers
13a-a, 13a-b, 13b-a and 13b-b.
References and notes
1. (a) Varki, A.; Cunnings, R.; Esko, J.; Freeze, H.; Hart, G.;
Marth, J. Essentials of Glycobiology; Cold Spring Harbor
Laboratory: New York, 1999; (b) Ernst, B.; Hart, G. W.;
Sinay, P. In Carbohydrates in Chemistry and Biology;
Willy-VCH: Weinheim, 2000; Vols. 3 and 4.
2. (a) Hilkens, J.; Ligtenberg, M. J. L.; Vos, H. L.; Litvinov,
S. L. Trends Biochem. Sci. 1992, 17, 359–363; (b) Verma,
M.; Davidson, E. A. Glycoconjugate J. 1994, 11, 172–179;
(c) Hanisch, F.-G. Biol. Chem. 2001, 382, 143–149.
3. For synthesis of core 2 class structure, see: (a) Paulsen, H.;
Rauwald, W.; Weichert, U. Liebigs Ann. Chem. 1988, 75–
88; (b) Qiu, D.; Koganty, R. R. Tetrahedron Lett. 1997,
38, 45–48; (c) Meinjohanns, E.; Meldal, M.; Schleyer, A.;
Paulsen, H.; Bock, K. J. Chem. Soc., Perkin Trans. 1 1996,
985–993; (d) Mathieux, N.; Paulsen, H.; Meldal, M.;
Transformation of 13a-a and 13b-a to 1a and 1b is as
follows. The simultaneous reduction of the azido and
Troc groups of 13a-a and 13b-a,13a followed by acetyl-
ation provided the corresponding N-acetyl derivatives
14a-a and 14b-a in 87% and 89% yields. Complete
deprotection of 14a-a and 14b-a was accomplished in
three steps involving removal of the Fmoc group by

1436
H. Tanaka et al. / Tetrahedron Letters 45 (2004) 1433–1436
Bock, K. J. Chem. Soc., Perkin Trans. 1 1997, 2359–2368;
(e) Takano, Y.; Habiro, M.; Someya, M.; Hojo, H.;
1h, the reaction mixture was cooled to )50 °C. A solution
of 6a (1.50 equiv), azeotroped three times with toluene, in
dry CH2Cl2 and dry toluene was added to the reaction
mixture. After 10 min, N-iodosuccinimide (2.00 equiv) and
a catalytic amount of trifluoromethanesulfonic acid was
added to the reaction mixture at )50 °C. After stirring at
the same temperature for 1.5 h, the reaction mixture was
neutralized with triethylamine and filtered through a pad
of Celite. The filtrate was poured into a mixture of
saturated aq NaHCO3 and saturated aq Na2S2O3 with
cooling. The aqueous layer was extracted with two
portions of ethyl acetate. The combined extracts were
washed with a mixture of saturated aq NaHCO3 and
saturated aq Na2S2O3 and brine, dried over MgSO4,
filtered and evaporated in vacuo. The residue was chro-
matographed on silica gel and further purified by gel
Nakahara, Y. Tetrahedron Lett. 2002, 43, 8395–8399.
4. For recent reviews of glycopeptides synthesis, see: (a)
Herzner, H.; Reipen, T.; Schultz, M.; Kunz, H. Chem.
Rev. 2000, 100, 4495–4537; (b) Seitz, O.; Heinemann, I.;
Mattes, A.; Waldmann, H. Tetrahedron 2001, 57, 2247–
2277; (c) Marcaurelle, L. A.; Bertozzi, C. R. Glycobiology
2002, 12, 69R–77R.
5. Raghavan, S.; Kahne, D. J. Am. Chem. Soc. 1993, 115,
1580–1581.
6. (a) Yamada, H.; Harada, T.; Miyazaki, H.; Takahashi, T.
Tetrahedron Lett. 1994, 35, 3979–3982; (b) Yamada, H.;
Harada, T.; Takahashi, T. J. Am. Chem. Soc. 1994, 116,
7919–7920.
€
7. Douglas, N. L.; Ley, S. L.; Lucking, U. L.; Warriner, S. L.
J. Chem. Soc., Perkin Trans. 1 1998, 51–65.
permeation chromatography (GPC) to give 12a-a and 12a-b
25
D
8. Zang, Z.; Ollmann, I. R.; Ye, X.-S.; Wischnat, R.; Baasov,
T.; Wong, C.-H. J. Am. Chem. Soc. 1999, 121, 734–753.
9. (a) Yamada, H.; Kato, T.; Takahashi, T. Tetrahedron
Lett. 1999, 40, 4581–4584; (b) Takahashi, T.; Adachi, M.;
Matsuda, A.; Doi, T. Tetrahedron Lett. 2000, 41, 2599–
2603; (c) Yamada, H.; Takimoto, H.; Ikeda, T.; Tsuka-
moto, H.; Harada, T.; Takahashi, T. Synlett 2001, 1751–
1754; (d) Tanaka, H.; Adachi, M.; Tsukamoto, H.; Ikeda,
T.; Yamada, H.; Takahashi, T. Org. Lett. 2002, 4, 4213–
4216, and references cited therein.
10. (a) Hashimoto, S.; Hayashi, M.; Noyori, R. Tetrahedron
Lett. 1984, 25, 1379–1382; (b) Kunz, H.; Sager, W. Helv.
Chim. Acta 1985, 68, 283–287; (c) Yoshizaki, H.; Fukuda,
N.; Sato, K.; Oikawa, M.; Fukase, K.; Suda, Y.; Kusu-
moto, S. Angew. Chem., Int. Ed. 2001, 40, 1475–1480.
11. Paulsen, H.; Stenzen, W. Angew. Chem., Int. Ed. 1975, 41,
558–559.
(75% yield, a:b ¼ 63:37). Spectra of 12a-a: ½aŠ +32.9°
1
(c 1.07, CHCl3); H NMR (400 MHz, CDCl3) d 8.07 (d,
2H), 7.74 (m, 2H), 7.56 (m, 2H), 7.14–7.45 (m, 34H), 6.13
(d, 1H, J ¼ 6:8 Hz), 6.14 (d, 1H, J ¼ 7:2 Hz), 5.74 (dd, 1H,
J ¼ 8:2 Hz, J ¼ 8:2 Hz), 5.58 (dd, 1H, J ¼ 9:7 Hz,
J ¼ 10:1Hz), 5.22 (d, 1H, J ¼ 12:1 Hz), 5.13 (d, 1H,
J ¼ 12:6 Hz), 5.05 (d, 1H, J ¼ 11:6 Hz), 4.94 (d, 1H,
J ¼ 10:6 Hz), 4.93 (dd, 1H, J ¼ 9:2 Hz, J ¼ 9:2 Hz), 4.77
(d · 2, 2H, J ¼ 7:7 Hz), 4.40–4.74 (m, 11H), 4.32 (m, 1H),
4.22 (m, 1H), 4.18 (dd, 1H, J ¼ 3:9 Hz, J ¼ 7:7 Hz), 4.00
(br s, 1H), 3.97 (m, 2H), 3.92 (br s, 1H), 3.87 (dd, 1H,
J ¼ 1:9 Hz, J ¼ 10:6 Hz), 3.49–3.72 (m, 9H), 3.21(ddd,
1H, J ¼ 6:8 Hz, J ¼ 7:6 Hz, J ¼ 9:2 Hz), 1.98, 1.93, 1.91
(3s, 9H); 13C NMR (100 MHz, CDCl3) d 170.5, 170.0,
169.5 · 2, 165.3, 155.8, 153.8, 143.7, 143.5, 141.2, 141.2,
138.4, 138.2, 137.4, 134.9, 132.8, 130.1, 129.7, 128.8, 128.6,
128.5, 128.3, 128.2, 128.0, 128.0, 127.8, 127.7, 127.6, 127.4,
127.1, 127.1, 125.0, 120.0, (103.0, 99.8, 98.8 (anomeric)),
95.6, 79.5, 77.5, 77.2, 75.3, 74.5, 74.1, 73.5, 72.7, 71.9, 71.8,
71.3, 70.9, 70.2, 69.6, 68.9, 68.7, 68.2, 67.7, 67.1, 62.0, 59.0,
56.9, 54.3, 47.0, 29.6, 20.5; IR (solid) 3333, 2927, 2110,
12. Lemieux, R. U.; Ratcliffe, R. M. Can. J. Chem. 1979, 57,
1244–1251.
13. (a) Windholz, T. B.; Johnston, D. B. R. Tetrahedron Lett.
1967, 8, 2555–2557; (b) Paulsen, H.; Helpap, B. Carbo-
hydr. Res. 1991, 216, 289–313; (c) Ellervik, U.; Magnus-
son, G. Carbohydr. Res. 1996, 280, 251–260; (d) Nakano,
J.; Ichiyanagi, T.; Ohta, H.; Ito, Y. Tetrahedron Lett. 2003,
44, 2853–2856.
1747, 1733, 1534, 1454, 1236, 1071, 795, 741, 699 cmÀ1
;
MS (FAB) calcd for C87H89Cl3N5O24 [M+H]þ 1695, found
25
D
1695; Spectra of 12a-b: ½aŠ )2.1° (c 1.02, CHCl3); 1H
NMR (400 MHz, CDCl3) d 8.10 (d, 2H), 7.75 (d, 2H),
7.04–7.54 (m, 34H), 6.15 (d, 1H, J ¼ 9:2 Hz), 5.73 (d, 1H,
J ¼ 9:7 Hz, J ¼ 10:1Hz), 5.62 (d, 1H, J ¼ 8:2 Hz), 5.41(d,
1H, J ¼ 13:0 Hz), 5.15 (d, 1H, J ¼ 13:0 Hz), 5.13 (dd, 1H,
J ¼ 8:7 Hz, J ¼ 11:6 Hz), 5.05 (d, 1H, J ¼ 11:6 Hz), 5.00
(d, 1H, J ¼ 11:6 Hz), 4.95 (dd, 1H, J ¼ 9:2 Hz,
J ¼ 10:1Hz), 4.79 (d, 1H, J ¼ 12:1Hz), 4.72 (d, 1H,
J ¼ 7:7 Hz), 4.69 (d, 1H, J ¼ 12:6 Hz), 4.65 (m, 3H), 4.63
(d, 1H, J ¼ 11:6 Hz), 4.60 (d, 1H, J ¼ 11:6 Hz), 4.56 (d · 2,
2H, J ¼ 12:6 Hz), 4.38 (m, 2H), 4.31(d, 1H, J ¼ 10:7 Hz),
4.23–4.30 (m, 2H), 4.11–4.18 (m, 3H), 4.02 (br s, 1H,
J ¼ 1:4 Hz), 3.92 (m, 1H), 3.55–3.82 (m, 9H), 3.40 (dd,
1H), 3.31 (dd, 1H, J ¼ 2:0 Hz, J ¼ 10:7 Hz), 3.03 (m, 1H),
2.04, 1.97, 1.94 (3s, 9H); 13C NMR (100 MHz, CDCl3)
d 170.6, 170.3, 169.4, 165.3, 155.8, 154.3, 143.8, 143.7,
141.2, 138.5, 137.9, 137.6, 135.0, 132.9, 130.1, 129.7, 129.3,
128.7, 128.6, 128.4, 128.2, 128.0, 127.9, 127.8, 127.7, 127.7,
127.6, 127.5, 125.3, 125.2, 119.9, (102.9, 102.8, 101.9
(anomeric)), 95.8, 80.0, 79.6, 75.2, 74.7, 74.6, 74.4, 74.3,
73.7, 73.6, 72.9, 72.3, 72.0, 71.9, 71.2, 69.9, 68.6, 67.5, 62.8,
61.8, 54.9, 54.5, 20.7, 20.6; IR (solid) 3436, 2928, 2113,
1734, 1454, 1233, 1072, 1028, 740, 699 cmÀ1; MS (FAB)
calcd for C87H89Cl3N5O24 [M+H]þ 1695, found 1695.
18. (a) Carpino, L. A.; Williams, J. R. J. Chem. Soc., Perkin
Trans. 1 1978, 450–451; (b) Carpino, L. A. E.; Mansour,
M. E.; Cheng, C. H.; Williams, J. R.; MacDonald, R.;
Knapczyk, J.; Carman, M.; Lopusinski, A. J. Org. Chem.
1983, 48, 661–665.
14. For intermolecular aglycon transfer of thioglycoside, see:
(a) Coutant, C.; Jacquinet, J.-C. J. Chem. Soc., Perkin
Trans. 1 1995, 1573–1581; (b) Leigh, D. A.; Smart, J. P.;
Truscello, A. M. Carbohydr. Res. 1995, 276, 417–424; (c)
Belot, F.; Jacquinet, J.-C. Carbohydr. Res. 1996, 290, 79–
86; (d) Biao, H. Y.; Wu, X.; Hui, Y.; Han, X. J. Chem.
Soc., Perkin Trans. 1 2000, 1445–1453; (e) Zhu, T.; Boons,
G.-J. Carbohydr. Res. 2000, 329, 709–715.
15. Matsumoto, T.; Maeta, H.; Suzuki, K.; Tsuchihashi, G.
Tetrahedron Lett. 1988, 29, 3567–3570.
16. (a) Konradsson, P.; Udodong, U.; Fraser-Reid, B. Tetra-
hedron Lett. 1990, 31, 4313–4316; (b) Veeneman, G. H.;
van Leeuwen, S. H.; van Boom, J. H. Tetrahedron Lett.
1990, 31, 1331–1334.
17. Procedure for the one-pot synthesis of the protected
oligosaccharide 12a: A mixture of 2a (1.40 equiv), 4a
(1.00 equiv) and pulverized activated MS-4A in dry
CH2Cl2 was stirred at room temperature for 10 min under
argon to remove trace amounts of water. Then the
reaction mixture was cooled to 0 °C. BF3ÆOEt2 (2.25 equiv)
was added to the reaction mixture. After 30 min, a solution
of 5 (1.45 equiv), azeotroped three times with toluene, in
dry CH2Cl2 was added to the reaction mixture at 0 °C.
After 10 min, a dichloromethane solution of ZrCp2(OTf)2,
prepared from ZrCp2Cl2 (2.90 equiv) and silver trifluo-
romethanesulfonate (5.80 equiv), was added to the reac-
tion mixture. After stirring at the same temperature for