Rapid oligosaccharide synthesis on a fluorous support

Article abstract of DOI:10.1016/j.tet.2004.07.027

The novel fluorous support Hfb (hexakisfluorous chain-type butanoyl) was easily prepared. The Hfb group was readily introduced into the anomeric hydroxyl group of a carbohydrate, and was recyclable after cleavage. The use of the Hfb group was applicable for the rapid oligosaccharide synthesis in which the synthetic intermediates could be purified using fluorous and normal organic solvents. Each synthetic intermediate could be monitored by TLC, NMR and mass spectrometry. Graphical Abstract

Full text of DOI:10.1016/j.tet.2004.07.027

Tetrahedron 60 (2004) 8845–8854
Rapid oligosaccharide synthesis on a fluorous support
Kohtaro Goto,a Tsuyoshi Miura,a,†,* Daisuke Hosaka,a Hiroharu Matsumoto,a Mamoru Mizuno,a
Hide-ki Ishidaa and Toshiyuki Inazua,b,
*
aThe Noguchi Institute, Labolatry of Glycoorganic Chemistry, 1-8-1 Kaga, Itabashi-ku, Tokyo 173-0003, Japan
bDepartment of Applied Chemistry, School of Engineering, and Institute of Glycotechnology, Tokai University, Kitakaname 1117, Hiratsuka,
Kanagawa 259-1292, Japan
Received 27 May 2004; revised 13 July 2004; accepted 13 July 2004
Available online 21 August 2004
Abstract—The novel fluorous support Hfb (hexakisfluorous chain-type butanoyl) was easily prepared. The Hfb group was readily
introduced into the anomeric hydroxyl group of a carbohydrate, and was recyclable after cleavage. The use of the Hfb group was applicable
for the rapid oligosaccharide synthesis in which the synthetic intermediates could be purified using fluorous and normal organic solvents.
Each synthetic intermediate could be monitored by TLC, NMR and mass spectrometry.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
disadvantages, such as the difficulty in large-scale synthesis
and the inability to monitor the reaction by TLC, NMR
spectroscopic analysis and mass spectrometry. The solid-
phase synthesis of oligosaccharide that uses a soluble
polymer support (PEG) has also been reported.2 This
strategy can overcome some of these disadvantages,
however, it cannot be monitored by TLC and the
intermediates cannot be purified by silica-gel column
chromatography. To rapidly and efficiently synthesize
oligosaccharides, we adopted another concept such as
Recently, it has been gradually revealed that oligosacchar-
ides on cell surfaces play important roles in various
biological processes such as cell-cell interaction, cell
adhesion and immunogenic recognition.1 In order to better
understand the functions of oligosaccharides, it is necessary
to rapidly and efficiently synthesize oligosaccharides.
However, it is difficult to synthesize oligosaccharides
because of two crucial problems. First, a multitude of
hydroxyl groups have similar reactivity of each monomer,
and the effective differentiation of each hydroxyl group is
required to afford the glycosyl donors and acceptors.
Secondly, a control of stereoselectivity at anomeric position
in each glycosylation is not easy. Due to these problems, the
synthesis of oligosaccharides needs a lengthy process that
requires the exact optimization of the reaction conditions
and chromatographic purification of the reaction mixture in
each step. Therefore, there is no commercially available
automatic synthesizer of an oligosaccharide. On the other
hand, peptides and nucleotides are easily prepared by a
commercially available automatic synthesizer using a solid-
phase synthesis. The solid-phase synthesis of oligosacchar-
ides has also been extensively studied,2 however, the usual
solid-phase method suffers from some serious
´
fluorous chemistry that was reported by Horvath and
Rabai as the fluorous biphasic system in 1994. A fluorous
3
´
(highly fluorinated) solvent such as perfluorohexane and
perfluoromethylcyclohexane is immiscible in most organic
solvents and water, and three layers are formed. A fluorous
compound exhibits a high solubility for fluorous solvents,
and is readily separated from non-fluorinated compounds by
´
a simple fluorous-organic solvent partition. Since Horvath
and Rabai reported this concept, it has been developed for
´
use in a combinatorial chemistry, a parallel synthesis and a
catalytic chemistry.4,5 In addition, since Curran and co-
workers described the fluorous synthesis5 (fluorous-tag
method) as a strategic alternative to solid-phase synthesis,
fluorous chemistry has become more popular in organic
synthesis, such as the Baeyer–Villigar6 or Swern7 oxidation,
Heck8 or Suzuki9 coupling, the Mitsunobu reaction,10
Friedel–Crafts acylation11 and so on.12 Furthermore, they
have also reported a fluorous mixture synthesis using a
fluorous silica-gel.13 The fluorous protecting groups are
essential for the fluorous synthesis performance. Several
fluorous hydroxy protecting groups such as acetal, silyl and
benzyl groups have already been reported.14,15 Other
Keywords: Fluorous; Glycosylation; Oligosaccharide; Synthetic method;
Support.
* Corresponding authors. Tel.: C81-3-5944-3215; fax: C81-3-5944-3214
(T.M.); tel.: C81-463-58-1211; fax: C81-463-50-2012 (T.I.);
e-mail: tmiura@cis.ac.jp
† Current address: Faculty of Pharmaceutical Sciences, Chiba Institute of
Science, Japan.
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.07.027

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K. Goto et al. / Tetrahedron 60 (2004) 8845–8854
fluorous protecting groups for amino or carboxyl groups
have also been reported.16 Curran and co-workers adapted
the fluorous-tag method to the fluorous disaccharide
synthesis using the fluorous benzyl protecting group by a
glycal method.15 Unfortunately, their glycosylation method
gave only the 2-deoxy disaccharides and could not
synthesize the longer chain oligosaccharides in order to
introduce the fluorous benzyl groups to the glycosyl donor.
In addition, the yield for the reaction step to introduce the
fluorous benzyl group to the hydroxyl group was not
satisfactory. Recently, we reported a method for the fluorous
oligosaccharide synthesis involving the novel fluorous acyl
protecting group Bfp (bisfluorous chain-type propanoyl).17,18
We also reported the fluorous support Hfb (hexakisfluorous
chain-type butanoyl) in a preliminary communication.19
Herein we describe the full details of the development of a
novel fluorous support Hfb and its application to the rapid
synthesis of oligosaccharides. Moreover, several glycosyla-
tion methods using the fluorous support Hfb was studied.
Our concept of fluorous oligosaccharide synthesis is shown
in Figure 1. We adopted the introduction of a fluorous
support only at the anomeric hydroxyl group of the glycosyl
acceptor in order to more efficiently synthesize the longer
chain oligosaccharides. The glycosyl acceptor containing
the fluorous support couples with the glycosyl donor to
afford the fluorous disaccharide. After partition of the
reaction mixture with fluorous and normal organic solvents,
the fluorous disaccharide is extracted by the fluorous layer,
and the excess amount of the glycosyl donor is extracted by
the organic layer. After selective deprotection, repeating
this procedure gives the fluorous oligosaccharide, which is
able to be purified only by liquid–liquid extraction without
column chromatography. Finally, the fluorous support is
removed to give the desired oligosaccharide extracted with
an organic solvent. The fluorous support is extracted by a
fluorous solvent and is recyclable.
2. Results and discussion
We designed and synthesized compound 10 with six
fluorous chains as a novel fluorous support. Compound 4,
which contains three fluorous chains, was prepared as a
precursor (Scheme 1). The reaction of Bfp-OH17 (1) with a
fluorous amine 217 provided compound 3 in 96% yield. The
treatment of 3 with aqueous sodium hydroxide gave the
fluorous carboxylic acid 4, which contains three fluorous
chains, in 98% yield.
We synthesized compound 10 by two methods using
compound 4, and first attempted to prepare compound 10
using route A (Scheme 2).19
The two primary amino groups of diethylenetriamine (5)
were protected with the triphenylmethyl group to provide
the amine 620 in 95% yield. Compound 6 was coupled with
methyl hydrogen glutarate to afford compound 7 in 98%
yield. Removal of the triphenylmethyl groups from 7 were
performed by treatment of HCl in dioxane to give
compound 8. Compound 8 was reacted with fluorous
carboxylic acid 4 (2 equiv.) to afford a fluorous ester 9,
which contains six fluorous chains, in 82% yield. The
treatment of 9 with aqueous sodium hydroxide gave a
fluorous support 10 in 98% yield. The acyl moiety of 10 was
Figure 1. Concept of oligosaccharide synthesis.

K. Goto et al. / Tetrahedron 60 (2004) 8845–8854
8847
Scheme 1. Preparation of fluorous carboxylic acid 4.
named Hfb (hexakisfluorous chain-type butanoyl). We
thought that the six fluorous chains of 10 enhance the
efficiency of the liquid–liquid extraction better than the Bfp
group containing two fluorous chains. Thus we achieved the
synthesis of Hfb-OH (10) by route A. However, route A is
unsuitable for the rapid and convenient synthesis of Hfb-
OH (10) due to the lengthy steps. We planned route B as
shown in Scheme 2. The two primary amino group of
diethylenetriamine (5) were directly reacted with 4
(2 equiv.) to provide a fluorous amine 11, which contains
six fluorous chains, in 92% yield. Compound 11 was
coupled with glutaric anhydride to produce Hfb-OH (10) in
high yield. Route A is 5 steps with a 75% overall yield from
5, on the other hand, route B is only 2 steps with 90% yield.
As a result, we improved the synthesis of Hfb-OH (10)
marking it more efficient and produced a higher yield than
the preliminary communication.19
At first, a synthesis of the disaccharide 17 was performed
(Scheme 3). Among the many useful methods for glycosy-
lation we selected Schmidt method as one of the most major
synthetic methods to prepare an oligosaccharide.21 The
fluorous support Hfb was easily introduced into the
anomeric hydroxyl group of the glucose derivative 12
Scheme 2. Synthesis of Hfb-OH (10).

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K. Goto et al. / Tetrahedron 60 (2004) 8845–8854
Scheme 3. Disaccharide synthesis on fluorous support Hfb.
using PyBOP and 4-dimethylaminopyridine (DMAP) to
give the fluorous compound 13.22 Removal of the TBDPS
group from 13 was achieved by treatment with HF-pyridine
in THF to afford the flourous glycosyl acceptor 14.22 The
fluorous disaccharide 1622 was obtained by the reaction of
14 with the excess glycosyl donor 1521 in the presence of
trimethylsilyl trifluoromethanesulfonate (TMS-OTf) in
ether–EtOC4F9.23 EtOC4F9 is miscible in most organic
solvents and fluorous solvents. The fluorous intermediates
13, 14 and 16 were respectively extracted with the fluorous
solvent FC-7224 by partitioning the product mixtures
between FC-72 and an organic solvent such as MeOH,
MeCN and toluene. No further purification such as silica-gel
column chromatography was carried out. The Hfb group of
16 was easily removed by treatment with NaOMe in
MeOH–EtOC4F9 to afford crude 17, which was extracted
with MeOH by partitioning the mixture between FC-72 and
MeOH. The methyl ester of Hfb (Hfb-OMe, 18) was
recovered from the FC-72 layer in 81% yield. Compound 18
was treated with aqueous sodium hydroxide to give Hfb-OH
(10), which was reused. After a single silica-gel column
chromatographic purification step, the disaccharide 17 was
obtained in 67% overall yield from 12 (4 steps). The benzyl
groups of compound 17 were removed by hydrogenation in
the presence of Pd/C to afford compound 19.25,26
achieved by treatment with HF-Pyr in THF to afford the
fluorous compound 22.22 The reaction of the glycosyl
acceptor 22 with the glycosyl donor 2321 under similar
glycosidation conditions afforded the fluorous trisaccharide
24.22,28 The fluorous intermediates 21, 22 and 24 were
respectively extracted with the fluorous solvent FC-72 by
partitioning the product mixtures between FC-72 and the
organic solvents. No further purification such as silica-gel
column chromatography was performed. The Hfb group of
24 was removed by the same method, as described above.
After a single silica-gel column chromatographic purifi-
cation step, the trisaccharide 25 was obtained in 42% overall
yield from 10 (6 steps). The benzyl groups of compound 25
were removed by hydrogenation in the presence of Pd/C to
afford compound 26.29,30
Among the many useful methods for glycosylation, we
attempted only Schmidt method as the major synthetic
method to provide oligosaccharide.21 Therefore, we applied
other glycosylation methods to the fluorous acceptor 14
(Scheme 5).
We performed the thioglycoside method,31 the Koenigs–
¨
Knorr method32 and the Suzuki method33 (Table 1). All
these methods gave the corresponding disaccharides as a
white solid in good yield. Especially, entry 5 (Suzuki
method) and entries 7 and 8 (thioglycoside method) show
that these methods gave the corresponding disaccharide in
good yields with the use of a small excess of the glycosyl
donor. As a result, it was found that the major glycosylation
Next, we synthesized the longer chain oligosaccharide, and
the fluorous glycosyl acceptor 14 was reacted with the
glycosyl donor 2027 to afford the fluorous disaccharide 21
(Scheme 4).22,28 Removal of the TBDPS group from 21 was

K. Goto et al. / Tetrahedron 60 (2004) 8845–8854
8849
Scheme 4. Trisaccharide synthesis on fluorous support Hfb.
Scheme 5.
Table 1. Study of glycosylation using various glycosylation methods on fluorous support Hfb
Entry
Temperature (8C)
Time
Solvent
R
Donor (equiv.)
Activator
Yield (%)a
a/b ratiob
1
2
3
4
5
6
7
8
0
0
K20
K20
K20
0
24 h
25 h
2.5 h
2.5 h
4 h
20 min
50 min
2.5 h
Ether–EtOC4F9
Ether–EtOC4F9
Ether–EtOC4F9
Ether–EtOC4F9
Ether–EtOC4F9
CH2Cl2–EtOC4F9
CH2Cl2–EtOC4F9
CH2Cl2–EtOC4F9
Cl
Cl
F
F
F
Sph
Sph
Sph
10
3
10
5
3
5
AgOTf–AgCl4
AgOTf–AgCl4
Cp2ZrCl2–AgClO4
Cp2ZrCl2–AgClO4
Cp2ZrCl2–AgClO4
NIS–TfOH
61
39
93
77
70
72
80
81
2.5:1
2.0:1
1.3:1
1.5:1
1.6:1
1.4:1
1.6:1
1.4:1
0
0
3
1.5
NIS–TfOH
NIS–TfOH
a
Isolated yield.
Detected by 1H NMR spectra of products after deprotection.
b
methods were available for the fluorous oligosaccharide
synthesis.
the synthesis of Hfb-OH (10) quite efficiently and rapidly
compared it with the previous method.19 The Hfb group was
readily introduced into the anomeric hydroxyl groups of the
glycosyl acceptor, and removed in high yield by the usual
procedure. Moreover, it was recyclable after cleavage. Each
fluorous synthetic intermediate could be obtained in a
straightforward manner by simple FC-72-organic solvent
extraction. The reaction conditions for each synthetic step
could be rapidly optimized, because the reactions could be
3. Conclusion
The use of the Hfb group as a fluorous support made it
possible to rapidly synthesize an oligosaccharide by
minimal column chromatography purification. We achieved

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K. Goto et al. / Tetrahedron 60 (2004) 8845–8854
monitored by TLC and mass spectrometry in contrast to the
usual solid-phase reactions. Although the fluorous inter-
mediates could also be measured by NMR spectroscopic
analysis, the peaks in the NMR of the fluorous compounds
containing the Hfb group are somewhat broad due to the
influence of the amide linkages and the fluorous groups.15
Although the fluorous intermediates could also be subjected
to silica-gel column chromatography, only the final
compounds were purified by chromatography. This fluorous
oligosaccharide synthesis should be applicable for a large-
scale synthesis. Furthermore, it was found that major
glycosylation methods were available to the fluorous
oligosaccharide synthesis. Thus the oligosaccharide syn-
thesis using the fluorous support Hfb is an excellent
alternative strategy to solid-phase method. Further appli-
cation for the synthesis of a bioactive carbohydrate and
glycoconjugate is now in progress.
RfZ0.56 (CHCl3–MeOH–H2OZ9:1:0.08); 1H NMR
(600 MHz, CDCl3): dZ1.81–1.96 (m, 4H), 2.01–2.17 (m,
4H), 2.47–2.79 (m, 8H), 3.39–3.55 (m, 4H), 3.57–3.75 (m,
4H); MALDI-TOF MS; Calcd for C39H25F51N2O4Na m/z
[MCNa]C: 1577.1, Found: 1576.5; Calcd for
C39H25F51N2O4K m/z [MCK]C: 1593.1, Found: 1592.3.
4.1.3. Compound 6.20 Diethylamine (6.0 mL, 61.2 mmol)
and chlorotriphenylmethane (17.0 g, 61.2 mmol) were
added to a solution of compound 5 (diethylenetriamine;
3.0 mL, 27.8 mmol) in 2-propanol (60 mL) at room
temperature. After stirring for 21 h at room temperature,
1 M aq. NaOH was added, and the reaction mixture was
adjusted to pH 11. The reaction mixture was extracted three
times with AcOEt. The combined AcOEt layers were
washed with brine, dried over anhydrous Na2SO4 and
concentrated. The crude product was purified by column
chromatography on silica-gel (CHCl3–MeOH, 20:1) to give
compound 6 (15.5 g, 95%) as a white amorphous solid.
4. Experimental
4.1. General
4.1.4. Compound 7. Triethylamine (51 mL, 0.37 mmol) and
PyBOP (143 mg, 0.275 mmol) were added to a solution of
compound 6 (108 mg, 0.184 mmol) and methyl hydrogen
glutarate (28 mL, 22 mmol) in CH2Cl2 (2 mL) at room
temperature. After stirring for 3 h at room temperature, the
reaction mixture was added to water, and then extracted
with AcOEt. The AcOEt layers were washed with water,
2 M aq. HCl, saturated aq. NaHCO3, and brine. The organic
layers were dried over anhydrous Na2SO4 and concentrated.
The crude product was purified by column chromatography
on silica-gel (hexane–AcOEt, 3:2) to give compound 7
(129 mg, 98%) as a white amorphous solid. 1H NMR
(600 MHz, CDCl3): dZ1.64 (brs, 2H), 1.96 (t, JZ7.6 Hz,
2H), 2.22 (t, JZ6.2 Hz, 2H), 2.26 (t, JZ6.2 Hz, 2H), 2.39
(t, JZ7.6 Hz, 2H), 2.45 (t, JZ7.6 Hz, 2H), 3.33 (t, JZ
6.2 Hz, 2H), 3.38 (t, JZ6.2 Hz, 2H), 3.33 (s, 3H), 7.12–7.44
(m, 30H); 13C NMR (150 MHz, CDCl3): dZ20.60, 32.28,
33.58, 42.09, 42.34, 45.91, 48.47, 51.50, 70.77, 70.94,
126.24, 126.79, 128.00, 128.41, 128.52, 145.62, 146.00,
172.61, 173.77; HRMS (ESI-TOF MS.): Calcd for
C48H50N3O3 m/z [MCH]C: 716.3847, Found: 716.3811.
1H NMR spectra were recorded using JEOL JNM-EX-400
(400 MHz) or JEOL JNM-ECA-600 (600 MHz) spec-
trometers. MALDI-TOF MS. were recorded using Voya-
ger-DE STR, and a-cyano-4-hydroxy cinnamic acid was
used as a matrix. ESI-TOF MS. were recorded on
Marinere. Part of the product was isolated by column
chromatography on silica-gel (Kanto Chemical, silica-gel
60 N, spherical, neutral, 40–50 mm). The fluorous solvent
FC-72 and Novec HFE-7200 were purchased from 3 M
Tokyo. The aqueous NH3 was 28% aqueous solution
purchased from Wako Pure Chemical Industries, Ltd.
4.1.1. Compound 3. Triethylamine (4.0 mL, 29.2 mmol)
and PyBOP (6.08 g, 17.7 mmol) were added to a solution of
compound 1 (Bfp-OH; 10.0 g, 9.77 mmol) and 2 (5.64 g,
9.77 mmol) in CH2Cl2 (120 mL) at room temperature. After
stirring for 20 h at room temperature, the reaction mixture
was added to water, and then extracted with CHCl3. The
CHCl3 layers were washed with water, 2 M aq. HCl,
saturated aq. NaHCO3 and brine. The organic layers were
dried over anhydrous Na2SO4, and concentrated. The crude
product was purified by column chromatography on silica-
gel (hexane–AcOEt, 1:1) to give compound 3 (14.9 g, 96%)
as a white amorphous solid. RfZ0.56 (hexane–AcOEt, 1:1);
1H NMR (600 MHz, CDCl3): dZ1.20–1.30 (m, 3H), 1.80–
1.95 (m, 4H), 2.01–2.17 (m, 4H), 2.46–2.79 (m, 8H), 3.36–
3.54 (m, 4H), 3.56–3.76 (m, 4H), 4.09–4.20 (m, 2H);
MALDI-TOF MS: Calcd for C41H30F51N2O4 m/z [MC
H]C: 1583.1, Found: 1583.7; Calcd for C41H29F51N2O4Na
m/z [MCNa]C: 1605.1, Found: 1606.1; Calcd for
C41H29F51N2O4K m/z [MCK]C: 1621.1, Found: 1622.4.
4.1.5. Compound 8. A solution of 4 M HCl in dioxane
(55 mL) was added to compound 7 (3.82 g, 5.43 mmol) at
room temperature. After stirring for 16 h at 60 8C, AcOEt
was added to the reaction mixture, and then filtered. The
crude product of 8 (1.64 g) was obtained as a white solid,
and used in the next step without further purification.
4.1.6. Compound 9. Triethylamine (3.87 mL, 27.9 mmol)
and PyBOP (12.5 g, 24.0 mmol) were added to a solution of
the crude compounds 8 (1.47 g) and 4 (17.2 g, 11.1 mmol)
in CH2Cl2 (400 mL) at room temperature. After stirring for
13 h at room temperature, toluene was added to the reaction
mixture and CH2Cl2 was concentrated. The toluene solution
was partitioned three times with FC-72. The combined FC-
72 layers were then concentrated. The residue was purified
by column chromatography on silica-gel (CHCl3–MeOH,
20:1) to give compound 9 (13.1 g, 82%) as a white
amorphous solid. RfZ0.54 (CHCl3–MeOH–H2OZ
4.1.2. Compound 4. To a solution of compound 3 (22.2 g,
14.0 mmol) in 1,4-dioxane (300 mL) was added 1 M aq.
NaOH (150 mL) at room temperature. After stirring for 4 h
at 50 8C, 2 M aq. HCl was added and the reaction mixture
was adjusted to pH 2. The reaction mixture was extracted
three times with AcOEt–EtOC4F9 (2:1), dried over
anhydrous Na2SO4, and concentrated. Compound 4
(21.5 g, 99%) was obtained as a white amorphous solid.
1
9:1:0.08); H NMR (600 MHz, CDCl3): dZ1.76–1.98 (m,
10H), 1.99–2.17 (m, 8H), 2.34–2.88 (m, 20H), 3.31–3.53
(m, 16H), 3.54–3.78 (m, 11H); MALDI-TOF MS: Calcd for

K. Goto et al. / Tetrahedron 60 (2004) 8845–8854
8851
C88H68F102N7O9 m/z [MCH]C: 3304.3, Found: 3305.8;
Calcd for C88H67F102N7O9Na m/z [MCNa]C: 3326.3,
Found: 3327.5; Calcd for C88H67F102N7O9K m/z [MC
K]C: 3342.3, Found: 3342.6.
(m, 2H), 5.69–5.76 (m, 1H, H-1), 6.73–7.21 (m, 1H), 7.30–
7.74 (m, 11H); MALDI-TOF-MS: Calcd for C115H99F102-
N7O17Na m/z [MCNa]C: 3838.5, Found: 3837.1.
4.1.10. Compound 14. HF-Pyr (4.45 mL, 159 mmol) was
added to a solution of crude 13 (2.45 g) in THF (38 mL).
After stirring for 20 h at room temperature, the reaction
mixture was added to saturated aq. NaHCO3 (150 mL).
Toluene (150 mL) was then added to the reaction mixture.
The reaction mixture was extracted three times with FC-72
(150 mL). The FC-72 layers were washed with brine, then
dried over anhydrous Na2SO4 and concentrated. The crude
product of 14 (2.30 g) was used in the next step without
further purification. RfZ0.36 (CHCl3–MeOH–H2OZ
4.1.7. Compound 10. Route A. To a solution of compound 9
(1.55 g, 0.454 mmol) in 1,4-dioxane (80 mL) was added
1 M aq. NaOH (40 mL) at room temperature. After stirring
for 24 h at 50 8C, 2 M aq. HCl was added, and the reaction
mixture was adjusted to pH 2. The reaction mixture was
extracted three times with AcOEt–EtOC4F9 (2:1), dried
over anhydrous Na2SO4 and concentrated. Compound 10
(1.44 g, 97%) was obtained then used in the next step
without further purification. RfZ0.54 (CHCl3–MeOH–
1
1
H2OZ9:1:0.08); H NMR (600 MHz, CDCl3): dZ1.80–
9:1:0.08); H NMR (600 MHz, CDCl3): dZ1.71–2.21 (m,
1.99 (m, 10H), 2.00–2.17 (m, 8H), 2.34–2.80 (m, 20H),
3.35–3.55 (m, 16H), 3.56–3.75 (m, 8H); MALDI-TOF MS;
Calcd for C87H66F102N7O9 m/z [MCH]C: 3290.3, Found:
3291.5; Calcd for C87H65F102N7O9Na m/z [MCNa]C:
3312.3, Found: 3315.5.
28H), 2.27–2.87 (m, 20H), 3.27–3.83 (m, 27H), 5.04–5.18
(m, 2H), 5.27–5.38 (m, 1H), 5.69–5.82 (m, 1H, H-1), 6.75–
7.23 (m, 1H), 7.29–7.96 (m, 1H); MALDI-TOF MS: Calcd
for C99H82F102N7O17Na m/z [MCNa]C: 3600.4, Found:
3600.9.
4.1.11. Compound 16. Using the Schmidt method.21
Molecular sieves 4A powder (1.4 g) was added to a solution
of the crude compound 14 (395 mg) and compound 15
(680 mg, 0.992 mmol) in ether (6.0 mL)–EtOC4F9 (3.2 mL)
under an argon atmosphere. After stirring for 2 h at room
temperature, TMS-OTf (140 mL, 0.773 mmol) was added to
the reaction mixture at 0 8C. After stirring for 20 min at
0 8C, triethylamine (0.5 mL) was added to the reaction
mixture. The reaction mixture was then filtered. The filtrate
was added to saturated aq. NaHCO3 and extracted three
times with AcOEt. The AcOEt layers were washed with
brine, dried over anhydrous Na2SO4 and concentrated. The
residue was partitioned between MeOH and FC-72 (!3).
The FC-72 layers were concentrated to give the crude
product of 16 (372 mg), and this residue was used in the
next step without further purification. RfZ0.47 (CHCl3–
MeOH–H2OZ9:1:0.08); 1H NMR (600 MHz, CDCl3): dZ
1.76–2.16 (m, 27H), 2.20–2.83 (m, 20H), 3.16–4.06 (m,
33H), 4.29–5.33 (m, 12H), 5.66–5.71 (m, 1H, H-1), 6.69–
7.17 (m, 2H), 7.02–7.44 (m, 20H); MALDI-TOF MS: Calcd
for C133H115F102N7O22Na m/z [MCNa]C: 4122.6, Found:
4121.4.
Route B. Triethylamine (197 mL, 1.42 mmol) and glutaric
anhydride (81.0 mg, 0.708 mmol) were added to a solution
of compound 11 (450 mg, 0.142 mmol) in EtOC4F9
(4.5 mL) and CH2Cl2 (4.5 mL) at room temperature. After
stirring for 3 h at room temperature, 2 M aq. HCl was added
and the reaction mixture was adjusted to pH 2. The reaction
mixture was extracted three times with AcOEt–EtOC4F9
(2:1), dried over anhydrous Na2SO4 and concentrated. The
crude product of 10 (464 mg, 99%) was used in the next step
without further purification.
4.1.8. Compound 11. Diethylenetriamine (81 mL,
0.75 mmol) and PyBOP (935 mg, 1.80 mmol) were added
to a solution of crude compound 4 (1.47 g) and triethyla-
mine (416 mL, 3.00 mmol) in CH2Cl2 (25 mL) at room
temperature. After stirring for 15 h at room temperature, the
reaction mixture was concentrated. The residue was
partitioned between MeOH and FC-72 (!3). The combined
FC-72 layers were concentrated. The crude product was
purified by column chromatography on silica-gel (CHCl3–
MeOH–aq. NH3Z85:15:0.6) to give compound 11 (2.20 g,
92%) as a white amorphous solid. RfZ0.46 (CHCl3–
1
MeOH–aq. NH3Z8:2:0.2); H NMR (600 MHz, CDCl3):
dZ1.78–1.97 (m, 8H), 2.00–2.17 (m, 8H), 2.42–2.64 (m,
12H), 2.66–2.82 (m, 8H), 3.26–3.52 (m, 12H), 3.55–3.74
(m, 8H); MALDI-TOF MS: Calcd for C82H60F102N7O6 m/z
[MCH]C: 3176.3, Found: 3177.6; Calcd for C82H59F102-
N7O6Na m/z [MCNa]C: 3198.3, Found: 3197.1.
General procedure for disaccharide 16 using thioglycoside
method.30 Molecular sieves 4A powder (1.6 g) was added to
a solution of compound 14 (133 mg, 37.2 mmol) and
compound 15a (70.6 mg, 0.112 mmol) in CH2Cl2
(2.0 mL)–EtOC4F9 (1.0 mL) under an argon atmosphere.
After stirring for 2 h at room temperature, NIS (50.0 mg,
0.223 mmol) and TfOH (2 mL, 22 mmol) were added to the
reaction mixture at 0 8C. After stirring for 50 min at 0 8C,
the reaction mixture was filtered. The filtrate was added to
saturated aq. NaHCO3, and extracted three times with
AcOEt. The AcOEt layers were washed with saturated aq.
NaHCO3, saturated aq. Na2S2O3 and brine. The organic
layers were dried over anhydrous Na2SO4 and concentrated.
The residue was partitioned between MeOH and FC-72 (!
3). The FC-72 layers were concentrated to give the crude
product of 16, and this residue was purified by column
chromatography on silica-gel (CHCl3–MeOHZ40:1) to
give compound 16 (122 mg, 80%) as a white amorphous
solid.
4.1.9. Compound 13. 4-Dimethylaminopyridine (243 mg,
1.98 mmol) and PyBOP (1.03 g, 1.98 mmol) were added to
a solution of compound 12 (1.00 g, 1.84 mmol) and Hfb-
OH (10, 2.17 g, 0.660 mmol) in CH2Cl2 (110 mL). After
stirring for 20 h at room temperature, MeOH (110 mL) was
added to the reaction mixture and only CH2Cl2 was
concentrated. The reaction mixture was extracted three
times with FC-72 (110 mL). The combined FC-72 layers
were then concentrated. The crude product of 13 (2.45 g)
was used in the next step without further purification. RfZ
0.47 (CHCl3–MeOH–H2OZ9:1:0.08); 1H NMR (600 MHz,
CDCl3): dZ1.03 (s, 9H) 1.76–2.19 (m, 27H), 2.30–2.85 (m,
20H), 3.26–3.82 (m, 27H), 5.07–5.17 (m, 1H), 5.18–5.27

8852
K. Goto et al. / Tetrahedron 60 (2004) 8845–8854
General procedure for disaccharide 16 using the Koenigs–
Knorr method.31 Molecular sieves 4A powder (1.5 g) was
added to a solution of compound 14 (131 mg, 36.5 mmol)
and AgOTf (204 mg, 0.365 mmol), AgClO4 (188 mg,
0.365 mmol) in ether (1.0 mL)–EtOC4F9 (1.5 mL) under
an argon atmosphere. After stirring for 2 h at room
temperature, compound 15b (204 mg, 0.365 mmol) in
ether (2.0 mL) was added to the reaction mixture at 0 8C.
After stirring for 24 h at 0 8C, the reaction mixture was
filtered. The filtrate was added to saturated aq. NaHCO3 and
extracted three times with AcOEt. The AcOEt layers were
washed with brine, dried over anhydrous Na2SO4, and
concentrated. The residue was partitioned between MeOH
and FC-72 (!3). The FC-72 layers were concentrated to
give the crude product of 16, and this residue was purified
by column chromatography on silica-gel (CHCl3–MeOHZ
40:1) to give compound 16 (91.4 mg, 61%) as a white
amorphous solid.
JZ3.4 Hz); 13C NMR (150 MHz, D2O): dZ61.06, 61.08,
65.82, 65.92, 68.41, 68.44, 69.20, 69.42, 69.45, 69.57,
70.06, 70.90, 71.39, 72.92, 74.03, 74.31, 75.85, 92.10,
96.03, 98.13, 98.17.
¨
1
Arolactose. H NMR (600 MHz, D2O): dZ4.29 (d, JZ
9.6 Hz), 4.31 (d, JZ8.3 Hz), 4.52 (d, JZ8.3 Hz), 5.10 (d,
JZ4.1 Hz); 13C NMR (150 MHz, D2O): dZ60.97, 68.57,
68.63, 68.65, 68.68, 69.42, 69.48, 70.44, 70.74, 71.39,
72.64, 74.01, 74.86, 75.11, 75.14, 75.62, 92.10, 95.94,
103.25.
4.1.14. Compound 21. Molecular sieves 4A powder (3.3 g)
was added to a solution of the crude compound 14 (953 mg)
and compound 20 (1.86 g, 2.23 mmol) in ether (14 mL)–
EtOC4F9 (8 mL) under an argon atmosphere. After stirring
for 2 h at room temperature, TMS-OTf (338 mL, 1.86 mmol)
was added to the reaction mixture at 0 8C. After stirring for
20 min at 0 8C, triethylamine (0.8 mL) was added to the
reaction mixture. The reaction mixture was then filtered.
The filtrate was added to saturated aq. NaHCO3 and
extracted three times with AcOEt. The AcOEt layers were
washed with brine, dried over anhydrous Na2SO4 and
concentrated. The residue was partitioned between MeCN
and FC-72 (!3). The FC-72 layers were concentrated to
give the crude product of 21 (1.07 g), and was used in the
next step without further purification.
General procedure for disaccharide 16 using the Suzuki
method.32 A mixture of Cp2ZrCl2 (161 mg, 0.55 mmol),
AgClO4 (114 mg, 0.55 mmol) and molecular sieves 4A
powder (1.0 g) in ether (2.5 mL) was stirred at K20 8C
under an argon atmosphere. After stirring for 10 min at
K20 8C, compound 14 (165 mg, 46.1 mmol) and compound
15c (75.1 mg, 0.138 mmol) in ether (5.0 mL)–EtOC4F9
(2.5 mL) were added to the reaction mixture. After stirring
for 4 h at K20 8C, the reaction mixture was filtered. The
filtrate was added to saturated aq. NaHCO3 and extracted
three times with AcOEt. The AcOEt layers were washed
with brine, dried over anhydrous Na2SO4 and concentrated.
The residue was partitioned between MeOH and FC-72
(!3). The FC-72 layers were concentrated to give the
crude product of 16, and this residue was purified by
column chromatography on silica-gel (CHCl3–MeOHZ
40:1) to give compound 16 (132 mg, 70%) as a white
amorphous solid.
4.1.15. Compound 22. HF-Pyr (1.75 mL, 62.4 mmol) was
added to a solution of the crude 21 (1.07 g) in THF (15 mL).
After stirring for 22 h at room temperature, the reaction
mixture was added to saturated aq. NaHCO3 (200 mL), then
toluene (200 mL) was added to the reaction mixture. The
reaction mixture was extracted three times with FC-72
(200 mL). The FC-72 layers were washed with brine, then
dried over anhydrous Na2SO4 and concentrated. The crude
product of 22 (952 mg) was used in the next step without
further purification.
4.1.12. Compound 17. A sodium methoxide solution (28%)
in methanol (10 mL) was added to a solution of the crude
compound 16 (349 mg) in EtOC4F9 (8 mL)–MeOH
(16 mL). After stirring for 16 h at room temperature,
Amberlite IR-120 (HC form) was added and the reaction
mixture was neutralized. After filtration, the filtrate was
concentrated. The residue was partitioned between MeOH
and FC-72 (!3). The MeOH layer was concentrated to give
the crude product of 17. The FC-72 layers were concen-
trated to afford the pure compound 18. The crude product of
17 was purified by column chromatography on silica-gel to
give pure compound 17 (50 mg, 67% in 4 steps) as a white
powder. HRMS (ESI-TOF MS.): Calcd for C40H46O11Na
m/z [MCNa]C: 725.2932, Found: 725.2959.
4.1.16. Compound 24. Molecular sieves 4A powder (6.0 g)
was added to a solution of the crude compound 22 (360 mg)
and compound 23 (884 mg, 1.79 mmol) in ether (29 mL)–
EtOC4F9 (3 mL) under an argon atmosphere. After stirring
for 2 h at room temperature, TMS-OTf (163 mL,
0.898 mmol) was added to the reaction mixture at 0 8C.
After stirring for 2 min at 0 8C, triethylamine (0.5 mL) was
added to the reaction mixture. The reaction mixture was
then filtered. The filtrate was added to saturated aq.
NaHCO3 and extracted three times with AcOEt. The
AcOEt layers were washed with brine, dried over anhydrous
Na2SO4 and concentrated. The residue was partitioned
between MeOH and FC-72 (!3). The FC-72 layers were
concentrated to give the crude product of 24 (360 mg), and
this residue was used in the next step without further
purification.
4.1.13. Compound 19.25,26A solution of 17 (31.0 mg) in
EtOH (9.0 mL) was added to a suspension 10% Pd/C
(40.0 mg) in EtOH (1.0 mL)–AcOH (1.0 mL). After bub-
bling with hydrogen for 14 h at room temperature, the
reaction mixture was filtered. After the filtrate was
concentrated, the compound 19 (16.0 mg, quant.) was
obtained as a white powder.
4.1.17. Compound 25. A sodium methoxide solution (28%)
in MeOH (10 mL) was added to a solution of the crude
compound 24 (360 mg) in EtOC4F9 (8 mL)–MeOH
(16 mL). After stirring for 14 h at room temperature,
Amberlite IR-120 (HC form) was added and the reaction
mixture was neutralized. After filtration, the filtrate was
concentrated. The residue was partitioned between MeOH
Melibiose. 1H NMR (600 MHz, D2O): dZ4.53 (d, JZ
7.6 Hz), 4.84 (d, JZ4.1 Hz), 4.85 (d, JZ3.4 Hz), 5.09 (d,

K. Goto et al. / Tetrahedron 60 (2004) 8845–8854
8853
Okumura, K.; Ohga, Y. Tetrahedron 2001, 57, 5565. (e)
Barrett, A. G. M.; Braddock, D. C.; Catterick, D.;
Chadwick, D.; Henschke, J. P.; McKinnell, R. M. Synlett
´
2000, 847. (f) Horvath, I. T. Acc. Chem. Res. 1998, 31,
641 and references cited therein.
and FC-72. The methanol layer was concentrated to give the
crude compound 25. The FC-72 layer was concentrated to
afford pure compound 18. The crude compound 25 was
purified by column chromatography on silica-gel to give
pure compound 25 (34.0 mg, 43% in 6 steps) as a white
powder. HRMS (ESI-TOF MS.): Calcd for C39H50O16Na
m/z [MCNa]C: 797.2991, Found: 797.2969.
5. (a) Zhang, Q.; Luo, Z.; Curran, D. P. J. Org. Chem. 2000, 65,
8866. (b) Curran, D. P. Pure Appl. Chem. 2000, 72, 1649. (c)
Curran, D. P. Angew. Chem., Int. Ed. 1998, 37, 1174 and
references cited therein.
4.1.18. Compound 26.29,30A solution of 25 (15.0 mg) in
EtOH (4.0 mL) was added to a suspension 10% Pd/C
(20.0 mg) in EtOH (1.0 mL)–AcOH (1.0 mL). After bub-
bling with hydrogen for 21 h at room temperature, the
reaction mixture was filtered. After the filtrate was
concentrated, the compound 26 (10.0 mg, quant.) was
obtained as a white powder.
6. Hao, X.; Yamazaki, O.; Yoshida, A.; Nishikido, J.
Tetrahedron Lett. 2003, 44, 4977.
7. Crich, D.; Neelamkavil, S. J. Am. Chem. Soc. 2001, 123, 7449.
8. (a) Vallin, K. S. A.; Zhang, Q.; Larhed, M.; Curran, D. P.;
Hallberg, A. J. Org. Chem. 2003, 68, 6639. (b) Moineau, J.;
Pozzi, G.; Quici, S.; Sinou, D. Tetrahedron Lett. 1999, 40, 7683.
9. Chen, D.; Qing, F.; Huang, Y. Org. Lett. 2002, 4, 1003.
10. (a) Dandapani, S.; Curran, D. P. Tetrahedron Lett. 2002, 58,
3855. (b) Dobbs, A. P.; McGregor-Johnson, C. Tetrahedron
O-(b-D-Glucopyranosyl)-(1/6)-O-(a-D-glucopyranosyl)-
1
(1/6)-D-glucopyranose. H NMR (600 MHz, D2O): dZ
´ ´ ´
Lett. 2002, 43, 2807. (c) Rabai, J.; Szabo, D.; Borbas,
4.34 (d, JZ8.3 Hz), 4.51 (d, JZ7.6 Hz), 4.79 (d, JZ
3.4 Hz), 4.80 (d, JZ4.1 Hz), 5.08 (d, JZ3.4 Hz); 13C NMR
(150 MHz, D2O): dZ92.14, 96.03, 97.96, 98.00, 102.57.
`
¨
¨
¨ ¨
E. K.; Kovesi, I.; Kovesdi, I.; Csampai, A.; Gomory, A.;
Pashinnik, V. E.; Shermolovich, Y. G. J. Fluorine Chem.
2002, 114, 199. (d) Markowicz, M. W.; Dembinski, R.
Org. Lett. 2002, 4, 3785.
O-(b-D-Glucopyranosyl)-(1/6)-O-(b-D-glucopyranosyl)-
1
11. Barrett, A. G. M.; Braddock, D.; Catterick, C. D.; Chadwick,
D.; Heschke, J. P.; McKinnell, R. M. Synlett 2000, 847.
12. (a) Tzschucke, C. C.; Markert, C.; Glatz, H.; Bannwarth, W.
Angew. Chem., Int. Ed. 2002, 41, 4500. (b) Markert, C.;
Bannwarth, W. Helv. Chim. Acta 2002, 85, 1887. (c) Hoshino,
M.; Degenkolb, P.; Curran, D. P. J. Org. Chem. 1997, 62,
8341. (d) Curran, D. P.; Hoshino, M. J. Org. Chem. 1996, 61,
6480.
(1/6)-D-glucopyranose. H NMR (600 MHz, D2O): dZ
4.34 (d, JZ8.3 Hz), 4.35 (d, JZ5.5 Hz), 4.36 (d, JZ
8.3 Hz), 4.38 (d, JZ6.9 Hz), 4.50 (d, JZ10.3 Hz), 5.07 (d,
JZ3.4 Hz); 13C NMR (150 MHz, D2O): dZ92.07, 95.90,
102.65, 102.70, 102.77, 102.79.
Acknowledgements
13. (a) Zhang, W.; Luo, Z.; Chen, C. H.; Curran, D. P. J. Am.
Chem. Soc. 2002, 124, 10443. (b) Curran, D. P.; Furukawa, T.
Org. Lett. 2002, 4, 2233. (c) Zhang, Q.; Rivkin, A.; Curran,
D. P. J. Am. Chem. Soc. 2002, 124, 5774. (d) Curran, D. P.
Synlett 2001, 1488. (e) Luo, Z.; Zhang, Q.; Oderaotoshi, Y.;
Curran, D. P. Science 2001, 291, 1766.
This work was partly supported by Grants-in-Aid for
Scientific Research (C) (No. 13680680) and a Grant-in-
Aid for Encouragement of Young Scientists (No. 13771349)
from the Japan Society for the Promotion of Science, by a
grant for Hi-Tech Research from Tokai University, and by
the Takeda Science Foundation. This work was performed
through the Noguchi Fluorous Project by our institute.
14. (a) Manzoni, L. Chem. Commun. 2003, 2930. (b) Wipf, P.;
Reeves, J. T.; Balachandran, R.; Giuliano, K. A.; Hamel, E.;
¨
Day, B. W. J. Am. Chem. Soc. 2000, 122, 9391. (c) Rover, S.;
Wipf, P. Tetrahedron Lett. 1999, 40, 5667. (d) Wipf, P.;
Reeves, J. T. Tetrahedron Lett. 1999, 40, 5139. (e) Wipf, P.;
Reeves, J. T. Tetrahedron Lett. 1999, 40, 4649. (f) Studer, A.;
Curran, D. P. Tetrahedron 1997, 53, 6681.
References and notes
15. Curran, D. P.; Ferritto, R.; Hua, Y. Tetrahedron Lett. 1998, 39,
4937.
1. (a) Varki, A. Glycobiology 1993, 3, 97. (b) Dwek, R. A. Chem.
Rev. 1996, 96, 683. (c) Blithe, D. L. Trends Glycosci.
Glycotechnol. 1993, 5, 81.
16. (a) Curran, D. P.; Amatore, M.; Guthrie, D.; Campbell, M.;
Go, E.; Luo, J. Z. J. Org. Chem. 2003, 68, 4643. (b) Schwinn,
D.; Bannwarth, W. Helv. Chim. Acta 2002, 85, 255. (c)
Filippov, D. V.; Zoelen, J. D.; Oldfield, S. P.; Marel, G. A.;
Overkleeft, H. S.; Drijfhout, J. W.; Boom, J. H. Tetrahedron Lett.
2. (a) Manabe, S.; Ito, Y. J. Am. Chem. Soc. 2002, 124, 12638. (b)
Ando, H.; Manabe, S.; Nakahara, Y.; Ito, Y. J. Am. Chem. Soc.
2001, 123, 3848. (c) Plante, O. J.; Palmacci, E. R.; Seeberger,
P. H. Science 2001, 291, 1523. (d) Eichler, E.; Yan, F.; Sealy,
J.; Whitfield, D. M. Tetrahedron 2001, 57, 6679. (e) Ito, Y.;
Kanie, O.; Ogawa, T. Angew. Chem., Int. Ed. Engl. 1996, 35,
2510. (f) Douglas, S. P.; Whitfield, D. M.; Krepinsky, J. J.
J. Am. Chem. Soc. 1995, 117, 2116 and references cited
therein.
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2002, 43, 7809. (d) Pardo, J.; Cobas, A.; Guitlan, E.; Castedo, L.
Org. Lett. 2001, 3, 3711. (e) Luo, Z.; Williams, J.; Read,
R. W.; Curran, D. P. J. Org. Chem. 2001, 66, 4261.
17. Miura, T.; Hirose, Y.; Ohmae, M.; Inazu, T. Org. Lett. 2001, 3,
3947.
18. Miura, T.; Inazu, T. Tetrahedron Lett. 2003, 44, 1819.
19. Miura, T.; Goto, K.; Hosaka, D.; Inazu, T. Angew. Chem., Int.
Ed. 2003, 42, 2047.
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3. Horvath, I. T.; Rabai, J. Science 1994, 266, 72.
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4. (a) Tzschucke, C. C.; Markert, C.; Bannwarth, W.; Roller, S.;
Hebel, A.; Haag, R. Angew. Chem., Int. Ed. 2002, 41, 3964. (b)
Nishikido, J.; Kamishima, M.; Matsuzawa, H.; Mikami, K.
Tetrahedron 2002, 58, 8345. (c) Rocaboy, C.; Gladysz, J. A. Org.
Lett. 2002, 4, 1993. (d) Nakamura, Y.; Takeuchi, S.;
20. Zang, E.; Sadler, P. J. Synth. Commun. 1997, 27(18), 3145.
21. Schmidt method: Schmidt, R. R.; Michel, J.; Roos, M. Liebigs
Ann. Chem. 1984, 1343.
22. The product mixtures containing the fluorous compounds 13,

8854
K. Goto et al. / Tetrahedron 60 (2004) 8845–8854
16 and 24 were partitioned between FC-72 and MeOH. Those
28. The starting materials 14 and 22 were not observed by TLC
after the glycosylation.
containing the fluorous compound 14 and 22 were partitioned
FC-72, toluene and water. The product containing the fluorous
compound 21 was partitioned between FC-72 and acetonitrile.
None of the fluorous compounds were detected by TLC of the
organic layer after three times extraction with FC-72, which
shows that these compounds were quantitatively extracted
with FC-72.
29. The anomer ratio of compound 26 (the newly formed anomeric
position) was determined to be a/bZ78:22 based on NMR
spectroscopic analysis. The glycoside linkages of compound
26 were analyzed using the above NMR spectroscopic analysis
in Ref. 25.
30. Compound 26 was identified by comparison of spectroscopic
data of an authentic sample: Koto, S.; Morishima, N.; Shichi,
S.; Haigoh, H.; Hirooka, M.; Okamoto, M.; Higuchi, T.;
Shimizu, K.; Hashimoto, Y.; Irisawa, T.; Kawasaki, H.;
Takahashi, Y.; Yamazaki, M.; Mori, Y.; Kudo, K.; Ikegaki,
T.; Suzuki, S.; Zen, S. Bull. Chem. Soc. Jpn 1992, 65, 3257.
31. Veeneman, G. H.; Van Leeuwen, S. H.; Van Boom, J. H.
Tetrahedron Lett. 1990, 31, 1331.
23. EtOC4F9 is a commercially available fluorocarbon solvent
(3 M, Tokyo), which is called Novece HFE-7200.
24. FC-72 is a commercially available fluorocarbon solvent (3M,
Tokyo), which consists of perfluorohexane (C6F14) isomers
and is called Fluorinerte FC-72.
25. The anomer ratio of compound 19 (the newly formed anomeric
position) was determined to be a/bZ60:40 by NMR spectro-
scopic analysis. Moreover, the correlation between anomeric
protons of galactose residue and 6-position carbons of glucose
residue of the compound 19 was observed by HMQC and
HMBC of NMR spectroscopic analysis.
¨
32. Koenigs, W.; Knurr, E. Chemische Berichte 1901, 34, 957.
33. (a) Matsumoto, T.; Maeta, H.; Suzuki, K.; Tsuchihashi, G.
Tetrahedron Lett. 1988, 29, 3567. (b) Matsumoto, T.; Maeta,
H.; Suzuki, K.; Tsuchihashi, G. Tetrahedron Lett. 1988, 29,
3571. (c) Matsumoto, T.; Maeta, H.; Suzuki, K.; Tsuchihashi,
G. Tetrahedron Lett. 1988, 29, 3575. (d) Suzuki, K.; Maeta,
H.; Matsumoto, T. Tetrahedron Lett. 1989, 30, 4853. (e)
Mukaiyama, T.; Murai, Y.; Shoda, S. Chem. Lett. 1981, 431.
26. Compound 19 was identified by comparison of spectroscopic
data of the authentic samples (melibiose and arolactose).
27. Xu, W.; Springfield, S. A.; Koh, J. T. Carbohydr. Res. 2000,
325, 169.