A facile synthesis of 1′-C-alkyl-α-disaccharides from 1-C-alkyl-hexopyranoses and methyl 1-C-methyl-hexopyranosides

Article abstract of DOI:10.1016/S0040-4020(01)00321-0

Direct O-glycosidations using the 1-C-alkyl-2,3,4,6-tetra-O-benzyl-hexopyranoses as the glycosyl donors were carried out with a catalytic amount (0.2 equiv.) of trimethylsilyl trifluoromethanesulfonate (TMSOTf). The glycosidations proceeded α-stereoselect

Full text of DOI:10.1016/S0040-4020(01)00321-0

TETRAHEDRON
Pergamon
Tetrahedron 57 -2001) 4297±4309
A facile synthesis of 10-C-alkyl-a-disaccharides from 1-C-alkyl-
hexopyranoses and methyl 1-C-methyl-hexopyranosides
Xiaoliu Li, Hiro Ohtake, Hideyo Takahashi and Shiro Ikegamip
School of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan
Received 27 December 2000; accepted 16 March 2001
AbstractÐDirect O-glycosidations using the 1-C-alkyl-2,3,4,6-tetra-O-benzyl-hexopyranoses as the glycosyl donors were carried out with
a catalytic amount -0.2 equiv.) of trimethylsilyl tri¯uoromethanesulfonate -TMSOTf). The glycosidations proceeded a-stereoselectively and
furnished the corresponding 10-C-alkyl-a-disaccharides in 71±90% yields. The O-transglycosidations from the benzylated and acetylated
methyl 1-C-methyl-a-hexopyranosides to the corresponding 10-C-methyl-a-O-disaccharides were also examined, respectively. These trans-
glycosidations took place on a-stereoselectivity and provided the 10-C-methyl-a-O-disaccharides as the sole products, implying that no
neighboring group participation occured in the reactions. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
stereoselectively. However, direct glycosidation using
1-hydroxyaldopyranoses as the glycosyl donors showed
less stereoselectivity [Scheme 1-a), in the case of aldo-
pyranose -RˆH)].10
The important biological signi®cance and potential
chemotherapeutic value of carbohydrate compounds have
stimulated much research activity on glycoside synthesis
in the recent years.1 Along with the achievements in the
synthesis of complex saccharides, new methodologies for
stereoselective glycosylations have been developed.2 For
the conventional methods, the anomeric centers of glycosyl
donors are activated by conversion to the suitable
derivatives, such as halides,3 trichloroacetimidates,4 thio-
glycosides,5 phosphorous-containing living groups,6 sulf-
oxides,7 pentenylglycosides,8 glycals,9 etc., from which
the intermediate A [Scheme 1-b), in the case of aldo-
pyranose -RˆH)], an oxocarbenium ion is generated in
the presence of proper promoter and then followed by
the combination of A -RˆH) with a sugar alcohol in a
stereospeci®c manner to afford the desired O-glycosides
We have reported an extremely ef®cient method for synthe-
sizing 10-C-methyl-a-O-disaccharides by the direct glyco-
sidation of 1-methylenesugars and sugar alcohols in
the presence of a catalytic amount of Lewis acid.11 The
O-glycosidation reaction showed a-stereoselectivity with
no neighboring group participation. It was noted that the
stereoselective glycosidations of 1-C-alkyl-hexopyranoses
has not been investigated extensively, although recent
methods for the glycosidations of 1-C-alkyl-hexopyranoses
have been described which employed the similar
activated derivatives as those for aldopyranoses [Scheme
1-b), in the case of ketopyranose -RˆAlkyl)].12 In light
of this, we explored the stereoselective O-glycosidation of
Scheme 1. P, protecting group; HA, Lewis acid; XˆF, Cl, Br, OC-NH)CCl3, SPh, SEt, S-O)Ph, SO2Ph, OP-O)-OR)2, OP-O)-NMe)2, O-CH2)3CHˆCH2, etc.;
Aldopyranose: RˆH, Ketopyranose: RˆAlkyl.
Keywords: 1-C-alkyl-hexopyranoses; methyl 1-C-methyl-a-hexopyranosides; 10-C-alkyl-a-disaccharides; O-glycosidation; O-transglycosidation.
Corresponding author. Tel.: 181-426-85-3728; fax: 181-426-85-1870; e-mail: shi-ike@pharm.teikyo-u.ac.jp
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020-01)00 321-0

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X. Li et al. / Tetrahedron 57 )2001) 4297±4309
1-C-alkyl-hexopyranoses [Scheme 1-a), in the case of keto-
pyranose -RˆAlkyl)] to investigate the differences between
aldopyranoses and ketopyranoses.
2. Results and discussion
1-C-alkyl-hexopyranoses could be readily prepared by reac-
tions of the corresponding hexopyranolactones with orga-
nometallic reagents,13 for example, the Reformatsky-type
reactions14 or the reactions with Grignard reagents15 or orga-
nolithium reagents.15a,16 However, in most cases the formed
ketopyranoses were directly used to synthesize modi®ed
sugars, especially C-glycosides by reductive treatment
with triethylsilane and boron tri¯uoride etherate,15a,16a,16c
and very little detailed analytical data for the 1-C-alkyl-
hexopyranose compounds has been reported. Thus, the
starting materials, 1-hydroxy-1-C-methyl-hexopyranoses
-2a±c), were conveniently prepared by the reaction of the
corresponding lactones 1a±c17 with methyllithium -1.2
equiv.) in THF solution at 2788C in yields of 83±97% as
shown in Scheme 2. Similarly, the 1-hydroxy-1-C-vinyl-
hexopyranoses 3a±c were obtained from the reaction of
lactones 1a±c and vinylmagnesium bromide in good yields.
The analytical data for the products 2 and 3 are listed in the
Experimental section.
Scheme 2. Reagents and conditions: -i) CH3Li -1.2 equiv.), THF, 2788C;
-ii) CH2ˆCHMgBr -1.5 equiv.), THF, 2788C.
Considering the excellent yields of disaccharides in the
O-glycosidation of 1-methylenesugars promoted by tri-
¯oromethanesulfonic acid -TfOH),11 we examined the
O-glycosidation of 2a under the same conditions as that of
the 1-methylenesugar reactions. We found that the O-glyco-
sidation did not complete well at 2788C even using 1.5
equiv. of TfOH -entry 1), with the starting material 2a
remaining unreacted after 3 h. Increasing reaction tempera-
ture brought about side reactions and did not improve the
While the O-glycosidations of aldopyranoses with both
activated and nonactivated anomeric centres have been
well documented,2±8,10 there has been, to the best of our
knowledge, no report on the O-glycosidation using 1-C-
alkyl-hexopyranoses as the glycosyl donors. Thus, we ®rst
investigated the conditions for the O-glycosidations using
2a, employing the methyl 2,3,4-tri-O-benzyl-a-d-gluco-
pyranoside 418 as the glycosyl acceptor -Scheme 3). The
results are summarized in Table 1.
Scheme 3.
Table 1. The glycosidation of the 1-C-methyl-glucopyranose 2a with the sugar alcohol 4
Entry
Catalyst -equiv.)
Solvent
Conditions
Yield of 5a -%)
1
2
3
4
5
6
7
8
TfOH -1.5)
TfOH -1.0)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Et2O
2788C, 3 h
2788C, 1 h; 08C, 1 h
08C, 4 h
08C, 2 h
08C, 2 h
08C, 2 h
08C, 4 h
08C, 4 h
08C, 2 h
75.1a
78.5
71.7a
90.3
86.2
79.8
83.1
80.9
77.9
70.3
73.8
76.6a
TMSOTf -0.05)
TMSOTf -0.2)
TMSOTf -0.5)
TMSOTf -1.0)
TMSOTf -0.5)
TMSOTf -0.5)
BF3´Et2O -1.0)
THF
9
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
10SnCl
11
12
-1.0)
TiCl4 -1.0)
ZnCl2 -1.0)
08C, 2 h
08C, 2 h
08C, 4 h
4
a
The starting material 2a was partly recovered.

X. Li et al. / Tetrahedron 57 )2001) 4297±4309
4299
yield markedly -entry 2). The results indicated that TfOH
was not as effective for promoting the O-glycosidation of
the 1-C-alkyl-hexopyranoses 2 as it was for catalyzing the
glycosidation of 1-methylenesugars.11 After screening the
reaction with a variety of Lewis acid catalysts -Table 1), it
was found that trimethylsilyl tri¯uoromethanesulfonate
-TMSOTf) was most effective for this glycosidation.
Although the reactions gave the disaccharide 5a in moderate
yields with both a low equivalent molar ratio -entry 3) and
high ratios -entry 5 and 6) of the catalyst, excellent yield
-90.3%) for the O-glycosidation was achieved using a cata-
lytic amount -0.2 equiv.) of TMSOTf in dichloromethane at
08C in the presence of molecular sieves 4A -entry 4). It
should be noteworthy that the O-glycosidation of the 1-C-
methyl-glucopyranose 2a took place stereoselectively and
provided the a-disaccharide 5a as the sole product. In
addition, it was found that the solvent did not have much
effect on the glycosidation yield and the stereochemistry
Figure 1.
Scheme 4. Reagents and conditions: -i) TMSOTf -0.2 equiv.), MS 4A, CH2Cl2, 08C.
Scheme 5. Reagents and conditions: -i) MeOH, TMSOTf -0.2 equiv.), MgSO4, CH2Cl2, 08C; -ii) Pd-OH)2 /C, H2, MeOH, r.t.; -iii) Ac2O, pyridine, r.t.,
overnight.

4300
X. Li et al. / Tetrahedron 57 )2001) 4297±4309
Figure 2.
-entry 5, 7, 8). Under the same conditions, the O-glyco-
sidations of 2b and 2c with 4 were performed and furnished
the corresponding a-disaccharides 5b and 5c, respectively
-Scheme 4). The structures and the a-con®gurations of the
disaccharides 5 were determined by the comparison of their
COSY and MS -FAB1). With the similar method to the
previous paper,11 the conformations of 10-anomeric carbons
in 6a and 6b were tentatively determined according to the
three bond coupling constant 3JH-2 ,C-a between H-20 and C-a
0
of the vinyl group -Fig. 2). The coupling constants, 1.1 and
1.0Hz for 6a and 6b, respectively, showed synclinal
arrangements between the 20-proton and the 10-C-vinyl
group, indicating a-con®gurations of the 10-anomeric
carbons.
1H NMR and 13C NMR spectra and the three bond coupling
3
constants JH-2 ,Me-1 between the H-20 and the carbon of
10-C-methyl with those of the known compounds prepared
from 1-methylenesugars -Fig. 1).11
0
0
Following the above described procedure, the O-glyco-
sidations of the 1-hydroxy-1-C-vinyl-hexopyranoses 3a±c
with the methyl 2,3,4-tri-O-benzyl-a-d-glucopyranoside 4
were carried out. The reactions proceeded smoothly using a
catalytic amount -0.2 equiv.) of TMSOTf at 08C and
provided exclusively the corresponding a-disaccharides
6a±c in good yields -Scheme 4). Similarly, the glyco-
sidations of the compounds 2a±c with methanol in the
presence of 0.2 equiv. of TMSOTf using anhydrous mag-
nesium sulfate -MgSO4) as the dehydrating reagent gave the
corresponding methyl 1-C-methyl-hexopyranosides 7a±c19
in excellent yields -Scheme 5).
In order to examine the scope of the glycosidation of keto-
pyranoses whose high reactivity and stereoselectivity may
result from the formation of the stable intermediate A
[Scheme 1, in the case of ketopyranose -RˆAlkyl)], we
explored the O-transglycosidation using the methyl
2,3,4,6-tetra-O-benzyl-1-C-methyl-hexopyranosides 7a±c
as the glycosyl donors and the methyl 2,3,4-tri-O-benzyl-
a-d-glucoside 4 as the glycosyl acceptor. In the reaction, the
1-C-methyl-hexopyranosyl moiety was transferred to the
acceptor 4 with the replacement of the methoxy group,
affording the 10-C-methyl-disaccharides 5a±c -Scheme 6).
Although the 1-C-alkyl-hexopyranoses and 1-methylen-
sugars were liable to form the oxocarbenium ion inter-
mediate A [Scheme 1, ketopyranose -RˆAlkyl)] in the
The structures of the compounds 6 and 7 were determined
by analyses of their spectral data of 1H NMR, 13C NMR, 2D-
Scheme 6. Reagents and conditions: -i) SnCl4 -1.0equiv.), MS 4A, CH 2Cl2, 08C, 3 h.

X. Li et al. / Tetrahedron 57 )2001) 4297±4309
4301
Table 2. The O-transglycosidation of the methyl 2,3,4,6-tetra-O-benzyl-1-
C-methylglucoside 7a with the sugar alcohol 4
The O-transglycosidations of the acetyl protected methyl
1-C-methyl-hexopyranosides 8a±c and 1021 were
performed in order to examine the neighboring group par-
ticipation effect -Scheme 7). Compared with the benzyl-
protected glycosides, the acetyl-protected glycosides
exhibited lower reactivity to glycosidation.11 We thought
that stronger conditions might bene®t the reaction. The
O-transglycosidations of 8a±c and 10, after scanning
several Lewis acids, were found to occur most favourably
Entry
Catalyst -equiv.)
Conditions
5a -%)
9 -%)
7a -%)
1
2
3
4
5
6
TfOH -0.5)
TMSOTf -1.0)
BF3´Et2O -1.0)
SnCl4 -0.5)
SnCl4 -1.0)
SnCl4 -1.5)
SnCl4 -1.0)
SnCl4 -1.0)
AlCl3 -1.0)
08C, 2 h
08C, 3 h
08C, 3 h
08C, 3 h
08C, 3 h
08C, 3 h
08C, 5 h
08C, 3 h
r.t., 3 h
31.2
33.4
36.2
60.6
80.6
71.3
73.7
65.6
40.8
62.8
28.3
12.1
8.2
9.1
±
19.7
36.5
32.9
28.2
6.8
±
±
13.1
20.0
15.6
58.8
±
5.8
5.6
3.4
9.5
4.2
±
7
in the presence of an excess amount -4.0equiv.) of SnCl
4
8a
and afforded the corresponding a-disaccharides 11a±c,
respectively. It was observed that under the strong con-
ditions, acetyl group migration occurred in the compound
10 accompanyed by the transglycosidation, leading in the
low yields of the disaccharides 11.22 The spectral data
showed that the conformations of the disaccharides 11
were identical to those of the corresponding known
compounds,11 implying that no neighboring group partici-
pation was present in the transglycosidations.
9
10TiCl
11
-1.0)
ZnCl2 -2.0)
08C, 3 h
r.t., 4 h
4
a
Without molecular sieves.
glycosidations catalyzed by Lewis acids, but the methyl
1-C-methyl-hexopyranosides 7 did not easily generate the
intermediate A due to the higher stability of the methyl
glycosidic ether bond.20 Therefore, several stronger Lewis
acids such as TiCl4, ZnCl2, TMSOTf, SnCl4, BF3´Et2O,
AlCl3, and TfOH were examined for their ability to catalyze
the O-transglycosidation of 7a -Table 2). It was found that
under the catalysis of the strong Lewis acids the O-trans-
glycosidation took place affording the disaccharide 5a
-Scheme 6) as did with the main side reaction forming the
by-product 9.11 The results showed that the Lewis acids
TMSOTf, TfOH, ZnCl2, BF3´Et2O and AlCl3 were not effec-
tive for catalyzing the transglycosidation reaction -Entries
1±3, 9 and 11). However, the reaction under the catalysis of
SnCl4 provided better yields than that catalyzed by TiCl4
even though the transglycosidations did not proceed to
completion in both cases. In addition, molecular sieves
was necessary for improving the transglycosidation by
removing the generated methanol from the reaction system
-Entry 8). Thus, the O-transglycosidation of 7a and 4 was
found to proceed well under the catalysis of SnCl4 -1.0
equiv.) in the presence of MS 4A at 08C and furnished the
disaccharide 5a in 80.6% yield -Entry 5). Similarly, the
transglycosidations of 7b±c and 4 were carried out under
the same conditions to afford 5b±c in good yields.
The successful O-transglycosidations substituting methoxy
groups as in 7 and 8 with glycosyl acceptors supported
the reaction mechanism shown in Scheme 8. In the
glycosidations and the transglycosidations, the stable
intermediate D -a tertiary oxocarbenium ion) was generated
from B or C, and then combined with sugar alcohols to form
the a-O-glycosides.11 The stability of the tertiary oxo-
carbenium ion D resulted in the a-stereoselectivity in the
glycosidations due to the anomeric effect and made the
O-transglycosidations possible.
Ulosonic acid derivatives, especially, the sialic acid glyco-
sides play important roles in various biological processes,23
and syntheses of sialyl glycosides and their analogues have
been well documented.24 Generally, the glycosidations of
sialic acid derivatives did not proceed as smoothly as
those of aldopyranoses due to a reduction in the reactivity
of the anomeric center caused by the steric and electronic
properties of the carboxyl group. In addition, owing to the
anomeric effects, the O-glycosidations of the sialic acid
derivatives tended to form the b-anomer which is
contrary to natural sialic acid glycosides.24c As the further
Scheme 7. Reagents and conditions: -a) SnCl4 -4.0equiv.), MS 4A, 0 8C, CH2Cl2, 2 h, then r.t., 1 h.

4302
X. Li et al. / Tetrahedron 57 )2001) 4297±4309
Scheme 8. P, protecting group, RˆAlkyl.
Scheme 9. Reagents and conditions: -i) NaOH / MeOH, CH2Cl2, O3, 2788C.
applications of the a-stereoselective 1-C-alkyl-hexopyrano-
syl glycosidation described above, we envisaged to synthe-
size ulosonyl glycoside derivatives employing the 10-C-
vinyldisaccharides 6 in which the vinyl group serves as
the precursor to the carboxylate group by a-O-glycosidation
of 1-C-vinyl-hexopyranosides 3 -Scheme 4) followed by
cleavage of the ole®nic bond into a carboxylate group
-Scheme 9).
pyranoses as glycosyl donors proceeded smoothly with a
catalytic amount of TMSOTf, providing a facile method
for the synthesis of 10-C-alkyl-a-disaccharides from sugar
lactones. The O-transglycosidations of methyl 1-C-methyl-
hexopyranosides were also achieved under the promotion of
the Lewis acid, SnCl4. Both of these reactions showed
a-stereoselectivity and no neighboring group participation.
Applications of the a-stereoselectivity of these O-glyco-
sidations for synthesis are being explored.
While transformation of ole®nic bonds into carboxyl groups
has been well developed,25 considering the 10-C-vinyl-
disaccharides 6 being sensitive to strong acidic conditions
and stable to basic conditions, we tried conversing 6 to 12 by
a modi®cation of Marshall0s method involving ozonolysis
of the ole®nic bond at 2788C in a solution of sodium
hydroxide±methanol and dichloromethane.26 Using this
method the corresponding methyl esters 12 were obtained
directly from 6. Since 1-C-alkyl-hexopyranoses having
different functional groups can be conveniently prepared
by reaction of the corresponding sugar lactones with
organometallic reagents, it is possible to synthesize 10-C-
alkyl-a-O-disaccharides containing a functional group by
the present O-glycosidation method.
3. Experimental
3.1. General methods
Melting points were measured on a YANACO Micro
Melting Point Apparatus and are uncorrected. IR spectra
were recorded on a Jasco FT/IR-800 Fourier-transform
1
infrared spectrometer. H-NMR, 13C-NMR and 2D-COSY
3
spectra, and the three bond coupling constants JH,C were
measured on a JEOL JNM-GSX400 -400 MHz) and a
JEOL-ECP600 -600 MHz) pulse Fourier-transform NMR
spectrometers in CDCl3 solution using tetramethylsilane
-Me4Si) as an internal standard. Mass spectra -MS) and
high resolution mass spectra -HRMS) were carried out on
In summary, direct O-glycosidation using 1-C-alkyl-hexo-

X. Li et al. / Tetrahedron 57 )2001) 4297±4309
4303
a JEOL JMS-SX102A mass spectrometer using FAB -Fast
Atomic Bombardment). Optical rotations were measured
with a Jasco DIP-370digital polarimeter. Thin-layer
chromatography -TLC) was performed on precoated
11.60Hz, CH 2Ph), 4.66±4.75 -m, 3H, CH2Ph), 4.93 -d,
1H, Jˆ11.60Hz, CH 2Ph), 4.97 -d, 1H, Jˆ10.99 Hz,
CH2Ph), 7.24±7.36 -m, 20H, ArH); 13C NMR -CDCl3): d
26.59 -CH3), 68.83 -6-C), 70.18 -5-C), 72.38 -CH2Ph),
73.40-CH 2Ph), 74.30-4-C), 74.45 -CH 2Ph), 75.75
-CH2Ph), 79.76 -2-C), 80.92 -3-C), 97.84 -1-C), 127.48
-Ph), 127.49 -Ph), 127.55 -Ph), 127.68 -Ph), 127.74 -Ph),
127.89 -Ph), 128.03 -Ph), 128.16 -Ph), 128.30 -Ph), 128.34
-Ph), 128.38 -Ph), 138.00 -Ph), 138.15 -Ph), 138.45 -Ph),
138.82 -Ph); HRMS -FAB): calcd for C35H38O6Na
577.2566, found 577.2570.
plates -Merck TLC aluminum sheets silica 60F
)
254
with detection by UV light or with phosphomolybdic
acid in EtOH/H2O followed by heating. Column
chromatography was performed using SiO2 -Wakogel
C-200, Wako). Ozone was generated by an O-3-2 type
Ozone generator -Nippon Ozone Co., Ltd.) using O2 as
the oxygen supply.
3.1.1. 2,3,4,6-Tetra-O-benzyl-1-C-methyl-a-d-glucopyra-
nose /2a). To a solution of 2,3,4,6-tetra-O-benzylglucono-
1,5-lactone -1a) -2.69 g, 5.0mmol) in 25 mL of dry THF
was added 6.0mL of methyl lithium in ethyl ether -1.0mol/
L) -1.2 equiv.) at 2788C under argon atmosphere. The
solution was stirred for 1 h and the reaction was quenched
with water. The mixture was extracted with AcOEt. The
organic phase was washed with water -100 mL£3), dried
over Na2SO4 and concentrated under reduced pressure.
The residue was submitted to a silica gel column chroma-
tography using Et2O: Hexaneˆ1:1 -v/v) as the eluent to
afford product 2a, -2.30g, 83.0%). White solid, mp: 92±
938C; ‰aŠ2D4: 124.78 -c 1.0, CHCl3); IR -KBr): 3464.57,
3063.33, 3030.54, 2932.16, 2903.22, 2868.50, 1603.04,
1585.68, 1496.94, 1454.50, 1404.35, 1363.84, 1199.87,
1153.57, 1086.06, 1043.62, 1028.18, 976.10, 871.93,
3.1.3. 2,3,4,6-Tetra-O-benzyl-1-C-methyl-a-d-mannopyra-
nose /2c). Following the procedure used to prepare 2a, the
compound 2c was prepared from 2.69 g -5.0mmol) of
2,3,4,6-tetra-O-benzylmannono-1,5-lactone
-1c)
and
6.0mL of methyl lithium in ethyl ether -1.0mol/L) -1.2
equiv.). The syrupy product 2c was obtained, 2.70g
-97.6%). ‰aŠ2D3: 114.88 -c 1.0, CHCl3); IR -neat): 3418.28,
3063.33, 3030.54, 2918.20, 2866.57, 1604.97, 1585.68,
1496.94, 1454.50, 1367.70, 1205.66, 1089.91, 902.80,
1
738.83, 696.39 cm21; H NMR -CDCl3): d 1.40-s, 3H,
CH3), 2.95 -s, br, 1H, OH), 3.61±3.73 -m, 2H, two 6-H),
3.69 -d, 1H, Jˆ2.75 Hz, 2-H, overlaped with 6-H), 3.84 -t,
1H, Jˆ9.46 Hz, 4-H), 3.94±3.99 -m, 1H, 5-H), 4.12 -dd, 1H,
Jˆ9.46 Hz, Jˆ2.75 Hz, 3-H), 4.51 -d, 1H, Jˆ10.99 Hz,
CH2Ph), 4.55 -d, 2H, Jˆ5.49 Hz, CH2Ph), 4.66 -d, 1H,
Jˆ11.60Hz, CH 2Ph), 4.73 -s, 2H, CH2Ph), 4.85 -d, 1H,
Jˆ10.99 Hz, CH2Ph), 4.95 -d, 1H, Jˆ11.60Hz, CH 2Ph),
7.15±7.38 -m, 20H, ArH); 13C NMR -CDCl3): d 26.30
-CH3), 69.73 -6-C), 72.52 -5-C), 72.55 -CH2Ph), 73.22
-CH2Ph), 74.69 -CH2Ph), 74.86 -CH2Ph), 75.06 -2-C),
78.14 -4-C), 81.43 -3-C), 98.03 -1-C), 127.42 -Ph), 127.48
-Ph), 127.86 -Ph), 127.92 -Ph), 127.97 -Ph), 128.01 -Ph),
128.12 -Ph), 128.22 -Ph), 128.32 -Ph), 138.28 -Ph), 138.39
-Ph), 138.53 -Ph), 138.61 -Ph); HRMS -FAB): calcd for
C35H38O6Na 577.2566, found 577.2561.
1
850.71, 760.05, 738.83, 698.32 cm21; H NMR -CDCl3):
d 1.39 -s, 3H, CH3), 2.86 -s, br, 1H, OH), 3.35 -d, 1H,
Jˆ9.46 Hz, 2-H), 3.64 -t, 1H, Jˆ9.77 Hz, 4-H), 3.64±3.66
-d, 1H, 6-H, overlapped with 4-H), 3.70-dd, 1H,
Jˆ10.68 Hz, Jˆ4.27 Hz, 6-H), 3.98 -t, 1H, Jˆ9.15 Hz, 3-
H), 3.99±4.05 -m, 1H, 5-H), 4.50 -d, 1H, Jˆ12.21 Hz,
CH2Ph), 4.55 -d, 1H, Jˆ10.99 Hz, CH2Ph), 4.59 -d, 1H,
Jˆ12.21 Hz, CH2Ph), 4.69 -d, 1H, Jˆ 10.99 Hz, CH2Ph),
4.82 -d, 1H, Jˆ10.98 Hz, CH2Ph), 4.88 -s, 2H, CH2Ph), 4.92
-d, 1H, Jˆ11.29 Hz, CH2Ph), 7.14±7.16 -m, 2H, ArH),
7.24±7.33 -m, 18H, ArH); 13C NMR -CDCl3): d 26.57
-CH3), 68.83 -6-C), 71.53 -5-C), 73.41 -CH2Ph), 74.82
-CH2Ph), 75.56 -CH2Ph), 75.66 -CH2Ph), 78.45 -4-C),
83.19 -3-C), 83.62 -2-C), 97.35 -1-C), 127.57 -Ph), 127.63
-Ph), 127.72 -Ph), 127.80-Ph), 127.82 -Ph), 127.89 -Ph),
127.95 -Ph), 128.27 -Ph), 128.32 -Ph), 128.33 -Ph), 128.40
-Ph), 137.88 -Ph), 138.22 -Ph), 138.26 -Ph), 138.65 -Ph);
HRMS -FAB): calcd for C35H38O6Na 577.2566, found
577.2564.
3.1.4. 2,3,4,6-Tetra-O-benzyl-1-C-vinyl-a-d-glucopyra-
nose /3a). 1.58 mL of Vinyl magnesium bromide -1.5
equiv.) in THF -0.95 mol/L) was added to a solution of
538 mg -1.0mmol) of 2,3,4,6-tetra- O-benzylglucono-1,5-
lactone -1a) in 10mL of dry THF at 2788C under argon
atmosphere. The solution was stirred for 1 h, then the reac-
tion temperature raised gradually up to 08C, and the reaction
was quenched with water. The mixture was extracted with
CH2Cl2. The organic phase was dried over Na2SO4 and
concentrated in vacuum. The residue was puri®ed by silica
gel column chromatography -Et2O-Hexane 1:1 v/v) to
provide 3a -462 mg, 81.6%). Colorless syrup; ‰aŠ2D2:
142.98 -c 1.0, CHCl3); IR -neat): 3418.28, 3063.33,
3030.54, 2920.58, 2866.57, 1952.20, 1875.04, 1811.38,
1604.97, 1587.61, 1496.94, 1454.50, 1361.91, 1209.51,
1070.62, 1028.18, 991.53, 939.54, 850.71, 734.97,
3.1.2. 2,3,4,6-Tetra-O-benzyl-1-C-methyl-a-d-galacto-
pyranose /2b). Following the procedure used to prepare
2a, the compound 2b was prepared from 2.69 g
-5.0mmol) of 2,3,4,6-tetra- O-benzylgalactono-1,5-lactone
-1b) and 6.0mL of methyl lithium in ethyl ether -1.0mol/
L) -1.2 equiv.). The syrupy product 2b was obtained, 2.36 g
-85.2%). ‰aŠ2D3: 122.08 -c 1.0, CHCl3); IR -neat): 3443.36,
3063.33, 3030.54, 2920.58, 2870.34, 1604.97, 1585.68,
1496.94, 1454.50, 1365.77, 1205.66, 1097.63, 1028.18,
1
698.32 cm21; H NMR -CDCl3): d 2.79 -s, br, 1H, OH),
3.44 -d, 1H, Jˆ9.16 Hz, 2-H), 3.69 -dd, 1H, Jˆ10.07 Hz,
Jˆ2.14 Hz, 6-H), 3.79 -t, 1H, Jˆ9.46 Hz, 4-H), 3.77 -dd,
1H, Jˆ10.68 Hz, Jˆ3.97Hz, 6-H), 3.98 -t, 1H, Jˆ9.16 Hz,
3-H), 4.06 -ddd, 1H, Jˆ10.07 Hz, Jˆ3.97 Hz, Jˆ1.83 Hz,
5-H), 4.51±4.66 -m, 4H, CH2Ph), 4.76±4.84 -m, 2H,
CH2Ph), 4.88 -2s, br, 2H, overlapped, CH2Ph), 5.30-dd,
1H, Jˆ10.68 Hz, Jˆ1.22 Hz, CH2ˆ), 5.61 -dd, 1H, Jˆ
17.39 Hz, Jˆ1.22 Hz, CH2ˆ), 6.00 -dd, 1H, Jˆ17.39 Hz,
1
736.90, 698.31 cm21; H NMR -CDCl3): d 1.40-s, 3H,
CH3), 2.61 -s, br, 1H, OH), 3.51±3.59 -m, 2H, two 6-H),
3.81 -d, 1H, Jˆ9.76 Hz, 2-H), 3.89 -dd, 1H, Jˆ9.46 Hz,
Jˆ3.44 Hz, 3-H), 4.00 -d, 1H, Jˆ2.44 Hz, 5-H), 4.11 -t,
1H, Jˆ7.02 Hz, 4-H), 4.43 -d, 1H, Jˆ12.20Hz, CH 2Ph),
4.48 -d, 1H, Jˆ11.90Hz, CH 2Ph), 4.61 -d, 1H, Jˆ

4304
X. Li et al. / Tetrahedron 57 )2001) 4297±4309
Jˆ10.68 Hz, -CHˆ), 7.16±7.33 -m, 20H, ArH); 13C NMR
-CDCl3): d 68.81 -6-C), 71.72 -5-C), 73.42 -CH2Ph), 74.91
-CH2Ph), 75.65 -two C, CH2Ph), 78.16 -4-C), 82.75 -3-C),
83.39 -2-C), 96.51 -1-C), 117.18 -CH2ˆ), 127.55 -Ph),
127.59 -Ph), 127.64 -Ph), 127.72 -Ph), 127.76 -Ph),
127.82 -Ph), 127.85 -Ph), 128.23 -Ph), 128.31 -Ph),
128.34 -Ph), 128.36 -Ph), 137.77 -Ph), 138.26 -Ph),
138.66 -Ph), 138.76 --CHˆ); HRMS -FAB): calcd for
C36H38O6Na 589.2566, found 589.2563.
3.2. The O-glycosidations of the 1-C-methyl-hexo-
pyranoses 2
3.2.1. The examination of the reaction conditions using
2a and 4. To a solution of 2a -55.4 mg, 0.1 mmol), methyl
2,3,4-tri-O-benzyl-a-d-glucoside -4) -69.6 mg, 0.15 mmol)
and MS 4A -100 mg) in dry dichloromethane -2.0 mL) was
added the given amount of Lewis acids under argon atmos-
phere. The mixture was stirred for a certain time, then 3
drops of Et3N was added to quench the reaction. The solu-
tion was concentrated in vacuum, and the residue was
submitted to a silica gel column chromatography -Et2O:
Hexaneˆ1:1 v/v) to afford the disaccharide 5a. The results
are summarized in Table 1.
3.1.5. 2,3,4,6-Tetra-O-benzyl-1-C-vinyl-a-d-galactopyra-
nose /3b). Following the procedure of preparing 3a, 2,3,
4,6-tetra-O-benzylgalactono-1,5-lactone -1b) -640mg,
1.2 mmol) reacted with vinyl magnesium bromide -1.5
equiv.) to provide the compound 3b -565 mg, 83.2%).
Colorless syrup; ‰aŠ2D4: 132.58 -c 1.0, CHCl3); IR -neat):
3406.55, 3063.33, 3030.54, 2922.08, 2868.22, 1604.97,
1496.94, 1454.50, 1361.92, 1209.51, 1073.02, 941.46,
3.2.2. Methyl O-/20,30,40,60-tetra-O-benzyl-10-C-methyl-
a-d-glucopyranosyl)-/10!6)-2,3,4-tri-O-benzyl-a-d-gluco-
side /5a). TMSOTf -1.8 mL, 0.02 mmol, 0.2 equiv.) was
added to the solution of 2a -55.4 mg, 0.1 mmol), methyl
2,3,4-tri-O-benzyl-a-d-glucoside -4) -69.6 mg, 0.15
mmol) and molecular sieves 4A -MS 4A, 100 mg) in
dichloromethane -2.0mL) was added at 0 8C under argon
atmosphere. The mixture was stirred for 2 h, and the reac-
tion was quenched by Et3N. The solvent was removed, and
the residue was submitted to a silica gel column chroma-
tography using Et2O: Hexane -1:1 v/v) as the eluent to afford
the disaccharide 5a -90.4 mg, 90.3%). Colorless syrup;
‰aŠ2D3: 147.78 -c 1.0, CHCl3) -lit.11 146.98).
3.2.3. Methyl O-/20,30,40,60-tetra-O-benzyl-10-C-methyl-
a-d-galactopyranosyl)-/10!6)-2,3,4-tri-O-benzyl-a-d-
glucoside /5b). Following the glycosidation procedure of 2a
and 4, the glycosidation of 2b -55.4 mg, 0.1 mmol) and 4
-69.6 mg, 0.15 mmol) was carried out and afforded the
disaccharide 5b -89.2 mg, 89.1%). Colorless syrup; ‰aŠ2D3:
150.88 -c 1.0, CHCl3) -lit.11 151.38).
1
736.72, 698.32 cm21; H NMR -CDCl3): d 2.90-s, br, 1H,
OH) 3.53±3.62 -m, 2H, two 6-H), 3.87, -d, 1H, Jˆ9.77 Hz,
2-H), 3.91 -dd, 1H, J ˆ9.77 Hz, Jˆ2.44 Hz, 3-H), 4.01 -s,
br, 1H, 4-H), 4.10-ddd, 1H, Jˆ11.59 Hz, Jˆ5.57 Hz,
Jˆ2.45 Hz, 5-H), 4.44 -d, 2H, Jˆ6.71 Hz, CH2Ph),
4.62 -d, 2H, Jˆ10.68 Hz, CH2Ph), 4.72 -s, 2H, CH2Ph),
4.82 -d, 1H, Jˆ10.68 Hz, CH2Ph), 4.94 -dd, 1H,
Jˆ11.59 Hz, CH2Ph), 5.26 -dd, 1H, Jˆ10.38 Hz,
Jˆ0.92 Hz, CH2ˆ), 5.57 -dd, 1H, Jˆ17.40Hz,
Jˆ0.92 Hz, CH2ˆ), 5.99 -dd, 1H, Jˆ17.40Hz,
Jˆ10.68 Hz, -CHˆ), 7.26±7.34 -m, 20H, ArH); 13C
NMR -CDCl3): d 68.72 -6-C), 70.35 -5-C), 72.67
-CH2Ph), 73.38 -CH2Ph), 74.48 -CH2Ph), 74.49
-4-C), 75.72 -CH2Ph), 79.10-3-C), 8.057 -2-C), 96.91
-1-C), 116.93 -CH2ˆ), 127.46 -Ph), 127.59 -Ph), 127.79
-Ph), 127.97 -Ph), 128.15 -Ph), 128.19 -Ph), 128.28 -Ph),
128.33 -Ph), 137.97 -Ph), 138.06 -Ph), 138.50 -Ph), 138.82
-two C, -CHˆ and Ph); HRMS -FAB): calcd for
C36H38O6Na 589.2566, found 589.2558.
3.2.4. Methyl O-/20,30,40,60-tetra-O-benzyl-10-C-methyl-
a-d-mannopyranosyl)-/10!6)-2,3,4-tri-O-benzyl-a-d-
glucoside /5c). Following the glycosidation procedure of 2a
and 4, the glycosidation of 2c -55.4 mg, 0.1 mmol) and 4
-69.6 mg, 0.15 mmol) was carried out and afforded the
disaccharide 5c -86.9 mg, 86.8%). Colorless syrup; ‰aŠ2D5:
144.08 -c 1.0, CHCl3) -lit.11 143.18).
3.1.6. 2,3,4,6-Tetra-O-benzyl-1-C-vinyl-a-d-mannopyra-
nose /3c). Following the procedure of preparing 3a,
2,3,4,6-tetra-O-benzylmannono-1,5-lactone -1c) -580mg,
1.1 mmol) reacted with vinyl magnesium bromide -1.5
equiv.) to provide the compound 3c -513 mg, 82.4%).
Colorless syrup; ‰aŠ2D3: 110.48 -c 1.0, CHCl3); IR -neat):
3383.55, 3063.33, 3032.47, 2918.65, 1604.97, 1496.94,
1454.50, 1365.77, 1275.10, 1209.51, 1072.55, 941.38,
3.3. The O-glycosidations of the 1-C-vinyl-hexopyranoses
3
1
738.83, 698.32 cm21; H NMR -CDCl3): d 2.66 -s, br, 1H,
OH), 3.72 -d, br, 2H, Jˆ3.66 Hz, two 6-H), 3.74 -d, 1H,
Jˆ2.75 Hz, 2-H), 3.93 -t, 1H, Jˆ9.76 Hz, 4-H), 4.02 -dt,
1H, Jˆ10.07 Hz, Jˆ3.66 Hz, 5-H), 5.12 -dd, 1H, Jˆ
9.64 Hz, Jˆ2.75 Hz, 3-H), 4.53±4.63 -m, 4H, CH2Ph),
3.3.1. Methyl O-/20,30,40,60-tetra-O-benzyl-10-C-vinyl-a-
d-glucopyranosyl)-/10!6)-2,3,4-tri-O-benzyl-a-d-gluco-
side /6a). A solution of 3a -803 mg, 1.42 mmol), 4 -985 mg,
2.12 mmol, 1.5 equiv.) and MS 4A -1.0g) in 30mL of dry
CH2Cl2 was cooled to 08C under argon atmosphere, and 25.6
mL -0.28 mmol, 0.2 equiv.) of TMSOTf was added. The
solution was stirred for 1 h, and 0.1 mL of Et3N was
added to quench the reaction. The solvent was removed,
and the residue was applied on a silica gel column chroma-
tography -Et2O: Hexaneˆ1:1.5 v/v) to give the disaccharide
6a -1.27 g, 88.3%). Colorless syrup; ‰aŠ2D3: 140.78 -c 1.0,
CHCl3); IR -neat): 3063.33, 3030.54, 2928.30, 1604.97,
1496.94, 1454.50, 1361.91, 1207.59, 1159.36, 1093.77,
4.70-s, 2H, CH Ph), 4.84 -d, 1H, Jˆ12.20Hz, CH 2Ph),
2
4.87 -dd, 1H, Jˆ11.29 Hz, CH2Ph), 5.20-d, 1H, Jˆ
10.68 Hz, CH2ˆ), 5.47 -d, 1H, Jˆ17.40Hz, CH 2ˆ), 6.11
-dd, 1H, Jˆ17.39 Hz, Jˆ10.68 Hz, -CHˆ), 7.17±7.36 -m,
20H, ArH); 13C NMR -CDCl3): d 69.66 -6-C), 72.37 -5-C),
72.88 -CH2Ph), 73.28 -CH2Ph), 74.60-CH 2Ph), 74.94
-CH2Ph), 74.97 -2-C), 78.82 -4-C), 81.34 -3-C), 97.30
-1-C), 115.90-CH ˆ), 127.33 -Ph), 127.36 -Ph), 127.46
2
-Ph), 127.78 -Ph), 127.86 -Ph), 127.97 -Ph), 128.02 -Ph),
128.22 -Ph), 128.30-Ph), 138.43 -Ph), 138.46 -Ph), 138.52
-Ph), 138.59 -Ph), 140.23 -CH2ˆ); HRMS -FAB): calcd. for
C36H38O6Na 589.2566, found 589.2573.
1
1028.18, 943.31, 910.51, 736.90, 698.32 cm-1; H NMR
-CDCl3): d 3.31±3.37 -m, 3H, 20-H, 4-H and 6-H), 3.35

X. Li et al. / Tetrahedron 57 )2001) 4297±4309
4305
-s, 3H, CH3O), 3.50-dd, 1H, Jˆ9.76 Hz, Jˆ3.66 Hz, 2-H),
3.60-dd, 1H, Jˆ11.29 Hz, Jˆ1.53 Hz, 60-H), 3.63±3.71 -m,
3H, 60-H, 40-H and 6-H), 3.81±3.86 -m, 1H, 5-H), 3.87±
3.91 -m, 1H, 50-H), 3.98 -t, 1H, Jˆ9.15 Hz, 3-H), 4.09 -t,
1H, Jˆ9.15 Hz, 30-H), 4.48±4.68 -m, 7H, CH2Ph and 1-H),
4.75±4.89 -m, 7H, CH2Ph), 4.96 -d, 1H, Jˆ10.99 Hz,
CH2Ph), 5.27 -dd, 1H, Jˆ10.69 Hz, Jˆ 1.83 Hz, CH2ˆ),
5.54 -dd, 1H, Jˆ17.70Hz, Jˆ1.83 Hz, CH2ˆ), 5.90-dd,
1H, Jˆ17.70Hz, Jˆ10.98 Hz, -CHˆ), 7.15±7.36 -m,
35H, ArH); 13C NMR -CDCl3): d 54.94 -OCH3), 61.45 -6-
C), 68.88 -60-C), 69.93 -5-C), 71.57 -50-C), 73.20-two C,
CH2Ph), 74.54 -CH2Ph), 74.84 -CH2Ph), 75.18 -CH2Ph),
75.33 -CH2Ph), 75.79 -CH2Ph), 78.39 -40-C), 78.55 -4-C),
80.16 -2-C), 82.35 -3-C), 82.73 -30-C), 84.49 -20-C), 97.51
-1-C), 99.58 -10-C), 118.94 -CH2ˆ), 127.37 -Ph), 127.38
-Ph), 127.45 -Ph), 127.49 -Ph), 127,57 -Ph), 127.60-Ph),
127.79 -Ph), 127.84 -Ph), 127.95 -Ph), 128.01 -Ph), 128.12
-Ph), 128.19 -Ph), 128.27 -Ph), 128.34 -Ph), 128.37 -Ph),
128.40-Ph), 135.42 --CH ˆ), 138.22 -Ph), 138.27 -Ph),
138.48 -Ph), 138.54 -Ph), 138.67 -Ph), 138.71 -Ph);
HRMS -FAB): calcd for C64H68O11Na 1035.4660, found
1035.4655.
CHCl3); IR -neat): 3063.33, 3030.54, 2910.94, 1603.04,
1496.94, 1454.50, 1361.91, 1275.10, 1205.66, 1095.70,
1
1028.18, 910.51, 827.56, 736.90, 698.32 cm21; H NMR
-CDCl3): d 3.30-s, 3H, CH O), 3.28±3.35 -m, 1H, 4-H,
3
overlapped with OCH3), 3.46 -dd, 1H, Jˆ11.00 Hz,
Jˆ6.05 Hz, 6-H), 3.54 -dd, 1H, Jˆ9.90Hz, Jˆ3.85 Hz,
2-H), 3.66 -dd, 1H, Jˆ11.54 Hz, Jˆ1.65 Hz, 60-H), 3.68
-dd, 1H, Jˆ10.45 Hz, Jˆ1.65 Hz, 6-H), 3.72 -dd, 1H, Jˆ
11.54 Hz, Jˆ4.95 Hz, 60-H), 3.72±3.75 -m, 1H, 5-H), 3.78
0
-ddd, 1H, Jˆ9.90Hz, Jˆ5.50Hz, Jˆ4.40Hz, 5 -H), 3.82
-d, 1H, Jˆ2.75 Hz, 20-H), 3.97 -t, 2H, Jˆ9.35 Hz, 40-H and
3-H), 4.09 -dd, 1H, Jˆ9.35 Hz, Jˆ2.75 Hz, 30-H), 4.44±
4.55 -m, 3H, CH2Ph and 1-H), 4.60±4.71 -m, 6H, CH2Ph),
4.75±4.90-m, 5H, CH Ph), 4.98 -d, 1H, Jˆ 10.68 Hz,
2
CH2Ph), 5.35 -dd, 1H, Jˆ10.38 Hz, Jˆ1.83 Hz, CH2ˆ),
5.54 -dd, 1H, Jˆ17.40Hz, Jˆ1.84 Hz, CH2ˆ), 5.65 -dd,
1H, Jˆ17.40Hz, Jˆ10.38 Hz, -CHˆ), 7.14±7.37 -m,
35H, ArH); 13C NMR -CDCl3): d 54.86 -OCH3), 60.52
-6-C), 69.37 -60-C), 69.64 -5-C), 71.91 -CH2Ph), 73.08
-CH2Ph), 73.11 -two C, 50-C and CH2Ph, overlapped),
74.62 -two C, 40-C and CH2Ph, overlapped), 74.71
-CH2Ph), 74.75 -CH2Ph), 75.70-CH 2Ph), 78.02 -4-C),
78.16 -20-C), 79.93 -2-C), 80.65 -30-C), 82.35 -3-C), 97.57
-1-C), 100.50 -10-C), 119.26 -CH2ˆ), 127.20-Ph), 127.23
-Ph), 127.27 -Ph), 127.43 -Ph), 127.45 -Ph), 127.49 -Ph),
127.55 -Ph), 127.59 -Ph), 127.66 -Ph), 127.81 -Ph), 127.84
-Ph), 127.93 -Ph), 127.96 -Ph), 127.98 -Ph), 128.08 -Ph),
128.11 -Ph), 128.13 -Ph), 128.22 -Ph), 128.32 -Ph), 128.39
-Ph), 135.84 --CHˆ), 138.16 -Ph), 138.20-Ph), 138.43 -Ph),
138.67 -Ph), 138.69 -Ph), 138.79 -Ph), 138.81 -Ph); HRMS
-FAB): calcd for C64H68O11Na 1035.4660, found
1045.4667.
3.3.2. Methyl O-/20,30,40,60-tetra-O-benzyl-10-C-vinyl-a-
d-galactopyranosyl)-/10!6)-2,3,4-tri-O-benzyl-a-d-gluco-
side /6b). Following the glycosidation procedure of 3a and
4, the glycosidation of 3b -380mg, 0.67 mmol) and
4
-464 mg, 1.0mmol, 1.5 equiv.) provided the disaccharide
6b -482 mg, 71.0%). Colorless syrup; ‰aŠ2D3: 136.08 -c 1.0,
CHCl3); IR -neat): 3063.33, 3030.54, 2926.37, 1496.94,
1454.50, 1361.91, 1205.66, 1097.63, 1049.40, 1028.18,
1
943.31, 912.44, 734.97, 698.32 cm21; H NMR -CDCl3):
d 3.23 -s, 3H, OCH3), 3.26 -t, 1H, Jˆ9.61 Hz, 4-H), 3.32
-dd, 1H, Jˆ10.68 Hz, Jˆ7.63 Hz, 60-H), 3.47 -dd, 1H, Jˆ
9.46 Hz, Jˆ3.66 Hz, 2-H), 3.53±3.61 -m, 2H, two 6-H),
3.71 -dd, 1H, J ˆ10.68 Hz, Jˆ1.52 Hz, 60-H), 3.80±3.85
-m, 1H, 5-H), 3.84 -d, 1H, Jˆ9.76 Hz, 20-H), 3.93 -s, br.,
1H, 40-H), 3.97 -t, 1H, Jˆ9.16 Hz, 3-H), 4.00±4.04 -m, 2H,
50-H and 30-H), 4.39±4.48 -m, 3H, CH2Ph), 4.55 -d, 1H,
Jˆ3.66 Hz, 1-H), 4.60±4.97 -m, 11H, CH2Ph), 5.23 -dd,
1H, Jˆ10.98 Hz, Jˆ1.83 Hz, CH2ˆ), 5.51 -dd, 1H, Jˆ
17.70Hz, J ˆ1.83 Hz, CH2ˆ), 5.89 -dd, 1H, Jˆ17.40Hz,
Jˆ10.99 Hz, -CHˆ), 7.21±7.34 -m, 35H, ArH); 13C NMR
-CDCl3): d 54.65 -OCH3), 61.58 -6-C), 68.95 -60-C), 69.90
3.3.4. Methyl 2,3,4,6-tetra-O-benzyl-1-C-methyl-a-d-
glucopyranoside /7a). To a mixture of 2.22 g -4.0mmol)
of 2a, 0.8 mL -20 mmol) of dry methanol and 2.0 g of anhy-
drous magnesium sulfate -MgSO4) in 20mL of dry CH 2Cl2
was added 72 mL of TMSOTf -0.2 equiv.) at 08C under
argon atmosphere. The solution was stirred at 08C for 1 h
and 0.1 mL of Et3N was added to quench the reaction. After
removing the solvent, the residue was applied on a silica gel
column chromatography using AcOEt: Hexaneˆ1:1.5 -v/v)
as the eluent to afford the product 7a, 2.08 g -91.5%). Color-
less syrup; ‰aŠ2D3: 121.38 -c 1.0, CHCl3); IR -neat): 3063.33,
3030.54, 2910.94, 2866.57, 1496.94, 1454.50, 1361.91,
-5-C), 70.07 -50-C), 72.40-CH Ph), 73.04 -CH2Ph), 73.10
2
-CH2Ph), 74.39 -CH2Ph), 74.83 -40-C), 75.08 -CH2Ph),
75.15 -CH2Ph), 75.67 -CH2Ph), 78.83 -4-C), 79.62 -30-C),
80.05 -2-C), 80.51 -20-C), 82.20-3-C), 97.38 -1-C), 99.90
-10-C), 118.82 -CH2ˆ), 127.22 -Ph), 127.33 -Ph), 127.35
-Ph), 127.39 -Ph), 127.42 -Ph), 127.48 -Ph), 127.53 -Ph),
127.59 -Ph), 127.63 -Ph), 127.74 -Ph), 127.79 -Ph), 127.83
-Ph), 127.90 -Ph), 128.00 -Ph), 128.09 -Ph), 128.13 -Ph),
128.25 -Ph), 128.28 -Ph), 128.33 -Ph), 135.18 --CHˆ),
138.16 -Ph), 138.28 -Ph), 138.62 -Ph), 138.70-Ph),
138.73 -Ph), 138.97 -Ph); HRMS -FAB): calcd for
C64H68O13Na 1035.4660, found 1035.4663.
1211.44, 1089.91, 1028.18, 736.90, 689.32 cm21 1H
;
NMR -CDCl3): d 1.27 -s, 3H, CH3), 3.22 -s, 3H, OCH3),
3.35 -d, 1H, Jˆ9.46 Hz, 2-H), 3.63±3.72 -m, 4H, two 6-H,
3-H and 4-H), 4.25±4.11 -m, 1H, 5-H), 4.50±4.54 -m, 2H,
CH2Ph), 4.61 -d, 1H, Jˆ12.21 Hz, CH2Ph), 4.69 -d, 1H, Jˆ
11.29 Hz, CH2Ph), 4.82±4.94 -m, 4H, CH2Ph), 7.14±7.16
-m, 2H, ArH), 7.257.32 -m, 18H, ArH); 13C NMR -CDCl3):
d 19.91 -CH3), 47.85 -OCH3), 68.76 -6-C), 71.47 -5-C),
73.33 -CH2Ph), 74.87 -CH2Ph), 75.49 -CH2Ph), 75.64
-CH2Ph), 78.57 -4-C), 83.29 -3-C), 83.79 -2-C), 100.26
-1-C), 127.47 -Ph), 127.50-Ph), 127.58 -Ph), 127.66 -Ph),
127.70-Ph), 127.77 -Ph), 128.23 -Ph), 128.25 -Ph), 128.28
-Ph), 128.33 -Ph), 128.71 -Ph), 137.93 -Ph), 138.15 -Ph),
138.18 -Ph), 138.70-Ph); HRMS -FAB): calcd for
C36H40O6Na 591.2723, found 591.2715.
3.3.3. Methyl O-/20,30,40,60-tetra-O-benzyl-10-C-vinyl-a-
d-mannopyranosyl)-/10!6)-2,3,4-tri-O-benzyl-a-d-gluco-
side /6c). Following the glycosidation procedure of 3a and
4, the glycosidation of 3c -504 mg, 0.89 mmol) and 4
-600 mg, 1.29 mmol, 1.45 equiv.) provided the disaccharide
6c -702 mg, 78.0%). Colorless syrup; ‰aŠ2D3: 130.98 -c 1.3,
3.3.5. Methyl 2,3,4,6-tetra-O-benzyl-1-C-methyl-a-d-
galactopyranoside /7b). Following the procedure of

4306
X. Li et al. / Tetrahedron 57 )2001) 4297±4309
preparing 7a, the compound 7b -1.62 g, 95.1%) was
obtained from 1.66 g -3.0mmol) of 2b. Colorless syrup;
‰aŠ2D3: 115.38 -c 1.0, CHCl3); IR -neat): 3063.33, 3030.54,
2916.72, 2868.50, 1604.97, 1585.68, 1496.94, 1454.50,
1363.84, 1197.94, 1095.70, 1049.40, 916.30, 734.97,
as the eluent to yield the acetylated product 8a -411 mg,
88.2%). White solid, mp. 74±768C; ‰aŠ2D5: 191.78 -c 1.0,
CHCl3); IR -KBr): 2997.74, 2964.95, 2839.56, 1747.72,
1435.21, 1371.55, 1240.38, 1122.71, 1037.83, 985.74,
1
908.58, 868.07 cm21; H NMR -CDCl3): d 1.35 -s, 3H,
1
698.32 cm21; H NMR -CDCl3): d 1.28 -s, 3H, CH3), 3.20
CH3), 1.98 -s, 3H, CH3CO), 2.03 -s, 3H, CH3CO), 2.09 -s,
3H, CH3CO), 2.10-s, 3H, CH CO), 3.28 -s, 3H, OCH3),
-s, 3H, OCH3), 3.50±3.60 -m, 2H, two 6-H), 3.74±3.78 -m,
1H, 5-H), 3.85 -d, 1H, Jˆ10.07 Hz, 2-H), 3.97 -s, br, 1H,
4-H), 4.02 -d, 1H, Jˆ9.77 Hz, 3-H), 4.41 -d, 1H, Jˆ
11.90Hz, CH 2Ph), 4.49 -d, 1H, Jˆ11.60Hz, CH 2Ph), 4.60
-d, 1H, Jˆ11.60Hz, CH 2Ph), 4.71 -d, 1H, Jˆ11.30Hz,
CH2Ph), 4.73 -s, br, 2H, CH2Ph), 4.92±4.96 -m, 2H,
CH2Ph), 7.24±7.38 -m, 20H, ArH); 13C NMR -CDCl3): d
20.09 -CH3), 48.14 -OCH3), 69.10-6-C), 70.21 -5-C), 72.79
-CH2Ph), 73.49 -4-C), 74.54 -CH2Ph), 74.96 -CH2Ph), 75.72
-CH2Ph), 80.26 -2-C), 80.60 -3-C), 100.73 -1-C), 127.49
-Ph), 127.67 -Ph), 127.76 -Ph), 128.12 -Ph), 128.16 -Ph),
128.21 -Ph), 128.37 -Ph), 138.06 -Ph), 138.26 -Ph), 138.71
-Ph), 138.89 -Ph); HRMS -FAB): calcd for C36H40O6Na
591.2723, found 591.2720.
3
3.86 -dq, 1H, Jˆ10.07 Hz, Jˆ2.44 Hz, 5-H), 4.09 -dd, 1H,
Jˆ12.51 Hz, Jˆ2.44 Hz, 6-H), 4.24 -dd, 1H, Jˆ12.21 Hz,
Jˆ4.89 Hz, 6-H), 5.01 -d, 1H, Jˆ10.07 Hz, 2-H), 5.08 -t,
1H, Jˆ9.77 Hz, 4-H), 5.47 -t, 1H, Jˆ9.62 Hz, 3-H); 13C
NMR -CDCl3): d 19.42 -1-CH3), 20.58 -two C, CH3),
20.67 -CH3), 20.71 -CH3), 48.22 -CH3O), 62.18 -6-C),
68.41 -5-C), 68.87 -4-C), 71.15 -3-C), 73.57 -2-C), 99.46
-1-C), 169.53 -CˆO), 169.96 -CˆO), 170.10 -CˆO),
170.65 -CˆO); HRMS -FAB): calcd for C16H24O10Na
399.1268, found 399.1275.
3.3.8. Methyl 2,3,4,6-tetra-O-acetyl-1-C-methyl-a-d-
galactopyranoside /8b). 7b -1.14 g, 2.0mmol) was deben-
zylated and then acetylated as described in the preparation
of 8a to give 8b -640mg, 85.1%). White solid, mp. 157±
1598C; ‰aŠ2D3: 1103.68 -c 1.0, CHCl3); IR -KBr): 2982.31,
2949.52, 1749.65, 1450.65, 1435.21, 1377.34, 1223.02,
1143.93, 1115.00, 1086.06, 1060.98, 1043.62, 962.60,
3.3.6. Methyl 2,3,4,6-tetra-O-benzyl-1-C-methyl-a-d-
mannopyranoside /7c). Following the procedure of pre-
paring 7a, the compound 7c -2.10g, 92.4%) was obtained
from 2.22 g -4.0mmol) of 2c. Colorless syrup; ‰aŠ2D3:
128.88 -c 1.0, CHCl3); IR -neat): 3063.33, 3030.54,
2912.65, 2866.52, 1604.97, 1496.94, 1454.50, 1363.23,
1
900.87, 846.85 cm21; H NMR -CDCl3): d 1.37 -s, 3H,
CH3), 1.96 -s, 3H, CH3CO), 2.05 -s, 3H, CH3CO), 2.10-s,
3H, CH3CO), 2.16 -s, 3H, CH3CO), 3.28 -s, 3H, CH3O),
4.04±4.08 -m, 1H, 5-H), 4.10±4.12 -m, 2H, two 6-H),
5.26 -d, 1H, Jˆ10.69 Hz, 2-H), 5.34 -dd, 1H, Jˆ
10.68 Hz, Jˆ3.36 Hz, 3-H), 5.45 -dd, 1H, Jˆ3.36 Hz,
Jˆ1.22 Hz, 4-H); 13C NMR -CDCl3): d 19.65 -1-CH3),
20.55 -CH3), 20.65 -two C, CH3), 20.78 -CH3), 48.31
-OCH3), 61.82 -6-C), 67.33 -5-C), 68.24 -4-C), 68.62
-3-C), 71.13 -2-C), 99.91 -C-1), 169.99 -CˆO), 170.19
-CˆO), 170.26 -CˆO), 170.39 -CˆO); HRMS -FAB):
calcd for C16H24O10Na 399.1268, found 399.1266.
1198.56, 1095.70 1049.40, 915.86, 735.82, 698.32 cm21
;
1H NMR -CDCl3): d 1.34 -s, 3H, CH3), 3.20-s, 3H,
OCH3), 3.60±3.64 -m, 1H, 5-H), 3.68 -d, 1H, Jˆ2.75 Hz,
2-H), 3.73±3.74 -m, 2H, two 6-H), 3.91 -t, 1H, Jˆ9.46 Hz,
4-H), 4.12 -dd, 1H, Jˆ9.16 Hz, Jˆ2.75 Hz, 3-H), 4.52 -d,
1H, Jˆ10.99 Hz, CH2Ph), 4.56 -d, 1H, Jˆ12.60Hz,
CH2Ph), 4.65 -d, 1H, Jˆ11.60Hz, CH 2Ph), 4.66 -d, 1H,
Jˆ11.60Hz, CH 2Ph), 4.74 -d, 2H, Jˆ2.44 Hz, CH2Ph),
4.85 -d, 1H, Jˆ10.99 Hz, CH2Ph), 4.97 -d, 1H, Jˆ
11.59 Hz, CH2Ph), 7.15±7.38 -m, 20H, ArH); 13C NMR
-CDCl3): d 19.24 -CH3), 47.64 -OCH3), 69.48 -6-C),
72.48 5-C), 72.98 -CH2Ph), 73.23 -CH2Ph), 74.80
-CH2Ph), 74.87 -CH2Ph), 74.92 -2-C), 78.29 -4-C), 81.65
-3-C), 101.14 -1-C), 127.28 -Ph), 127.39 -Ph), 127.41 -Ph),
127.46 -Ph), 127.66 -Ph), 127.94 -Ph), 128.00 -Ph), 128.11
-Ph), 128.17 -Ph), 128.22 -Ph), 128.30-Ph), 138.45 -Ph),
138.55 -Ph), 138.59 -Ph), 138.69 -Ph); HRMS -FAB): calcd
for C36H40O6Na 591.2723, found 591.2724.
3.3.9. Methyl 2,3,4,6-tetra-O-acetyl-1-C-methyl-a-d-
mannopyranoside /8c). 7c -1.14 g, 2.0mmol) was deben-
zylated and then acetylated as described in the preparation
of 8a to give 8c -658 mg, 87.5%). White solid, mp. 95±
968C; ‰aŠ2D5: 165.98 -c 1.0, CHCl3); IR -KBr): 2970.74,
2910.94 2839.56, 1747.72, 1435.21, 1371.55, 1224.95,
1124.64, 1086.06, 1057.12, 991.53, 958.74, 906.65,
1
862.29 cm21; H NMR -CDCl3): d 1.29 -s, 3H, CH3), 1.96
-s, 3H, CH3CO), 2.04 -s, 3H, CH3CO), 2.10-s, 3H, CH 3CO),
2.17 -s, 3H, CH3CO), 3.23 -s, 3H, OCH3), 3.80±3.86 -m,
1H, 5-H), 4.10±4.26 -m, 2H, two 6-H), 5.20 -t, 1H,
Jˆ10.07 Hz, 4-H), 5.23 -d, 1H, Jˆ3.05 Hz, 2-H), 5.44
-dd, 1H, Jˆ10.06 Hz, Jˆ3.06 Hz, 3-H); 13C NMR
-CDCl3): d 18.36 -1-CH3), 20.62 -CH3), 20.70 -CH3),
20.73 -CH3), 20.76 -CH3), 48.11 -CH3O), 62.90-6-C),
66.07 -5-C), 69.38 -4-C), 69.87 -2-C), 71.48 -3-C), 100.06
-1-C), 169.81 -CˆO), 169.90-C ˆO), 170.01 -CˆO),
170.64 -CˆO); HRMS -FAB): calcd for C16H24O10Na
399.1268, found 399.1271.
3.3.7. Methyl 2,3,4,6-tetra-O-acetyl-1-C-methyl-a-d-
glucopyranoside /8a). A mixture of 738 mg -1.33 mmol)
of 7a, 200 mg of Pd-OH)2/C -20wt%) and 26 mL of anhy-
drous methanol was stirred vigorously under atmospheric
pressure of H2 at room temperature until the starting
material disappeared -TLC: CH2Cl2/CH3OHˆ10:1). The
catalyst was ®ltered out and the solvent was removed
under reduced pressure and dried in vacuum overnight to
afford debenzylated product quantitatively. The crude
product -257 mg 1.24 mmol) was dissolved in 9.0mL of
dry pyridine and 4.0mL of acetic anhydride. The solution
was stirred under argon atmosphere at room temperature
overnight, then poured into 200 g of ice-water. The mixture
was extracted with AcOEt -50mL £3). The organic solution
was washed with water -50mL £5), dried over Na2SO4 and
concentrated in vacuum. The residue was applied on a silica
gel column chromatography using AcOEt: Hexane -1:1.5)
3.4. The O-transglycosidations of the methyl 2,3,4,6-
tetra-O-benzyl-1-C-methyl-hexopyranosides 7
3.4.1. The examination of the reaction conditions using
7a and 4. To a solution of 7a -114 mg, 0.2 mmol), methyl

X. Li et al. / Tetrahedron 57 )2001) 4297±4309
4307
2,3,4-tri-O-benzyl-a-d-glucoside -4) -140mg, 0.3 mmol,
1.5 equiv.) and MS 4A -500 mg) in dry dichloromethane
-5.0mL) was added a certain amount of Lewis acids
under argon atmosphere. The mixture was stirred for the
given time, then 0.1 mL of Et3N was added to quench the
reaction. After removing the solvent, the residue was
submitted to a silica gel column chromatography -Et2O:
Hexaneˆ1:1 v/v) to afford the disaccharide 5a. The results
are listed in Table 2.
the disaccharide 11b -41.8 mg, 63.0%). Colorless syrup;
‰aŠD25: 1138.28 -c 1.0, CHCl3) -lit.11 1140.78).
3.5.3. Methyl O-/20,30,40,60-tetra-O-acetyl-10-C-methyl-
a-d-mannopyranosyl)-/10!6)-2,3,4-tri-O-acetyl-a-d-
glucoside /11c). Following the reaction procedure of 8a and
10, the transglycosidation of 8c -38 mg, 0.1 mmol) afforded
the disaccharide 11c -55.0mg, 82.8%). Colorless syrup;
‰aŠD24: 1104.88 -c 1.0, CHCl3) -lit.11 1102.68).
3.5.4. Methyl O-/20,30,40,60-tetra-O-benzyl-10-C-methoxy-
carbonyl-a-d-glucopyranosyl)-/10!6)-2,3,4-tri-O-benzyl-
a-d-glucoside /12a). 5.0mL of a methanolic NaOH solu-
tion -2.5 mol/L, 10.0 equiv.) was added to a solution of
1.27 g -1.25 mmol) of 6a in 20mL of dry CH 2Cl2 at
2788C with stirring, and ozone was passed through the
solution for 4 h. The reaction mixture was diluted with
ether and water, allowed to warm to room temperature
and extracted with ether. The organic phase was washed
with water, dried over MgSO4 and concentrated under
reduced pressure. The residue was submitted to a silica
gel column chromatography -Et2O: Hexane 1:1) to afford
the product 12a -425 mg, 32.5%). Colorless syrup; ‰aŠ2D3:
133.4 -c 1.0, CHCl3); IR -neat): 3063.33, 3030.54,
2926.37, 1755.44, 1496.94, 1454.50, 1361.91, 1273.17,
3.4.2. The O-transglycosidation of the methyl 2,3,4,6-
tetra-O-bezyl-1-C-methyl-a-d-glucopyranoside 7a. To a
solution of 7a -114 mg, 0.2 mmol), methyl 2,3,4-tri-O-ben-
zyl-a-d-glucoside -4) -140mg, 0.3 mmol, 1.5 equiv.) and
MS 4A -500 mg) in dry dichloromethane -5.0 mL) was
added SnCl4 -23 mL, 0.2 mmol, 1.0 equiv.) at 08C under
argon atmosphere. The mixture was stirred for 3 h at 08C,
then 0.1 mL of Et3N was added to quench the reaction. The
solvent was removed, and the residue was submitted to a
silica gel column chromatography using Et2O: Hexane -1:1
v/v) as the eluent to afford the disaccharide 5a -161.4 mg,
80.6%) with the recovery of 7a -7.8 mg, 6.8%). 5a: colorless
syrup; ‰aŠ2D3: 146.18 -c 1.0, CHCl3) -lit.11 146.98).
3.4.3. The O-transglycosidation of the methyl 2,3,4,6-
7b.
1
1209.51, 1049.40, 910.51, 738.83, 698.32 cm21; H NMR
tetra-O-bezyl-1-C-methyl-a-d-galactopyranoside
The reaction of 7b -114 mg, 0.2 mmol) and 4 -140mg,
0.3 mmol, 1.5 equiv.) was carried out following the pro-
cedure of the O-transglycosidation of 7a, and the disac-
charide 5b -156.4 mg, 78.1%) was obtained as colorless
syrup with the recovery of 7b -9.8 mg, 8.6%). 5b: ‰aŠ2D3:
152.48 -c 1.0, CHCl3) -lit.11 151.38).
-CDCl3): d 3.21 -dd, 1H, Jˆ10.38 Hz, Jˆ8.85 Hz, 4-H),
3.38 -s, 3H, CH3O), 3.49 -dd, 1H, Jˆ9.46 Hz, Jˆ
3.36 Hz, 2-H), 3.52 -s, 3H, CH3OCO), 3.54 -dd, 1H, Jˆ
9.77 Hz, Jˆ8.24 Hz, 6-H), 3.60-dd, 1H, Jˆ12.60Hz, Jˆ
1.84 Hz, 60-H), 3.67 -dd, 1H, Jˆ11.29 Hz, Jˆ3.97 Hz,
60-H), 3.68 -t, 1H, Jˆ9.15 Hz, 40-H), 3.82 -d, 1H, Jˆ
9.46 Hz, 20-H), 4.01 -t, 1H, Jˆ9.16 Hz, 3-H), 4.05 -t, 1H,
Jˆ9.16 Hz, 30-H), 4.04±4.09 -m, 2H, 5-H and 50-H), 4.21
-dd, 1H, Jˆ10.37 Hz, Jˆ1.22 Hz, 6-H), 4.46 -d, 1H,
Jˆ12.21 Hz, CH2Ph), 4.52±4.61 -m, 5H, CH2Ph and 1-H),
4.65 -d, 1H, Jˆ12.21 Hz, CH2Ph), 4.73±4.87 -m, 7H,
CH2Ph), 4.96 -d, 1H, Jˆ10.69 Hz, CH2Ph), 7.13±7.34
-m, 35H, ArH); 13C NMR -CDCl3): d 52.22 -CH3OCO),
55.02 -OCH3), 63.58 -6-C), 68.41 -60-C), 69.84 -5-C),
72.56 -50-C), 73.06 -CH2Ph), 73.08 -CH2Ph), 74.57 -two
C, CH2Ph), 74.70-CH 2Ph), 75.31 -CH2Ph), 75.68
-CH2Ph), 77.92 -40-C), 78.80 -4-C), 80.01 -2-C), 81.39
-20-C), 82.19 -3-C), 82.45 -30-C), 97.35 -1-C), 99.16
-10C), 127.40-Ph), 127.46 -Ph), 127.50-Ph), 127.59 -Ph),
127.67 -Ph), 127.69 -Ph), 127.73 -Ph), 127.90-Ph), 128.09
-Ph), 128.12 -Ph), 128.20-Ph), 128.22 -Ph), 128.27 -Ph),
128.33 -Ph), 137.94 -Ph), 138.13 -Ph), 138.18 -Ph), 138.28
-Ph), 138.34 -Ph), 138.41 -Ph), 138.69 -Ph), 167.66
--COO-); HRMS -FAB): calcd C64H68O13Na 1067.4558,
found 1067.4560.
3.4.4. The O-transglycosidation of the methyl 2,3,4,6-
tetra-O-bezyl-1-C-methyl-a-d-mannopyranoside 7c. The
reaction of 7c -114 mg, 0.2 mmol) and 4 -140mg,
0.3 mmol, 1.5 equiv.) was carried out following the pro-
cedure of the O-transglycosidation of 7a, and the disac-
charide 5c -169.8 mg, 84.8%) was obtained as colorless
syrup with the recovery of 7c -7.4 mg, 6.4%). 5c: ‰aŠ2D3:
142.08 -c 1.0, CHCl3) -lit.11 143.18).
3.5. The O-transglycosidations of methyl 2,3,4,6-tetra-O-
acetyl-1-C-methyl-hexopyranosides 8
3.5.1. Methyl O-/20,30,40,60-tetra-O-acetyl-10-C-methyl-
a-d-glucopyranosyl)-/10!6)-2,3,4-tri-O-acetyl-a-d-gluco-
side /11a). To a solution of 8a -38 mg, 0.1 mmol), methyl
2,3,4-tri-O-acetyl-a-d-glucoside -10) -64 mg, 0.2 mmol)
and MS 4A -100 mg) in dry CH2Cl2 -2 mL) was added
SnCl4 -46.7 mL, 0.4 mmol, 4.0 equiv.) under argon atmos-
phere at 08C. The mixture was stirred for 2 h at 08C, and 1 h
at room temperature, then 0.1 mL of Et3N was added to
quench the reaction. The solvents were removed, and the
residue was applied on a silica gel column chromatography
-AcOEt: Hexaneˆ1.5:1) to afford the disaccharide 11a
-20.0 mg, 30.1%). Colorless syrup; [a]D: 1116.58 -c 1.0,
CHCl3) -lit.11 1118.78).
3.5.5. Methyl O-/20,30,40,60-tetra-O-benzyl-10-C-methoxy-
carbonyl-a-d-galactopyranosyl)-/10!6)-2,3,4-tri-O-ben-
zyl-a-d-glucoside /12b). Following the ozonolysis
procedure of 6a, the compound 6b -280mg, 0.276 mmol)
was oxidized to afford the compound 12b -87.0mg, 30.2%).
Colorless syrup; ‰aŠ2D3: 135.18 -c 1.85, CHCl3); IR -neat):
3063.33, 3030.54, 2916.72, 1753.51, 1496.94, 1454.50,
1361.91, 1271.24, 1093.77, 912.44, 738.83, 698.32 cm21
;
3.5.2. Methyl O-/20,30,40,60-tetra-O-acetyl-10-C-methyl-
a-d-galactopyranosyl)-/10!6)-2,3,4-tri-O-acetyl-a-d-
glucoside /11b). Following the reaction procedure of 8a and
10, the transglycosidation of 8b -38 mg, 0.1 mmol) afforded
1H NMR -CDCl3): d 3.15 -t, 1H, Jˆ10.07 Hz, 4-H), 3.20
-s, 3H, OCH3), 3.45 -dd, 1H, Jˆ10.77 Hz, Jˆ3.36 Hz, 2-H),
3.49 -s, 3H, CH3OCO), 3.51±3.60-m, 3H, 6-H and two

4308
X. Li et al. / Tetrahedron 57 )2001) 4297±4309
60-H), 3.95±4.04 -m,04H, 40-H, 30-H, 3-H and 5-H), 4.11 -t,
br, 1H, Jˆ6.10Hz, 5 -H), 4.18 -d, br, 1H, Jˆ9.15 Hz, 6-H),
4.33 -d, 1H, Jˆ9.77 Hz, 20-H), 4.38 -d, 1H, Jˆ12.21 Hz,
CH2Ph), 4.44 -d, 1H, Jˆ11.90Hz, CH 2Ph), 4.48 -d, 1H,
Jˆ11.30Hz, CH 2Ph), 4.53 -d, 1H, Jˆ3.66 Hz, 1-H),
4.61±4.84 -m, 9H, CH2Ph), 4.94 -d, 1H, Jˆ10.68 Hz,
CH2Ph), 4.96 -d, 1H, Jˆ11.60Hz, CH 2Ph), 7.21±7.33 -m,
35H, ArH); 13C NMR -CDCl3): d 52.26 -CH3OCO), 54.73
-CH3O), 63.68 -6-C), 68.55 -60-C), 69.75 -5-C), 71.28 -50-
C), 72.42 -CH2Ph), 73.08 -CH2Ph), 73.12 -CH2Ph), 74.40
-CH2Ph), 74.63 -two C, 400-C and CH2Ph), 74.81 -CH2Ph),
75.69 -CH2Ph), 77.30-2 -C), 79.12 -4-C), 79.62 -3-C),
79.95 -2-C), 82.13 -30-C), 97.35 -1-C), 99.68 -10-C),
127.26 -Ph), 127.47 -Ph), 127.49 -Ph), 127.51 -Ph),
127.61 -Ph), 127.67 -Ph), 127.78 -Ph), 127.92 -Ph),
128.04 -Ph), 128.14 -Ph), 128.23 -Ph), 128.32 -Ph),
128.35 -Ph), 128.37 -Ph), 128.42 -Ph), 138.14 -Ph),
138.16 -Ph), 138.38 -Ph), 138.76 -Ph), 167.47 --COO-);
HRMS -FAB): calcd for C64H68O13Na 1067.4558, found
1067.4556.
P.; Wong, C. H. Angew. Chem. Int. Eng. 1999, 38, 2300±2324.
-c) Davis, A. P.; Wareham, R. S. Angew. Chem. Int. Eng.
1999, 38, 2978±2996. -d) St. Hilaire, P. M.; Meldal, M.
Angew. Chem. Int. Eng. 2000, 39, 1162±1179. -e) Davis,
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2000, 39, 836±863. -g) Vankar, Y. D.; Schmidt, R. R.
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2. -a) Schmidt, R. R.; Castro-Palomino, J. C.; Retz, O. Pure
Appl. Chem. 1999, 71, 729±744. -b) Boons, G.-J. Carbo-
hydrate Chemistry; Blackie Academic and Professional:
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3.5.6. Methyl O-/20,30,40,60-tetra-O-benzyl-10-C-methoxy-
carbonyl-a-d-mannopyranosyl)-/10!6)-2,3,4-tri-O-ben-
zyl-a-d-glucoside /12c). Following the ozonolysis pro-
cedure of 6a, the compound 6c -540mg, 0.53 mmol) was
oxidized to afford the compound 12c -172 mg, 31.1%).
Colorless syrup; ‰aŠ2D3: 133.38 -c 1.0, CHCl3); IR -neat):
3063.33, 3030.54, 2920.66, 1751.86, 1496.94, 1454.50,
1361.91, 1272.36, 1199.98, 1056.12, 911.58, 738.83,
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1
698.32 cm21; H NMR -CDCl3): d 3.31 -s, 3H, OCH3),
3.32±3.35 -m, 2H, 4-H and 6-H), 3.47±3.53 -m, 2H, 2-H
and 60-H), 3.59 -s, 3H, CH3OCO-), 3.69±3.83 -m, 5H, 60-H,
5-H, 50-H, 20-H and 6-H), 3.97±4.06 -m, 3H, 30-H, 40-H and
3-H), 4.46±4.63 -m, 5H, CH2Ph and 1-H), 4.67±4.71 -m,
3H, CH2Ph), 4.76±4.80-m, 3H, CH 2Ph), 4.87±4.91 -m, 2H,
CH2Ph), 4.96±5.01 -m, 2H, CH2Ph), 7.14±7.34 -m, 35H,
ArH); 13C NMR -CDCl3): d 52.25 -CH3OCO), 55.08
-CH3O), 62.86 -6-C), 68.59 -60-C), 69.25 -5-C), 72.25
-CH2Ph), 73.16 -50-C), 73.23 -CH2Ph), 73.84 -CH2Ph),
74.41 -CH2Ph), 74.53 -CH2Ph), 74.62 -40-C), 74.95
6. -a) Sabesan, S.; Neira, S. Carbohydr. Res. 1992, 223, 169±
185. -b) Hashimoto, S.; Umeo, K.; Sano, A.; Watanabe, N.;
Nakajima, M.; Ikegami, S. Tetrahedron Lett. 1995, 36, 2251±
2254. -c) Hashimoto, S.; Sakamoto, H.; Honda, T.; Ikegami, S.
Tetrahedron Lett. 1997, 38, 5181±5184. -d) Hashimoto, S.;
Sakamoto, H.; Honda, T.; Abe, H.; Nakajima, M.; Ikegami, S.
Tetrahedron Lett. 1997, 38, 8969±8972. -e) Plante, O. J.;
Andrade, R. B.; Seeberger, P. H. Org. Lett. 1999, 1, 211±214.
7. -a) Brrown, D. S.; Ley, S. V.; Vile, S. Tetrahedron Lett. 1988,
29, 4873±4876. -b) Kahne, D.; Walker, S.; Cheng, Y.; Van
Engen, D. J. Am. Chem. Soc. 1989, 111, 6881±6882.
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1580±1581.
-CH2Ph), 75.70-CH Ph), 76.68 -20-C), 77.51 -4-C), 79.86
2
-2-C), 80.33 -30-C), 82.20-3-C), 97.67 -1-C), 99.23 -1 -C),
0
127.37 -Ph), 127.45 -Ph), 127.47 -Ph), 127.52 -Ph), 127.59
-Ph), 127.62 -Ph), 127.67 -Ph), 127.74 -Ph), 127.78 -Ph),
127.82 -Ph), 127. 88 -Ph), 127.98 -Ph), 128.12 -Ph), 128.138
-Ph), 128.22 -Ph), 128.30-Ph), 128.34 -Ph), 128.43 -Ph),
137.90-Ph), 137.92 -Ph), 138.10-Ph), 138.42 -Ph),
138.66 -Ph), 167.31 --COO-); HRMS -FAB): calcd for
C64H68O13Na 1067.4558, found 1067.4563.
8. -a) Mootoo, D. R.; Date, V.; Fraser-Reid, B. J. Am. Chem. Soc.
1988, 110, 2662±2663. -b) Fraser-Reid, B.; Udodong, U. E.;
Wu, Z.; Ottosson, H.; Merritt, J. R.; Rao, C. S.; Roberts, C.;
Madsen, R. Synlett 1992, 927±942.
Acknowledgements
9. -a) Friesen, R. W.; Danishefsky, S. J. J. Am. Chem. Soc. 1989,
111, 6656±6660. -b) Halcomb, R. L.; Danishefsky, S. J. J. Am.
Chem. Soc. 1989, 111, 6661±6666. -c) Danishefsky, S. J.;
Bilodeau, M. T. Angew. Chem. Int. Ed. Engl. 1996, 35,
1380±1419. -d) Bussolo, V. D.; Kim, Y. J.; Gin, D. Y.
J. Am. Chem. Soc. 1998, 120, 13515±13516. -e) Bussolo,
V. D.; Liu, J.; Hujjman, Jr, L. G.; Gin, D. Y. Angew. Chem.
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We are grateful to Miss J. Shimode and Miss M. Kitsukawa
for spectroscopic measurements. Partial ®nancial support
for this research from the Ministry of Education, Science,
Sports and Culture of Japan is gratefully acknowledged.
X. L. thanks the JSPS for a postdoctoral fellowship.
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