Comparative investigations on the regioselective mannosylation of 2,3,4-triols of mannose

Article abstract of DOI:10.1016/j.tetasy.2008.05.032

Regioselective glycosylation of 2,3,4-unprotected benzyl α-d-mannopyranoside and allyl α- and -β-d-mannopyranosides has been investigated. The configuration at the anomeric centre influences the outcome of the reaction. Possible role of hydrogen-bonding n

Full text of DOI:10.1016/j.tetasy.2008.05.032

Tetrahedron: Asymmetry 19 (2008) 1494–1503
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Comparative investigations on the regioselective mannosylation
of 2,3,4-triols of mannose
Piotr Cmoch a,b, Zbigniew Pakulski a,
*
a Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warszawa, Poland
b Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warszawa, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Regioselective glycosylation of 2,3,4-unprotected benzyl
a-D-mannopyranoside and allyl a- and -b-D-
Received 12 May 2008
Accepted 29 May 2008
Available online 24 June 2008
mannopyranosides has been investigated. The configuration at the anomeric centre influences the out-
come of the reaction. Possible role of hydrogen-bonding network in glycosylation of the above triols used
as glycosidic acceptors is discussed.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
A practical, chemical synthesis of oligosaccharides is commonly
recognized as a difficult task. The control of the regiochemistry is
usually complicated by the necessity of using a protection–depro-
tection strategy for differentiation of hydroxyl groups of similar
reactivity which makes the synthetic scheme lengthly, laborious
and time consuming.1 Such difficulties can be avoided by regio-
selective glycosylation of non-protected or partially-protected
glycosyl acceptors. However, despite its potential importance, reg-
ioselective glycosylation of glycosyl acceptors having polyol frag-
ments remains almost unexplored. This results, most probably,
from serious difficulties which may appear during purification,
separation and identification of the final products. To date, only
very few examples of regioselective glycosylation of non-protected
glycosyl acceptors have been reported.2 Similarly, saccharide triols
were only occasionally used as acceptors.3 Reports on the combi-
natorial synthesis of oligosaccharide libraries with the use of
non-protected glycosyl acceptors were also published.4 By compar-
ison, regioselective glycosylation of sugar diols5,6 as well as in situ
Sn-promoted7 or arylboronic derivative8 glycosylation were stud-
ied intensively.
To elucidate the relationship between the regioselectivity, the
structure of the glycosyl donor, structure of glycosyl acceptor,
and the reaction conditions we examined the glycosylation of the
allyl (both
a- and b-anomers) and benzyl a-D-mannosides 1–3,
respectively, in which the most reactive primary hydroxyl group
at the C-6 position was protected as a tert-butyldiphenylsilyl ether.
This trick simplifies the identification of the products and prevents
the formation of undesired trisaccharides. As glycosyl donors com-
pounds 4–6 have been chosen. Glycosylation of triol acceptors 1–3
with glycosyl donors 4–6 provided the expected disaccharides 7–
15 (Scheme 1).
2.1. Glycosylation of allyl 6-O-tert-butyldiphenylsilyl-a-D-
mannopyranoside 1
Initially, the glycosylation of allyl 6-O-tert-butyldiphenylsilyl-
-D-mannopyranoside 1 according to a number of commonly used
a
glycosylation methods, was tested, and the results are summarized
in Table 1. Surprisingly, reactions employing phenyl 2,3,4,6-tetra-
O-benzoyl-1-thio-a-D
-mannopyranoside9 6 as a glycosyl donor
In this context, we turned our attention to regioselective glyco-
sylation of unprotected non-reducing glycosyl acceptors. Such a
methodology reduces the number of necessary steps and simplifies
the synthetic scheme. Herein, we report regioselective mannosyla-
tion of 2,3,4-triols of allyl and benzyl mannosides.
completely failed and did not lead to the desired products, irre-
spective of the reaction conditions and the promoters used. In most
cases, unchanged starting materials were isolated. Application of
Schmidt’s
trichloroacetimidate
glycosylation
methodology
employing the donor 4 gave a mixture of expected disaccharides
7–9. The regioselectivity of the glycosylation reaction depended
mostly on the solvent. In dichloromethane, the (1?3)-linked iso-
mer was obtained as the sole product in good yield (56% for
TMSOTf as catalyst and 70% for BF3ꢀOEt2). Both regioselectivity
and yield were lower in acetonitrile, although the (1?3)-linked
isomer predominated strongly. The chemical yield was much
* Corresponding author.
E-mail address: pakul@icho.edu.pl (Z. Pakulski).
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.05.032

P. Cmoch, Z. Pakulski / Tetrahedron: Asymmetry 19 (2008) 1494–1503
1495
BzO
BzO
O
BzO
BzO
7: R = OAll, R' = H
10: R = H, R' = OAll
13: R = OBn, R' = H
O
TBDPSO
O
R'
HO
HO
R
BzO
OTBDPS
BzO
BzO
O
OH
O
OBz
O
HO
TBDPSO
BzO
BzO
8: R = OAll, R' = H
11: R = H, R' = OAll
14: R = OBn, R' = H
BzO
O
R'
HO
R'
HO
+
HO
BzO
O
R
R"
R
1: R = OAll, R' = H
2: R = H, R' = OAll
3: R = OBn, R' = H
4: R" = OC(NH)CCl3
5: R" = Br
6: R" = SPh
BzO
BzO
O
OTBDPS
OH
BzO
9: R = OAll, R' = H
12: R = H, R' = OAll
15: R = OBn, R' = H
BzO
O
R'
O
HO
R
Scheme 1.
Table 1
Glycosylation of allyl 6-O-tert-butyldiphenylsilyl-
a
-D-mannopyranoside 1
Donor
Catalyst
Solvent
Temp (°C)
Time
Regioselectivitya
Yielda (%)
7
8
9
4
TMSOTf
TMSOTf
TMSOTf
TMSOTf
BF3ꢀOEt2
BF3ꢀOEt2
TMSOTf
TMSOTf
TMSOTf
DCM
MeCN
MeCN
DMF
DCM
DMF
[bmim]PF6/DCM
[eoemim]PF6/DCM
[bmim]dca
[bmim]NTf2
DCM
MeCN
DCM
DCM
DCM
ꢁ40
ꢁ40
ꢁ40
ꢁ40 to 20
ꢁ40
ꢁ40
20
20
20
20
20
40 min
30 min
30 min
2 h
40 min
2 h
0
1
4
100
92
78
0
7
18
56
10
52
—
70
—
16
—
—
45
85
61
—
—
—
4
4b
4
No reaction
100
No reaction
77
No reaction
No reaction
53
4
4
4
4
4
4
5
5
6
6
6
6
0
3
0
30 min
30 min
20
TMSOTf
30 min
24 h
48 h
2 h
13
3
15
34
18
14
AgOTf/TMU
Hg(CN)2/HgBr2
NIS/TMSOTf
MeOTf
DMTST
NIS/TfOH
TMSOTf
79
71
20
ꢁ40
0 to 20
20
ꢁ30 to 20
ꢁ40
20
Decomposition
No reaction
No reaction
No reaction
43
4 d
24 h
48 h
1 h
48 h
24 h
DCE/diethyl ether
DCM
DCM
—
9
32
—
4c
5c
6c
53
Traces
4
11
AgOTf/TMU
DMTST
88
DCM
20
No reaction
a
Determined by HPLC with 250-4 LiChrospher 100 RP-18 (5
A solution of 4 was added dropwise to a reaction mixture.
Stannylene acetals of 1 were used as acceptors.
lm) column; eluent MeCN–H2O 96:4; flow 0.6 mL/min.
b
c
better when a solution of donor 4 was added dropwise to the reac-
tion mixture but at the cost of regioselectivity. No products were
obtained in DMF, even at room temperature. Reactions with man-
nopyranosyl bromide 510 were highly efficient; chemical yields
were good to excellent, although the regioselectivity was lower
than in the previous cases.
regioselectivity was low. Similar transformations performed in a
mixture of 1-ethoxyethyl-3-methylimidazolium hexafluorophos-
phate ([eomim]PF6) and dichloromethane did not afford any
product.
Finally, we tried the application of stannylene acetals7 prepared
in situ by treatment of mannoside 1 with dibutyltin oxide followed
by glycosylation with donors 4–6. Glycosylation of stannylene ace-
tal of 1 with trichloroacetimidate 4 proceeded with low regioselec-
tivity and chemical yield but, interestingly, with a slight preference
for the (1?2)-linked product 7. Using the donor 5 allowed us to
obtain a mixture of (1?3)- and (1?4)-linked disaccharides in
acceptable yield. Donor 6 was not reactive under the reaction
conditions.
Ionic liquids are known as good solvents for glycosylation.11
However, the poor solubility of the acceptor 1 limited the reaction
scope. The highest solubility of 1 was observed in 1-butyl-3-meth-
ylimidazolium dicyanamide ([bmim]dca), but in this solvent, the
reaction did not take place. A slightly lower solubility of 1 was also
observed in 1-butyl-3-methylimidazolium bis(trifluoromethylsul-
fonyl)imide ([bmim]NTf2) but its glycosylation with 4 afforded
the expected disaccharides 7–9 in good yield. Regioselectivity
was, however, poor; only a slight preference for the (1?3)-linked
product 8 was observed, and significant amounts of the (1?4)-
linked product 9 were obtained. Complete dissolution of 1 in 1-bu-
tyl-3-methylimidazolium hexafluorophosphate ([bmim]PF6) was
not possible; thus a small amount of dichloromethane was added
as a cosolvent. However, in this case the yield (16%) as well as
2.2. Glycosylation of allyl 6-O-tert-butyldiphenylsilyl-b-
D-
mannopyranoside 2
In most cases, glycosylation of
a-D-mannoside 1 strongly pre-
ferred the (1?3)-linked product 8; additionally significant
amounts of (1?4)-linked disaccharide 9 were detected, whereas

1496
P. Cmoch, Z. Pakulski / Tetrahedron: Asymmetry 19 (2008) 1494–1503
Table 2
Glycosylation of allyl 6-O-tert-butyldiphenylsilyl-b-D-mannopyranoside 2
Donor
Catalyst
Solvent
Temp (°C)
Time
Regioselectivitya
Yielda (%)
10
11
12
4
4
4
4
4
4
5
TMSOTf
BF3ꢀOEt2
TMSOTf
TMSOTf
TMSOTf
TMSOTf
AgOTf/TMU
DCM
DCM
MeCN
[bmim]PF6/DCM
[bmim]NTf2
[eoemim]PF6/DCM
DCM
ꢁ40
ꢁ40
ꢁ40
20
20
20
1 h
1 h
1 h
30 min
30 min
30 min
24 h
32
47
30
38
53
62
30
—
8
35
46
24
—
27
—
No reaction
60
No reaction
48
30
28
10
24
20
68
a
Determined by HPLC with 250-4 LiChrospher 100 RP-18 (5 lm) column; eluent MeCN–H2O 96:4; flow 0.6 mL/min.
the (1?2)-linked derivative 7 was observed only in minute quan-
tities. By comparison, the regioselectivity of the glycosylation of b-
2.4. Discussion
D
-mannoside 2 was completely different (Table 2). In all the cases
The practical usefulness of the proposed strategy is limited by
the possibility of isolating the pure isomers. As we have found,
there is a considerable difference in polarity between the (1?3)-
linked isomer and (1?2)/(1?4)-linked compounds. The first one
shows relatively low polarity and may be easily separated from
the others, highly polar isomers by column chromatography. Sep-
aration of (1?2)- and (1?4)-linked compounds is usually not triv-
ial. However, careful selection of substrates and reaction
conditions may selectively provide, except the usually preferred
(1?3)-derivative, the (1?2)- or (1?4)-linked products (Tables
1–3).
studied, a strong preference for (1?2)- and (1?3)-linked com-
pounds (10 and 11, respectively) was observed, whereas (1?4)-
linked isomer 12 was usually detected in much lower yield. An
almost equimolar amount of 10 and 11 was obtained in good yield
during the glycosylation of mannoside 2 with trichloroacetimidate
4 in the presence of BF3ꢀOEt2; the (1?4)-linked isomer 12 was not
detected in this case. In the presence of TMSOTf in dichlorometh-
ane solution, all possible isomers 10–12 were obtained in similar
proportions; a noticeable preference for the (1?3)-linked product
11 was observed in acetonitrile. The best chemical yield was
obtained for glycosylation of 2 with mannosyl bromide 5 but the
regioselectivity was low.
The observed significant differences between the reactivity of
2,3,4-triols having an
is difficult to explain. The strong preference for the formation of
(1?3)-linked disaccharides from allyl and benzyl -mannosides
a- or b-configuration at the anomeric centre
2.3. Glycosylation of benzyl 6-O-tert-butyldiphenylsilyl-
mannopyranoside 3
a
-D
-
a
1 and 3 is in accordance with previous literature evidence.2 How-
ever, formation of a large amount of (1?2)-linked product from
allyl b-mannoside 2 was completely unexpected. The results
reported in this article suggest that an intramolecular hydrogen-
bonding network13 may play a significant role in the formation
of the glycosidic bond.14
Results of glycosylation of benzyl 6-O-tert-butyldiphenylsilyl-
-D
-mannopyranoside12 3 with donors 4–6 are summarized in Ta-
a
ble 3. In almost all cases studied, the strong preference for the for-
mation of (1?3)-linked product 14 was noted. Glycosylation of
mannoside 3 with trichloroacetimidate 4 in dichloromethane solu-
tion in the presence of TMSOTf afforded (1?3)-linked disaccharide
14 exclusively. Here, the ionic liquids were very promising solvents
for the glycosylation; chemical yields were high, (1?3)-linked
product 14 predominated strongly and only traces of (1?2)-linked
derivative 15 was detected. Almost equimolar amounts of
(1?3)- and (1?4)-linked products were obtained in good yield
(39%) during the glycosylation of stannylene acetal of 3 with
imidate 4 in the presence of the TMSOTf; (1?2)-linked isomer
was not found.
It is known that the formation of the glycosidic bond proceeds
via a nucleophilic substitution at the electron-deficient anomeric
carbon (Scheme 2).15 The hydroxyl groups involved in the hydro-
gen bond acting as hydrogen donors have increased electron den-
sity at the oxygen atom which makes this atom a more reactive
nucleophile. As a result, this hydroxyl group should be more reac-
tive in formation of the glycosidic linkage. In the case of b-anomer
2, the hydroxyl group at the C-2 position may be included into
three, theoretically possible, hydrogen bonds (Fig. 1, structures
2a–2a00). Its nucleophilicity should be increased by comparison
Table 3
Glycosylation of benzyl 6-O-tert-butyldiphenylsilyl-
a
-D-mannopyranoside 3
Donor
Catal.
Solvent
Temp (°C)
Time
Regioselectivitya
Yielda (%)
13
14
15
4
4
4
4
4
4
4
5
TMSOTf
DCM
DCM
MeCN
[bmim]PF6/DCM
[bmim]NTf2
[eoemim]PF6/DCM
[eoemim]dca/DCM
DCM
MeCN
DCM
DCM
DCM
ꢁ40
ꢁ40
ꢁ40
20
20
20
20
20
20
20
1 h
1 h
1 h
30 min
30 min
30 min
30 min
24 h
24 h
6 d
0
11
12
0
2
0
100
83
75
85
97
86
0
6
13
15
1
34
29
23
69
46
68
—
59
22
—
BF3ꢀOEt2
TMSOTf
TMSOTf
TMSOTf
TMSOTf
TMSOTf
AgOTf/TMU
Hg(CN)2/HgBr2
NIS/TMSOTf
TMSOTf
14
No reaction
4
18
71
25
21
5
61
No reaction
47
6
4b
5b
0
20
1 h
24 h
—
1
53
15
39
35
AgOTf/TMU
84
a
Determined by HPLC with 250-4 LiChrospher 100 RP-18 (5 lm) column; eluent MeCN–H2O 96:4; flow 0.6 mL/min.
Stannylene acetals of 3 were used as acceptors.
b

P. Cmoch, Z. Pakulski / Tetrahedron: Asymmetry 19 (2008) 1494–1503
1497
cal samples of disaccharides 7–15 by classical method to obtain
compounds with a well-defined structure in pure form.
BzO
BzO
BzO
BzO
O
O
activator
LG
BzO
BzO
+
BzO
BzO
Glycosylation of allyl
a-D-mannoside 17 bearing the free –OH
O
group at the C-2 position with trichloroacetimidate 4 proceeded
smoothly in the presence of TMSOTf under the standard conditions
and yielded compound 18. The butane 3,4-bisacetal protecting
group was removed by acidic hydrolysis, which provided disaccha-
ride 7 fully characterized further as diacetate 19. A similar reaction
sequence was employed in the synthesis of its benzyl congeners 13
and 23 (Scheme 3).
BzO
BzO
+
H
BzO
BzO
BzO
BzO
BzO
BzO
O
O
-
O+
R
OR
LG = leaving group
H
Attempts to prepare the b-anomer 10 by the same method
failed due to high stability of the bisacetal protection. Compound
Scheme 2.
with a-anomer, in which only two hydrogen bonds may be consid-
ered (Fig. 1, structures 1a–1a0). On the other hand, reactivity of the
hydroxyl groups located at the C-3 and C-4 centres should not be
changed. Therefore, a higher preference for the formation of
(1?2)-linked compound may be noted for the b-acceptor. At the
moment, this is only a plausible suggestion which needs further
study.
BzO
OTBDPS
BzO
O
OH
O
OR"
BzO
TBDPSO
BzO
O
a
R'
R'
HO
R"O
O
HO
R
R
1: R = OAll, R' = H
8: R = OAll, R' = R" = H
29: R = OAll, R' = H, R" = Ac
b
b
b
2.5. Synthesis of the reference disaccharides 7–15
11: R = R" = H, R' = OAll
30: R = H, R' = OAll, R" = Ac
2: R = H, R' = OAll
3: R = OBn, R' = H
Determination of the composition of the reaction mixture was
performed by HPLC chromatography. For reliable peak recognition,
samples of reference compounds having independently confirmed
structures were needed. Therefore, we decided to prepare analyti-
14: R = OBn, R' = R" = H
31: R = OBn, R' = H, R" = Ac
Scheme 5. Reagents: (a) 4, TMSOTf, 4 Å, DCM; (b) Ac2O, pyridine.
RO
H
RO
H
RO
H
RO
H
RO
H
O
O
O
O
O
O
O
O
O
O
OAll
OAll
OAll
OAll
OAll
H
H
O
H
O
H
O
H
O
H
O
O
O
O
O
O
H
H
H
H
1a
1a'
2a
2a'
2a"
Figure 1.
BzO
BzO
BzO
BzO
BzO
BzO
BzO
BzO
O
O
OR'
HO
OMe
O
O
O
O
TBDPSO
TBDPSO
OMe
b
c
O
O
O
R'O
R'O
OR
O
OMe
O
OR
OR
OMe
18: R = All
22: R = Bn
16: R = All, R' = H
17: R = All, R' = TBDPS
7: R = All, R' = H
19: R = All, R' = Ac
a
a
d
d
20: R = Bn, R' = H
21: R = Bn, R' = TBDPS
13: R = Bn, R' = H
23: R = Bn, R' = Ac
Scheme 3. Reagents and conditions: (a) TBDPSCl, imidazole, DMF; (b) 4, TMSOTf, 4 Å, DCM; (c) 90% CF3CO2H, DCM; (d) Ac2O, pyridine.
BzO
BzO
O
BzO
OH
OR
O
TBDPSO
TBDPSO
BzO
O
d
a
HO
R'O
OAll
OAll
O
O
HO
R'O
R'O
OAll
RO
RO
2
24: R = -C(O)CH2Cl, R' = H
25: R = -C(O)CH2Cl, R' = Ac
26: R = H, R' = Ac
27: R = Ac, R' = TBDPS
28: R = R' = H
10: R = H, R' = TBDPS
e
f
b
c
Scheme 4. Reagents and conditions: (a) trimethyl orthochloroacetate, p-TsOH, MeCN then 90% CF3CO2H; (b) Ac2O, pyridine; (c) thiourea, 2,4-lutidine, DCM, MeOH; (d) 4,
TMSOTf, 4 Å, DCM; (e) HCl in MeOH. (f) TBDPSCl, imidazole, DMF.

1498
P. Cmoch, Z. Pakulski / Tetrahedron: Asymmetry 19 (2008) 1494–1503
BzO
BzO
BzO
BzO
BzO
BzO
BzO
BzO
O
O
OTBDPS
OTBDPS
OTBDPS
O
O
OR"
O
O
O
a
b
R'
R'
R'
O
O
HO
O
O
R"O
R
R
CMe2
R
CMe2
32: R = OAll, R' = H
33: R = OAll, R' = H
9: R = OAll, R' = H, R" = H
34: R = OAll, R' = H, R" = Ac
c
c
35: R = H, R' = OAll
37: R = OBn, R' = H
36: R = H, R' = OAll
38: R = OBn, R' = H
12: R = H, R' = OAll, R" = H
15: R = OBn, R' = H, R" = H
39: R = OBn, R' = H, R" = Ac
Scheme 6. Reagents: (a) 4, TMSOTf, 4 Å, DCM; (b) p-TsOH, EtOAc, MeOH; (c) Ac2O, pyridine.
10 was prepared by the treatment of mannoside 2 with trimethyl
orthochloroacetate followed by the regioselective opening of the
orthochloroacetate ring to form chloroacetate 24, acetylation to
form 25, selective hydrolysis of chloroacetate group to form 26
and glycosylation of 26 with 4 under the standard conditions to
form 27. Both acetate and silyl groups were then removed simulta-
neously by treatment with methanolic HCl to yield 28 and final
introduction of tert-butyldiphenylsilyl ether protection at the O-6
position afforded the required disaccharide 10 (Scheme 4).
(1?3)-Linked disaccharides 8, 11 and 14 were prepared by the
direct glycosylation of mannosides 1–3 with trichloroacetimidate 4
under the standard conditions. Products 8, 11 and 14 were isolated
by column chromatography and characterized as diacetates 29–31
(Scheme 5). The 1H NMR spectra of diacetates 29–31 showed the
H-2 and H-4 resonances of the central mannose residues being
deshielded by ca. 1.0–1.6 ppm with respect to those of H-3. The
13C NMR spectra of 29–31 indicated characteristic deshielding
effects of the C-3 resonances. These observations clearly proved
that the glycosidic linkages were at the O-3 position of the
mannose ring.
matic groups observed for the typical values were omitted for sim-
plicity. High resolution mass spectra (HRMS) were acquired with a
MARINER mass spectrometer. Optical rotations were measured
with a JASCO P-1020 or with a JASCO P-2000 automatic polarime-
ters. Configurational assignments were based on the NMR mea-
surements including DEPT and two-dimensional techniques,
including gradient-selected COSY, as well as 1H–13C gradient se-
lected HSQC (g-Heteronuclear Single Quantum Correlation; C, H
correlation via double INEPT transfer in the phase sensitive mode).
4.2. Allyl 6-O-tert-butyldiphenylsilyl-
a-D-mannopyranoside 1
To a solution of allyl a-D
-mannopyranoside2g (2.20 g, 10 mmol)
and imidazole (1.2 g, 17.5 mmol) in DMF (20 mL) cooled to 0 °C,
tert-butylchlorodiphenylsilane (TBDPSCl, 3.2 g, 11.5 mmol) in
DMF (5 mL) was added slowly. The mixture was stirred at room
temperature for 24 h, solvents were evaporated under diminished
pressure and the residue was purified by column chromatography
(9:1 hexane–EtOAc?5:3:1 hexane–EtOAc–MeOH) to afford 4.31 g
(94%) of the title compound as a thick syrup. ½a D20
¼ <1 (c 0.6,
ꢂ
Glycosylation of allyl
a-
D-mannoside 32 bearing a free –OH
CHCl3). 1H NMR d: 5.86 (m, 1H, CH@), 5.25 (m, 1H, @CHH), 5.18
(m, 1H, @CHH), 4.84 (s, 1H, H-1), 4.12 (m, 1H, OCH), 3.81–3.95
(m, 6H), 3.67 (m, 1H, H-5), 1.07 (s, 9H, tBu). 13C NMR d: 117.5
(OCH2), 98.6 (C-1), 71.7, 70.6, 70.5, 70.4, 67.9 (@CH2), 65.2 (C-6),
26.8 (tBu), 19.2 (SiC). HRMS-ESI calcd for C25H34NaO6Si (M+Na)+:
481.2017, found: 481.2034. Anal. Calcd for C25H34O6Siꢀ0.5H2O: C,
64.21; H, 7.54, Found: C, 64.47; H, 7.63.
group at the C-4 position with trichloroacetimidate 4 took place
smoothly by treatment with TMSOTf under standard conditions
and yielded compound 33. The isopropylidene protecting group
was removed by acidic hydrolysis to give disaccharide 9, fully char-
acterized as diacetate 34. A similar reaction sequence was em-
ployed in the synthesis of its b-allyl and benzyl congeners 12 and
15 (Scheme 6).
4.3. Allyl 6-O-tert-butyldiphenylsilyl-b-D-mannopyranoside 2
3. Conclusions
Allyl b-
D
-mannopyranoside2g was converted into the title com-
pound using the procedure described for 1 to yield 2 (86%) as a
In conclusion, we have performed a systematic study on the
regioselective glycosylation of mannoside 2,3,4-triol acceptors.
Although some of the glycosyl couplings described in this paper
proceeded only in moderate yields, this protocol is very competi-
tive with the ‘clasical’ methods and allows us to avoid sequential
protection–deprotection steps.This method may be used as a sim-
ple, fast and efficient procedure for the preparation of some partic-
ular disaccharides.
thick syrup. ½a 2D0
ꢂ
¼ ꢁ49:5 (c 0.6, CHCl3). 1H NMR d: 5.91 (m, 1H,
CH@), 5.27 (m, 1H, @CHH), 5.21 (m, 1H, @CHH), 4.53 (d, 1H, J1,2
1.1 Hz, H-1), 4.36 (m, 1H, OCHH), 4.11 (m, 1H, OCHH), 4.00 (dd,
0
1H, J2,3 3.4 Hz, H-2), 3.96 (dd, 1H, J6,5 4.9, J6;6 10.7 Hz, H-6), 3.93
(dd, 1H, J6 ;5 5.3 Hz, H-60), 3.81 (t, 1H, J4,3 = J4,5 = 9.3 Hz, H-4), 3.53
0
(dd, 1H, H-3), 3.33 (m, 1H, H-5), 1.06 (s, 9H, tBu). 13C NMR d:
118.1 (CH2), 98.3 (C-1), 74.8, 74.4, 70.5, 70.1, 69.7 (CH2), 64.8 (C-
6), 26.7 (tBu), 19.2 (SiC). HRMS-ESI calcd for
C25H34NaO6Si
(M+Na)+: 481.2017, found: 481.2041. Anal. Calcd for C25H34O6Siꢀ
4. Experimental
0.5H2O: C, 64.21; H, 7.54, Found: C, 64.36; H, 7.51.
4.1. General methods
4.4. (20S,30S)-Allyl 3,4-O-(20,30-dimethoxybutane-20,30-diyl)-6-O-
tert-butyldiphenylsilyl-
a-D-mannopyranoside 17
Silica gel HF-254 and Silica Gel 230–400 mesh (E. Merck) were
used for TLC and column chromatography, respectively. 1H and 13
C
(20S,30S)-Allyl
3,4-O-(20,30-dimethoxybutane-20,30-diyl)-
a-D-
NMR spectra were recorded at 303 K with a Bruker Avance DRX-
500 spectrometer (500 MHz and 125 MHz, respectively) or with a
Varian Mercury 400BB spectrometer (400 MHz and 100 MHz,
respectively) for solutions in CDCl3. An internal TMS was used as
the 1H and 13C NMR chemical shift standard. Signals of the aro-
mannopyranoside16 16 was converted into the title compound
using the procedure described for 1 to yield 17 (65%) as a thick
syrup. ½a 2D0
ꢂ
¼ þ118:0 (c 0.5, CHCl3). 1H NMR d: 5.89 (m, 1H,
CH@), 5.25 (m, 1H, @CHH), 5.18 (m, 1H, @CHH), 4.90 (d, 1H, J1,2

P. Cmoch, Z. Pakulski / Tetrahedron: Asymmetry 19 (2008) 1494–1503
1499
1.4 Hz, H-1), 4.18 (m, 1H, OCHH), 4.05 (m, 2H), 3.99 (m, 1H, OCHH),
3.84–3.95 (m, 4H), 3.28 (s, 3H, OCH3), 3.14 (s, 3H, OCH3), 1.31 (s,
3H, CH3), 1.26 (s, 3H, CH3), 1.04 (s, 9H, tBu). 13C NMR d: 117.7
(CH2@), 100.3 (C-20), 99.8 (C-30), 98.7 (C-1), 71.7, 69.8, 68.5, 67.7
(OCH2), 63.0, 62.4 (C-6), 48.1 (OCH3), 47.9 (OCH3), 26.7 (tBu),
19.3 (C–Si), 17.8 (CH3), 17.7 (CH3). HRMS-ESI calcd for C31H44NaO8-
Si [M+Na]+: 595.2698, found: 595.2724.
(C). HRMS-ESI calcd for C31H39ClNaO9Si [M+Na]+: 641.1944, found:
641.1957. Anal. Calcd for C31H39ClO9Si: C, 60.13; H, 6.35; Cl, 5.73.
Found: C, 59.96; H, 6.53; Cl, 5.79.
4.8. Allyl 3,4-di-O-acetyl-6-O-tert-butyldiphenylsilyl-b-D-
mannopyranoside 26
A mixture of 25 (336 mg, 0.54 mM), thiourea (100 mg) and 2,4-
lutidine (0.06 mL) in dichloromethane (3 mL) and MeOH (15 mL)
was stirred at 50 °C for 48 h, evaporated under diminished pres-
sure and purified by column chromatography (5:1?7:3 hexane–
4.5. (20S,30S)-Benzyl 3,4-O-(20,30-dimethoxybutane-20,30-diyl)-
-mannopyranoside 20
a-
D
To
a
solution of benzyl
a-D
-mannopyranoside17 (2.70 g,
EtOAc) to afford 200 mg (55%) of 26 as a foam. ½a D20
¼ ꢁ20:6 (c
ꢂ
10 mmol) in methanol (30 mL) trimethyl orthoformate (5.5 mL,
50 mmol), 2,3-butanedione (1.3 mL, 15 mmol), and camphorsulfo-
nic acid (250 mg) were added and the mixture was refluxed for
19 h under an argon atmosphere, cooled to room temperature
and neutralized by the addition of triethylamine (1 mL). Solvents
were evaporated under diminished pressure and the residue was
purified by column chromatography (7:3 hexane–EtOAc?5:3:0.5
hexane–EtOAc–MeOH) to afford 2.33 g (61%) of the title compound
0.5, CHCl3). 1H NMR d: 5.93 (m, 1H, CH@), 5.37 (t, 1H,
J4,3 = J4,5 = 9.9 Hz, H-4), 5.30 (m, 1H, @CHH), 5.25 (m, 1H, @CHH),
4.96 (dd, 1H, J3,2 3.1 Hz, H-3), 4.63 (d, 1H, J1,2 1.0 Hz, H-1), 4.40
(m, 1H, OCHH), 4.16 (m, 1H, OCHH), 4.12 (dd, 1H, H-2), 3.79 (dd,
1H, J6,5 5.7, J6;6 11.6 Hz, H-6), 3.72 (dd, 1H, J6 ;5 2.4 Hz, H-60), 3.49
(m, 1H, H-5), 2.09 (s, 3H, CH3), 1.90 (s, 3H, CH3), 1.06 (tBu). 13C
NMR d: 170.5 (C@O), 169.3 (C@O), 118.3 (CH2), 97.7 (C-1), 75.1,
73.4, 69.7 (CH2), 69.3, 66.2, 62.9 (CH2), 26.6 (tBu), 20.9 (CH3),
20.6 (CH3), 19.2 (C). HRMS-ESI calcd for C29H38NaO8Si [M+Na]+:
565.2228, found: 565.2212.
0
0
as a foam. ½a 2D0
ꢂ
¼ þ202:8 (c 0.5, CHCl3); 1H NMR d: 4.93 (d, 1H, J1,2
1.4 Hz, H-1), 4.70 and 4.51 (ABq, 2H, J 11.8 Hz, OCH2), 4.12 (dd, 1H,
J6,5 9.4, J6;6 10.3 Hz, H-6), 4.05 (dd, 1H, J6 ;5 3.1 Hz, H-60), 3.96 (m,
1H), 3.81 (m, 3H), 3.27 (s, 3H, OCH3), 3.26 (s, 3H, OCH3), 1.32 (s,
0
0
4.9. Allyl 6-O-tert-butyldiphenylsilyl-2,3-O-isopropylidene-a-D-
mannopyranoside 32
13
3H, CH3), 1.29 (s, 3H, CH3). C NMR d: 100.3 (C-20), 99.9 (C-30),
99.3 (C-1), 70.7, 69.8, 69.4 (OCH2), 68.1, 63.0, 61.3 (C-6), 48.1
(OCH3), 47.9 (OCH3), 17.8 (CH3), 17.7 (CH3). HRMS-ESI calcd for
C
To a solution of 1 (530 mg, 1.15 mmol) in dimethoxypropane
(10 mL) camphorsulfonic acid (30 mg) was added and the mixture
was stirred at room temperature for 18 h. The catalyst was neutral-
ized by the addition of 25% aq NH3 (0.5 mL) and solvents were
evaporated under diminished pressure. Column chromatography
of the residue (9:1?7:3 hexane–EtOAc) gave 546 mg (95%) of the
19H28NaO8 [M+Na]+: 407.1676, found: 407.1695.
4.6. (20S,30S)-Benzyl 3,4-O-(20,30-dimethoxybutane-20,30-diyl)-6-
O-tert-butyldiphenylsilyl- -mannopyranoside 21
a-D
Compound 20 was converted into the title compound using the
title compound as a colourless oil. ½a D20
ꢂ
¼ þ2:6 (c 0.4, CHCl3). 1H
procedure described for
1
to yield 21 (89%) as
a
foam.
NMR d: 5.88 (m, 1H, CH@), 5.26 (m, 1H, @CHH), 5.19 (m, 1H,
@CHH), 5.04 (s, 1H, H-1), 4.16 (m, 2H), 4.11 (t, 1H,
J4,3 = J4,5 = 7.2 Hz, H-4), 3.97 (m, 1H, OCH), 3.90 (m, 2H), 3.79 (m,
1H), 3.67 (m, 1H), 1.50 (s, 3H, CH3), 1.35 (s, 3H, CH3), 1.06 (s, 9H,
tBu). 13C NMR d: 117.9 (OCH2), 109.5 (CMe2), 96.2 (C-1), 78.2,
75.4, 70.8, 69.5, 67.9 (@CH2), 64.6 (C-6), 27.9 (CH3), 26.8 (tBu),
26.1 (CH3), 19.2 (SiC). HRMS-ESI calcd for C28H38NaO6Si [M+Na]+:
521.2330, found: 521.2333. Anal. Calcd for C28H38O6Si: C, 67.44;
H, 7.68. Found: C, 67.47; H, 7.46.
½
a 2D0
ꢂ
¼ þ124:7 (c 0.7, CHCl3). 1H NMR d: 4.91 (d, 1H, J1,2 1.3 Hz,
H-1), 4.71 and 4.51 (ABq, 2H, J 11.9 Hz, OCH2), 4.05 (m, 2H), 3.92
(m, 4H), 3.27 (s, 3H, CH3), 3.15 (s, 3H, CH3), 1.31 (s, 3H, CH3),
13
1.26 (s, 3H, CH3), 1.06 (s, 9H, 3 ꢃ CH3). C NMR d: 100.2 (C-20),
99.8 (C-30), 98.6 (C-1), 71.8, 69.8, 68.7 (OCH2), 68.5, 63.1, 62.4 (C-
6), 48.1 (OCH3), 47.9 (OCH3), 26.8 (tBu), 19.3 (SiC), 17.8 (CH3),
17.7 (CH3). HRMS-ESI calcd for C35H46NaO8Si [M+Na]+: 645.2854,
found: 645.2857. Anal. Calcd for C35H46O8SiꢀH2O: C, 65.60; H,
7.55. Found: C, 65.56; H, 7.49.
4.10. Allyl 6-O-tert-butyldiphenylsilyl-2,3-O-isopropylidene-b-
4.7. Allyl 3,4-di-O-acetyl-6-O-tert-butyldiphenylsilyl-2-O-
D-mannopyranoside 35
chloroacetyl-b-D-mannopyranoside 25
Compound 2 was converted into the title compound using the
To a stirred solution of 2 (700 mg, 1.53 mM) in acetonitrile
(30 mL) trimethyl orthochloroacetate (0.43 mL, 3.2 mM) and p-
TsOH (30 mg) were added. After 15 min, the solvents were evapo-
rated under diminished pressure, the residue was dissolved in ace-
tonitrile (25 mL), aqueous trifluoroacetic acid (90%, 0.5 mL) was
added, the mixture was stirred at room temperature for 3 h and
concentrated. The residue (crude 24) was acetylated under the
standard conditions (pyridine, acetic anhydride) for 2 h. Solvents
were evaporated under diminished pressure and the residue was
purified by column chromatography (20:1?5:1 hexane–EtOAc)
procedure described for 32 to yield 35 (84%) as an oil.
½
a 2D0
ꢂ
¼ ꢁ54:1 (c 0.3, CHCl3). 1H NMR d: 5.89 (m, 1H, CH@), 5.25
(m, 1H, @CHH), 5.19 (m, 1H, @CHH), 4.78 (d, 1H, J1,2 2.4 Hz, H-1),
4.35 (m, 1H, OCHH), 4.24 (dd, 1H, J2,3 6.1 Hz, H-2), 4.12 (m, 2H,
H-3, OCHH), 3.99 (m, 1H, H-5), 3.91 (m, 2H, H-6, H-60), 3.38 (m,
1H, H-4), 1.56 (s, 3H, CH3), 1.39 (s, 3H, CH3), 1.06 (s, 9H, tBu). 13C
NMR d: 118.2 (CH2), 110.9 (C), 96.8 (C-1), 79.7, 74.2, 73.7, 71.9,
69.9 (CH2), 65.4 (CH2), 27.7 (CH3), 26.8 (tBu), 26.2 (CH3), 19.1 (C).
HRMS-ESI calcd for C28H38NaO6Si [M+Na]+: 521.2330, found:
521.2312. Anal. Calcd for C28H38O6Si: C, 67.44; H, 7.68. Found: C,
67.25; H, 7.56.
to afford 500 mg (53%) of 25 as an oil; ½a D20
¼ ꢁ18:8 (c 0.43 CHCl3).
ꢂ
1H NMR d: 5.89 (m, 1H, CH@), 5.51 (dd, 1H, J2,1 0.9, J2,3 3.2 Hz, H-2),
5.21–5.34 (m, 3H, H-4, @CH2), 5.07 (dd, 1H, J3,4 10.1 Hz, H-3), 4.70
(d, 1H, H-1), 4.35 (m, 1H, OCHH), 4.18 (ABq, 2H, J 15.3 Hz, CH2Cl),
4.11. General procedure for the glycosylation reaction
4.12 (m, 1H, OCHH), 3.81 (dd, 1H, J6,5 5.3, J6;6 11.5 Hz, H-6), 3.73
A solution of trichloroacetimidate 42e (1.1 mmol) and a suitable
acceptor (1.0 mmol) in dichloromethane (25 mL) solution was stir-
red for 1 h at room temperature over molecular sieves (4 Å,
800 mg, finely ground), then cooled to ꢁ40 °C and TMSOTf
0
(dd, 1H, J6 ;5 2.2 Hz, H-60), 3.50 (m, 1H, H-5), 2.00 (s, 3H, CH3),
0
1.91 (s, 3H, CH3), 1.06 (tBu). 13C NMR d: 170.1 (C@O), 169.3
(C@O), 167.1 (C@O), 118.3 (CH2), 96.5 (C-1), 75.2, 71.2, 71.0, 69.8
(CH2), 65.9, 62.7 (CH2), 40.8 (CH2), 26.6 (tBu), 20.6 (CH3), 19.2
(50 lL) was added. After 30 min, the reaction was quenched with

1500
P. Cmoch, Z. Pakulski / Tetrahedron: Asymmetry 19 (2008) 1494–1503
Et3N (0.2 mL), and the solvents were evaporated under diminished
pressure. Column chromatography (9:1?5:1 hexane–EtOAc) of the
residue gave the disaccharide.
(dd, 1H, J1,2 1.8 Hz, H-20), 5.80 (m, 1H, CH@), 5.47 (d, 1H, H-10), 5.22
(m, 1H, @CHH), 5.15 (m, 1H, @CHH), 4.75 (d, 1H, J1,2 1.6 Hz, H-1),
4.71 (m, 2H, H-50,60), 4.53 (dd, 1H, J6 ;5 5.2, J6;6 12.3 Hz, H-60),
4.15 (dd, 1H, J2,3 3.1 Hz, H-2), 4.08 (m, 2H, J4,3 = J4,5 = 9.3 Hz, H-4,
OCHH), 4.03 (dd, 1H, H-3), 3.95 (m, 2H, H-6,6), 3.90 (m, 1H, OCHH),
3.70 (m, 1H, H-5), 1.09 (tBu). 13C NMR d: 166.3 (C@O), 165.7 (C@O),
165.5 (C@O), 165.3 (C@O), 117.7 (OCH2), 99.6 (C-10), 98.6 (C-1),
80.7 (C-3), 71.7 (C-5), 70.4 (C-2,20), 70.2 (C-30), 69.3 (C-50), 68.1
(C-4), 68.0 (@CH2), 67.1 (C-40), 64.5 (C-6), 63.3 (C-60), 26.9 (tBu),
0
0
4.11.1. Allyl 2,3,4,6-tetra-O-benzoyl-
a-D-mannopyranosyl-
(1?2)-6-O-tert-butyldiphenylsilyl-3,4-O-(20,30-dimethoxy-
butane-20,30-diyl)-
a-D-mannopyranoside 18
Yield 83%, as a foam. ½a D20
ꢂ
¼ þ7:0 (c 0.4, CHCl3). 1H NMR d: 6.08
(t, 1H, J4,3 = J4,5 = 10.0 Hz, H-40), 5.97 (dd, 1H, J2,1 1.6, J2,3 3.2 Hz, H-
20), 5.95 (dd, 1H, H-30), 5.89 (m, 1H, CH@), 5.46 (d, 1H, H-10), 5.26
(m, 1H, @CHH), 5.18 (m, 1H, @CHH), 5.00 (br s, 1H, H-1), 4.74
19.2 (SiC). HRMS-ESI calcd for
C
59H60NaO15Si (M+Na)+:
1059.3594, found: 1059.3599. Anal. Calcd for C59H60O15Si: C,
68.32; H, 5.83. Found: C, 68.08; H, 5.90.
(dd, 1H, J6,5 2.4, J6;6 12.0 Hz, H-60), 4.55 (m, 1H, H-50), 4.48 (dd,
0
1H, J6 ;5 4.4 Hz, H-60), 4.21 (m, 2H, J4,3 = J4,5 =10.1 Hz, H-4, OCHH),
0
4.11 (dd, 1H, J3,2 2.7 Hz, H-3), 4.07 (m, 1H, H-2), 4.01 (m, 2H, H-
6, 6), 3.97 (m, 1H, OCHH), 3.91 (m, 1H, H-5), 3.26 (s, 3H, CH3),
3.23 (s, 3H, CH3), 1.23 (s, 6H, 2 ꢃ CH3), 1.12 (s, 9H, tBu). 13C NMR
d: 166.2 (C@O), 165.5 (C@O), 164.9 (C@O), 164.8 (C@O), 117.6
(@CH2), 100.1 (C), 99.6 (C), 99.4 (C-10), 98.3 (C-1), 76.7 (C-2), 72.6
(C-5), 70.2 (C-20), 70.1 (C-30), 69.2 (C-50), 68.8 (C-3), 67.7 (OCH2),
67.2 (C-40), 63.4 (C-4), 63.0 (C-60), 62.7 (C-6), 48.0 (CH3), 47.9
(CH3), 26.9 (Me3C), 19.4 (CSi), 17.6 (CH3), 17.5 (CH3). HRMS-ESI
calcd for C65H70NaO17Si [M+Na]+: 1173.4275, found: 1173.4277.
Anal. Calcd for C65H70O17SiꢀH2O: C, 66.76; H, 6.21. Found: C,
66.96; H, 6.02.
4.11.5. Allyl 2,3,4,6-tetra-O-benzoyl-
(1?3)-6-O-tert-butyldiphenylsilyl-b-
a-D-mannopyranosyl-
D-mannopyranoside 11
Yield 35%, as a foam. ½a D20
ꢂ
¼ ꢁ31:0 (c 0.6, CHCl3). 1H NMR d: 6.12
(t, 1H, J4,3 = J4,5 = 10.1 Hz, H-40), 5.98 (dd, 1H, J3,2 3.3 Hz, H-30), 5.88
(m, 1H, CH@), 5.85 (dd, 1H, J2,1 1.8 Hz, H-20), 5.41 (d, 1H, H-10), 5.27
(m, 1H, @CHH), 5.21 (m, 1H, @CHH), 4.84 (m, 1H, H-50), 4.71 (dd,
1H, J6,5 2.5, J6;6 12.2 Hz, H-60), 4.49 (m, 2H, J6,5 4.5, H-1,60), 4.33
0
(m, 1H, OCHH), 4.24 (d, 1H, J2,3 2.8 Hz, H-2), 4.12 (m, 2H, H-4,
OCHH), 3.98 (m, 2H, H-6,6), 3.66 (dd, 1H, J3,4 9.3 Hz, H-3), 3.35
(m, 1H, H-5), 1.09 (s, 9H, tBu). 13C NMR d: 166.3 (C@O), 165.6
(C@O), 165.5 (C@O), 165.4 (C@O), 118.1 (OCH2), 99.8 (C-10), 98.0
(C-1), 83.6 (C-3), 75.4 (C-5), 70.8 (C-2), 70.4 (C-20), 70.3 (C-30),
69.6 (@CH2), 69.3 (C-50), 67.5 (C-4), 66.9 (C-40), 64.4 (C-6), 63.1
(C-60), 26.8 (tBu), 19.2 (SiC). HRMS-ESI calcd for C59H60NaO15Si
(M+Na)+: 1059.3594, found: 1059.3624. Anal. Calcd for
4.11.2. Benzyl 2,3,4,6-tetra-O-benzoyl-
a-D-mannopyranosyl-
(1?2)-6-O-tert-butyldiphenylsilyl-3,4-O-(20,30-dimethoxy-
butane-20,30-diyl)-
a-D-mannopyranoside 22
Yield 53%, as a foam. ½a D20
ꢂ
¼ þ14:7 (c 0.4, CHCl3). 1H NMR d: 6.08
C59H60O15Si: C, 68.32; H, 5.83. Found: C, 68.02; H, 5.85.
(t, 1H, J4,3 = J4,5 = 10.0 Hz, H-40), 5.97 (dd, 1H, J2,1 1.0, J2,3 3.3 Hz, H-
20), 5.93 (dd, 1H, H-30), 5.45 (d, 1H, H-10), 5.03 (s, 1H, H-1), 4.77 and
4.11.6. Benzyl 2,3,4,6-tetra-O-benzoyl- -mannopyranosyl-
(1?3)-6-O-tert-butyldiphenylsilyl-a-D-mannopyranoside 14
a-D
0
4.48 (ABq, 2H, J 11.7 Hz, OCH), 4.67 (dd, 1H, J6,5 2.4, J6;6 12.0 Hz, H-
60), 4.48 (m, 1H, H-50), 4.44 (dd, 1H, J6 ;5 4.1 Hz, H-60), 4.22 (t, 1H,
Yield 34%, as a foam. ½a D20
ꢂ
¼ ꢁ10:4 (c 0.6, CHCl3). 1H NMR d: 6.07
0
J4,3 = J4,5 = 9.8 Hz, H-4), 4.11 (m, 2H, H-2,3), 4.02 (m, 2H, H-6, 6),
3.96 (m, 1H, H-5), 3.26 (s, 3H, CH3), 3.21 (s, 3H, CH3), 1.23 (s, 3H,
CH3), 1.22 (s, 3H, CH3), 1.13 (tBu). 13C NMR d: 166.2 (C@O), 165.5
(C@O), 164.9 (C@O), 164.8 (C@O), 100.1 (C), 99.6 (C), 99.4 (C-1),
98.4 (C-1), 76.6, 72.7, 70.2, 70.1, 69.1, 68.9, 68.8 (OCH2), 67.1,
63.4, 62.9 (C-6), 62.7 (C-6), 48.1 (OCH3), 47.9 (OCH3), 26.9
(tBu), 19.4 (CSi), 17.6 (CH3), 17.5 (CH3). HRMS-ESI calcd for
C69H72NaO17Si [M+Na]+: 1223.4431, found: 1223.4413. Anal. Calcd
for C69H72O17Siꢀ2H2O: C, 66.97; H, 6.19. Found: C, 67.19; H, 5.73.
(t, 1H, J3,2 = J3,4 = 10.0 Hz, H-40), 5.95 (dd, 1H, J3,2 3.3 Hz, H-30), 5.85
(dd, 1H, J2,1 1.8 Hz, H-20), 5.47 (d, 1H, H-10), 4.78 (d, 1H, J1,2 1.5 Hz,
H-1), 4.72 (m, 2H), 4.63 and 4.42 (ABq, 2H, J 11.9 Hz, OCH2), 4.52
(dd, 1H, J 4.8 and 12.0 Hz), 4.18 (m, 1H), 4.09 (m, 2H), 3.96 (m,
2H), 3.73 (m, 1H), 1.10 (s, 9H, t-Bu). 13C NMR d: 166.3 (C@O),
165.7 (C@O), 165.5 (C@O), 165.4 (C@O), 99.6 (C-1), 98.6 (C-1),
80.9 (C-3), 72.0, 70.4, 70.2, 69.3, 68.9 (OCH2), 67.9, 67.1, 64.5 (C-
6), 63.3 (C-6), 26.9 (3 ꢃ CH3), 19.2 (SiC). HRMS-ESI calcd for
C
63H62O15NaSi [M+Na]+: 1109.3750, Found: 1109.3733. Anal. Calcd
for C63H62O15Si: C, 69.60; H, 5.75. Found: C, 69.43; H, 5.97.
4.11.3. Allyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-
(1?2)-3,4-di-O-acetyl-6-O-tert-butyldiphenylsilyl-b-
D
-
4.11.7. Allyl 2,3,4,6-tetra-O-benzoyl- -mannopyranosyl-
a-D
mannopyranoside 27
(1?4)-6-O-tert-butyldiphenylsilyl-2,3-O-isopropylidene-a-D-
Yield 87%, as a foam. ½a D20
ꢂ
¼ ꢁ37:0 (c 0.5, CHCl3). 1H NMR d: 6.21
mannopyranoside 33
(t, 1H, J4,3 = J4,5 = 10.2 Hz, H-40), 5.98 (dd, 1H, J3,2 3.3 Hz, H-30), 5.92
(m, 1H, @CH), 5.75 (dd, 1H, J2,1 1.8 Hz, H-20), 5.20–5.36 (m, 4H,
J4,3 = J4,5 = 9.8 Hz, H-10, H-4, @CH2), 5.08 (dd, 1H, J3,2 3.1 Hz, H-3),
5.01 (m, 1H, H-50), 4.64 (2H, J6,5 2.5 Hz, H-1, H-60), 4.44 (m, 1H,
Yield 86%, as a foam. ½a D20
ꢂ
¼ ꢁ3:5 (c 0.25, CHCl3). 1H NMR d: 6.12
(t, 1H, J4,3 = J4,5 = 10.1 Hz, H-40), 5.90 (m, 1H, HC@), 5.79 (m, 2H, J3,2
3.2 Hz, H-20,30), 5.64 (br s, 1H, H-10), 5.29 and 5.22 (2m, 2H, @CH2),
5.12 (br s, 1H, H-1), 4.40 (m, 2H), 4.20 (m, 4H), 4.03 (m, 4H), 3.84
(m, 1H), 1.52 (s, 3H, CH3), 1.33 (s, 3H, CH3), 1.10 (s, 9H, 3 ꢃ CH3).
13C NMR d: 166.0 (C@O), 165.5 (C@O), 165.3 (C@O), 165.2 (C@O),
117.9 (@CH2), 109.8 (CMe2), 96.2 (C-1), 95.9 (C-1), 78.2, 76.0,
73.0, 70.5, 70.1, 69.4, 68.8, 67.7 (OCH2), 66.5, 63.3 (C-6), 62.6 (C-
6), 27.9 (CH3), 27.0 (3 ꢃ CH3), 26.3 (CH3), 19.4 (SiC). HRMS-ESI
calcd for C62H64NaO15Si [M+Na]+: 1099.3907, found: 1099.3914.
OCHH), 4.38 (dd, 1H, J6,5 2.8, J6;6 12.3 Hz, H-60), 4.22 (dd, 1H, H-
0
0
2), 4.15 (m, 1H, OCHH), 3.97 (dd, 1H, J6,5 6.6, J6;6 11.5 Hz, H-6),
3.78 (dd, 1H, J6,5 2.3 Hz, H-6), 3.54 (m, 1H, H-5), 2.13 (s, 3H,
CH3), 1.86 (s, 3H, CH3), 1.10 (tBu). 13C NMR d: 170.6 (C@O), 169.4
(C@O), 166.2 (C@O), 165.5 (C@O), 165.2 (C@O), 165.0 (C@O),
118.8 (@CH2), 98.7 (C-10), 98.2 (C-1), 75.8 (C-2 or C-5), 75.7 (C-2
or C-5), 72.9 (C-3), 70.9 (C-20), 70.3 (CH2), 69.9 (C-30), 68.6 (C-50),
67.3 (C-40), 66.9 (C-4), 63.5 (C-6), 62.6 (C-60), 26.8 (tBu), 20.7
(CH3), 20.6 (CH3), 19.2 (C). HRMS-ESI calcd for C63H64NaO17Si
[M+Na]+: 1143.3805, found: 1143.3763.
4.11.8. Allyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-
(1?4)-6-O-tert-butyldiphenylsilyl-2,3-O-isopropylidene-b-D-
mannopyranoside 36
Yield 94%, as a foam. ½a D20
ꢂ
¼ ꢁ30:3 (c 0.4, CHCl3). 1H NMR d: 6.12
4.11.4. Allyl 2,3,4,6-tetra-O-benzoyl-
a-
D-mannopyranosyl-
(t, 1H, J4,3 = J4,5 = 10.1 Hz, H-40), 5.96 (m, 1H, @CH), 5.81 (dd, 1H, J3,2
3.2 Hz, H-30), 5.75 (dd, 1H, J2,1 2.0 Hz, H-20), 5.61 (d, 1H, H-10), 5.28
(m, 2H, @CH2), 4.85 (d, 1H, J1,2 1.9 Hz, H-1), 4.45 (m, 1H, OCHH),
(1?3)-6-O-tert-butyldiphenylsilyl-a-D-mannopyranoside 8
Yield 56%, as a foam. ½a D20
ꢂ
¼ ꢁ17:7 (c 0.6, CHCl3). 1H NMR d: 6.06
(t, 1H, J4,3 = J4,5 = 10.1 Hz, H-40), 5.95 (dd, 1H, J3,2 3.3 Hz, H-30), 5.84
4.40 (dd, 1H, J6,5 2.2, J6;6 12.3 Hz, H-60), 4.35 (m, J3,4 ffi 6.1 Hz, 1H,
0

P. Cmoch, Z. Pakulski / Tetrahedron: Asymmetry 19 (2008) 1494–1503
1501
H-3), 4.29 (dd, 1H, J2,3 5.8 Hz, H-2), 4.22 (m, 2H, H-50, OCHH), 4.15
(m, 2H, H-4, H-60), 4.08 (m, 2H, H-6, H-6), 3.55 (m, 1H, H-5), 1.55 (s,
3H, CH3), 1.37 (s, 3H, CH3), 1.10 (s, 9H, tBu). 13C NMR d: 166.0
(C@O), 165.5 (C@O), 165.3 (C@O), 165.3 (C@O), 118.6 (CH2),
111.3 (C), 96.9 (C-1), 96.2 (C-1), 79.4, 75.0, 74.7, 73.3, 70.5, 70.1
(CH2), 70.0, 69.6, 66.4, 63.8 (CH2), 62.5 (CH2), 27.7 (CH3), 26.9
(tBu), 26.2 (CH3), 19.4 (C). HRMS-ESI calcd for C62H64NaO15Si
[M+Na]+: 1099.3907, found: 1099.3904. Anal. Calcd for
(C@O), 100.3 (C-1), 97.7 (C-1), 80.4, 72.2, 71.5, 70.3, 70.1, 69.6,
69.4, 68.9 (OCH2), 66.6, 64.7 (C-6), 62.9 (C-6), 26.9 (tBu), 19.3
(CSi). HRMS-ESI calcd for C63H62NaO15Si [M+Na]+: 1109.3750,
found: 1109.3733. Anal. Calcd for C63H62O15Si: C, 69.60; H, 5.75.
Found: C, 69.38; H, 5.71.
4.14. Allyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-(1?2)-
b-D-mannopyranoside 28
C62H64O15Siꢀ3H2O: C, 65.82; H, 6.24. Found: C, 65.74; H, 5.79.
To a stirred solution of 27 (188 mg, 0.17 mM) in MeOH (10 mL)
4.11.9. Benzyl 2,3,4,6-tetra-O-benzoyl- -mannopyranosyl-
(1?4)-6-O-tert-butyldiphenylsilyl-2,3-O-isopropylidene-a-D-
mannopyranoside 38
a
-
D
a mixture of MeOH (5 mL) and acetyl chloride (0.1 mL) was added.
Stirring was continued for 20 h, the solvents were evaporated un-
der diminished pressure with the aid of toluene and the residue
was purified by column chromatography (7:3 hexane–EtOAc, then
5:3:0.5 hexane–EtOAc–MeOH) to yield 28 (93 mg, 70%) as a foam.
Starting from benzyl 6-O-tert-butyldiphenylsilyl-2,3-O-isopro-
pylidene-a-D
-mannopyranoside12 37, the title compound was ob-
tained as a foam in 82% yield. ½a D20
ꢂ
= +11.6 (c 0.3, CHCl3). 1H
½
a 2D0
ꢂ
¼ ꢁ46:3 (c 0.3, CHCl3). 1H NMR d: 6.16 (t, 1H,
NMR d: 6.11 (t, 1H, J4,3 = J4,5 = 10.1 Hz, H-40), 5.81 (dd, 1H, J3,2
3.2 Hz, H-30), 5.77 (m, 1H, H-20), 5.64 (d, 1H, J1,2 1.6 Hz, H-10),
5.14 (br s, 1H, H-1), 4.72 and 4.52 (ABq, 2H, J 11.8 Hz, OCH2),
4.40 (m, 2H, H-30, 6), 4.23 (m, 1H, H-50), 4.20 (d, 1H, J2,3 5.7 Hz,
J4,3 = J4,5 = 10.2 Hz, H-40), 5.99 (dd, 1H, J3,2 3.3 Hz, H-30), 5.94 (dd,
1H, J2,1 1.7 Hz, H-20), 5.90 (m, 1H, @CH), 5.49 (d, 1H, H-10), 5.31
(m, 1H, @CHH), 5.17 (m, 1H, @CHH), 5.02 (m, 1H, H-50), 4.65 (dd,
1H, J6,5 2.7, J6;6 12.3 Hz, H-60), 4.61 (br s, 1H, H-1), 4.41 (m, 1H,
0
H-2), 4.14 (dd, 1H, J6,5 3.6, J6;6 12.3 Hz, H-60), 4.03–4.09 (m, 3H,
OCHH), 4.37 (dd, 1H, J6,5 3.1 Hz, H-60), 4.22 (d, 1H, H-2), 4.11 (m,
2H, H-4, OCHH), 4.04 (m, 2H, H-6, H-6), 3.74 (dd, 1H, J3,2 3.0, J3,4
9.5 Hz, H-3), 3.36 (m, 1H, H-5). 13C NMR d: 166.3 (C@O), 166.1
(C@O), 165.6 (C@O), 165.4 (C@O), 118.2 (CH2), 99.2 (C-1), 98.9
(C-1), 76.2, 74.6, 70.9, 70.5 (CH2), 70.4, 68.5, 68.3, 66.7, 62.7
(CH2), 62.4 (CH2). HRMS-ESI calcd for C43H42NaO15 [M+Na]+:
821.2416, found: 821.2435.
0
H-4, 6, 6), 3.90 (m, 1H, H-5), 1.51 (s, 3H, CH3), 1.32 (s, 3H, CH3),
1.11 (s, 9H, 3 ꢃ CH3). 13C NMR d: 166.0 (C@O), 165.5 (C@O),
165.3 (C@O), 165.2 (C@O), 109.8 (CMe2), 96.2 (C-10), 95.8 (C-1),
78.2 (C-3), 76.0 (C-2), 73.1 (C-4), 70.4 (C-20), 70.1 (C-30), 69.4 (C-
50), 68.9 (C-5), 68.6 (OCH2), 66.5 (C-40), 63.5 (C-6), 62.5 (C-60),
27.9 (CH3), 27.0 (3 ꢃ CH3), 26.3 (CH3), 19.4 (SiC). HRMS-ESI calcd
for C66H66NaO15Si [M+Na]+: 1149.4063, found: 1149.4057. Anal.
Calcd for C66H66O15Siꢀ3H2O: C, 67.10; H, 6.14. Found: C, 66.91; H,
5.83.
4.15. Allyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-(1?2)-
6-O-tert-butyldiphenylsilyl-b- -mannopyranoside 10
D
4.12. Allyl 2,3,4,6-tetra-O-benzoyl-
a
-
D
-mannopyranosyl-(1?2)-
Compound 28 (172 mg, 0.22 mM) was converted into disac-
charide 10 using the procedure described for 1 to yield 10
6-O-tert-butyldiphenylsilyl- -mannopyranoside 7
a-D
(154 mg, 70%) as a foam. ½a D20
ꢂ
¼ ꢁ30:7 (c 0.3, CHCl3). 1H NMR d:
To a solution of 18 (194 mg, 0.17 mM) in dichloromethane
(2 mL) was added 90% aqueous trifluoroacetic acid (1 mL) and
the whole mixture was stirred for 5 min. Solvents were evaporated
under diminished pressure and the residue was immediately puri-
fied by column chromatography (5:1?7:3 hexane–EtOAc, then
5:3:0.2 hexane–EtOAc–MeOH) to afford 7 as a foam (100 mg,
6.16 (t, 1H, J4,3 = J4,5 = 10.1 Hz, H-40), 5.90 (m, 3H, H-20, H-30,
@CH), 5.46 (d, 1H, J1,2 1.6 Hz, H-10), 5.28 (m, 1H, @CHH), 5.16
(m, 1H, @CHH), 4.98 (m, 1H, H-50), 4.66 (dd, 1H, J6,5 2.7, J6;6
0
12.3 Hz, H-60), 4.55 (br d, 1H, J1,2 < 1 Hz, H-1), 4.37 (m, 2H, J6,5
3.1 Hz, H-60, OCHH), 4.20 (br d, 1H, H-2), 4.05 (m, 4H, H-4, H-6,
H-6, OCHH), 3.71 (dd, 1H, J3,2 3.0, J3,4 9.4 Hz, H-3), 3.37 (m, 1H,
H-5), 1.11 (s, 9H, tBu). 13C NMR d: 166.3 (C@O), 165.4 (2 ꢃ C@O),
165.3 (C@O), 118.2 (CH2), 99.0 (C-10), 98.8 (C-1), 76.2 (C-2), 74.8
(C-3), 74.5 (C-5), 71.0 (C-4), 70.6 (C-30), 70.3 (C-20), 70.2 (CH2),
68.4 (C-50), 66.8 (C-40), 65.8 (C-6), 62.7 (C-60), 26.8 (tBu), 19.2
58%).
½
a 2D0
ꢂ
¼ ꢁ19:6 (c 0.3, CHCl3). 1H NMR d: 6.09 (t, 1H,
J4,3 = J4,5 = 10.1 Hz, H-40), 5.87 (dd, 1H, J2,1 1.7, J2,3 3.3 Hz, H-20),
5.83 (dd, 1H, H-30), 5.80 (m, 1H, CH@), 5.36 (d, 1H, H-10), 5.21
(m, 1H, @CHH), 5.16 (m, 1H, @CHH), 5.11 (br s, 1H, H-1), 4.66
(dd, 1H, J6,5 2.3, J6;6 12.2 Hz, H-60), 4.59 (m, 1H, H-50), 4.49 (dd,
(C). HRMS-ESI calcd for C
59H60NaO15Si [M+Na]+: 1059.3594,
found: 1059.3559. Anal. Calcd for C59H60O15Si: C, 68.32; H, 5.83,
Found: C, 68.16; H, 5.85.
0
1H, J6 ;5 4.6 Hz, H-60), 4.06 (m, 5H, H-2, 3, 4, 6, OCHH), 3.80 (m,
0
1H, OCHH), 3.71 (m, 1H, H-5), 1.10 (s, 9H, tBu). 13C NMR d: 166.2
(C@O), 165.5 (C@O), 165.5 (C@O), 165.2 (C@O), 117.3 (@CH2),
100.3 (C-10), 97.7 (C-1), 80.4, 71.9, 71.4, 70.3, 70.1, 69.7, 69.5,
67.9 (OCH2), 66.6, 64.7 (C-6), 62.9 (C-6), 26.9 (tBu), 19.2 (CSi).
HRMS-ESI calcd for C59H60NaO15Si [M+Na]+: 1059.3594, found:
1059.3646. Anal. Calcd for C59H60O15Si: C, 68.32; H, 5.83. Found:
C, 68.19; H, 5.84.
4.16. Allyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-(1?4)-
6-O-tert-butyldiphenylsilyl- -mannopyranoside 9
a-D
To a solution of 33 (160 mg, 0.15 mM) in EtOAc (3 mL) and
MeOH (3 mL) was added solution of p-toluenesulfonic acid
(80 mg) in EtOAc (1 mL) and MeOH (1 mL), and stirred at room
temperature for 2.5 h. Then Et3N (0.5 mL) was added, solvents
were evaporated under diminished pressure, and the residue was
purified by column chromatography (7:3 hexane–EtOAc, then
5:3:0.5 hexane–EtOAc–MeOH) to afford 9 (64 mg, 42%) as a foam.
4.13. Benzyl 2,3,4,6-tetra-O-benzoyl- -mannopyranosyl-
a
-
D
(1?2)-6-O-tert-butyldiphenylsilyl- -D-mannopyranoside 13
a
Compound 22 (258 mg, 0.21 mM) was converted into the title
compound using the procedure described for 7 to yield 13
½
a 2D0
ꢂ
¼ þ10:9 (c 0.3, CHCl3). 1H NMR d: 6.10 (t, 1H,
(147 mg, 63%) as a foam. ½a D20
ꢂ
¼ ꢁ9:4 (c 0.3, CHCl3). 1H NMR d:
J4,3 = J4,5 = 10.0 Hz, H-40), 5.93 (m, 1H, @CH), 5.82 (m, 2H, H-20,
30), 5.58 (d, 1H, J1,2 1.6 Hz, H-10), 5.32 (m, 1H, @CHH), 5.23 (m,
1H, @CHH), 4.92 (d, 1H, J1,2 1.2 Hz, H-1), 3.83–4.29 (m, 11H, other
protons), 1.07 (s, 9H, tBu). 13C NMR d: 166.0 (C@O), 165.8 (C@O),
165.5 (C@O), 165.3 (C@O), 117.8 (@CH), 98.7 (C-1), 98.2 (C-1),
75.9, 71.9, 71.5, 71.5, 70.6, 70.1, 69.8, 67.9 (OCH2), 66.3, 63.6 (C-
6), 62.4 (C-6), 26.8 (tBu), 19.3 (SiC). HRMS-ESI calcd for
6.08 (t, 1H, J4,3 = J4,5 = 10.0 Hz, H-40), 5.88 (dd, 1H, H-20), 5.84 (dd,
1H, J3,2 3.2 Hz, H-30), 5.37 (d, 1H, H-10), 5.16 (br s, 1H, H-1), 4.64
and 4.33 (ABq, 2H, J 11.8 Hz, OCH2), 4.54 (m, 2H, H-50, 60), 4.46
(dd, 1H, J6,5 4.6, J6;6 12.3 Hz, H-60), 4.09 (m, 4H, H-2, 3, 4, 6), 4.01
0
0
(dd, 1H, J6,5 5.1, J6;6 10.8 Hz, H-6), 3.78 (m, 1H, H-5), 1.12 (s, 9H,
tBu). 13C NMR d: 166.1 (C@O), 165.5 (C@O), 165.4 (C@O), 165.2

1502
P. Cmoch, Z. Pakulski / Tetrahedron: Asymmetry 19 (2008) 1494–1503
C59H60NaO15Si [M+Na]+: 1059.3600, found: 1059.3599. Anal. Calcd
for C59H60O15Si: C, 68.32; H, 5.83. Found: C, 68.11; H, 5.97.
67.1 (C-4), 67.0 (C-40), 63.5 (C-6), 62.9 (C-60), 26.8 (tBu), 20.8
(CH3), 20.6 (CH3), 19.2 (CSi). Anal. Calcd for C63H64O17SiꢀH2O: C,
66.42; H, 5.84. Found: C, 66.69; H, 5.61.
4.17. Allyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-(1?4)-
6-O-tert-butyldiphenylsilyl-b- -mannopyranoside 12
D
4.19.2. Benzyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-
(1?2)-3,4-di-O-acetyl-6-O-tert-butyldiphenylsilyl-a-D-
Compound 36 (168 mg, 0.15 mM) was converted into the title
compound using the procedure described for 9 to yield 12 (96
mannopyranoside 23
As a foam. ½a 2D0
ꢂ
¼ ꢁ5:2 (c 0.4, chloroform). 1H NMR d: 6.14 (t,
mg, 59%) as a foam. ½a D20
ꢂ
¼ ꢁ29:7 (c 0.35, CHCl3). 1H NMR d:
1H, J4,3 = J4,5 = 10.1 Hz, H-40), 5.94 (dd, 1H, J3,2 3.3 Hz, H-30), 5.76
(dd, 1H, J2,1 1.8 Hz, H-20), 5.41 (dd, 1H, J3,2 3.3, J3,4 9.3 Hz, H-3),
5.37 (t, 1H, J4,3 = J4,5 = 9.3 Hz, H-4), 5.23 (d, 1H, H-10), 5.12 (d, 1H,
H-1), 4.82 and 4.48 (ABq, 2H, J 11.9 Hz, OCH2), 4.53 (m, 2H, H-50,
60), 4.43 (m, 1H, H-60), 4.25 (dd, 1H, H-2), 3.98 (m, 2H, H-5, 6),
3.80 (m, 1H, H-6), 2.18 (s, 3H, CH3), 1.91 (s, 3H, CH3), 1.15 (tBu).
13C NMR d: 170.5 (C@O), 169.3 (C@O), 166.1 (C@O), 165.5 (C@O),
165.2 (C@O), 165.0 (C@O), 99.5 (C-10), 97.2 (C-1), 77.3 (C-2), 71.9
(C-5), 70.6 (C-3), 70.5 (C-20), 69.5 (C-30), 69.4 (C-50), 68.9 (OCH2),
67.1 (C-4), 66.9 (C-40), 63.5 (C-6), 62.7 (C-60), 26.8 (tBu), 20.8
(CH3), 20.6 (CH3), 19.2 (SiC). Anal. Calcd for C67H66O17SiꢀH2O: C,
67.66; H, 5.76. Found: C, 67.94; H, 5.56.
6.10 (t, 1H, J4,3 = J4,5 = 10.1 Hz, H-40), 5.96 (m, 1H, @CH), 5.86
(dd, 1H, J3,2 3.2 Hz, H-30), 5.83 (dd, 1H, Hz, H-20), 5.72 (d, 1H,
J1,2 1.5 Hz, H-10), 5.32 (m, 1H, @CHH), 5.25 (m, 1H, @CHH), 4.60
0
(br s, 1H, H-1), 4.42 (m, 1H, OCHH), 4.35 (dd, 1H, J6,5 2.2, J6;6
12.3 Hz, H-60), 4.24 (m, 1H, H-50), 4.16 (m, 2H, H-60, OCHH),
4.09 (m, 2H, H-6, H-6), 4.03 (m, 2H, H-4, H-2), 3.82 (m, 1H, H-
3), 3.46 (m, 1H, H-5), 1.08 (s, 9H, tBu). 13C NMR d: 166.0
(C@O), 165.6 (C@O), 165.3 (C@O), 165.3 (C@O), 118.2 (CH2),
98.3 (C-1), 98.2 (C-1), 75.3, 75.0, 74.6, 71.2, 70.6, 70.0, 69.7,
69.6 (CH2), 66.5, 63.5 (CH2), 62.5 (CH2), 26.8 (tBu), 19.3 (C).
HRMS-ESI calcd for C59H60NaO15Si [M+Na]+: 1059.3594, found:
1059.3590. Anal. Calcd for C59H60O15Si: C, 68.32; H, 5.83. Found:
C, 68.34; H, 5.92.
4.19.3. Allyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-
(1?3)-2,4-di-O-acetyl-6-O-tert-butyldiphenylsilyl-a-D-
4.18. Benzyl 2,3,4,6-tetra-O-benzoyl-
a
-
D
-mannopyranosyl-
mannopyranoside 29
(1?4)-6-O-tert-butyldiphenylsilyl-
a
-D
-mannopyranoside 15
As a foam. ½a 2D0
ꢂ
¼ ꢁ7:4 (c, 2.85, CHCl3). 1H NMR d: 6.12 (t, 1H,
J4,3 = J4,5 = 10.1 Hz, H-40), 5.83 (m, 1H, CH@), 5.78 (dd, 1H, J3,2
3.2 Hz, H-30), 5.44 (dd, 1H, J2,1 1.9 Hz, H-20), 5.40 (dd, 1H, J2,3 3.4,
J2,1 1.6 Hz, H-2), 5.37 (t, 1H, J4,3 = J4,5 = 9.9 Hz, H-4), 5.28 (d, 1H,
H-10), 5.25 (m, 1H, @CHH), 5.19 (m, 1H, @CHH), 4.89 (d, 1H, H-1),
Compound 38 (158 mg, 0.14 mM) was converted into the title
compound using the procedure described for 9 to yield 15 (77
mg, 51%) as a foam. ½a D20
ꢂ
¼ þ19:7 (c 0.3, CHCl3). 1H NMR d: 6.11
(t, 1H, J4,3 = J4,5 = 9.9 Hz, H-40), 5.84 (m, 2H, H-20, 30), 5.58 (d, 1H,
J1,2 1.6 Hz, H-10), 4.96 (d, 1H, J1,2 1.3 Hz, H-1), 4.79 and 4.56 (ABq,
4.66 (dd, 1H, J6,5 2.3, J6;6 12.2 Hz, H-60), 4.57 (m, 1H, H-50), 4.49
0
(dd, 1H, J6,5 3.9 Hz, H-60), 4.32 (dd, 1H, H-3), 4.19 (m, 1H, OCHH),
4.00 (m, 1H, OCHH), 3.80 (m, 2H, H-5,5), 3.68 (m, 1H, H-6), 2.30
(s, 3H, Ac), 2.03 (s, 3H, Ac), 1.08 (s, 9H, Me3C). 13C NMR d: 170.6
(C@O), 169.9 (C@O), 166.2 (C@O), 165.5 (C@O), 165.3 (C@O),
165.2 (C@O), 118.1 (@CH2), 98.8 (C-10), 96.1 (C-1), 75.1 (C-3),
72.0 (C-5), 71.2 (C-2), 70.8 (C-20), 69.5 (C-50), 69.3 (C-30), 68.2 (C-
4), 68.0 (OCH2), 66.6 (C-40), 63.1 (C-6), 62.7 (C-60), 26.7 (Me3C),
21.0 (Ac), 20.6 (Ac), 19.2 (CMe3). HRMS-ESI calcd for C63H64NaO17Si
(M+Na)+: 1143.3805, found: 1143.3824.
2H, J 11.9 Hz, OCH2), 4.30 (dd, 1H, J6,5 2.4, J6;6 12.3 Hz, H-60), 4.20
0
(m, 2H, J3,2 3.5, J3,4 8.8 Hz, H-3, 50), 4.13 (dd, 1H, J6 ;5 3.4 Hz, H-60),
0
0
0
4.07 (dd, 1H, J6,5 5.5, J6;6 11.2 Hz, H-6), 4.04 (dd, 1H, J6 ;5 2.1 Hz,
H-6), 3.98 (m, 2H, H-2, 4), 3.92 (m, 1H, H-5), 1.09 (s, 9H,
3 ꢃ CH3). 13C NMR d: 166.0 (C@O), 165.8 (C@O), 165.5 (C@O),
165.3 (C@O), 98.8 (C-1), 98.0 (C-1), 76.0, 71.9, 71.6, 71.5, 70.6,
70.1, 69.8, 68.7 (OCH2), 66.3, 63.6 (C-6), 62.4 (C-6), 26.8 (tBu),
19.3 (SiC). HRMS-ESI calcd for
C
63H62NaO15Si [M+Na]+:
1109.3750, found: 1109.3772. Anal. Calcd for C63H62O15SiꢀH2O: C,
68.46; H, 5.84. Found: C, 68.93; H, 5.95.
4.19.4. Allyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-
(1?3)-2,4-di-O-acetyl-6-O-tert-butyldiphenylsilyl-b-D-
4.19. General procedure for acetylation
mannopyranoside 30
As a foam. ½a 2D0
ꢂ
¼ ꢁ31:9 (c 1.8, CHCl3). 1H NMR d: 6.14 (t, 1H,
An analytical sample of disaccharide (20–30 mg) was dissolved
in pyridine (2 mL) and acetic anhydride (1 mL) was added. The
mixture was kept overnight at room temperature, then solvents
were evaporated under diminished pressure and the residue was
purified by column chromatography (5:3:0.2 hexane–EtOAc–
MeOH).
J4,3 = J4,5 = 10.1 Hz, H-40), 5.91 (m, 1H, CH@), 5.76 (dd, 1H, J3,2
3.2 Hz, H-30), 5.59 (br d, 1H, J2,3 3.3 Hz, H-2), 5.41 (dd, 1H, J2,1
1.8 Hz, H-20), 5.34 (t, 1H, J4,3 = J4,5 = 9.9 Hz, H-4), 5.30 (m, 1H,
@CHH), 5.25 (d, 1H, H-10), 5.22 (m, 1H, @CHH), 4.75 (dd, 1H, J6,5
2.3, J6;6 12.3 Hz, H-60), 4.69 (m, 1H, H-50), 4.59 (br s, 1H, H-1),
0
4.48 (dd, 1H, J6,5 3.8 Hz, H-60), 4.38 (m, 1H, OCH), 4.11 (m, 1H,
0
OCH), 3.99 (dd, 1H, H-3), 3.86 (dd, 1H, J6,5 6.1, J6;6 11.6 Hz, H-6),
4.19.1. Allyl 2,3,4,6-tetra-O-benzoyl-
(1?2)-3,4-di-O-acetyl-6-O-tert-butyldiphenylsilyl-a-D-
mannopyranoside 19
a
-
D
-mannopyranosyl-
3.71 (dd, 1H, J6,5 2.3 Hz, H-6), 3.39 (m, 1H, H-5), 2.35 (s, 3H, Ac),
2.03 (s, 3H, Ac), 1.08 (s, 9H, Me3C). 13C NMR d: 171.0 (C@O),
169.8 (C@O), 166.1 (C@O), 165.5 (C@O), 165.3 (C@O), 165.2
(C@O), 117.9 (@CH2), 98.7 (C-10), 97.2 (C-1), 76.5 (C-3), 75.5 (C-
5), 70.8 (C-20), 70.6 (C-2), 69.8 (OCH2), 69.6 (C-50), 69.2 (C-30),
68.5 (C-4), 66.5 (C-40), 63.1 (C-6), 62.5 (C-60), 26.7 (Me3C), 21.1
(Ac), 20.6 (Ac), 19.2 (CSi). HRMS-ESI calcd for C63H64NaO17Si
(M+Na)+: 1143.3805, found: 1143.3843. Anal. Calcd for
C63H64O17Siꢀ3H2O: C, 64.38; H, 6.00. Found: C, 64.36; H, 5.54.
As a foam. ½a 2D0
ꢂ
¼ ꢁ23:2 (c 0.5, chloroform). 1H NMR d: 6.12 (t,
1H, J4,3 = J4,5 = 10.1 Hz, H-40), 5.93 (dd, 1H, J3,2 3.3 Hz, H-30), 5.86 (m,
1H, @CH), 5.74 (dd, 1H, J2,1 1.9Hz, H-20), 5.36 (dd, 1H, J3,2 3.3, J3,4
9.5 Hz, H-3), 5.32 (t, 1H, J4,3 = J4,5 = 9.4 Hz, H-4), 5.27 (m, 1H,
@CHH), 5.20 (m, 2H, H-10, @CHH), 5.07 (d, 1H, J1,2 1.9 Hz, H-1),
4.67 (dd, 1H, J6,5 2.5, J6;6 12.1 Hz, H-60), 4.58 (m, 1H, H-50), 4.50
0
(dd, 1H, J6 ;5 4.7 Hz, H-60), 4.23 (m, 1H, OCHH), 4.18 (dd, 1H, H-2),
0
3.92 (m, 3H, H-5, 6, OCHH), 3.75 (m, 1H, H-6), 2.14 (s, 3H, CH3),
1.86 (s, 3H, CH3), 1.11 (s, 9H, 3 ꢃ CH3). 13C NMR d: 170.6 (C@O),
169.3 (C@O), 166.1 (C@O), 165.6 (C@O), 165.2 (C@O), 165.0
(C@O), 117.7 (@CH2), 99.6 (C-10), 97.4 (C-1), 77.4 (C-2), 71.8 (C-
5), 70.6 (C-3), 70.5 (C-20), 69.5 and 69.5 (C-30, 50), 68.0 (OCH2),
4.19.5. Benzyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-
(1?3)-2,4-di-O-acetyl-6-O-tert-butyldiphenylsilyl-a-D-
mannopyranoside 31
As a foam. ½a 2D0
ꢂ
¼ ꢁ3:0 (c 0.6, CHCl3). 1H NMR d: 6.14 (t, 1H,
J4,3 = J4,5 = 10.1 Hz, H-40), 5.78 (dd, 1H, J3,2 3.2 Hz, H-30), 5.44 (m,

P. Cmoch, Z. Pakulski / Tetrahedron: Asymmetry 19 (2008) 1494–1503
1503
2H, H-2, 20), 5.42 (t, 1H, J4,3 = J4,5 = 9.8 Hz, H-4), 5.29 (d, 1H, J1,2
References
1.7 Hz, H-10), 4.92 (d, 1H, J1,2 1.6 Hz, H-1), 4.73 and 4.53 (ABq,
2H, J 11.9 Hz, OCH2), 4.66 (dd, 1H, J6,5 2.4, J6;6 12.3 Hz, H-60), 4.58
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0
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3.4 Hz, H-3), 3.83 (m, 2H, H-5,6), 3.68 (m, 1H, H-6), 2.29 (s, 3H,
CH3), 2.05 (s, 3H, CH3), 1.10 (s, 9H, 3 ꢃ CH3). 13C NMR d: 170.6
(C@O), 170.0 (C@O), 166.2 (C@O), 165.5 (C@O), 165.3 (C@O),
165.3 (C@O), 98.8 (C-10), 96.1 (C-1), 75.2 (C-3), 72.1 (C-5), 71.1
(C-2 or C-20), 70.8 (C-2 or C-20), 69.5 (C-50), 69.3 (C-30),
68.8 (OCH2), 68.1 (C-4), 66.5 (C-40), 63.0 (C-6), 62.6 (C-60), 26.8
(3 ꢃ CH3), 21.0 (CH3), 20.7 (CH3), 19.2 (SiC). HRMS-ESI calcd
for C67H66NaO17Si [M+Na]+: 1193.3962, found: 1193.3973. Anal.
Calcd for C67H66O17Siꢀ3H2O: C, 65.67; H, 5.92. Found: C, 65.81; H,
5.49.
4.19.6. Allyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-
(1?4)-2,3-di-O-acetyl-6-O-tert-butyldiphenylsilyl-a-D-
mannopyranoside 34
As a foam. ½a 2D0
ꢂ
¼ þ8:0 (c 0.4, chloroform). 1H NMR d: 6.12 (t,
1H, J4,3 = J4,5 = 10.2 Hz, H-40), 5.94 (m, 1H, @CH), 5.78 (dd, 1H, J3,2
3.2 Hz, H-30), 5.61 (dd, 1H, H-20), 5.48 (dd, 1H, J3,2 3.3, J3,4 9.9 Hz,
H-3), 5.42 (d, 1H, J1,2 1.8 Hz, H-10), 5.34 (m, 2H, H-2, @CHH), 5.25
(m, 1H, @CHH), 4.89 (d, 1H, J1,2 1.5 Hz, H-1), 4.31 (m, 2H, H-4,
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301; (b) Garegg, P. J.; Maloisel, J.-L.; Oscarson, S. Synthesis 1995, 409–414; (c)
Nicolaou, K. C.; van Delft, F. L.; Conley, S. R.; Mitchell, H. J.; Jin, Z.; Rodríguez, R.
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60), 4.21 (m, 2H, H-50, OCHH), 4.16 (dd, 1H, J6,5 4.6, J6;6 11.3 Hz,
0
H-6), 4.02 (m, 3H, H-6, 60, OCHH), 3.92 (m, 1H, H-5), 2.15 (s, 3H,
CH3), 2.10 (s, 3H, CH3), 1.09 (s, 9H, tBu). 13C NMR d: 170.3 (C@O),
170.0 (C@O), 165.9 (C@O), 165.3 (C@O), 165.3 (C@O), 165.2
(C@O), 118.2 (@CH2), 99.5 (C-10), 96.2 (C-1), 73.9 (C-4), 72.1 (C-
5), 71.6 (C-3), 70.5 (C-20), 70.1 (C-2), 69.9 (C-50), 69.6 (C-30), 68.2
(OCH2), 66.2 (C-40), 63.1 (C-6), 62.2 (C-60), 26.8 (tBu), 20.9 (CH3),
20.8 (CH3), 19.3 (CSi). Anal. Calcd for C63H64O17SiꢀH2O: C, 66.42;
H, 5.84. Found: C, 66.85; H, 5.80.
4.19.7. Benzyl 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl-
(1?4)-2,3-di-O-acetyl-6-O-tert-butyldiphenylsilyl-a-D-
mannopyranoside 39
8. (a) Oshima, K.; Aoyama, Y. J. Am. Chem. Soc. 1999, 121, 2315–2316; (b) Oshima,
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2002, 75, 1319–1324.
As a foam. ½a 2D0
ꢂ
¼ þ16:7 (c 0.4, chloroform). 1H NMR d: 6.12 (t,
1H, J4,3 = J4,5 = 10.1 Hz, H-40), 5.78 (dd, 1H, J3,2 3.2 Hz, H-30), 5.62 (m,
1H, H-20), 5.51 (dd, 1H, J3,2 3.3, J3,4 9.9 Hz, H-3), 5.41 (d, 1H, J1,2
1.9 Hz, H-10), 5.39 (dd, 1H, J2,1 1.8 Hz, H-2), 4.88 (d, 1H, H-1),
4.75 and 4.57 (ABq, 2H, J 12.0 Hz, OCH2Ph), 4.32 (m, 2H, H-4, 60),
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16. Marwood, R. D.; Riley, A. M.; Jenkins, D. J.; Potter, B. V. L. J. Chem. Soc., Perkin
Trans. 1 2000, 1935–1947.
4.20 (m, 1H, H-50), 4.16 (dd, 1H, J6,5 4.7, J6;6 11.3 Hz, H-6),
0
4.00 (m, 2H, H-6, 60), 3.93 (m, 1H, H-5), 2.15 (s, 3H, CH3), 2.08 (s,
3H, CH3), 1.10 (tBu). 13C NMR d: 170.3 (C@O), 170.0 (C@O),
165.9 (C@O), 165.3 (C@O), 165.2 (2 ꢃ C@O), 99.5 (C-10), 96.1
(C-1), 73.9 (C-4), 72.2 (C-5), 71.6 (C-3), 70.5 (C-20), 70.0 (C-2),
69.9 (C-50), 69.6 (C-30), 68.9 (OCH2Ph), 66.2 (C-40), 63.0 (C-60),
62.2 (C-6), 26.8 (tBu), 20.9 (CH3), 20.8 (CH3), 19.3 (SiC). Anal.
Calcd for C67H66O17SiꢀH2O: C, 67.66; H, 5.76. Found: C, 67.87; H,
5.72.
Acknowledgement
This work was financed by the Grant No. PBZ-KBN-126/T09/07
from the Ministry of Science and Higher Education, Poland.
17. Dziewiszek, K.; Zamojski, A. Carbohydr. Res. 1986, 150, 163–171.