Efficient and practical syntheses of three pentasaccharides core structures corresponding to N-glycans

Article abstract of DOI:10.1016/S0040-4020(00)01161-3

Three branched pentasaccharide derivatives and one tetrasaccharide were synthesized efficiently. The advantages of this method include a one-pot facile synthesis of 3,6-differentially protected mannose building block and an efficient strategy for oligosac

Full text of DOI:10.1016/S0040-4020(00)01161-3

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 1757±1763
Ef®cient and practical syntheses of three pentasaccharides core
structures corresponding to N-glycans
Yuguo Du, Meimei Zhang and Fanzuo Kongp
Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, Beijing 100085,
People's Republic of China
Dedicated to Professor Joachim Thiem on the occasion of his 60th birthday
Received 11 September 2000; revised 4 December 2000; accepted 14 December 2000
AbstractÐThree branched pentasaccharide derivatives and one tetrasaccharide were synthesized ef®ciently. The advantages of this method
include a one-pot facile synthesis of 3,6-differentially protected mannose building block and an ef®cient strategy for oligosaccharide
assembly. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
remains a highly specialized and time consuming task. We
present here, a very ef®cient and practical method4 for the
synthesis of 3,6-branched oligosaccharide moieties that
occur in most complex N-glycans.
Asparagine-linked glycoprotein oligosaccharides play a
vital role in fundamental biological processes such as cell
differentiation, malignant transformation, viral, bacterial
and parasitic infections and protein transportations.1 They
are usually divided into three major subgroups, i.e. high-
mannose type, complex type and hybrid type, and each of
them may consist of diverse structures in living cells.2
Pentasaccharides A, B, C (Fig. 1) are typical sub-structures
corresponding to the aforementioned three different types of
N-glycan, respectively. Obviously, they are the bases for the
synthesis of advanced N-glycans. Intensive research into the
biological role of these carbohydrates and related glyco-
conjugates has led to an increased need for the practical
synthesis of these core structures. Although remarkable
progress has been made in the ®eld of N-glycan synthesis,3
further innovations are still required since the synthesis
2. Results and discussion
To supply enough samples for glycobiology studies on the
relationship between N-glycans and diseases, we have been
seeking practical methods for the synthesis of N-glycan core
structures. Scheme 1 depicts the synthesis of key synthon 2
via a one-pot manner. The transformation of allyl a-d-
mannopyranoside (1) into allyl 2,4-di-O-benzoyl-3-O-tert-
butyldimethylsilyl-6-O-triphenylmethyl-a-d-mannopyrano-
side (2) was successfully achieved through three sequential
reactions. Thus, 1 was selectively tritylated with triphenyl-
methyl chloride (TrCl, 1.25 equiv.) in pyridine at 808C for
Figure 1.
Keywords: carbohydrates; glycosylations; glycopeptides.
Corresponding author. Tel.: 186-10-629-366-13; fax: 186-10-629-235-63; e-mail: fzkong@mail.rcees.ac.cn
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)01161-3

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Y. Du et al. / Tetrahedron 57 (2001) 1757±1763
Scheme 1. Regioselective synthesis of versatile building block 2. Reaction conditions: (a) TrCl, Py, DMAP; TBSCl in DMF; BzCl in Py, 79% in one-pot;
(b) 90% TFA, 91%; (c) TBAF, THF, 66%; (d) FeCl3´6H2O, CH2Cl2, 88%.
16 h, then cooled down to 08C. This mixture was treated
with 2 equiv. of imidazole, and ®nally 1.1 equiv. of tert-
butylchlorodimethylsilane (TBDMSCl) in DMF was
added into the reaction ¯ask portion by portion during 2 h.
The mixture was stirred at rt overnight, then premixed
benzoyl chloride (2.5 equiv.) and pyridine was added. The
reaction mixture was stirred at 508C overnight to afford
compound 2 in 79% overall yield.
asymmetrical (C-3 and C-6 linked by non-identical sugar
residues) trisaccharide core structure. Treatment of
compound 2 with 90% tri¯uoroacetic acid (TFA)5 gave
diol 3 in 91% yield which could be used for the synthesis
of symmetrical analogs (see Scheme 2). When 2 was treated
with tetrabutylammonium ¯uoride in tetrahedrofuran
(THF),6 3-OH derivative 4 was obtained in 66% yield,
and 4 could be used to synthesize 1 ! 3 linked structure
(see Scheme 3). Treatment of 2 with ferric chloride hexa-
hydrate (FeCl3´6H2O)7 afforded 5 (88%) as a useful
synthon for the synthesis of 1 ! 6 linked structure (see
Scheme 4).
It is noteworthy that 2 could be easily transformed into a
suitable acceptor for the synthesis of either symmetrical
(C-3 and C-6 connected with identical sugar residues) or
Scheme 2. Synthesis of pentasaccharides 10 and 12. Reaction conditions: (a) TMSOTf, CH2Cl2, 08C, 80% (for 7); 82% (for 10); 50% (for 12); (b) 5% HCl
(gas) in MeOH±CH2Cl2 (1:1), 78%.

Y. Du et al. / Tetrahedron 57 (2001) 1757±1763
1759
Scheme 3. Synthesis of pentasaccharide 16. Reaction conditions: (a) TMSOTf, CH2Cl2, 08C, 85%; (b) PdCl2, NaOAc, 90% HOAc, then CCl3CN, DBU, 83%
(2 steps); (c) TMSOTf, CH2Cl2, 2158C, then TMSOTf (50 mL), rt, 80%; (d) TMSOTf, CH2Cl2, 08C, 85%.
Scheme 4. Synthesis of asymmetrical tetrasaccharide 20. Reaction conditions: (a) TMSOTf, CH2Cl2, 08C, 84%; (b) 5% HCl (gas) in MeOH±CH2Cl2 (1:1),
70%; (c) 2.2 equiv. of 6, TMSOTf, CH2Cl2, 08C, 73%.
Pentasaccharide 10 or 12 consists of three differently linked
sugar residues, which necessitates a corresponding protec-
tive group pattern for these building blocks. Previous
research focused on the use of benzyl ether as hydroxyl
protection group. However, readily removable acyl groups
are generally more attractive. We chose acetyl as a
temporary protective group and benzoyl as a permanent
one. Coupling of diol 3 with 2.1 equiv. of 2-O-acetyl-
3,4,6-tri-O-benzoyl-a-d-mannopyranosyl 2,2,2 trichloro-
acetimidate (6) in anhydrous CH2Cl2 using TMSOTf as
catalyst gave symmetrical trisaccharide 7 in 80% yield.
Selective deacetylation8 of 7 in the presence of benzoyl
groups was carried out smoothly using 5% HCl (gas) in
methanol±CH2Cl2 (1:1) co-solvent to give deacetylated
trisaccharide 8 in 78% yield. Glycosylation of trisaccharide
diol 8 with donor 9 under the same reaction conditions as
described in the preparation of 7 furnished pentasaccharide
10 in 82% yield. Similarly, coupling of 8 with 2.5 equiv. of
3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-a-d-glucopyranosyl
2,2,2 trichloroacetimidate (11) afforded pentasaccharide 12
in 50% yield, together with some unidenti®ed tetra-
saccharides. The quick consumption of the donor 11 may
be responsible for the low yield in this reaction.
equiv.) as catalyst gave trisaccharide 13 in 85% yield.
Deallylation on 13 with PdCl2 (2 equiv.) and NaOAc
(4 equiv.) in 90% aqueous acetic acid,9 followed by
anomeric Schmidt activation10 with trichloroactonitrile
furnished trisaccharide donor 14 in 83% yield (2 steps).
Convergently, coupling of donor 9 with acceptor 4 was
accomplished in 40 min using TMSOTf (0.1 equiv.) as
catalyst at 2158C. Tri¯uoacetic acid (TFA, 1 mL) or more
TMSOTf was added into this reaction mixture and the
mixture was stirred at room temperature for 2 h to afford
disaccharide acceptor 15 in one-pot (80%). Trisaccharide
donor 14 and disaccharide acceptor 15 were treated under
the same glycosylation conditions affording pentasaccharide
16 in 85% yield. Coupled 13C NMR spectrum of 10, 13 and
1
16 showed all JC-1,H-1 values in a range 170±173 Hz, indi-
cating the a-linkage of mannose residues in them.
Mono-hydroxyl acceptor 17 was synthesized starting from
its corresponding methyl a-d-mannopyranoside using the
same procedure as described in the preparation of 5.
TMSOTf promoted coupling reaction of 17 with donor 6
in anhydrous CH2Cl2 at 08C afforded disaccharide 18 in
84% yield. Simultaneous desilylation and deacetylation of
18 in the presence of benzoyl groups was carried out using
5% HCl (gas) in methanol±CH2Cl2 (1:1) co-solvent giving
disaccharide diol 19 in 70% yield. Further glycosylation of
diol 19 with donor 6 under the same reaction conditions
furnished asymmetrical tetrasaccharide 20 in 73% yield.
Pentasaccharide 16, which contains both 1 ! 3 and 1 ! 6
linkages, best exhibits the advantages of our synthetic
strategy. Coupling of diol 3 with trichloroacetimidate 9
(2.1 equiv.) in anhydrous CH2Cl2 using TMSOTf (10%

1760
Y. Du et al. / Tetrahedron 57 (2001) 1757±1763
25
91%); [a]D ˆ226 (c 1, CHCl3); nmax (liquid ®lm): 3443,
3. Experimental
2925, 1608; dH (400 MHz, CDCl3) 3.74 (dd, 1H, J5,6a
ˆ
4.1 Hz, J6a,6bˆ12.6 Hz, H-6a), 3.81 (dd, 1H, J5,6bˆ2.3 Hz,
J6a,6bˆ12.6 Hz, H-6b), 3.98 (ddd, 1H, J5,6bˆ2.3 Hz,
J5,6aˆ4.1 Hz, J4,5ˆ9.9 Hz, H-5), 4.09 (m, 1H, CH2vCH±
CH2±), 4.26 (m, 1H, CH2vCH±CH2±), 4.46 (dd, 1H,
J2,3ˆ3.5 Hz, J3,4ˆ9.9 Hz, H-3), 5.10 (d, 1H, J1,2ˆ1.6 Hz,
H-1), 5.25±5.34 (m, 2H, CH2vCH±CH2±), 5.43 (dd, 1H,
J2,3ˆ3.5 Hz, J1,2ˆ1.6 Hz, H-2), 5.51 (t, 1H, J3,4ˆ9.9 Hz,
J4,5ˆ9.9 Hz, H-4), 5.91±5.96 (m, 1H, CH2vCH±CH2±),
7.25±8.10 (m, 10H, Ph). Anal. Calcd for C23H24O8: C,
64.48; H, 5.61. Found: C, 64.40; H, 5.66.
3.1. General methods
Optical rotations were determined at 258C with a Perkin±
Elmer Model 241-Mc automatic polarimeter. Melting points
1
were determined with a `Mel-Temp' apparatus. H NMR,
1
1
13C NMR and H±1H COSY and H±13C COSY spectra
were recorded with Bruker ARX 400 spectrometers for
solutions in CDCl3. Chemical shifts are given in ppm down-
®eld from internal Me4Si. Mass spectra were measured
using MALTI±TOF±MS with CCA as matrix or recorded
with a VG PLATFORM mass spectrometer using the ESI
technique to introduce the sample. IR spectra were recorded
with a Hitachi 270-30 spectrometer. Thin-layer chromato-
graphy (TLC) was performed on silica gel HF254 with detec-
tion by charring with 30% (v/v) H2SO4 in MeOH or in some
cases by a UV detector. Column chromatography was
3.1.3. Allyl 2-O-acetyl-3,4,6-tri-O-benzoyl-a-d-manno-
pyranosyl-ꢀ1 ! 3†-[2-O-acetyl-3,4,6-tri-O-benzoyl-a-d-
mannopyranosyl-ꢀ1 ! 6†Š-2,4-di-O-benzoyl-a-d-manno-
pyranoside (7). To a cooled solution (08C) of 3 (2.1 g,
4.91 mmol) and 6 (6.99 g, 10.3 mmol) in anhydrous
CH2Cl2 (80 mL) was added TMSOTf (40 mL, 0.22 mmol).
The mixture was stirred at this temperature for 2 h, and then
quenched with Et3N (2 drops). The solvents were evapo-
rated in vacuo to give a residue, which was puri®ed by silica
gel column chromatography (petroleum ether±EtOAc,
1.5:1) to give trisaccharide 7 as a syrup (5.73 g, 80%);
conducted by elution of
a
column (16£240 mm2,
18£300 mm2, 35£400 mm2) of silica gel (100±200 mesh)
with EtOAc±petroleum ether (60±908C) as the eluent.
Solutions were concentrated at ,608C under reduced
pressure.
25
[a]D ˆ212 (c 1, CHCl3); nmax (liquid ®lm): 3442, 2926,
3.1.1. Allyl 2,4-di-O-benzoyl-3-O-tert-butyldimethylsilyl-
6-O-triphenylmethyl-a-d-mannopyranoside (2). To a
solution of allyl a-d-mannopyranoside (1) (2.2 g,
10 mmol) in pyridine (15 mL) was added TrCl (3.5 g,
12.5 mmol) and catalytic amount of 4-dimethylaminopyri-
dine (DMAP). The mixture was stirred at 808C for 16 h, then
cooled down to 08C. To the above reaction mixture was
added imidazole (1.36 g, 20 mmol) in one portion. A solu-
tion of TBDMSCl (1.66 g, 11 mmol) in DMF (5 mL) was
®nally added portion by portion during 2 h. The mixture was
stirred at rt overnight, then a premixed solution of benzoyl
chloride (2.9 mL, 25 mmol) and pyridine (3 mL) was added.
The reaction mixture was stirred at 508C overnight, and then
poured into ice-cold water, extracted with EtOAc. The
organic phase was concentrated to dryness by repeating
co-evaporation with toluene. The residue was subjected to
column chromatography on silica gel with petroleum ether±
EtOAc as the eluent (12:1) to give 2 as a syrup (6.19 g,
1730, 1452, 1270, 1110, 1070, 711 cm21; dH (400 MHz,
CDCl3) 1.882, 2.095 (2s, 6H, 2CH3CO), 3.726 (dd, 1H,
J5,6aˆ1.8 Hz, J6a,6bˆ10.6 Hz, H-6aA), 4.080±4.190 (m, 2H,
H-6bA, one proton of CH2vCH±CH2±), 4.285 (ddd, 1H,
J5,6aˆ1.8 Hz, J5,6bˆ3.5 Hz, J4,5ˆ9.7 Hz, 1H, H-5A),
4.300±4.550 (m, 7H, H-5B,C, 2£H-6B,C, one proton of
CH2vCH±CH2±), 4.617 (dd, 1H, J2,3ˆ3.3 Hz, J3,4ˆ
9.7 Hz, H-3A), 4.979 (d, 1H, J1,2ˆ1.6 Hz, H-1B), 5.110±
5.130 (m, 2H, H-1A, H-2C), 5.189 (d, 1H, J1,2ˆ1.8 Hz,
H-1C), 5.290±5.507 (m, 2H, CH2vCH±CH2±), 5.513 (dd,
1H, J1,2ˆ1.6 Hz, J2,3ˆ2.9 Hz, H-2B), 5.582 (dd, 1H,
J2,3ˆ3.3 Hz, J3,4ˆ9.8 Hz, H-3C), 5.690 (dd, 1H, J1,2ˆ
1.6 Hz, J2,3ˆ3.6 Hz, H-2A), 5.793 (t, 1H, J3,4ˆ9.8 Hz,
J4,5ˆ9.8 Hz, H-4C), 5.841 (t, 1H, J3,4ˆ9.7 Hz, J4,5ˆ9.7 Hz,
H-4A), 5.865±5.890 (m, 3H, H-3B, H-4B, CH2vCH±CH2±),
7.252±8.093 (m, 40H, Ph). Anal. Calcd for C81H72O26: C,
66.58; H, 4.93. Found: C, 66.61; H, 4.94.
25
79%); [a]D ˆ231 (c 1, CHCl3); nmax (liquid ®lm): 2932,
3.1.4. Allyl 3,4,6-tri-O-benzoyl-a-d-mannopyranosyl-
ꢀ1 ! 3†-[3,4,6-tri-O-benzoyl-a-d-mannopyranosyl-
ꢀ1 ! 6†Š-2,4-di-O-benzoyl-a-d-mannopyranoside (8). To
a cooled solution (08C) of 7 (720 mg, 0.49 mmol) in CH2Cl2
(10 mL) and MeOH (10 mL) was added acetyl chloride
(1 mL). The mixture was stirred at rt overnight, then diluted
with CH2Cl2 (200 mL), neutralized with Et3N and washed
with water. The organic phase was dried over anhydrous
Na2SO4 and concentrated. The residue was puri®ed on a
silica gel column using EtOAc±petroleum ether (1:2) as
1734, 1602; dH (400 MHz, CDCl3) 20.15, 0.04 (2s, 2£3H,
(CH3)2Si), 0.62, (s, 9H, t-Bu), 3.75 (dd, 1H, J5,6aˆ1.8 Hz,
J6a,6bˆ11.2 Hz, H-6a), 3.84 (dd, 1H, J5,6bˆ5.3 Hz, J6a,6b
ˆ
11.2 Hz, H-6b), 3.98 (ddd, J5,6aˆ1.8 Hz, J5,6bˆ5.3 Hz,
J4,5ˆ9.9 Hz,1H, H-5), 4.09 (m, 1H, CH2vCH±CH2±),
4.28 (m, 1H, CH2vCH±CH2±), 4.38 (dd, 1H, J2,3ˆ
3.5 Hz, J3,4ˆ9.4 Hz, H-3), 5.03 (d, 1H, J1,2ˆ1.4 Hz, H-1),
5.24±5.36 (m, 2H, CH2vCH±CH2±), 5.40 (dd, J1,2ˆ
1.4 Hz, J2,3ˆ3.5 Hz, 1H, H-2), 5.73 (dd, 1H, J3,4ˆ9.4 Hz,
J4,5ˆ9.9 Hz, H-4), 5.91±5.96 (m, 1H, CH2vCH±CH2±),
7.20±8.30 (m, 25H, Ph). Anal. Calcd for C48H52O8Si: C,
73.47; H, 6.63. Found: C, 73.51; H, 6.58.
25
the elutant giving 8 as a syrup (526 mg, 78%); [a]D ˆ26
(c 1, CHCl3); nmax (liquid ®lm): 3444, 2960, 1731, 1603; dH
(400 MHz, CDCl3) 2.300±2.500 (br d, 2H, 2OH), 3.797 (dd,
1H, J5,6aˆ1.2 Hz, J6a,6bˆ10.8 Hz, H-6aA), 4.05±4.460 (m,
12H, H-6bA, H-2B,C, CH2vCH±CH2±, H-5A,B,C, 2£H-
3.1.2. Allyl 2,4-di-O-benzoyl-a-d-mannopyranoside (3).
Compound 2 (2.5 g, 3.19 mmol) was dissolved into 90%
aqueous TFA (15 mL) and the solution was stirred at rt
for 4 h. Toluene (50 mL) was added and then the solvents
were evaporated in vacuo to give a residue, which was
puri®ed by silica gel column chromatography (petroleum
ether±EtOAc, 1:1) to give 3 as a white foam (1.24 g,
6
B,C), 4.618 (dd, 1H, J2,3ˆ3.4 Hz, J3,4ˆ8.7 Hz, H-3A),
5.070 (bs, 1H, H-1B), 5.154 (d, 1H, J1,2ˆ2.0 Hz, H-1A),
5.229 (bs, 1H, H-1C), 5.260±5.440 (m, 2H, CH2vCH±
CH2±), 5.450 (dd, 1H, J2,3ˆ3.1 Hz, J3,4ˆ9.7 Hz, H-3C),
5.673 (dd, 1H, J1,2ˆ2.0 Hz, J2,3ˆ3.4 Hz, H-2A), 5.714 (dd,

Y. Du et al. / Tetrahedron 57 (2001) 1757±1763
1761
1H, J2,3ˆ3.1 Hz, J3,4ˆ10.0 Hz, H-3B), 5.841 (t, 1H,
J3,4ˆ9.7 Hz, J4,5ˆ9.7 Hz, H-4C), 5.865 (t, 1H, J3,4ˆ
10.0 Hz, J4,5ˆ10.0 Hz, H-4B), 5.930 (t, 1H, J3,4ˆ8.7 Hz,
J4,5ˆ8.7 Hz, H-4A), 5.955 (m, 1H, CH2vCH±CH2±),
7.258±8.201 (m, 40H, Ph). Anal. Calcd for C77H68O24: C,
67.15; H, 4.94. Found: C, 67.09; H, 4.99.
(400 MHz, CDCl3) 1.780, 1.821, 1.834, 1.852, 1.964,
1.974 (6s, 6£3H, 6CH3CO), 3.370 (dd, 1H, J5,6aˆ1.6 Hz,
J6a,6bˆ11.4 Hz, H-6aA), 3.529 (dd, 1H, J5,6bˆ3.7 Hz,
J6a,6bˆ11.4 Hz, H-6bA), 3.631 (dd, 1H, J5,6ˆ1.1 Hz,
J6a,6bˆ10.8 Hz, H-6), 3.620±3.690 (m, 2H, H-6), 3.702±
3.780 (m, 2H, H-5, H-6), 3.800 (dd, 1H, J5,6ˆ3.8 Hz,
J6a,6bˆ10.8 Hz, H-6), 3.900 (dd, 1H, J5,6ˆ3.7, J6a,6b
ˆ
3.1.5. Allyl 2,3,4,6-tetra-O-benzoyl-a-d-mannopyrano-
syl-ꢀ1 ! 2†-3,4,6-tri-O-benzoyl-a-d-mannopyranosyl-
ꢀ1 ! 6†-[2,3,4,6-tetra-O-benzoyl-a-d-mannopyranosyl-
ꢀ1 ! 2†-3,4,6-tri-O-benzoyl-a-d-mannopyranosyl-ꢀ1 ! 3†Š-
2,4-di-O-benzoyl-a-d-mannopyranoside (10). To a cooled
solution (08C) of 8 (200 mg, 0.14 mmol) and 9 (290 mg,
0.39 mmol) in anhydrous CH2Cl2 (7 mL) was added
TMSOTf (5 mL, 0.028 mmol). The mixture was stirred at
this temperature for 2 h, and then quenched with Et3N (1
drop). The solvents were evaporated in vacuo to give a
residue, which was puri®ed by silica gel column chromato-
graphy twice (petroleum ether±EtOAc, 2:1 and toluene±
petroleum ether±EtOAc, 0.75:1.5:1.0) to give pentasaccharide
11.0 Hz, H-6), 3.995 (dd, 1H, J1,2,1.0 Hz, J2,3ˆ3.2 Hz,
H-2C), 4.050±4.260 (m, 6H, H-2E, H-5A,C,D,E, 2H-6) 4.269
(m, 1H, H-5B), 4.350±4.437 (m, 3H, H-3A, CH2vCH±
CH2±), 4.462 (dd, 1H, J1,2,1.0 Hz, J2,3ˆ3.4 Hz, H-2B),
4.627 (d, 1H, J1,2,1.0 Hz, H-1B), 4.688 (d, 1H, J1,2
8.5 Hz, H-1E), 4.795 (t, J1,2ˆ8.9 Hz, J2,3ˆ8.9 Hz, H-2D),
4.914 (s, 1H, H-1C), 5.011 (t, 1H, J3,4ˆ8.7 Hz,
J4,5ˆ8.7 Hz, H-4E), 5.070 (d, 1H, J1,2,1 Hz, H-1A), 5.163
(dd, 1H, J2,3ˆ3.2 Hz, J3,4ˆ10.1 Hz, H-3C), 5.300±5.480 (m,
4H, J1,2ˆ8.8 Hz, J3,4ˆ9.8 Hz, H-1D, H-4D, CH2vCH±
CH2±), 5.493 (t, 1H, J3,4ˆ10.1 Hz, J4,5ˆ10.1 Hz, H-4C),
5.520 (dd, 1H, J1,2,1 Hz, J2,3ˆ3.2 Hz, H-2A), 5.555 (dd,
1H, J2,3ˆ3.4 Hz, J3,4ˆ9.2 Hz, H-3B), 5.677 (t, 1H, J3,4ˆ
10.4 Hz, J4,5ˆ10.4 Hz, H-4A), 5.701 (t, 1H, J2,3ˆ9.3 Hz,
J3,4ˆ9.3 Hz, H-3D), 5.783 (t, 1H, J2,3ˆ10.3 Hz, J3,4ˆ
10.3 Hz, H-3E), 5.900±6.000 (m, 1H, CH2vCH±CH2±),
7.250±8.307 (m, 48H, Ph). dC (100 MHz, CDCl3) 96.60
(1JC-1,H-1ˆ170 Hz), 98.20 (1JC-1,H-1ˆ173 Hz), 98.50
(1JC-1,H-1ˆ162 Hz), 99.10 (1JC-1,H-1ˆ165 Hz), 99.40
(1JC-1,H-1ˆ174 Hz). MALDI-TOF MS: M1Na calcd: 2233,
found: 2233.99; Anal. Calcd for C117H106N2O42: C, 63.53;
H, 4.80. Found: C, 63.47; H, 4.76.
25
10 as white solid (290 mg, 82%); [a]D ˆ249 (c 1, CHCl3);
n
max (liquid ®lm): 3440, 2958, 1730, 1603, 1452, 1270, 1110,
1071; dH (400 MHz, CDCl3) 3.647 (dd, 1H, J5,6a,1 Hz,
J6a,6bˆ10.4 Hz, H-6aA), 3.987 (dd, 1H, J5,6bˆ5.0 Hz,
J6a,6bˆ10.4 Hz, H-6bA), 4.032 (bs, 1H, H-2C), 4.179±4.230
(m, 3H, H-5A, Jˆ5.1 Hz, 12.0 Hz, 2H-6), 4.319 (bs, 1H,
H-2B), 4.320±4.500 (m, 6H), 4.502 (s, 1H, H-1E), 4.505±
4.635 (m, 6H), 4.640 (dd, 1H, J2,3ˆ2.5 Hz, J3,4ˆ9.9 Hz,
H-3A), 5.090 (s, 1H, H-1D), 5.184 (s, 1H, H-1A), 5.205 (s,
1H, H-1B), 5.312, 5.550 (2dd, 2H, Jˆ1.2 Hz, 11.2, 16.8 Hz,
CH2vCH±CH2±), 5.481 (s, 1H, H-1C), 5.563 (bs, 1H, H-2E),
5.688 (dd, J2,3ˆ2.1 Hz, J3,4ˆ10.6 Hz, H-3C), 5.741 (bs, 1H,
H-2A), 5.825 (s, 1H, H-2D), 5.827±6.005 (m, 8H, H-4A, H-3E,
H-4E, H-4C, H-3B, H-4B, H-3D, CH2vCH±CH2±), 6.095 (t,
1H, J3,4ˆ10.1 Hz, J4,5ˆ10.1 Hz, H-4D), 7.245±8.140 (m, 80H,
Ph). dC (100 MHz, CDCl3) 166.31, 166.19 (2C), 166.00,
165.94, 165.57, 165.50, 165.35, 165.27, 165.23, 165.03,
164.94, 164.88, 164.83, 164.80, 164.51 (16PhCO), 118.89
(CH2vCH±CH2±), 100.00, 99.72, 99.39, 98.21, 96.66 (5C-
3.1.7. Allyl 2,3,4,6-tetra-O-benzoyl-a-d-mannopyrano-
syl-ꢀ1 ! 3†-[2,3,4,6-tetra-O-benzoyl-a-d-mannopyrano-
syl-ꢀ1 ! 6†Š-2,4-di-O-benzoyl-a-d-mannopyranoside
(13). To a cooled solution (08C) of 3 (1.5 g, 3.5 mmol) and 9
(5.45 g, 7.36 mmol) in anhydrous CH2Cl2 (50 mL) was
added TMSOTf (25 mL, 0.14 mmol). The mixture was stir-
red at this temperature for 2 h, and then quenched with Et3N
(2 drops). The solvents were evaporated in vacuo to give a
residue, which was puri®ed by silica gel column chromato-
graphy (petroleum ether±EtOAc, 1.5:1) to give trisacchar-
1
1, JC-1,H-1ˆ169, 170, 170, 171, 173 Hz), 78.4, 77.47, 77.21,
25
75.21, 71.96, 70.57, 70.07, 69.89, 69.74 (3C), 69.63, 69.53,
69.47, 69.23, 68.70 (CH2vCH±CH2±), 68.75 (2C), 67.19,
67.13, 66.61, 66.37, 63.65, 63.50, 62.82, 62.62 (sugar
carbons). MALDI-TOF MS: M1Na calcd: 2555, found:
2555.62; Anal. Calcd for C145H120O42: C, 68.72; H, 4.94.
Found: C, 68.76; H, 4.88.
ide 13 as a syrup (4.72 g, 85%); [a]D ˆ2271 (c 1, CHCl3);
nmax (liquid ®lm): 3444, 2956, 1731, 1602, 1452, 1267,
1109, 1070, 710 cm21; dH (400 MHz, CDCl3) 3.80 (dd,
1H, J5,6,1 Hz, J6a,6bˆ9.1 Hz, H-6), 4.15±4.25 (m, 2H,
2H-6), 4.32±4.42 (m, 4H, H-5, 3H-6), 4.50±4.56 (m, 2H,
2H-5), 4.58±4.64 (m, 2H, CH2vCH±CH2±), 4.70 (dd, 1H,
J2,3ˆ3.2 Hz, J3,4ˆ11.0 Hz, H-3), 5.16 (d, 1H, J1,2ˆ1.4 Hz,
H-1), 5.20 (d, 1H, J1,2ˆ1.2 Hz, H-1), 5.30±5.35 (m, 1H,
CH2vCH±CH2±), 5.36±5.39 (m, 2H, H-1, H-2), 5.41±
5.50 (m, 1H, CH2vCH±CH2±), 5.76 (dd, 1H, J2,3ˆ
3.1 Hz, J3,4ˆ12 Hz, H-3), 5.77 (dd, 1H, J1,2ˆ1.6 Hz,
J2,3ˆ3.3 Hz, H-2), 5.79 (dd, 1H, J1,2ˆ1.8 Hz, J2,3ˆ3.1 Hz,
H-2), 5.94 (t, 1H, J3,4ˆ10.4 Hz, J4,5ˆ10.4 Hz, H-4), 6.00±
6.06 (m, 3H, H-3, H-4, CH2vCH±CH2±), 6.15 (t, 1H,
J3,4ˆ10.6 Hz, J4,5ˆ10.6 Hz, H-4), 7.25±8.17 (m, 50H,
Ph). dC (100 MHz, CDCl3) 166.14, 166.02, 165.99,
165.56, 165.41, 165.18, 165.11 (2C), 164.59, 164.57
(PhCO), 118.66 (CH2vCH±CH2±), 99.54, 97.43, 96.48
3.1.6. Allyl 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-b-
d-glucopyranosyl-ꢀ1 ! 2†-3,4,6-tri-O-benzoyl-a-d-manno-
pyranosyl-ꢀ1 ! 6†-[3,4,6-tri-O-acetyl-2-deoxy-2-phthal-
imido-b-d-glucopyranosyl-ꢀ1 ! 2†-3,4,6-tri-O-benzoyl-
a-d-mannopyranosyl-ꢀ1 ! 3†Š-2,4-di-O-benzoyl-a-d-
mannopyranoside (12). To a cooled solution (08C) of 8
(200 mg, 0.14 mmol) and 11 (208 mg, 0.36 mmol) in
anhydrous CH2Cl2 (5 mL) was added TMSOTf (3 mL,
0.016 mmol). The mixture was stirred at this temperature
for 2 h, and then quenched with Et3N (1 drop). The solvents
were evaporated in vacuo to give a residue, which was
puri®ed by silica gel column chromatography twice
(petroleum ether±EtOAc, 1.0:1 and toluene±petroleum
ether±EtOAc, 0.2:1.0:1.0) to give pentasaccharide 12 as a
1
(3C-1, JC-1,H-1ˆ170, 170, 173 Hz), 76.52, 71.87, 70.19,
70.13, 70.00, 69.68, 69.53, 69.27, 68.79, 68.71
(CH2vCH±CH2±), 68.45, 66.88, 66.53, 66.35, 62.57,
62.42. Anal. Calcd for C91H76O26: C, 68.94; H, 4.80.
Found: C, 68.97; H, 4.78.
25
syrup (167 mg, 50%); [a]D ˆ248 (c 1, CHCl3); nmax
(liquid ®lm): 3442, 2932, 1743, 1455, 1259; dH

1762
Y. Du et al. / Tetrahedron 57 (2001) 1757±1763
3.1.8.
2,3,4,6-Tetra-O-benzoyl-a-d-mannopyranosyl-
syl-ꢀ1 ! 3†Š-2,4-di-O-benzoyl-a-d-mannopyranosyl-
ꢀ1 ! 6†-[2,3,4,6-tetra-O-benzoyl-a-d-mannopyranosyl-
ꢀ1 ! 3†Š-2,4-di-O-benzoyl-a-d-mannopyranoside (16).
To a cooled solution (08C) of 14 (2 g, 1.18 mmol) and 15
(1.13 g, 1.12 mmol) in dry CH2Cl2 (15 mL) was added
TMSOTf (20 mL). The mixture was stirred at this tempera-
ture for 2 h, then neutralized with Et3N (2 drops), and
concentrated. The residue was puri®ed by silica gel column
chromatography to give 16 as a syrup (2.42 g, 85%);
ꢀ1 ! 3†-[2,3,4,6-tetra-O-benzoyl-a-d-mannopyranosyl-
ꢀ1 ! 6†Š-2,4-di-O-benzoyl-a-d-mannopyranosyl trichloro-
acetimidate (14). A solution of 13 (850 mg, 0.54 mmol) in
90% aqueous acetic acid (10 mL) was added NaOAc
(177 mg, 2.16 mmol) and PdCl2 (191 mg, 1.08 mmol).
The mixture was stirred at rt overnight and then neutralized
with saturated aqueous NaHCO3. The mixture was extracted
with CH2Cl2 (3£50 mL) and the organic phase was concen-
trated. The residue was puri®ed by a silica gel column chro-
matography to give hemiacetal trisaccharide intermediate as
syrup. A solution of the above syrup, CCl3CN (0.22 mL,
4 equiv.) and DBU (0.02 mL) in dry CH2Cl2 (5 mL) was
stirred at rt for 2 h. The solvents were removed in vacuo.
The residue was puri®ed by silica gel ¯ash column chroma-
tography to give trichloroacetimidate 14 (752 mg, 83%) as a
25
[a]D ˆ254 (c 1.5, CHCl3); nmax (liquid ®lm): 3443,
2957, 1730, 1603, 1452, 1266, 1110, 1070, 711; dH
(400 MHz, CDCl3) 3.44 (br d, 1H, J6a,6bˆ9.2 Hz, H-6),
3.82 (dd, 1H, J5,6bˆ1.7 Hz, J6a,6bˆ9.2 Hz, H-6), 4.01 (dd,
1H, J5,6bˆ6.8 Hz, J6a,6bˆ12.0 Hz, H-6), 4.10±4.15 (m, 1H,
H-5), 4.20±4.53 (m, 12H), 4.58 (dd, 1H, J5,6bˆ3.5 Hz,
J6a,6bˆ10.1 Hz, H-6), 4.67 (dd, 1H, J2,3ˆ3.2 Hz, J3,4ˆ
10.2 Hz, H-3), 4.73 (dd, 1H, J2,3ˆ3.4 Hz, J3,4ˆ10.0 Hz,
H-3), 4.78 (d, 1H, J1,2ˆ1.5 Hz, H-1), 5.17±5.19 (m, 2H,
H-1 and one proton of CH2vCH±CH2±), 5.21 (d, 1H,
J1,2ˆ1.2 Hz, H-1), 5.29±5.32 (m, 3H, H-1, H-2, and one
proton of CH2vCH±CH2±), 5.37 (d, 1H, J1,2ˆ1.6 Hz,
H-1), 5.44 (dd, 1H, J1,2ˆ2.0 Hz, J2,3ˆ3.0 Hz, H-2), 5.57
(dd, 1H, J1,2ˆ2.0 Hz, J2,3ˆ3.0 Hz, H-2), 5.65 (dd, 1H,
J2,3ˆ2.8 Hz, J3,4ˆ10.0 Hz, H-3), 5.69±5.74 (m, 2H, H-2,
H-3), 5.82 (dd, 1H, J1,2ˆ1.5 Hz, J2,3ˆ3.4 Hz, H-2), 5.85±
6.01 (m, 4H, H-3, 2H-4, CH2vCH±CH2±), 6.04 (t, 1H,
J2,3ˆ10.1 Hz, J3,4ˆ10.1 Hz, H-4), 6.07 (t, 1H, J2,3ˆ
10.8 Hz, J3,4ˆ10.8 Hz, H-4), 6.08 (t, 1H, J2,3ˆ10.0 Hz,
J3,4ˆ10.0 Hz, H-4), 7.18±8.35 (m, 80H, Ph); dC
(100 MHz, CDCl3) 166.13, 166.10, 166.08, 166.05,
165.92, 165.75, 165.57, 165.47, 165.17, 165.14, 165.06,
165.02, 164.65 (2C), 164.62, 164.55 (16 PhCO), 118.41
(CH2vCH±CH2±), 100.07, 99.61, 97.54, 97.31, 96.67
25
white foam; [a]D ˆ240 (c 1, CHCl3); dH (400 MHz,
CDCl3) 3.84 (dd, 1H, J5,6a,1 Hz, J6a,6bˆ9.2 Hz, H-6a),
4.15 (dd, 1H, J5,6bˆ6.3 Hz, J6a,6bˆ11.0 Hz, H-6b), 4.30±
4.37 (m, 2H), 4.48±4.58 (m, 5H), 4.73 (dd, 1H,
J2,3ˆ3.4 Hz, J3,4ˆ9.8 Hz, H-3), 5.10 (d, 1H, J1,2ˆ1.2 Hz,
H-1), 5.38±5.41 (m, 2H, H-1, H-2), 5.69±5.73 (m, 2H, H-
2, H-3), 5.90±5.95 (m, 2H), 6.01 (t, 1H, J3,4ˆ10.8 Hz,
J4,5ˆ10.8 Hz, H-4), 6.07 (t, 1H, J3,4ˆ10.0 Hz, J4,5ˆ
10.0 Hz, H-4), 6.12 (t, 1H, J3,4ˆ10.0 Hz, J4,5ˆ10.0 Hz,
H-4), 6.59 (d, 1H, J1,2ˆ1.5 Hz, H-1), 7.00±8.13 (m, 50H,
Ph), 9.00 (s, 1H, NH). Anal. Calcd for C90H72Cl3NO26: C,
63.96; H, 4.26; found: C, 63.88; H, 4.24.
3.1.9. Allyl 2,3,4,6-tetra-O-benzoyl-a-d-mannopyrano-
syl-ꢀ1 ! 3†-2,4-di-O-benzoyl-a-d-mannopyranoside (15).
To a stirred solution of 2 (2 g, 2.55 mmol) in THF (50 mL)
was added TBAF (800 mg, 2.55 mmol). The mixture was
stirred at rt for 4 h, then evaporated to dryness (,408C
water both) under reduced pressure. The residue was puri®ed
by silica gel column chromatography to give 4 as a white
solid (1.13 g, 66%). To a cooled solution (2158C) of 4
(1.062 g, 1.58 mmol) and 9 (1.23 g, 1.66 mmol) in dry
CH2Cl2 (15 mL) was added TMSOTf (20 mL, 0.11 mmol),
and the mixture was stirred at this temperature for 40 min,
another portion of TMSOTf (50 mL) was added. The reaction
was warmed up to rt and stirred for 2 h further, then concen-
trated. The residue was puri®ed by silica gel column chro-
matography to give 15 as a white solid (1.276 g, 80%);
1
(5C-1, JC-1,H-1ˆ171, 172, 172, 173, 174 Hz), 77.71,
77.24, 72.06, 72.00, 70.20, 70.14, 69.57, 69.50, 69.45,
69.37, 69.32, 68.77, 68.63, 68.20, 68.08, 66.45, 66.27,
66.13, 62.50, 62.43. Anal. Calcd for C145H120O42: C,
68.72; H, 4.74. Found: C, 68.79; H, 4.81.
3.1.11. Methyl 2,4-di-O-benzoyl-3-O-tert-butyldimethyl-
silyl-a-d-mannopyranoside (17). 2.0 equiv. of FeCl3´6H2O
was added to a mixture of methyl 2,4-di-O-benzoyl-3-O-
tert-butyldimethylsilyl-6-O-triphenylmethyl-a-d-manno-
pyranoside (3 g, 3.96 mmol) in CH2Cl2 (25 mL). The
mixture was stirred for 2 h at rt, then diluted with
more CH2Cl2 (50 mL), washed with ice-cold water
twice. The washings were re-extracted with CH2Cl2
(20 mL). The organic phase was combined, dried and
concentrated, then subjected to column chromatography
on silica gel with petroleum ether±EtOAc (4:1) as the
25
[a]D ˆ242 (c 1.4, CHCl3); nmax (liquid ®lm): 3444, 2926,
1731, 1602, 1452, 1317, 1266, 1110, 1070, 1028, 711 cm21;
dH (400 MHz, CDCl3) 2.89 (bs, H, OH), 3.75±3.80 (m, 2H,
0
0
2H-6), 3.92±3.95 (m, 1H, H-5), 4.07 (ddd, 1H, J4 ,5
0
ˆ
10.0 Hz, J5 ,6 aˆ3.6 Hz, J5 ,6 bˆ2.4 Hz, H-50), 4.18±4.25 (m,
0
0
0
0
0
1H, CH2vCH±CH2±), 4.35 (dd, 1H, J5 ,6 aˆ3.6 Hz,
25
J6 a,6 bˆ12.3 Hz, H-60a), 4.44±4.50 (m, 1H, CH2vCH±
eluent to give syrupy 17 (1.78 g, 87%); [a]D ˆ2255 (c
0
0
0
0
0
0
CH2±), 4.61 (dd, 1H, J5 ,6 bˆ2.4 Hz, J6 a,6 bˆ12.3 Hz,
0.8, CHCl3); nmax (liquid ®lm): 3443, 3066, 2927, 1319,
1452, 1267, 1110, 1070, 1030; dH (400 MHz, CDCl3)
20.08, 0.06 (2s, 2£3H, Si(CH3)2), 0.62 (s, 9H, t-Bu),
2.50 (bs, 1H, OH), 3.46 (s, 3H, OCH3), 3.71 (dd, 1H,
J5,6aˆ4.4 Hz, J6a,6bˆ12.6 Hz, H-6a), 3.75 (dd, 1H,
J5,6bˆ2.4 Hz, J6a,6bˆ12.6 Hz, H-6b), 3.88 (ddd, 1H,
J4,5ˆ9.4 Hz, J5,6aˆ4.4 Hz, J5,6bˆ2.4 Hz, H-5), 4.44 (dd,
1H, J2,3ˆ3.6 Hz, J3,4ˆ9.4 Hz, H-3), 4.89 (d, 1H,
J1,2ˆ1.6 Hz, H-1), 5.37 (dd, 1H, J1,2ˆ1.6 Hz, J2,3ˆ3.6 Hz,
H-2), 5.55 (t, 1H, J3,4ˆ9.4 Hz, J4,5ˆ9.4 Hz, H-4), 7.40±8.14
(m, 10H, Ph). Anal. Calcd for C27H36O8Si: C, 62.79; H,
6.98. Found: C, 62.82; H, 6.92.
H-60b), 4.70 (dd, 1H, J2,3ˆ3.5 Hz, J3,4ˆ9.8 Hz, H-3), 5.15
(d, 1H, J1,2ˆ1.4 Hz, H-1), 5.23±5.36 (m, 3H, H-2 and
0
0
0
CH2vCH±CH2±), 5.41 (d, 1H, J1 ,2 ˆ1.7 Hz, H-1 ), 5.65±
5.69 (m, 2H, H-20, H-30), 5.72 (t, 1H, J3,4ˆ10.0 Hz,
J4,5ˆ10.0 Hz, H-4), 5.89 (m, 1H, CH2vCH±CH2±), 6.02
0
0
0
0
0
(t, 1H, J3 ,4 ˆ10.0 Hz, J4 ,5 ˆ10.0 Hz, H-4 ), 7.19±8.25 (m,
30H, Ph). Anal. Calcd for C57H50O17: C, 67.99; H, 4.97.
Found: C, 67.96; H, 4.99.
3.1.10. Allyl 2,3,4,6-tetra-O-benzoyl-a-d-mannopyrano-
syl-ꢀ1 ! 6†-[2,3,4,6-tetra-O-benzoyl-a-d-mannopyrano-

Y. Du et al. / Tetrahedron 57 (2001) 1757±1763
1763
3.1.12.
Methyl
2-O-acetyl-3,4,6-tri-O-benzoyl-a-d-
to give tetrasaccharide 20 as a syrup (588 mg, 73%);
25
mannopyranosyl-ꢀ1 ! 6†-2,4-di-O-benzoyl-3-O-tert-butyl-
dimethylsilyl-a-d-mannopyranoside (18). To a cooled solu-
tion (08C) of 17 (850 mg, 1.65 mmol) and 6 (1.28 g,
1.89 mmol) in anhydrous CH2Cl2 (15 mL) was added
TMSOTf (25 mL, 0.14 mmol). The mixture was stirred at
this temperature for 1 h, and then quenched with Et3N (2
drops). The solvents were evaporated in vacuo to give a resi-
due, which was puri®ed by silica gel column chromatography
(petroleum ether±EtOAc, 2:1) to give disaccharide 18 as a
[a]D ˆ216 (c 1.5, CHCl3); nmax (liquid ®lm): 3441,
2928, 1730, 1452, 1269, 1108, 1068, 756, 710 cm21; dH
(400 MHz, CDCl3) 1.87, 2.05 (2 s, 6H, 2CH3CO), 3.48 (s,
3H, CH3), 3.63 (dd, 1H, J5,6aˆ2.4 Hz, J6a,6bˆ11 Hz, H-6aA),
3.98 (dd, 1H, J5,6bˆ5.8 Hz, J6a,6bˆ11 Hz, H-6bA), 4.15 (ddd,
1H, J4,5ˆ9.5 Hz, J5,6aˆ2.4 Hz, J5,6bˆ5.8 Hz, H-5A), 4.26
(dd, J1,2ˆ1.6 Hz, J2,3ˆ2.1 Hz, H-2B), 4.35±4.56 (m, 10H,
H-3A, H-5B,5C,5D, 2H-6B, 2H-6C, 2H-6D), 4.95 (d, 1H,
J1,2ˆ1.5 Hz, H-1A), 4.96 (d, 1H, J1,2ˆ1.6 Hz, H-1B), 5.12
(dd, 1H, J1,2ˆ1.2 Hz, J2,3ˆ3.2 Hz, H-2C), 5.14 (d, 1H,
J1,2ˆ1.7 Hz, H-1D), 5.16 (d, 1H, J1,2ˆ1.2 Hz, H-1C), 5.57
(dd, 1H, J2,3ˆ3.2 Hz, J3,4ˆ9.9 Hz, H-3C), 5.60 (dd, 1H,
J1,2ˆ1.7 Hz, J2,3ˆ3.6 Hz, H-2D), 5.66 (dd, 1H, J1,2ˆ
1.5 Hz, J2,3ˆ3.8 Hz, H-2A), 5.75 (t, 1H, J3,4ˆ9.9 Hz,
J4,5ˆ9.9 Hz, H-4C), 5.80 (t, 1H, J3,4ˆ9.5 Hz, J4,5ˆ9.5 Hz,
H-4A), 5.83±5.89 (m, 3H, H-3B, H-3D, H-4D), 5.96 (t, 1H,
J3,4ˆ9.8 Hz, J4,5ˆ9.8 Hz, H-4B), 7.25±8.40 (m, 55H, Ph).
Anal. Calcd for C106H92O34: C, 66.67; H, 4.82. Found: C,
66.71; H, 4.78.
25
syrup (1.43 g, 84%); [a]D ˆ2103 (c 1.1, CHCl3); nmax
(liquid ®lm): 3440, 2925, 1730; dH (400 MHz, CDCl3)
20.11, 0.06 (2s, 2£3H, Si(CH3)2), 0.63 (s, 9H, t-Bu), 2.05
(s, 3H, CH3CO), 3.56 (s, 3H, OCH3), 3.67 (dd, 1H,
J5,6aˆ2.2 Hz, J6a,6bˆ10.5 Hz, H-6a), 4.04 (dd, 1H, J5,6b
ˆ
6.4 Hz, J6a,6bˆ10.5 Hz, H-6b), 4.15 (ddd, 1H, J4,5ˆ9.6 Hz,
J5,6aˆ2.2 Hz, J5,6bˆ6.4 Hz, H-5), 4.32 (ddd, 1H,
0
0
0
0
0
0
0
J4 ,5 ˆ9.6 Hz, J5 ,6a ,1.0 Hz, J5 ,6b ˆ5.2 Hz, H-5 ), 4.38±
4.47 (m, 3H, H-3, 2H-60), 4.88 (d, 1H, J1,2ˆ1.5 Hz, H-1),
0
0
0
4.94 (d, 1H, J1 ,2 ˆ1.7 Hz, H-1 ), 5.40 (dd, 1H, J1,2ˆ1.5 Hz,
0
0
0
0
J2,3ˆ3.6 Hz, H-2), 5.44 (dd, 1H, J1 ,2 ˆ1.7 Hz, J2 ,3 ˆ3.1 Hz,
H-20), 5.67 (dd, 1H, J3,4ˆ10.0 Hz, J4,5ˆ9.6 Hz, H-4), 5.82
Acknowledgements
0
0
0
0
0
(dd, J2 ,3 ˆ3.1 Hz, J3 ,4 ˆ10.8 Hz, H-3 ), 5.88 (dd, 1H,
0
0
0
0
0
J3 ,4 ˆ10.8 Hz, J4 ,5 ˆ9.6 Hz, H-4 ), 7.36±8.11 (m, 25H, Ph).
Anal. Calcd for C56H60O17Si: C, 65.12; H, 5.81. Found: C,
65.09; H, 5.88.
This work was supported by CAS KIP-RCEES9904,
KJ952J1510, KJ952J1561, and NNSF of China (Projects
39970179 and 29972053).
3.1.13. Methyl 3,4,6-tri-O-benzoyl-a-d-mannopyranosyl-
ꢀ1 ! 6†-2,4-di-O-benzoyl-a-d-mannopyranoside (19). To
a cooled solution (08C) of 18 (916 mg, 0.89 mmol) in
CH2Cl2 (7 mL) and MeOH (7 mL) was added acetyl chloride
(1 mL). After 12 h, another portion of AcCl (0.4 mL) was
added. The mixture was further stirred at rt for 24 h, then
diluted with CH2Cl2 (50 mL), neutralized with Et3N and
washed with water. The organic phase was concentrated.
The residue was puri®ed on a silica gel column using
EtOAc±petroleum ether (5:4) as the elutant gave 19 as a
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2. Dwek, R. A. Chem. Rev. 1996, 96, 683±720.
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Int. Ed. 1998, 37, 1241. (b) Ogawa, T.; Katano, K.; Sasajima,
K.; Matsui, M. Tetrahedron 1981, 37, 2779. (c) Ogawa, T.;
Sasajima, K. Tetrahedron 1981, 37, 2787. (d) Guo, Z.;
Nakahara, Y.; Ogawa, T. Tetrahedron Lett. 1997, 38, 4799.
(e) Depre, D.; Duffels, A.; Green, L. G.; Lenz, R.; Ley, S. V.;
Wong, C.-H. Chem. Eur. J. 1999, 5, 3326. (f) Dan, A.;
Lergenmuller, M.; Amano, M.; Nakahara, Y.; Ogawa, T.;
Ito, Y. Chem. Eur. J. 1998, 4, 2182. (g) Unverzagt, C.; Seifert,
J. Tetrahedron Lett. 1997, 38, 7857. (h) Weiler, S.; Schmidt,
R. R. Tetrahedron Lett. 1998, 39, 2292. (i) Garegg, P. J.;
Oscarson, S.; Tiden, A. Carbohydr. Res. 1990, c3. (j) Wang,
W.; Kong, F. Angew. Chem. Int. Ed. 1999, 38, 1247.
(k) Becker, B.; Furneaux, R. H.; Reck, F.; Zubkov, O. A.
Carbohydr. Res. 1999, 315, 148. (l) Ogawa, T.; Katano, K.;
Matsui, M. Carbohydr. Res. 1978, 64, c3.
25
syrup (544 mg, 70%); [a]D ˆ125 (c 0.5, CHCl3); nmax
(liquid ®lm): 3444, 3067, 2926, 1731; dH (400 MHz,
CDCl3) 2.04 (bs, 1H, OH), 2.31 (bs, 1H, OH), 3.52 (s, 3H,
OCH3), 3.75 (dd, 1H, J5,6aˆ1.9 Hz, J6a,6bˆ10.9 Hz, H-6a),
4.08±4.28 (m, 5H, H-5, H-50, H-6b, H-60a, H-60b), 4.36
(bs, 1H, H-20), 4.40 (dd, 1H, J2,3ˆ3.5 Hz, J3,4ˆ10.1 Hz,
H-3), 4.96 (d, 1H, J1,2ˆ1.3 Hz, H-1), 5.04 (d, 1H,
0
0
0
J1 ,2 ˆ1.2 Hz, H-1 ), 5.44 (dd, 1H, J1,2ˆ1.3 Hz, J2,3ˆ3.5 Hz,
0
0
0
0
0
H-2), 5.74 (dd, 1H, J2 ,3 ˆ3.2 Hz, J3 ,4 ˆ6.1 Hz, H-3 ), 5.77 (t,
1H, J3,4ˆ10.1 Hz, J4,5ˆ10.1 Hz, H-4), 7.25±8.17 (m, 25H,
Ph). Anal. Calcd for C48H44O16: C, 65.75; H, 5.02. Found: C,
65.69; H, 5.10.
3.1.14. Methyl 2-O-acetyl-3,4,6-tri-O-benzoyl-a-d-manno-
pyranosyl-ꢀ1 ! 2†-3,4,6-tri-O-benzoyl-a-d-mannopyrano-
syl-ꢀ1 ! 6†-[2-O-acetyl-3,4,6-tri-O-benzoyl-a-d-manno-
pyranosyl-ꢀ1 ! 3†Š-2,4-di-O-benzoyl-a-d-mannopyrano-
side (20). To a cooled solution (08C) of 19 (370 mg,
0.42 mmol) and 6 (630 mg, 0.93 mmol) in anhydrous
CH2Cl2 (15 mL) was added TMSOTf (20 mL, 0.11 mmol).
The mixture was stirred at this temperature for 3 h, and then
quenched with Et3N (2 drops). The solvents were evapo-
rated in vacuo to give a residue, which was puri®ed by silica
gel column chromatography (petroleum ether±EtOAc, 2:3)
4. Du, Y.; Zhang, M.; Kong, F. Chinese Pat. Appl. 00107723.6.
5. Protection Groups in Organic Synthesis, Greene, T. W., Wuts,
P. G. M., Eds.; Wiley: New York, 1991.
6. Du, Y.; Pan, Q.; Kong, F. Carbohydr. Res. 2000, 323, 28.
7. Ding, X.; Wang, W.; Kong, F. Carbohydr. Res. 1997, 303,
445.
8. Lowary, T. L.; Eichler, E.; Bundle, D. R. J. Org. Chem. 1995,
60, 7316.
9. EI-Sokkary, S. I.; Silwanis, B. A.; Nashed, M. A.; Paulsen, H.
Carbohydr. Res. 1990, 203, 319.
10. Schmidt, R. R.; Michel, J. J. Carbohydr. Chem. 1985, 4, 141.