Convergent synthesis of a galactofuranosylated mannan, the repeating unit of Trichophyton mentagrophytes IFO 5466 and Trichophyton rubrum IFO 5467

Article abstract of DOI:10.1016/j.tetasy.2004.03.041

An undecasaccharide repeating unit of the polysaccharide of Trichophyton mentagrophytes IFO 5466 and Trichophyton rubrum IFO 5467, α-D-Manp- (1→2)-α-D-Manp-(1→6)-[β-D-Galf-(1→3)] -α-D-Manp-(1→2)-[β-D-Galf-(1→3)]-α-D-Manp-(1→2) -α-D-Manp-(1→2)-α-D-Manp-(1→

Full text of DOI:10.1016/j.tetasy.2004.03.041

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 1517–1525
Convergent synthesis of a galactofuranosylated mannan, the
repeating unit of Trichophyton mentagrophytes IFO 5466
and Trichophyton rubrum IFO 5467
Zuchao Ma, Jianjun Zhang and Fanzuo Kong*
Research Center for Eco-Environmental Sciences, Academia Sinica, PO Box 2871, Beijing 100085, PR China
Received 10 March 2004; accepted 25 March 2004
Abstract—An undecasaccharide repeating unit of the polysaccharide of Trichophyton mentagrophytes IFO 5466 and Trichophyton
rubrum IFO 5467, a-
(1 fi 2)-a- -Manp-(1 fi 2)-a-
coupling of a octasaccharide trichloroacetimidate donor 19 with a trisaccharide acceptor 28. The donor 19 and 28 were obtained
with allyl 3-O-acetyl-2-O-benzoyl-a- -mannopyranoside 2, allyl 3-O-acetyl-4,6-di-O-benzoyl-a- -mannopyranoside 9, allyl 3,4,6-
tri-O-benzoyl-a- -mannopyranosyl-(1 fi 2)-3,4,6-tri-O-benzoyl-a- -mannopyranoside 13, 6-O-acetyl-2,3,4-tri-O-benzoyl-a-
-galactofuranosyl trichloroacetimidate 16 as the key
D
-Manp-(1 fi 2)-a-
D
-Manp-(1 fi 6)-[b-
D
-Galf-(1 fi 3)]-a-
D
-Manp-(1 fi 2)-[b-
D
-Galf-(1 fi 3)]-a-
D-Manp-
D
D
-Manp-(1 fi 6)-a-
D
-Manp-(1 fi 2)-[b-
D
-Galf-(1 fi 3)]-Manp was synthesized as its allyl glycoside by
D
D
D
D
D-
mannopyranosyl trichloroacetimidate 26 and 2,3,5,6-tetra-O-benzoyl-b-
synthons by appropriate combination through simple transformation.
ꢀ 2004 Elsevier Ltd. All rights reserved.
D
1. Introduction
the cell wall polysaccharides of T. mentagrophytes and
T. rubrum have been studied and characterized, with two
kinds of polysaccharides being found.4 One is mannan
consisting of an a-(1 fi 6)-linked backbone with
a-(1 fi 2)-linked monosaccharide side chains, while the
second one is galactomannan consisting of an a-(1 fi 2)-
and a-(1 fi 6)-linked mannose backbone with galacto-
furanose side chains. A possible structure of the
galactomannan is shown in Figure 1.
The anthropophilic dermatophytes Trichophyton menta-
grophytes and Trichophyton rubrum cause chronic, rel-
atively uninflamed, skin infections of the feet, groin
and body. Around 90% of chronic dermatophyte infec-
tions are caused by the fungi T. mentagrophytes and
T. rubrum.1 One of the causes of the chronic infection
resides in the immunosuppressive effects of the cell wall
components of these organisms.2 The cell wall polysac-
charides of these fungi are known to be the major
immunologically active substances.3 The structures of
The synthesis of the above galactomannan may be
useful for understanding the role galactofuranose plays
Figure 1. Possible structure of galactomannan of T. mentagrophytes IFO 5466 and T. rubrum IFO 5467.
* Corresponding author. Tel.: +86-10-629-366-13; fax: +86-10-629-235-63; e-mail: fzkong@mail.rcees.ac.cn
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.03.041

1518
Z. Ma et al. / Tetrahedron: Asymmetry 15 (2004) 1517–1525
in microorganisms and for studying the biosynthesis of
furanosyl-containing glycoconjugates. The galactoman-
nan could also be used an inhibitor to probe the devel-
opment of infections or to develop diagnostic methods,
or to be used as a vaccine. The synthesis of the above
galactomannan is also of interest for synthetic chemists
because of its large size and complex structure, which
contains different mannose linkages and rare galacto-
furanose residues. So far there have been very few
reports dealing with the synthesis of galactofuranosy-
lated mannan.5 We report herein a convergent synthesis
of an undecasaccharide, the repeating unit of the
polysaccharide of T. mentagrophytes IFO 5466 and
T. rubrum IFO 5467.
by acetylation of 21. The obtained product 22 showed in
its NMR spectrum a sharp singlet at d 5.46 for H-10
indicating b-linkage, and a doublet of doublets at 5.42
with J1;2 1.4 Hz and J2;3 3.5 Hz for H-2 indicating the 3-
glycosylation. Hydrolysis of 22 to cleave benzylidene
group followed by benzoylation and selective deacetyl-
ation produced disaccharide acceptor 25. Condensation
of 25 with the donor 6-O-acetyl-2,3,4-tri-O-benzoyl-a-D-
mannopyranosyl trichloroacetimidate 26 gave trisac-
charide 27, and subsequent deacetylation gave the tri-
saccharide acceptor 28. Finally, coupling of acceptor 28
with octasaccharide donor 19 afforded the undecasac-
charide 29 (79%); debenzoylation in a saturated solution
of NH3 in methanol yielded target compound 30 (85%).
1
The H and 13C NMR spectra of 30 showed all of the
characteristic signals such as at d 5.20, 5.16, 5.15, 5.11,
5.07, 5.02, 4.99 (7s, 11H) for H-1; d 104.88, 104.85,
104.35 for Galf C-1; 102.28, 101.71, 101.61, 100.76,
100.69, 98.26, 98.10, 97.59 for Manp C-1. A bioassay of
sample 30 is currently in progress, with the results to be
reported in due course.
2. Results and discussion
We previously reported a method6 for mannose oligo-
saccharide syntheses using unprotected or lightly pro-
tected sugars as the glycosyl acceptors, resulting in a
variety of complex oligosaccharides being synthesized
efficiently.7 In the present research, a concise syntheses
of the undecasaccharide repeating unit of the polysac-
charide of T. mentagrophytes IFO 5466 and T. rubrum
IFO 5467 was achieved. Scheme 1 shows the syntheses
of octasaccharides donor 19. Allyl 3-O-acetyl-4,6-O-
3. Conclusion
In summary, a convergent synthesis of a complex
galacto-mannosyl undecamer was achieved via a regio-
and stereoselective manner with readily accessible
materials. The described method is suitable for the
preparation of other oligosaccharides consisting of
mannan backbone linked by either an a-(1 fi 2) or
a-(1 fi 6) with galactofuranose side chains.
benzylidene-a-D
-mannopyranoside 18 was chosen as the
starting material. Benzoylation of 1 followed by
debenzylidenation afforded the monosaccharide accep-
tor 2. Subsequent coupling with perbenzoylated
a-(1 fi 2)-linked mannosyl disaccharide trichloroacet-
imidate 39 selectively produced the (1 fi 6)-linked tri-
saccharide 4 (79%). The regioselective coupling was
confirmed by benzoylation of 4 to give 5, which showed
in its 1H NMR spectrum a new signal at d 5.88 ppm with
J3;4 ¼ J4;5 ¼ 10:1 Hz for H-4 compared to 4. Deallyl-
4. Experimental
4.1. General methods
10
ation with PdCl2 followed by trichloroacetimidate
formation11 yielded trisaccharide donor 7. The other
mannose component containing a potential hydroxyl
group at C-3 was prepared from allyl 3-O-acetyl-2-O-
Optical rotations were determined at 25 ꢁC with a Per-
kin–Elmer Model 241-Mc automatic polarimeter. 1H
NMR and 13C NMR spectra were recorded with Bruker
1
chloroacetyl-a-
D
-mannopyranoside 8. Benzoylation of 8
ARX 400 spectrometers (400 MHz for H, 100 MHz for
followed by dechloroacetylation with thiourea afforded
monosaccharide acceptor 9. Condensation of 9 with
donor 7 gave tetrasaccharide 10 (80%), and subsequent
deallylation followed by trichloroacetimidate formation
produced tetrasaccharide donor 12 (73%), which con-
tained two potential hydroxyl groups at C-3 and C-30.
Coupling of donor 12 with disaccharide acceptor 139
afforded hexasaccharide 14 (68%), whose selective de-
acetylation12 with MeCOCl/MeOH–CH2Cl2 gave hexa-
saccharide acceptor 15 (73%) with C-300 and C-3000 free
hydroxyl groups. Coupling of 15 with 2,3,5,6-tetra-O-
13C) for solutions in CDCl3 or D2O as indicated.
Chemical shifts are given in ppm downfield from inter-
nal Me4Si. Mass spectra were measured using MALTI-
TOF-MS with CCA as matrix or recorded with a VG
PLATFORM mass spectrometer using the ESI mode.
Thin-layer chromatography (TLC) was performed on
silica gel HF254 with detection by charring with 30% (v/
v) H2SO4 in MeOH or in some cases by a UV detector.
Column chromatography was conducted by elution of a
column (16 · 240 mm, 18 · 300 mm, 35 · 400 mm) of sil-
ica gel (100–200 mesh) with EtOAc–petroleum ether
(60–90 ꢁC) as the eluent. Solutions were concentrated at
<60 ꢁC under reduced pressure.
benzoyl-b-D
-galactofuranosyl trichloroacetimidate 1613
gave octasaccharide 17 (73%); subsequent deallylation
and trichloroacetimidate formation afforded octasac-
charide donor 19 (71%).
4.2. General procedure for the glycosylations
Trisaccharide acceptor 28 was similarly prepared as
D
shown in Scheme 2. Thus, allyl 4,6-O-benzylidene-a-
-
A mixture of the donor and acceptor was dried together
under high vacuum for 2 h, then dissolved in anhydrous
CH2Cl2. TMSOTf (0.05 equiv) was added dropwise at
)20 ꢁC with nitrogen protection. The reaction mixture
mannopyranoside 20 was selectively coupled with 16 to
give b-(1 fi 3)-linked disaccharide 21 in good yield
(71%). The regio- and stereoselectivity were confirmed

Z. Ma et al. / Tetrahedron: Asymmetry 15 (2004) 1517–1525
1519
BzO
OBz
O
BzO
OBz
O
BzO
BzO
BzO
BzO
1
4 R = H, R = All
BzO
O
a
O
BzO
1
O
BzO
BzO
5 R = Bz, R = All
O
d
HO
BzO
BzO
OCNHCCl3
Ph
1
O
OBz
O
OH
6 R = Bz, R = H
O
e
O
HO
AcO
i. a
3
1
7 R = Bz, R = CNHCCl
3
c
AcO
O
ii. b
OBz
O
1
OAll
2
OAll
RO
AcO
OR1
BzO
OBz
O
BzO
BzO
BzO
O
O
BzO
BzO
BzO
HO
10 R = All
11 R = H
OH
OCA
O
d
e
O
i. a
ii. f
BzO
AcO
c
HO
O
AcO
OBz
O
7
12 R = CNHCCl
3
9
OAll
BzO
BzO
AcO
8
OAll
BzO
O
O
BzO
AcO
OR
BzO
OBz
O
BzO
BzO
O
O
BzO
BzO
BzO
OH
O
O
OBz
BzO
O
BzO
BzO
RO
c
14 R = Ac
BzO
12
+
g
O
O
BzO
15 R = H
O
BzO
BzO
O
BzO
RO
OAll
13
BzO
O
O
BzO
BzO
BzO
O
O
BzO
BzO
OAll
BzO
OBz
O
BzO
BzO
BzO
O
O
BzO
BzO
O
OBz
O
BzO
O
O
O
OCNHCCl3
17 R = All
d
e
OBz
OBz
18 R = H
19 R = CNHCCl
c
BzO
BzO
O
15
+
3
O
OBz OBz
OBz OBz
O
O
OBz
OBz
BzO
OBz
O
O
BzO
BzO
16
OBz OBz
OBz
BzO
O
O
BzO
BzO
OR
Scheme 1. Reagents and conditions: (a) BzCl–pyridine, 85% for 5, 88% for 24; (b) 90% TFA, rt, 2 h, 87% for 2, 82% for 23; (c) TMSOTf (0.01–
0.05 equiv), CH2Cl2, )20 to 0 ꢁC, 2–4 h, 79% for 4, 80% for 10, 68% for 14, 73% for 17, 71% for 21, 77% for 27 and 79% for 29, respectively; (d) PdCl2,
CH3OH, rt, 4 h, 81% for 6, 81% for 11, 80% for 18; (e) CCl3CN, DBU, CH2Cl2, 2 h, 88% for 7, 90% for 12, 89% for 19; (f) (NH2)2CS, CH2Cl2–
CH3OH, reflux, 16 h, 84%; (g) methanol/2–6% CH3COCl, rt, 12 h, 73% for 15, 75% for 25, 81% for 28; (h) Ac2O–pyridine, 96%; (i) satd NH3–MeOH,
rt, 72 h, 85%.
was stirred for 3 h, during which time the temperature
was gradually increased to ambient temperature. The
mixture was then neutralized with Et3N. Concentration
of the reaction mixture, followed by purification on a
silica-gel column, gave the desired products.
4.3. Allyl 3-O-acetyl-2-O-benzoyl-a-D-mannopyranoside
2
Compound 2 was obtained from 18 by benzoylation
followed by debenzylidenation. To a solution of 1

1520
Z. Ma et al. / Tetrahedron: Asymmetry 15 (2004) 1517–1525
R1O
OR
R1O
O
1
21 R = H, R = CHPh
Ph
O
h
OH
O
O
1
O
22 R = Ac, R = CHPh
c
O
OAll
b
a
g
OBz
1
HO
+
16
23 R = Ac, R = H
1
OAll
24 R = Ac, R = Bz
20
OBz OBz
OBz
1
25 R = H, R = Bz
RO
OBz
O
BzO
BzO
AcO
BzO
O
OBz
O
27 R = Ac
28 R = H
O
O
c
g
BzO
BzO
BzO
25
+
O
OCNHCCl3
OAll
OBz
26
OBz OBz
OBz
RO
OR
O
RO
RO
RO
O
O
RO
RO
O
OR
O
RO
O
O
OR
RO
O
O
RO
OR
OR
OR
OR
O
O
29 R = Bz
30 R = H
i
c
RO
O
19
+
28
O
RO
RO
OR
OR
OR
RO
O
O
RO
RO
O
OR
O
RO
RO
RO
O
O
RO
O
O
OAll
OR
OR OR
OR
Scheme 2. Reagents and conditions: (a) BzCl–pyridine, 85% for 5, 88% for 24; (b) 90% TFA, rt, 2 h, 87% for 2, 82% for 23; (c) TMSOTf (0.01–
0.05 equiv), CH2Cl2, )20 to 0 ꢁC, 2–4 h, 79% for 4, 80% for 10, 68% for 14, 73% for 17, 71% for 21, 77% for 27 and 79% for 29, respectively; (d) PdCl2,
CH3OH, rt, 4 h, 81% for 6, 81% for 11, 80% for 18; (e) CCl3CN, DBU, CH2Cl2, 2 h, 88% for 7, 90% for 12, 89% for 19; (f) (NH2)2CS, CH2Cl2–
CH3OH, reflux, 16 h, 84%; (g) methanol/2–6% CH3COCl, rt, 12 h, 73% for 15, 75% for 25, 81% for 28; (h) Ac2O–pyridine, 96%; (i) satd NH3–MeOH,
rt, 72 h, 85%.
(0.70 g, 2.0 mmol) in pyridine (5 mL) was added benzoyl
chloride (0.28 mL, 2.4 mmol). After stirring the mixture
overnight at rt, TLC (2:3 petroleum ether–EtOAc)
indicated that the reaction was complete. Methanol
(2 drops) was added to the reaction mixture and stirring
continued for 10 min. Water (10 mL) was added, the
mixture extracted with CH2Cl2 (3 · 10 mL), the extracts
were washed with 1 M HCl and satd aq NaHCO3, dried
over Na2SO4 and concentrated. The residue was dis-
solved in 90% TFA (10 mL) and stirred for 2 h at rt,
after which TLC (2:1 petroleum ether–EtOAc) indicated
that the reaction had gone to completion. The mixture
was diluted with toluene (40 mL) and concentrated in
vacuo directly. The residue was passed through a short
silica-gel column with 2.5:1 petroleum ether–EtOAc as
the eluent to give 2 (0.55 g, 75% for two steps) as a
25
D
syrup. ½aꢀ ¼ ꢁ3:5 (c 1.0, CHCl3); 1H NMR (400 MHz,
CDCl3): d 8.06–7.45 (m, 5H, Ph), 5.97–5.97 (m, 1H,

Z. Ma et al. / Tetrahedron: Asymmetry 15 (2004) 1517–1525
1521
–CH2–CH@CH2), 5.49 (dd, 1H, J1;2 ¼ 1:7 Hz,
4.6. 2,3,4,6-Tetra-O-benzoyl-a-
D-mannopyranosyl-
-mannopyranosyl-
J2;3 ¼ 3:3 Hz, H-2), 5.33 (dd, 1H, J2;3 ¼ 3:3 Hz, J3;4
¼
(1 fi 2)-3,4,6-tri-O-benzoyl-a-
D
10:0 Hz, H-3), 5.35–5.23 (m, 2H, –CH2–CH@CH2), 4.98
(d, 1H, J1;2 ¼ 1:7 Hz, H-1), 4.26–4.03 (m, 3H, H-4,
–CH2–CH@CH2), 3.95–3.94 (m, 2H, H-6), 3.84–3.81
(m, 1H, H-5), 2.05 (s, 3H, CH3CO). Anal. Calcd for
C18H22O8: C, 59.01; H, 6.05. Found: C, 59.22; H, 6.10.
(1 fi 6)-3-O-acetyl-2,4-di-O-benzoyl-a-
D-mannopyrano-
syl trichloroacetimidate 7
To a solution of 5 (0.89 g, 0.58 mmol) in anhydrous
MeOH (10 mL) was added PdCl2 (30 mg). After stirring
the mixture at rt for 2 h, TLC (2:1 petroleum ether–
EtOAc) indicated that the reaction was complete. The
mixture was filtered, the solution concentrated to dryness
and the resultant residue purified by flash chromatogra-
phy (2.5:1 petroleum ether–EtOAc) to give 6 (0.70 g,
81%) as a white foam. A mixture of 6 (0.70 g, 0.47 mmol),
trichloroacetonitrile (94 lL, 0.94 mmol) and 1,8-diaza-
bicyclo[5.4.0]-undecene (DBU) (30 lL) in dry CH2Cl2
(10 mL) was stirred under nitrogen for 3 h and then
concentrated. The residue was purified by flash chroma-
tography (3:1 petroleum ether–EtOAc) to give 7 (0.67 g,
4.4. Allyl 2,3,4,6-tetra-O-benzoyl-a-
(1 fi 2)-3,4,6-tri-O-benzoyl-a- -mannopyranosyl-
(1 fi 6)-3-O-acetyl-2-O-benzoyl-a- -mannopyranoside 4
D-mannopyranosyl-
D
D
As described in the general procedure, 2 (0.40 g,
1.1 mmol) and 39 (1.1 g, 0.92 mmol) were coupled, and
the product purified by silica-gel column chromatogra-
phy with 2.5:1 petroleum ether–EtOAc as the eluent to
25
D
give 4 (1.0 g, 79%) as a foamy solid. ½aꢀ ¼ ꢁ78:6 (c 1.0,
25
1
1
CHCl3); H NMR (400 MHz, CDCl3): d 8.07–7.23 (m,
88%) as a foamy solid: ½aꢀ ¼ ꢁ68:4 (c 1.0, CHCl3); H
D
40H, 8Ph), 6.10 (dd, 1H, J3
¼ 10:0 Hz, H-400),
NMR (400 MHz, CDCl3): d 9.01 (s, 1H, CNHCCl3),
8.15–7.26 (m, 45H, 9Ph), 6.51 (s, 1H, H-1), 6.10 (dd, 1H,
00 ;400
00 ;500
¼ J4
6.03 (dd, 1H, J3 ;4 ¼ J4 ;5 ¼ 9:8 Hz, H-40), 6.06–5.90 (m,
0
0
0
0
3H, H-30, H-300, –CH2–CH@CH2), 5.85 (dd, 1H,
J3
¼ J4
¼ 10:1 Hz, H-400), 6.05–5.80 (m, 7H, H-2,
00 ;400
00 ;500
¼ 1:8 Hz, J2
¼ 3:0 Hz, H-200), 5.50 (dd, 1H,
H-200, H-3, H-30, H-300, H-4, H-40), 5.22 (s, 1H, H-100), 5.12
(s, 1H, H-10), 4.66–3.69 (m, 10H, H-20, H-5, H-6), 1.92 (s,
3H, CH3CO). Anal. Calcd for C85H70Cl3NO26: C, 62.72;
H, 4.33. Found: C, 62.82; H, 4.41.
00 ;200
J1
00 ;300
J1;2 ¼ 1:6 Hz, J2;3 ¼ 3:2 Hz, H-2), 5.37–5.20 (m, 4H, H-
100, H-3, –CH2–CH@CH2), 5.07 (d, 1H, J1 ;2 ¼ 1:5 Hz,
H-10), 4.95 (d, 1H, J1;2 ¼ 1:6 Hz, H-1), 4.68–3.85 (m,
13H, H-20, H-4, H-5, H-6, –CH2–CH@CH2), 2.07 (s,
3H, CH3CO) Anal. Calcd for C79H70O25: C, 66.85; H,
4.97. Found: C, 67.09; H, 5.03.
0
0
4.7. Allyl 3-O-acetyl-4,6-di-O-benzoyl-a-D-mannopyr-
anoside 9
4.5. Allyl 2,3,4,6-tetra-O-benzoyl-a-
D
-mannopyranosyl-
Compound 8 (0.34 g, 1.0 mmol) was benzoylated under
the same conditions as those used in the preparation of 5
from 4, to give a residue. To a solution of the residue in
MeOH (15 mL)–CH2Cl2 (20 mL) was added thiourea
(0.15 g), and the mixture was refluxed for 16 h, after
which TLC (1:1 petroleum ether–EtOAc) indicated that
the reaction had gone to completion. The mixture was
then concentrated and the residue passed through a
silica-gel column with 3:1 petroleum ether–EtOAc as the
(1 fi 2)-3,4,6-tri-O-benzoyl-a-
D
-mannopyranosyl-
(1 fi 6)-3-O-acetyl-2,4-di-O-benzoyl-a-
side 5
D-mannopyrano-
To a solution of 4 (0.98 g, 0.69 mmol) in pyridine (10 mL)
was added benzoyl chloride (97 lL, 0.83 mmol). After
stirring the mixture overnight at rt, TLC (2:1 petroleum
ether–EtOAc) indicated that the reaction was complete.
Methanol (2 drops) was added to the reaction mixture,
and stirring was continued for 10 min. Water (20 mL) was
added, the mixture extracted with CH2Cl2 (3 · 20 mL), the
extract washed with 1 M HCl and satd aq NaHCO3, dried
over Na2SO4 and concentrated. Purification by flash
eluent to give 9 (0.33 g, 71% for two steps) as a foamy
25
D
solid. ½aꢀ ¼ þ43:6 (c 1.0, CHCl3); 1H NMR (400 MHz,
CDCl3): d 8.03–7.37 (m, 10H, 2Ph), 5.98–5.89 (m, 1H,
–CH2–CH@CH2), 5.73 (dd, 1H, J3;4 ¼ J4;5 ¼ 10:0 Hz, H-
4), 5.56 (dd, 1H, J2;3 ¼ 3:2 Hz, J3;4 ¼ 10:0 Hz, H-3),
5.34–5.22 (m, 2H, –CH2–CH@CH2), 5.00 (d, 1H,
J1;2 ¼ 1:6 Hz, H-1), 4.55 (dd, 1H, J5;6a ¼ 5:1 Hz,
J6a;6b ¼ 12:0 Hz, H-6a), 4.44 (dd, 1H, J5;6b ¼ 5:5 Hz,
J6a;6b ¼ 12:0 Hz, H-6b), 4.32–4.06 (m, 4H, H-2, H-5,
–CH2–CH@CH2), 2.00 (s, 3H, CH3CO). Anal. Calcd for
C25H26O9: C, 63.82; H, 5.57. Found: C, 63.96; H, 5.62.
chromatography (2.5:1 petroleum ether–EtOAc) gave 5
25
D
as a foamy solid (0.90 g, 85%). ½aꢀ ¼ ꢁ70:2 (c 1.0,
1
CHCl3); H NMR (400 MHz, CDCl3): d 8.04–7.26 (m,
45H, 9Ph), 6.10 (dd, 1H, J3
¼ J4
¼ 10:1 Hz, H-400),
00 ;400
00 ;500
6.06–5.96 (m, 4H, H-30, H-300, H-40, –CH2–CH@CH2),
5.88 (dd, 1H, J3;4 ¼ J4;5 ¼ 10:1 Hz, H-4), 5.84 (dd, 1H,
¼ 3:0 Hz, H-200), 5.74 (dd, 1H,
00 ;200
00 ;300
J1
¼ 1:1 Hz, J2
J2;3 ¼ 3:3 Hz, J3;4 ¼ 10:1 Hz, H-3), 5.60 (dd, 1H,
J1;2 ¼ 1:4 Hz, J2;3 ¼ 3:3 Hz, H-2), 5.46–5.29 (m, 2H,
4.8. Allyl 2,3,4,6-tetra-O-benzoyl-a-
(1 fi 2)-3,4,6-tri-O-benzoyl-a- -mannopyranosyl-
-mannopyrano-
-mannopyr-
D-mannopyranosyl-
–CH2–CH@CH2), 5.23 (d, 1H, J1
¼ 1:1 Hz, H-100), 5.10
D
00 ;200
(d, 1H, J1 ;2 ¼ 1:3 Hz, H-10), 5.08 (d, 1H, J1;2 ¼ 1:4 Hz, H-
1), 4.65–3.66 (m, 12H, H-20, H-5, H-6, –CH2–CH@CH2),
1.89 (s, 3H, CH3CO); 13C NMR (100 MHz, CDCl3): d
170.01, 166.10, 165.91, 165.60, 165.46, 165.40, 165.38,
165.22, 164.95, 164.78, 118.38, 99.79, 98.46, 96.73, 70.54,
70.39, 70.06, 69.74, 69.62, 69.55, 69.33, 68.86, 68.77, 67.22,
67.13, 66.62, 66.33, 63.46, 62.62, 20.60. Anal. Calcd for
C86H74O26: C, 67.80; H, 4.90. Found: C, 67.66; H, 4.97.
(1 fi 6)-3-O-acetyl-2,4-di-O-benzoyl-a-
D
0
0
syl-(1 fi 2)-3-O-acetyl-4,6-di-O-benzoyl-a-
D
anoside 10
Donor 7 (0.65 g, 0.40 mmol) was coupled with acceptor
9 (0.22 g, 0.48 mmol) as described in the general proce-
dure, and the product purified by chromatography with
2:1 petroleum ether–EtOAc as the eluent to give 10

1522
Z. Ma et al. / Tetrahedron: Asymmetry 15 (2004) 1517–1525
25
(0.62 g, 80%) as a foamy solid. ½aꢀ ¼ ꢁ71:2 (c 1.0,
(d, 1H, J1;2 ¼ 1:3 Hz, H-1), 4.67–3.72 (m, 24H, 4H-2,
6H-5, 12H-6, –CH2–CH@CH2), 2.04 (s, 3H, CH3CO),
1.97 (s, 3H, CH3CO); 13C NMR (100 MHz, CDCl3): d
170.05, 169.89, 166.14, 166.04, 165.99, 165.66, 165.61,
165.58, 165.57, 165.50, 165.43, 165.38, 165.32, 165.30,
164.81, 163.38, 100.26, 100.13, 99.76, 99.64, 98.84,
97.99, 71.09, 70.38, 70.26, 70.11, 69.96, 69.86, 69.70,
69.58, 68.99, 68.85, 68.75, 67.89, 67.45, 67.12, 67.04,
66.33, 66.10, 65.19, 63.68, 63.57, 63.23, 61.98, 60.34,
20.76, 20.65. Anal. Calcd for C162H138O50: C, 67.45; H,
4.82. Found: C, 67.68; H, 4.73.
D
1
CHCl3); H NMR (400 MHz, CDCl3): d 8.06–7.26 (m,
000 ;4000
00 ;500
000 ;5000
55H, 11Ph), 6.11 (dd, 1H, J3
¼ J4
¼ 10:0 Hz, H-
4000), 6.10 (dd, 1H, J3
¼ J4
¼ 10:0 Hz, H-400), 6.04–
00 ;400
5.75 (m, 7H, H-2000,H-30, H-300, H-3000, H-4, H-40, –CH2–
0
0
0
0
CH@CH2), 5.70 (dd, 1H, J1 ;2 ¼ 1:7 Hz, J2 ;3 ¼ 3:1 Hz,
H-20), 5.67 (dd, 1H, J2;3 ¼ 3:2 Hz, J3;4 ¼ 9:8 Hz, H-3),
5.28 (d, 1H, J1
¼ 1:6 Hz, H-1000), 5.26–5.12 (m, 2H,
000 ;2000
00 ;200
–CH2–CH@CH2), 5.24 (d, 1H, J1
¼ 1:5 Hz, H-100),
5.10 (d, 1H, J1 ;2 ¼ 1:7 Hz, H-10), 4.98 (d, 1H,
J1;2 ¼ 1:9 Hz, H-1), 4.63–3.64 (m, 16H, H-20, H-200, H-5,
H-6, –CH2–CH@CH2), 2.06 (s, 3H, CH3CO), 1.94 (s,
3H, CH3CO); 13C NMR (100 MHz, CDCl3): d 170.45,
169.84, 166.29, 166.17, 165.95, 165.50, 165.47, 165.43,
165.38, 164.81, 163.38, 99.89, 99.83, 98.93, 97.95, 70.73,
70.43, 70.28, 70.08, 69.87, 69.60, 69.05, 68.96, 68.93,
68.73, 67.91, 67.14, 66.64, 66.56, 65.91, 63.77, 63.38,
62.50, 60.38, 21.02, 20.72. Anal. Calcd for C108H94O34:
C, 67.01; H, 4.89. Found: C, 66.88; H, 4.79.
0
0
4.11. Allyl 2,3,4,6-tetra-O-benzoyl-a-
(1 fi 2)-3,4,6-tri-O-benzoyl-a- -mannopyranosyl-
(1 fi 6)-2,4-di-O-benzoyl-a- -mannopyranosyl-(1 fi 2)-
4,6-di-O-benzoyl-a- -mannopyranosyl-(1 fi 2)-3,4,6-tri-
O-benzoyl-a- -mannopyranosyl-(1 fi 2)-3,4,6-tri-O-benz-
oyl-a- -mannopyranoside 15
D-mannopyranosyl-
D
D
D
D
D
To a solution of 14 (0.42 g, 0.15 mmol) in anhydrous
CH2Cl2 (5 mL) was added anhydrous MeOH (25 mL),
then acetyl chloride (1 mL) added to the reaction mix-
ture at 0 ꢁC. The solution was stoppered in a flask and
stirred at rt until TLC (1:1 petroleum ether–EtOAc)
showed that the reaction was complete. The solution
was neutralized with Et3N, then concentrated to dry-
ness. The residue was passed through a short silica-gel
4.9. 2,3,4,6-Tetra-O-benzoyl-a-
(1 fi 2)-3,4,6-tri-O-benzoyl-a- -mannopyranosyl-
-mannopyranos-
-mannopyr-
D-mannopyranosyl-
D
(1 fi 6)-3-O-acetyl-2,4-di-O-benzoyl-a-
D
yl-(1 fi 2)-3-O-acetyl-4,6-di-O-benzoyl-a-
D
anosyl trichloroacetimidate 12
Deallylation of tetrasaccharide 10 (0.60 g, 0.31 mmol)
followed by trichloroacetimidation under the same
conditions as those used in the preparation of 7 from 5
gave a residue, which was purified by flash chromato-
column to give 15 (0.30 g, 73%) as a foamy solid.
25
D
½aꢀ ¼ þ12:7 (c 1.0, CHCl3); d 8.04–7.15 (m, 85H,
17Ph), 6.12 (dd, 1H, J3;4 ¼ J4;5 ¼ 10:0 Hz, H-4), 6.08–
5.51 (m, 12H, 2H-2, 4H-3, 5H-4, –CH2–CH@CH2), 5.36
(s, 1H, H-1), 5.31 (s, 1H, H-1), 5.30–5.20 (m, 2H, –CH2–
CH@CH2), 5.30 (s, 1H, H-1), 5.18 (s, 1H, H-1), 5.12 (s,
1H, H-1), 5.11 (s, 1H, H-1), 4.66–3.92 (m, 26H, 4H-2,
2H-3, 6H-5, 12H-6, –CH2–CH@CH2); 13C NMR
(100 MHz, CDCl3): d 167.14, 166.75, 166.63, 166.16,
166.14, 166.10, 166.02, 165.97, 165.77, 165.73, 165.63,
165.56, 165.52, 165.37, 165.29, 165.09, 164.78, 100.28,
100.26, 99.92, 99.74, 98.81, 98.04, 72.96, 71.33, 71.20,
70.14, 70.04, 69.73, 69.67, 69.57, 69.20, 69.08, 68.78,
68.02, 66.94, 66.37, 65.29, 63.78, 63.66, 63.48, 63.33,
62.99, 62.16, 60.43. Anal. Calcd for C158H134O48: C,
67.76; H, 4.82. Found: C, 67.93; H, 4.91.
graphy (2:1 petroleum ether–EtOAc) to give 12 (0.46 g,
25
D
73% for two steps) as a foamy solid. ½aꢀ ¼ ꢁ69:5 (c 1.0,
1
CHCl3); H NMR (400 MHz, CDCl3): d 8.88 (s, 1H,
CNHCCl3), 8.05–7.26 (m, 55H, 11Ph), 6.56 (s, 1H, H-1),
6.12 (dd, 1H, J3
¼ 10:0 Hz, H-4000), 6.09 (dd,
000 ;4000
000 ;5000
¼ J4
¼ 10:0 Hz, H-400), 6.04–5.68 (m, 8H,
00 ;400
1H, J3
00 ;500
¼ J4
H-20, H-2000, H-3, H-30, H-300, H-3000, H-4, H-40), 5.36 (s,
1H, H-1000), 5.25 (s, 1H, H-100), 5.00 (d, 1H,
J1 ;2 ¼ 1:7 Hz, H-10), 4.67–3.72 (m, 14H, H-20, H-200, H-
5, H-6), 2.09 (s, 3H, CH3CO), 1.95 (s, 3H, CH3CO).
Anal. Calcd for C107H90Cl3NO34: C, 62.99; H, 4.45.
Found: C, 63.22; H, 4.53.
0
0
4.10. Allyl 2,3,4,6-tetra-O-benzoyl-a-
(1 fi 2)-3,4,6-tri-O-benzoyl-a- -mannopyranosyl-
(1 fi 6)-3-O-acetyl-2,4-di-O-benzoyl-a- -mannopyranos-
yl-(1 fi 2)-3-O-acetyl-4,6-di-O-benzoyl-a- -mannopyr-
anosyl-(1 fi 2)-3,4,6-tri-O-benzoyl-a- -mannopyranosyl-
(1 fi 2)-3,4,6-tri-O-benzoyl-a- -mannopyranoside 14
D-mannopyranosyl-
D
D
4.12. Allyl 2,3,4,6-tetra-O-benzoyl-a-
(1 fi 2)-3,4,6-tri-O-benzoyl-a- -mannopyranosyl-
(1 fi 6)-[2,3,5,6-tetra-O-benzoyl-b- -galactofuranosyl-
(1 fi 3)]-2,4-di-O-benzoyl-a- -mannopyranosyl-(1 fi 2)-
[2,3,5,6-tetra-O-benzoyl-b- -galactofuranosyl-(1 fi 3)]-
4,6-di-O-benzoyl-a- -mannopyranosyl-(1 fi 2)-3,4,6-tri-
O-benzoyl-a- -mannopyranosyl-(1 fi 2)-3,4,6-tri-O-benz-
oyl-a- -mannopyranoside 17
D-mannopyranosyl-
D
D
D
D
D
D
D
Compound 12 (0.46 g, 0.22 mmol) and 13 (0.27 g,
0.27 mmol) were coupled under the same conditions as
D
D
those used in the preparation of 10 from 7 and 9, giving
D
25
D
17 (0.44 g, 68%) as a foamy solid. ½aꢀ ¼ ꢁ16:5 (c 1.0,
1
CHCl3); H NMR (400 MHz, CDCl3): d 8.13–7.26 (m,
Acceptor 15 (0.29 g, 0.10 mmol) was coupled with donor
16 (0.18 g, 0.24 mmol) as described in the general pro-
cedure, and the product purified by chromatography
85H, 17Ph), 6.26 (dd, 1H, J3;4 ¼ J4;5 ¼ 10:0 Hz, H-4),
6.14–5.65 (m, 14H, 2H-2, 6H-3, 5H-4, –CH2–
CH@CH2), 5.42 (d, 1H, J1;2 ¼ 1:6 Hz, H-1), 5.30–5.18
(m, 2H, –CH2–CH@CH2), 5.27 (d, 1H, J1;2 ¼ 1:2 Hz, H-
1), 5.22 (d, 1H, J1;2 ¼ 1:1 Hz, H-1), 5.11 (d, 1H,
J1;2 ¼ 1:4 Hz, H-1), 5.08 (d, 1H, J1;2 ¼ 1:1 Hz, H-1), 4.94
with 1.5:1 petroleum ether–EtOAc as the eluent to give
25
D
17 (0.30 g, 73%) as a foamy solid. ½aꢀ ¼ ꢁ18:6 (c 1.0,
1
CHCl3); H NMR (400 MHz, CDCl3): d 8.14–6.89 (m,
125H, 25Ph), 6.32 (dd, 1H, J3;4 ¼ J4;5 ¼ 10:0 Hz, H-4),

Z. Ma et al. / Tetrahedron: Asymmetry 15 (2004) 1517–1525
1523
6.14–5.75 (m, 14H, Galf 2H-5, Manp 2H-2, 4H-3, 5H-4,
–CH2–CH@CH2), 5.57 (d, 1H, J3;4 ¼ 4:5 Hz, Galf H-3),
5.49 (d, 1H, J3;4 ¼ 5:1 Hz, Galf H-3), 5.48 (s, 2H, Galf
2H-1), 5.44 (s, 1H, Manp H-1), 5.41 (s, 2H, Galf 2H-2),
5.33 (s, 1H, Manp H-1), 5.29 (s, 2H, Manp 2H-1), 5.27–
5.13 (m, 2H, –CH2–CH@CH2), 4.95 (s, 1H, Manp H-1),
4.75–3.86 (m, 32H, Galf 2H-4, 4H-6, Manp 4H-2, 2H-3,
6H-5, 12H-6, –CH2–CH@CH2); 13C NMR (100 MHz,
CDCl3): d 167.07, 166.09, 165.95, 165.82, 165.69, 165.65,
165.57, 165.55, 165.52, 165.41, 165.33, 165.28, 165.26,
165.01, 164.99, 164.84, 164.77, 104.27, 102.24, 100.65,
100.56, 100.17, 99.74, 98.96, 97.98, 83.06, 82.83,
82.22, 81.62, 75.10, 73.91, 71.91, 71.59, 70.92, 70.20,
70.07, 69.94, 69.77, 69.66, 69.54, 68.99, 68.86,
68.73, 68.64, 67.88, 67.52, 67.25, 66.94, 66.63, 66.30,
65.74, 63.93, 63.71, 63.35, 62.08, 60.34. Anal. Calcd
for C226H186O66: C, 68.58; H, 4.74. Found: C, 68.75; H,
4.78.
H-1), 4.74 (dd, 1H, J3;4 ¼ 5:5 Hz, J2;3 ¼ 3:1 Hz, Galf H-
4), 4.60–3.82 (m, 10H, Galf H-6, Manp H-2, H-3, H-4,
H-5, H-6, –CH2–CH@CH2). Anal. Calcd for C50H46O15:
C, 67.71; H, 5.23. Found: C, 67.97; H, 5.30.
4.15. Allyl 2,3,5,6-tetra-O-benzoyl-b-D-galactofuranosyl-
(1 fi 3)-2-O-acetyl-4,6-di-O-benzylidene-a-
anoside 22
D-mannopyr-
To a solution of compound 21(0.42 g, 0.47 mmol) in
pyridine (10 mL) was added Ac2O (5 mL, 5 mmol). The
reaction mixture was stirred at rt for 12 h and concen-
trated to give the crude product, which was purified by
flash chromatography (2.5:1 petroleum ether–EtOAc) to
25
give 22 (0.42 g, 96%) as a foamy solid. ½aꢀ ¼ ꢁ14:5 (c
D
1.3, H2O); 1H NMR (400 MHz, CDCl3): d 8.02–7.16 (m,
25H, 5Ph), 5.95–5.85 (m, 2H, Galf H-5, –CH2–
CH@CH2), 5.53 (s, 1H, PhCH), 5.47 (d, 1H,
J3;4 ¼ 5:4 Hz, Galf H-3), 5.43 (s, 1H, Galf H-1), 5.42 (dd,
1H, J1;2 ¼ 1:4 Hz, J2;3 ¼ 3:5 Hz, Manp H-2), 5.41 (s, 1H,
Galf H-2), 5.33–5.22 (m, 2H, –CH2–CH@CH2), 4.86 (d,
1H, J1;2 ¼ 1:3 Hz, Manp H-1), 4.70 (dd, 1H,
J3;4 ¼ 5:3 Hz, J2;3 ¼ 3:0 Hz, Galf H-4), 4.64–3.81 (m, 9H,
Galf H-6, Manp H-3, H-4, H-5, H-6, –CH2–CH@CH2).
Anal. Calcd for C52H48O16: C, 67.23; H, 5.21. Found: C,
67.01; H, 5.15.
4.13. 2,3,4,6-Tetra-O-benzoyl-a-
(1 fi 2)-3,4,6-tri-O-benzoyl-a- -mannopyranosyl-
(1 fi 6)-[2,3,5,6-tetra-O-benzoyl-b- -galactofuranosyl-
(1 fi 3)]-2,4-di-O-benzoyl-a- -mannopyranosyl-(1 fi 2)-
[2,3,5,6-tetra-O-benzoyl-b- -galactofuranosyl-(1 fi 3)]-
4,6-di-O-benzoyl-a- -mannopyranosyl-(1 fi 2)-3,4,6-tri-
O-benzoyl-a- -mannopyranosyl-(1 fi 2)-3,4,6-tri-O-benz-
oyl-a- -mannopyranosyl trichloroacetimidate 19
D-mannopyranosyl-
D
D
D
D
D
D
D
4.16. Allyl 2,3,5,6-tetra-O-benzoyl-b-
(1 fi 3)-2-O-acetyl-4,6-di-O-benzoyl-a-
side 24
D
-galactofuranosyl-
D-mannopyrano-
Deallylation of tetrasaccharide 17 (0.28 g, 71 lmol) fol-
lowed by trichloroacetimidation under the same condi-
tions as those used for the preparation of 7 from 5 gave
a residue, which was purified by flash chromatography
Compound 22 (0.40 g, 0.43 mmol) was dissolved in 90%
TFA (10 mL), and the mixture stirred for 2 h at rt, at the
end of which time TLC (2:1 petroleum ether–EtOAc)
indicated that the reaction was complete. The mixture
was diluted with toluene (40 mL) and concentrated in
vacuo directly to give crude product 23. Benzoylation of
compound 23 under the same conditions used in the
preparation of 5 from 4 gave a residue, which was
purified by flash chromatography (3:1 petroleum ether–
EtOAc) to give 24 (0.31 g, 72% for two steps) as a foamy
(3:2 petroleum ether–EtOAc) to give 19 (0.20 g, 71% for
25
D
two steps) as a foamy solid. ½aꢀ ¼ ꢁ13:5 (c 1.0,
1
CHCl3); H NMR (400 MHz, CDCl3): d 8.63 (s, 1H,
CNHCCl3), 8.14–6.92 (m, 125H, 25Ph), 6.62 (s, 1H,
Manp H-1), 6.31 (dd, 1H, J3;4 ¼ J4;5 ¼ 10:4 Hz, H-4),
6.15–5.74 (m, 13H, Galf 2H-5, Manp 2H-2, 4H-3, 5H-4),
5.60 (s, 1H, Manp H-1), 5.57 (d, 1H, J3;4 ¼ 4:5 Hz, Galf
H-3), 5.50 (d, 1H, J3;4 ¼ 5:1 Hz, Galf H-3), 5.47 (s, 2H,
Galf 2H-1), 5.42 (s, 2H, Galf 2H-2), 5.33 (s, 2H, Manp
2H-1), 5.30 (s, 1H, Manp H-1), 4.92 (s, 1H, Manp H-1),
4.78–3.92 (m, 30H, Galf 2H-4, 4H-6, Manp 4H-2, 2H-3,
6H-5, 12H-6). Anal. Calcd for C225H182Cl3NO66: C,
66.53; H, 4.52. Found: C, 66.25; H, 4.44.
25
1
solid. ½aꢀ ¼ þ8:7 (c 1.0, CHCl3); H NMR (400 MHz,
D
CDCl3): d 8.03–7.15 (m, 30H, 6Ph), 5.98–5.86 (m, 2H,
Galf H-5, –CH2–CH@CH2), 5.72 (dd, 1H,
J3;4 ¼ J4;5 ¼ 10:0 Hz, Manp H-4), 5.49 (s, 1H, Galf H-1),
5.47 (dd, 1H, J1;2 ¼ 1:7 Hz, J2;3 ¼ 3:4 Hz, Manp H-2),
5.43 (d, 1H, J3;4 ¼ 5:1 Hz, Galf H-3), 5.35 (s, 1H, Galf
H-2), 5.33–5.22 (m, 2H, –CH2–CH@CH2), 4.98 (d, 1H,
J1;2 ¼ 1:7 Hz, Manp H-1), 4.70 (dd, 1H, J3;4 ¼ 5:3 Hz,
J2;3 ¼ 3:0 Hz, Galf H-4), 4.62–4.05 (m, 9H, Galf H-4, H-
6, Manp H-3, H-5, H-6, –CH2–CH@CH2). Anal. Calcd
for C59H52O18: C, 67.55; H, 5.00. Found: C, 67.63; H,
4.95.
4.14. Allyl 2,3,5,6-tetra-O-benzoyl-b-
D-galactofuranosyl-
(1 fi 3)-4,6-di-O-benzylidene-a- -mannopyranoside 21
D
As described in the general procedure, 16 (0.36 g,
0.49 mmol) and 20 (0.18 g, 0.59 mmol) were coupled,
and the product purified by silica-gel column chroma-
tography with 2.5:1 petroleum ether–EtOAc as the elu-
25
D
ent to give 7 (0.43 g, 71%) as a foamy solid. ½aꢀ ¼ þ10:2
1
(c 1.0, CHCl3); H NMR (400 MHz, CDCl3): d 8.04–
4.17. Allyl 2,3,5,6-tetra-O-benzoyl-b-
D-galactofuranosyl-
7.19 (m, 25H, 5Ph), 5.96–5.86 (m, 2H, Galf H-5, –CH2–
CH@CH2), 5.55 (dd, 1H, J2;3 ¼ 1:2 Hz, J3;4 ¼ 5:5 Hz,
Galf H-3), 5.50 (s, 1H, PhCH), 5.44 (s, 1H, Galf H-1),
5.43 (d, 1H, J2;3 ¼ 1:2 Hz, Galf H-2), 5.34–5.22 (m, 2H,
–CH2–CH@CH2), 4.99 (d, 1H, J1;2 ¼ 1:2 Hz, Manp
(1 fi 3)-4,6-di-O-benzoyl-a- -mannopyranoside 25
D
Deacetylation of 24 (0.29 g, 0.27 mmol) under the same
conditions as those used in the preparation of 15 from
14 gave the crude product, which was purified by flash

1524
Z. Ma et al. / Tetrahedron: Asymmetry 15 (2004) 1517–1525
chromatography (2.5:1 petroleum ether–EtOAc) to
furnish 25 (0.21 g, 75%) as a foamy solid. ½aꢀ ¼ þ17:2
4.20. Allyl 2,3,4,6-tetra-O-benzoyl-a-
(1 fi 2)-3,4,6-tri-O-benzoyl-a- -mannopyranosyl-
(1 fi 6)-[2,3,5,6-tetra-O-benzoyl-b- -galactofuranosyl-
(1 fi 3)]-2,4-di-O-benzoyl-a- -mannopyranosyl-(1 fi 2)-
[2,3,5,6-tetra-O-benzoyl-b- -galactofuranosyl-(1 fi 3)]-
4,6-di-O-benzoyl-a- -mannopyranosyl-(1 fi 2)-3,4,6-tri-
O-benzoyl-a- -mannopyranosyl-(1 fi 2)-3,4,6-tri-O-benz-
oyl-a- -mannopyranosyl-(1 fi 6)-2,3,4-tri-O-benzoyl-a-
D-mannopyranosyl-
D
D
1
(c 1.0, CHCl3); H NMR (400 MHz, CDCl3): d 8.00–
D
7.23 (m, 30H, 6Ph), 5.99–5.89 (m, 1H, –CH2–
CH@CH2), 5.82–5.77 (m, 2H, Galf H-5, Manp H-4),
5.58 (dd, 1H, J2;3 ¼ 1:5 Hz, J3;4 ¼ 5:1 Hz, Galf H-3), 5.47
(s, 1H, Galf H-1), 5.36 (d, 1H, J2;3 ¼ 1:5 Hz, Galf H-2),
5.33–5.22 (m, 2H, –CH2–CH@CH2), 5.10 (d, 1H,
J1;2 ¼ 1:4 Hz, Manp H-1), 5.47 (dd, 1H, J1;2 ¼ 1:7 Hz,
J2;3 ¼ 3:4 Hz, Manp H-2), 4.70 (dd, 1H, J3;4 ¼ 5:3 Hz,
J2;3 ¼ 3:0 Hz, Galf H-4), 4.57–4.12 (m, 10H, Galf H-4,
H-6, Manp H-2, H-3, H-5, H-6, –CH2–CH@CH2).
Anal. Calcd for C57H50O17: C, 67.99; H, 5.00. Found: C,
68.12; H, 5.09.
D
D
D
D
D
D
-mannopyranosyl-(1 fi 2)-[2,3,5,6-tetra-O-benzoyl-b-
D-
galactofuranosyl-(1 fi 3)]-4,6-di-O-benzoyl-a-
D-manno-
pyranoside 29
Donor 19 (0.19 g, 46 lmol) was coupled with acceptor 28
(82 mg, 55 lmol) as described in the general procedure
to give the crude product, which was purified by flash
chromatography (1.2:1 petroleum ether–EtOAc) to give
4.18. Allyl 6-O-acetyl-2,3,4-tri-O-benzoyl-a-
pyranosyl-[2,3,5,6-tetra-O-benzoyl-b- -galactofuranosyl-
(1 fi 3)]-4,6-di-O-benzoyl-a- -mannopyranoside 27
D
-manno-
target compound 29 (0.20 g, 79%) as a foamy
25
D
D
solid. ½aꢀ ¼ ꢁ41:7 (c 1.0, CHCl3); 1H NMR (400 MHz,
D
CDCl3): d 8.04–6.91 (m, 170H, 34Ph), 6.33 (dd, 1H,
J3;4 ¼ J4;5 ¼ 9:9 Hz, H-4), 6.21 (dd, 1H, J3;4
¼
Donor 26 (0.15 g, 0.22 mmol) was coupled with acceptor
25 (0.18 g, 0.18 mmol) as described in the general pro-
cedure, and the product purified by chromatography
J4;5 ¼ 10:0 Hz, H-4), 6.15–5.63 (m, 18H, Galf 3H-5,
Manp 3H-2, 5H-3, 6H-4, –CH2–CH@CH2), 5.59 (d, 1H,
J3;4 ¼ 4.4 Hz, Galf H-3), 5.50–5.46 (m, 5H, Galf 3H-1,
2H-3), 5.43 (s, 2H, Galf 2H-2), 5.34 (s, 1H, Manp H-1),
5.32 (s, 1H, Galf H-2), 5.28 (s, 1H, Manp H-1), 5.26 (s,
2H, Manp 2H-1), 5.24–5.07 (m, 2H, –CH2–CH@CH2),
5.23 (s, 2H, Manp 2H-1), 5.21 (s, 1H, Manp H-1), 4.92
(s, 1H, Manp H-1), 4.68–3.68 (m, 43H, Galf 3H-4, 6H-6,
Manp 5H-2, 3H-3, 8H-5, 16H-6, –CH2–CH@CH2); 13C
NMR (100 MHz, CDCl3): d 166.88, 166.23, 166.00,
165.94, 165.80, 165.75, 165.72, 165.55, 165.48, 165.43,
165.36, 165.29, 165.19, 165.16, 165.07, 164.76, 164.73,
164.64, 164.58, 163.17, 104.12, 102.73, 102.21, 101.12,
100.61, 100.19, 99.62, 98.83, 98.44, 98.32, 95.92, 82.85,
82.76, 82.62, 82.10, 81.50, 75.24, 74.78, 73.78, 72.87,
71.99, 71.72, 71.46, 70.33, 70.15, 69.98, 69.86, 69.79,
69.51, 69.36, 68.93, 68.74, 67.56, 67.20, 67.02, 66.85,
66.65, 66.51, 66.24, 66.05, 63.97, 63.75, 63.49, 63.21,
63.05, 61.83. Anal. Calcd for C307H252O90: C, 68.52; H,
4.72. Found: C, 68.78; H, 4.64.
with 2:1 petroleum ether–EtOAc as the eluent to give 27
25
D
(0.22 g, 78%) as a foamy solid. ½aꢀ ¼ ꢁ20:2 (c 1.0,
1
CHCl3); H NMR (400 MHz, CDCl3): d 8.09–6.98 (m,
45H, 9Ph), 6.07–5.88 (m, 6H, Galf H-5, Manp H-20, H-
30, H-4, H-40, –CH2–CH@CH2), 5.62 (d, 1H,
J1 ;2 ¼ 1:0 Hz, Manp H-10), 5.52 (d, 1H, J3;4 ¼ 4:4 Hz,
Galf H-3), 5.51 (s, 1H, Galf H-1), 5.43 (s, 1H, Galf H-2),
5.36–5.24 (m, 2H, –CH2–CH@CH2), 5.18 (d, 1H,
J1;2 ¼ 1:2 Hz, Manp H-1), 4.65–4.10 (m, 13H, Galf H-4,
H-6, Manp H-2, H-3, H-5, H-50, H-6, H-60, –CH2–
CH@CH2); 13C NMR (100 MHz, CDCl3): d 170.49,
166.32, 166.12, 165.62, 165.55, 165.11, 164.98, 164.63,
102.83, 100.70, 98.19, 82.82, 75.75, 72.73, 70.06, 69.74,
69.26, 69.05, 68.69, 67.64, 67.30, 64.06, 63.82, 63.07,
20.67. Anal. Calcd for C86H74O26: C, 67.80; H, 4.90.
Found: C, 68.03; H, 5.01.
0
0
4.19. Allyl 2,3,4-tri-O-benzoyl-a-
(1 fi 2)-[2,3,5,6-tetra-O-benzoyl-b-
(1 fi 3)]-4,6-di-O-benzoyl-a- -mannopyranoside 28
D
-mannopyranosyl-
D
-galactofuranosyl-
4.21. Allyl a-
anosyl-(1 fi 6)-[b-
mannopyranosyl-(1 fi 2)-[b-
a- -mannopyranosyl-(1 fi 2)-a-
D
-mannopyranosyl-(1 fi 2)-a-
-galactofuranosyl-(1 fi 3)]-a-
-galactofuranosyl-(1 fi 3)]-
-mannopyranosyl-
-mannopyranosyl-(1 fi 6)-a- -mannopyrano-
-galactofuranosyl-(1 fi 3)]-a- -manno-
D-mannopyr-
D
D
D-
D
Deacetylation of compound 27 (0.20 g, 0.13 mmol) was
carried out under the same conditions as those used in
the preparation of 15 from 14, giving the crude product,
which was purified by flash chromatography (2:1
D
D
(1 fi 2)-a-
D
D
syl-(1 fi 2)-[b-
D
D
pyranoside 30
petroleum ether–EtOAc) to give 28 (0.16 g, 81%) as a
25
D
foamy solid. ½aꢀ ¼ ꢁ52:5 (c 1.0, CHCl3); 1H NMR
Undecasaccharide 29 (0.19 g, 34 lmol) was dissolved in
satd NH3–MeOH (30 mL). After 96 h at rt, the reaction
mixture was concentrated, and the residue purified by
(400 MHz, CDCl3): d 7.98–6.99 (m, 45H, 9Ph), 6.12 (dd,
1H, J2 ;3 ¼ 3:4 Hz, J3 ;4 ¼ 10:0 Hz, Manp H-30) 6.05 (dd,
0
0
0
0
1H, J1 ;2 ¼ 1:5 Hz, J2 ;3 ¼ 3:4 Hz, Manp H-20), 5.98–5.87
(m, 3H, Galf H-5, Manp H-40, –CH2–CH@CH2), 5.84
(dd, 1H, J3;4 ¼ J4;5 ¼ 10:0 Hz, Manp H-4), 5.67 (d, 1H,
chromatography on Sephadex LH-20 (MeOH) to afford
0
0
0
0
25
30 (54 mg, 85%) as a foamy solid. ½aꢀ ¼ þ8:5 (c 1.0,
D
H2O); 1H NMR (400 MHz, D2O): d 5.88–5.98 (m,
1H, –CH2–CH@CH2), 5.35–5.31 (dd, 1H, J ¼ 17:1 Hz,
–CH2–CH@CHtrans), 5.26–5.24 (dd, 1H, J ¼ 10:4 Hz,
–CH2–CH@CHcis), 5.20, 5.16, 5.15, 5.11, 5.07, 5.02, 4.99
(7s, 11H, 11H-1); 13C NMR (100 MHz, D2 O): d 104.88,
104.85, 104.35, 102.28, 101.71, 101.61, 100.76, 100.69,
98.26, 98.10, 97.59, 78.79, 78.68, 78.47, 77.05, 76.84,
75.78, 75.55, 75.23, 74.24, 73.99, 73.34, 73.26, 73.21,
J1 ;2 ¼ 1:5 Hz, Manp H-10), 5.52 (d, 1H, J3;4 ¼ 4:9 Hz,
Galf H-3), 5.51 (s, 1H, Galf H-1), 5.42 (s, 1H, Galf H-2),
5.34–5.23 (m, 2H, –CH2–CH@CH2), 5.16 (d, 1H,
J1;2 ¼ 1:6 Hz, Manp H-1), 4.64–3.80 (m, 13H, Galf H-4,
H-6, Manp H-2, H-3, H-5, H-50, H-6, H-60, –CH2–
CH@CH2). Anal. Calcd for C84H72O25: C, 68.10; H,
4.90. Found: C, 68.21; H, 4.95.
0
0

Z. Ma et al. / Tetrahedron: Asymmetry 15 (2004) 1517–1525
1525
(c) Grando, S. A.; Hostager, B. S.; Herron, M. J.; Dahl,
M. V.; Nelson, R. D. J. Invest. Dermatol. 1992, 98, 876–
880.
72.95, 72.68, 71.80, 71.58, 70.72, 70.69, 70.64, 70.46,
70.32, 70.26, 70.03, 69.97, 69.91, 68.15, 67.09, 67.03,
66.89, 66.50, 65.97, 65.40, 65.29, 65.23, 64.51, 62.84,
62.78, 61.17, 60.94, 60.88, 60.82. Anal. Calcd for
C69H116O56: C, 45.00; H, 6.35. Found: C, 45.11; H, 6.38.
4. Ikuda, K.; Shibata, N.; Blake, J. S.; Dahl, M. V.; Nelson,
R. D.; Hisamichi, K.; Kobayashi, H.; Suzuki, S.; Okawa,
Y. Biochem. J. 1997, 323, 297–305.
5. Randell, K. D.; Johnston, B. D.; Brown, P. N.; Pinto,
B. M. Carbohydr. Res. 2000, 325, 253–262.
6. (a) Zhang, J.; Kong, F. Tetrahedron: Asymmetry 2002, 13,
243–252; (b) Kong, F. Curr. Org. Chem. 2003, 7, 841–865.
7. (a) Ma, Z.; Zhang, J.; Kong, F. Tetrahedron: Asymmetry
2003, 14, 2595–2603; (b) Zhang, J.; Ma, Z.; Kong, F.
Carbohydr. Res. 2003, 338, 2039–2046; (c) Zhang, J.;
Kong, F. Bioorg. Med. Chem. 2003, 11, 4027–4037.
8. Zhang, J.; Ma, Z.; Kong, F. Carbohydr. Res. 2003, 338,
1711–1718.
Acknowledgements
This work was supported by The Chinese Academy of
Sciences (KZCX3-J-08) and by The National Natural
Science Foundation of China (Projects 30070185 and
39970864).
9. Zhu, Y.; Kong, F. Synlett 2000, 1783–1787.
10. Ogawa, T.; Yamamoto, H. Carbohydr. Res. 1985, 137, 79–
86.
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