Concise syntheses of arabinogalactans with β-(1→6)-linked galactopyranose backbones and α-(1→3)- and α-(1→2)-linked arabinofuranose side chains

Article abstract of DOI:10.1016/j.bmc.2004.10.035

4-Methoxyphenyl glycosides of 2,3″-bis-α-l-arabinofuranosyl branched β-d-(1→6)-linked galactopyranosyl tetraose (16), 3′,2″″-bis-α-l-arabinofuranosyl branched β-d-(1→6)-linked galactopyranosyl hexaose (27), and a twentyose (42) consisting of β-(1→6)-linked d-galactopyranosyl pentadecaoligosaccharide backbone with α-l-arabinofuranosyl side chains alternately attached at C-2 and C-3 of the middle galactose residue of each consecutive β-(1→6)-linked galactotriose unit of the backbone, were synthesized with isopropyl 3-O-allyl-2,4-di-O-benzoyl-1-thio-β-d- galactopyranoside (6), 2,3,4,6-tetra-O-benzoyl-α-d-galactopyranosyl trichloroacetimidate (7), 2,3,5-tri-O-benzoyl-α-l-arabinofuranosyl trichloroacetimidate (12), 6-O-acetyl-2,3,4-tri-O-benzoyl-α-d- galactopyranosyl trichloroacetimidate (17), 4-methoxyphenyl 2,3,4-tri-O-benzoyl- β-d-galactopyranoside (19), and 2,6-di-O-acetyl-3,4-di-O-benzoyl-α-d- galactopyranosyl trichloroacetimidate (28) as the key synthons. Condensation of 6 with 7 gave the disaccharide donor 8, and subsequent condensation of 8 with 4-methoxyphenyl 2,3,4-tri-O-benzoyl-β-d-galactopyranosyl-(1→6)-2-O- acetyl-3,4-di-O-benzoyl-β-d-galactopyranoside (9) followed by selective deacetylation afforded the tetrasaccharide acceptor 11. Coupling of 11 with 12 gave the pentasaccharide 13, its deallylation followed by coupling with 12, and debenzoylation gave the hexasaccharide 16 with β-(1→6)-linked galactopyranose backbone and 2- and 3″-linked α-l-arabinofuranose side chains. The octasaccharide 27 was similarly synthesized, while the twentyoside 42 was synthesized with tetrasaccharides 33 or 24 as the donors and 23, 36, 38, and 40 as the acceptors by consecutive couplings followed by deacylation.

Full text of DOI:10.1016/j.bmc.2004.10.035

Bioorganic & Medicinal Chemistry 13 (2005) 839–853
Concise syntheses of arabinogalactans with b-(1!6)-linked
galactopyranose backbones and a-(1!3)- and a-(1!2)-linked
arabinofuranose side chains
Aixiao Li and Fanzuo Kong*
Research Center for Eco-Environmental Sciences, Academia Sinica, PO Box 2871, Beijing 100085, PR China
Received 9 September 2004; revised 14 October 2004; accepted 16 October 2004
Abstract—4-Methoxyphenyl glycosides of 2,300-bis-a-L-arabinofuranosyl branched b-D-(1!6)-linked galactopyranosyl tetraose (16),
30,20000-bis-a-L-arabinofuranosyl branched b-D-(1!6)-linked galactopyranosyl hexaose (27), and a twentyose (42) consisting of b-
(1!6)-linked D-galactopyranosyl pentadecaoligosaccharide backbone with a-L-arabinofuranosyl side chains alternately attached
at C-2 and C-3 of the middle galactose residue of each consecutive b-(1!6)-linked galactotriose unit of the backbone, were synthe-
sized with isopropyl 3-O-allyl-2,4-di-O-benzoyl-1-thio-b-D-galactopyranoside (6), 2,3,4,6-tetra-O-benzoyl-a-D-galactopyranosyl
trichloroacetimidate (7), 2,3,5-tri-O-benzoyl-a-L-arabinofuranosyl trichloroacetimidate (12), 6-O-acetyl-2,3,4-tri-O-benzoyl-a-D-
galactopyranosyl trichloroacetimidate (17), 4-methoxyphenyl 2,3,4-tri-O-benzoyl-b-D-galactopyranoside (19), and 2,6-di-O-acetyl-
3,4-di-O-benzoyl-a-D-galactopyranosyl trichloroacetimidate (28) as the key synthons. Condensation of 6 with 7 gave the disacchar-
ide donor 8, and subsequent condensation of 8 with 4-methoxyphenyl 2,3,4-tri-O-benzoyl-b-D-galactopyranosyl-(1!6)-2-O-acetyl-
3,4-di-O-benzoyl-b-D-galactopyranoside (9) followed by selective deacetylation afforded the tetrasaccharide acceptor 11. Coupling
of 11 with 12 gave the pentasaccharide 13, its deallylation followed by coupling with 12, and debenzoylation gave the hexasaccharide
16 with b-(1!6)-linked galactopyranose backbone and 2- and 300-linked a-L-arabinofuranose side chains. The octasaccharide 27 was
similarly synthesized, while the twentyoside 42 was synthesized with tetrasaccharides 33 or 24 as the donors and 23, 36, 38, and 40 as
the acceptors by consecutive couplings followed by deacylation.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
reticuloendothelial system activating properties.5 The
arabinogalactans with b-(1!6)-linked galactopyranose
backbone and a-(1!2)-linked arabinofuranose side
chains may exist in Echinacea purpurea, which have
immunomodulating activity,1a while b-(1!6)-linked
galactan containing at least three galactopyranosyl
residues functionalized at 3-OH with an a-linked L-arab-
inofuranose unit was supposed to be the epitope recog-
nized by the CCRC-M7 antibody.6 Although the
presence of 2,6- and 3,6-branched residues in arabinoga-
lactan is well known, the exact structure of these saccha-
rides remains to be established. Thus far, there has been
no definite conclusion regarding the core structure or
fragment of arabinogalactans with immunomodulating
activity. Is the arabinogalactan with b-(16)-linked
galactopyranose backbone and a-(1!2)-linked arabin-
ofuranose side chains active, or the arabinogalactan
with the same backbone but with a-(1!3)-linked arab-
inofuranose branches active, or the arabinogalactan
with the same backbone but with mixed a-(1!2)- and
a-(1!3)-linked arabinofuranose branches active? To
Arabinogalactans from certain sources have immuno-
modulating activity,1 and they are often classified in
three groups: arabino-4-galactans (Type I), arabino-
3,6-galactans (Type II), and polysaccharides with arab-
inogalactan side chains.2 The latter type is also called
the real pectins. One of the first arabinogalactans for
which an activity on the complement system was shown
was an arabinogalactan from a hot water extract of the
roots of the Chinese herb Angelica acutiloba,3 such
activity was not found in arabinogalactan from larch
wood.4 An arabinogalactan isolated from the roots of
Saposhnikova divaricata or Panex notoginseng had
Keywords: Arabinofuranose; Galactopyranose; Regio- and stereo-
selective synthesis.
*
Corresponding author. Tel.: +86 1062936613; fax: +86
1062923563; e-mail: fzkong@mail.rcees.ac.cn
0968-0896/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmc.2004.10.035

840
A. Li, F. Kong / Bioorg. Med. Chem. 13 (2005) 839–853
answer this question, the synthesis of a series model
structures of arabinogalactans, and consequent study
on the biological activity of the synthetic samples is
necessary.
tri-O-benzoyl-a-L-arabinofuranosyl
trichloroacetimi-
date (12)14 gave the pentasaccharide 13 (87%). Deallyl-
ation of 13 with PdCl2 followed by coupling with 12,
and finally deacylation with saturated NH3–MeOH gave
the target hexasaccharide 16 consisting of b-(1!6)-
linked galactopyranosyl tetrasaccharide backbone and
a-L-arabinofuranose side chains at C-2 and C-300,
respectively.
Some examples on the chemical syntheses of the 2-arab-
inofuranosyl branched galactans7,8 and 3-arabinofuran-
osyl branched galactans9 have been reported. Since most
of the synthetic samples were obtained very recently,
there has been no report regarding their bioactivity so
far. We believe that after the successful syntheses of
samples with definite and different structures of arabino-
galactans and their bioactivity study, the puzzle regard-
ing the active core structure of arabinogalactans will be
solved soon. As a part of this effort, we present herein
convergent syntheses of a hexasaccharide consisting of
b-(1!6)-linked galactose tetrasaccharide backbone with
2- and 300-arabinose side chains, an octasaccharide con-
sisting of b-(1!6)-linked galactose hexasaccharide
backbone with 30- and 20000-arabinose side chains and a
twentysaccharide consisting of b-(1!6)-linked galactose
pentadecasaccharide backbone with arabinofuranose
side chains alternately attached at C-2 and C-3 of the
middle galactose residue of each consecutive b-(1!6)-
linked galactotriose unit of the backbone.
The octasaccharide 27 was prepared in a similar way as
outlined in Scheme 2. Coupling of the donor 1710 with
the acceptor 6 produced the disaccharide 18 that was
coupled with the acceptor 1910 to give the trisaccharide
20. Subsequent deallylation followed by coupling with
12 gave 22,9b then oxidative cleavage of 4-methoxyphenyl
group and tricholoroacetimidate formation gave the
tetrasaccharide donor 24. Meanwhile, selective deacetyl-
ation of 22 gave 23.9b Condensation of the donor 2510
with the acceptor 23 followed by deacylation gave the
target octasaccharide 27 consisting of two tetrasac-
charide fragments, one of which had b-(1!6)-linked
galactopyranosyl trisaccharide backbone with a-L-arab-
inofuranose side chain at C-30, and another one had the
same backbone but with a-L-arabinofuranose side chain
at C-20.
The twentysaccharide 42 was synthesized according to
Scheme 3. Coupling of the donor 2810 with the acceptor
19 produced the disaccharide 29, and subsequent selec-
tive 20,60-O-deacetylation with MeCOCl/CH2Cl2/MeOH
(3mL/50mL/50mL) yielded the disaccharide acceptor
30. Condensation of 17 with the acceptor 30 regio-
and sterospecifically afforded the trisaccharide 31 in
81% yield. No (1!2)-linked trisaccharide was detected
2. Results and discussion
In the past few years, most of the synthetic work was fo-
cused on tetrasaccharide or trisaccharide of the arabino-
galactans7,8 and our group contributed, very recently,
the facile syntheses of higher arabinogalactans including
octaoses and nonaoses with b-(1!6)-linked galactose
backbone and a-(1!3)-,9 and a-(1!2)-linked arabinose
side chains.10 However, with the reported methods, only
the arabinogalactans with either sole a-(1!3)-linked
arabinose branches or sole a-(1!2)-linked arabinose
branches could be synthesized, the arabinogalactans
with mixed a-(1!3)- and a-(1!2)-linked side chains
could not be achieved by the reported methods. We pre-
sent herewith concise syntheses of the arabinogalactans
with both a-(1!3)- and a-(1!2)-linked arabinose
branches. Scheme 1 shows the synthesis of hexasacchar-
ides 16. Isopropyl 1-thio-b-D-galactopyranoside (3),
prepared readily from penta-O-acetyl-b-D-galactopyra-
nose 1 by coupling with isopropyl thiol and subsequent
deacetylation, was chosen as the starting material. Selec-
tive 3-O-allylation of 3 via dibutyltin complex11 gave
compound 4 in satisfactory yield (79%), and subsequent
selective 6-O-tritylation followed by benzoylation and
detritylation produced the glycosyl acceptor 6. Conden-
sation of 6 with perbenzoylated galactopyranosyl tri-
chloroacetimidate12 7 afforded the disaccharide 8.
Then, condensation of 4-methoxyphenyl 2,3,4-tri-O-
benzoyl-b-D-galactopyranosyl-(1!6)-2-O-acetyl-3,4-di-
O-benzoyl-b-D-galactopyranoside (9)10 with 8 gave the
tetrasaccharide 10 (92%) with two potential hydroxyl
groups at C-2 and C-300, respectively. Thus, selective
deacetylation13 of 10 with MeCOCl/CH2Cl2/MeOH
(3mL/50mL/50mL) afforded the tetrasaccharide accep-
tor 11 (78%), and subsequent condensation with 2,3,5-
1
from H NMR and TLC. Coupling of the acceptor 31
with 12 afforded the tetrasaccharide 32, subsequent
oxidative cleavage of 4-methoxyphenyl group and trichl-
oroacetimidate formation gave the tetrasaccharide
donor 33, while selective removal of 600-O-acetyl group
of 32 afforded the tetrasaccharide acceptor 34. The octa-
saccharide acceptor 36 was obtained from condensation
of 23 with 33 followed by 6-O-deacetylation with Me-
COCl/CH2Cl2/MeOH. Condensation of 24 with the
acceptor 36 afforded 37, subsequent 6-O-deacetylation
yielded the dodecasaccharide acceptor 38. Coupling of
38 with 33 followed by deacetylation produced the hexa-
decasaccharide acceptor 40. Then condensation of the
donor 24 with the acceptor 40 followed by deacylation
gave the target twentysaccharide 42.
In the above syntheses, selective deacetylations of 22 to
give 23, 32 to give 34, 35 to give 36, 37 to give 38, and 39
to give 40, went out smoothly with no benzoyl group
migration as indicated by TLC that showed a neat spot
for the product. Also the couplings of 25 with 23, 33
with 23, 24 with 36, 38 with 33, and 40 with 24, were car-
ried out easily with high yields indicating the high activ-
ity of the primary OH of the acceptors. The b-(1!6)-
linkages of galactopyranose and a-(1!2)- or a-(1!3)-
linkages of arabinofuranose were also confirmed by
the 1H and 13C NMR spectra of the compounds9,10 from
the chemical shifts and coupling constants of specific
signals.

A. Li, F. Kong / Bioorg. Med. Chem. 13 (2005) 839–853
841
OH
OH
OAc
O
OH
AllO
OH
HO
OAc
O
OAc
AcO
OAc
AcO
b
c
O
d
O
a
SiPr
O
SiPr
SiPr
OAc
SiPr
OH
OH
OAc
OAc
4
3
2
1
OBz
OBz
O
OBz
O
OH
OTr
O
OBz
OBz
AllO
BzO
OBz
AllO
f
BzO
O
BzO
e
6
+
O
SiPr
BzO
SiPr
OBz
OBz
AllO
OBz
OCNHCCl3
OBz
7
6
5
8
OBz
OBz
BzO
O
O
BzO
BzO
OH
O
OBz
O
O
AllO
O
BzO
BzO
8
BzO
h
BzO
O
BzO
g
O
O
BzO
OMp
BzO
BzO
BzO
OAc
O
10
OMp
9
BzO
OAc
OBz
O
OBz
BzO
OBz
OBz
BzO
OCNHCCl3
O
OBz
O
O
O
BzO
BzO
BzO
AllO
BzO
BzO
O
OBz
O
12
O
i
O
AllO
BzO
BzO
f
BzO
BzO
O
O
O
BzO
O
BzO
BzO
BzO
BzO
13
BzO
O
11
O
OMp
BzO
OMp
BzO
O
OBz
O
OH
OBz
O
BzO
OR
OBz
BzO
OR
RO
OBz
O
O
O
BzO
BzO
RO
RO
O
O
O
BzO
O
15 R = Bz
16 R= H
HO
O
O
OR
j
12
BzO
RO
RO
RO
O
O
O
O
O
RO
f
BzO
BzO
OR
BzO
RO
RO
RO
14
O
O
OMp
OMp
BzO
O
OBz
O
O
OR
BzO
RO
OBz
OR
Schcme 1. Reagents and conditions: (a) CH2Cl2, iPrSH, Et2OÆBF3, rt, 1.5h, 75%. (b) CH3OH/CH3ONa, pH10, rt, 5h, 81%. (c) CH3OH, Bu2SnO,
reflux 2h, then AllBr, Bu4NI, toluene, 60ꢁC, 24h, 79%. (d) Trityl chloride, (1.1equiv), pyridine, 50ꢁC, 24h, then PhCOCl, (2.4equiv), 50ꢁC,
overnight, 71%. (e) 1:500:500 MeCOCl/CH3OH/CH2Cl2, rt, 3h, 80%. (f) TMSOTf, CH2Cl2, ꢀ20ꢁC to rt, 2–4h; 85% for 8, 87% for 13, 89% for 15. (g)
TMSOTf (0.1–0.5equiv), CH2Cl2, NIS (1.5equiv), ꢀ20ꢁC to rt, 2–4h; 92%. (h) 3:50:50 MeCOCl/CH3OH/CH2Cl2, rt, 48h, 78%. (i) PdCl2, CH3OH,
40ꢁC, 5h, 90% (j) satd NH3/MeOH, rt, 7d, 90%.
An alternative strategy of 8+12 for the preparation of
42 was also carried out. Thus, coupling of the tetrasac-
charide acceptor 34 with the donor 24 followed by C-1-
activation gave the octasaccharide trichloroacetimidate

842
A. Li, F. Kong / Bioorg. Med. Chem. 13 (2005) 839–853
OAc
O
OH
OBz
OMp BzO
OBz
BzO
OAc
O
OBz
BzO
20 R = All
21 R = H
O
O
c
O
OAc
O
BzO
OBz
BzO
BzO
OBz
BzO
O
a
19
BzO
O
6
+
O
RO
SiPr
BzO
BzO
b
BzO
AllO
OCNHCCl3
O
OBz
OMp
18
17
BzO
BzO
OAc
OBz
BzO
O
O
BzO
BzO
12
O
O
a
O
O
OBz
BzO
BzO
O
OMp
OBz
BzO
BzO
OBz
BzO
22
d
e
OH
O
OAc
OBz
BzO
O
O
O
BzO
BzO
BzO
BzO
BzO
O
O
BzO
O
O
O
O
O
OBz
O
OBz
BzO
BzO
BzO
O
O
OMp
BzO
BzO
BzO
BzO
OBz
OBz
BzO
BzO
OR
OCNHCCl3
24
23
OR
O
O
RO
RO
RO
RO
OBz
OBz
BzO
O
O
O
RO
O
a
RO
RO
26 R = Bz
O
O
23
BzO
O
f
+
BzO
OR
O
27 R = H
O
O
RO
BzO
OR
OR
BzO
BzO
O
O
O
O
O
OBz
RO
BzO
RO
RO
BzO
OBz
25
O
OCNHCCl3
O
O
O
OR
RO
RO
RO
O
OMp
RO
OR
RO
Schcme 2. Reagents and conditions: (a) TMSOTf, CH2Cl2, ꢀ20ꢁC to rt, 2–4h; 83% for 18, 81% for 26. (b) TMSOTf (0.1–0.5equiv), CH2Cl2, NIS
(1.5equiv), ꢀ20ꢁC to rt, 2–4h; 90%. (c) PdCl2, CH3OH, 40ꢁC, 5h, 94%. (d) 1:50:50 MeCOCl/CH3OH/CH2Cl2, rt, 48h, 87%. (e) (i) CAN in MeCN–
H2O, rt, 0.5h; (ii) CH2Cl2, CCl3CN, K2CO3, rt, 10h. (f) satd NH3/MeOH, rt, 7d, 85%.
44. However, when the donor 44 was reacted with the
dodecasaccharide acceptor 38, very complex and hardly
separated product was obtained. This indicated that the
octasaccharide donor did not match the dodecasacchar-
ide acceptor, and tetrasaccharides were suitable building
blocks for preparation of high arabinogalactans.

A. Li, F. Kong / Bioorg. Med. Chem. 13 (2005) 839–853
843
R1
OBz
O
29 R1 = R2 = OAc
30 R1 = R2 = OH
OH
OAc
O
O
OBz
BzO
OBz
BzO
b
BzO
a
O
R2
BzO
+
OMp
O
OBz
OMp
OAc
BzO
OCNHCCl3
OBz
19
28
OAc
OBz
O
O
OAc
BzO
OBz
BzO
BzO
12
BzO
O
30
O
O
a
a
BzO
OBz
BzO
BzO
HO
31
OCNHCCl3
O
OMp
17
BzO
R3
OBz
BzO
32 R1 = OMp, R2 = H, R3 = OAc
O
O
c
33 R1 = H, R2 = OC(NH)CCl3, R3 = OAc
BzO
BzO
BzO
O
32 R1 = OMp, R2 = H, R3 = OAc
34 R1 = OMp, R2 = H, R3 = OH
O
BzO
d
BzO
O
O
O
OBz
R1
R2
BzO
BzO
BzO
OBz
OR
O
OBz
O
BzO
BzO
O
O
a
BzO
BzO
23
O
35 R = Ac
36 R = H
33
OR
+
O
O
d
24
O
OBz
BzO
a
BzO
OBz
BzO
BzO
OBz
O
O
OBz
O
O
BzO
BzO
BzO
BzO
BzO
O
O
O
O
O
O
BzO
BzO
BzO
O
OBz
O
BzO
BzO
O
O
OBz
OMp
O
BzO
BzO
BzO
BzO
BzO
OBz
OBz
OBz
O
O
BzO
BzO
BzO
O
O
BzO
37 R = Ac
38 R = H
BzO
d
33
O
O
OBz
O
O
a
BzO
BzO
BzO
OBz
O
OBz
O
BzO
BzO
BzO
O
O
O
BzO
O
BzO
O
OBz
OMp
BzO
BzO
BzO
OBz
Schcme 3. Reagents and conditions: (a) TMSOTf, CH2Cl2, ꢀ20ꢁC to rt, 2–4h; 89% for 29, 81% for 31, 89% for 32, 81% for 35, 75% for 37, 71%
for 39, 65% for 41, 81% for 43. (b) 3:50:50 MeCOCl/CH3OH/CH2Cl2, rt, 48h, 71%. (c) (i) CAN in MeCN–H2O, rt, 0.5h; (ii) CH2Cl2, CCl3CN,
K2CO3, rt, 10h. (d) 1:50:50 MeCOCl/CH3OH/CH2Cl2, rt, 48h; 83% for 34, 81% for 36, 71% for 38, 71% for 40. (e) satd NH3/MeOH, rt, 7d,
85%.

844
A. Li, F. Kong / Bioorg. Med. Chem. 13 (2005) 839–853
OR
O
BzO
BzO
O
BzO
BzO
O
O
BzO
BzO
O
O
BzO
O
O
OBz
BzO
O
O
BzO
BzO
OBz
BzO
BzO
BzO
O
O
39 R = Ac
40 R = H
24
d
BzO
O
O
BzO
O
O
a
OBz
BzO
BzO
BzO
BzO
O
O
OBz
BzO
BzO
BzO
O
O
R1O
BzO
BzO
O
O
O
O
OBz
BzO
BzO BzO
BzO
RO
RO
O
O
O
BzO
O
OBz
O
O
RO
BzO
BzO
O
RO
O
RO
O
BzO
O
O
O
O
BzO
RO
O
OMp
O
OR
OBz
RO
BzO
RO
O
BzO
RO
O
BzO
RO
OBz
O
O
RO
OR
RO
RO
RO
O
O
RO
O
O
RO
RO
OR
RO
RO
O
O
OR
2
O
O
RO
RO
RO
41 R = Bz, R1 = Ac
42 R = H, R1 = H
RO
O
e
OMp
O
OR
O
OR
RO
RO
OAc
O
RO
OBz
OR
O
BzO
BzO
BzO
O
O
O
O
OBz
BzO
BzO
O
BzO
O
BzO
BzO
43 R1 = OMp, R2 = H
BzO
OBz
c
O
44 R1 = H, R2 = OC(NH)CCl3
a
O
BzO
24
34
+
BzO
BzO
O
O
BzO
BzO
O
O
OBz
O
R1
R2
BzO
BzO
BzO
OBz
a
44
+
38
Scheme 3 (continued)
3. Conclusion
of hexaose, octaose, and twentyose consisting of b-D-
galactopyranosyl (1!6)-linked backbone and a-L-arab-
inofuranosyl side chains linked at C-2 or C-3 of the
galactose residue. This method is simple, highly regio-
In summary, here we described a method by which we
can efficiently synthesize 4-methoxyphenyl glycosides

A. Li, F. Kong / Bioorg. Med. Chem. 13 (2005) 839–853
845
and chemoselective, and can be used in preparation of
structurally different arabinogalactans.
for 24h, at the end of which time TLC (1:1 petroleum
ether–EtOAc) indicated that the reaction was complete.
The reaction mixture was cooled to 0ꢁC, and then
benzoyl chloride (17.2mL, 123mmol) was added drop-
wise within 30min to keep the reaction temperature at
0ꢁC. The mixture was stirred at 50ꢁC for 12h. Water
(300mL) was added to the reaction mixture, and
stirring was continued for 30min. The mixture was
extracted with CH2Cl2 (3 · 100mL), and the combined
extracts were washed with 1N HCl and satd aq
NaHCO3, dried (Na2SO4) and concentrated to a syrup
that was subjected to column chromatography with
5:1 petroleum ether–EtOAc as the eluent to give 5
(30.0g, 71%) as a solid. To a solution of 5 (30.0g,
41.2mmol) in CH3OH (100mL)–CH2Cl2 (100mL) was
added CH3COCl (0.2mL) and the mixture was stirred
at rt for 3h, at the end of which time TLC (2:1 petro-
leum ether–EtOAc) indicated that the reaction was com-
plete. The mixture was neutralized with triethylamine,
then concentrated, and the residue was passed
through a silica gel column with 2:1 petroleum ether–
EtOAc as the eluent to give 6 (15.6g, 80%) as a syrup.
4. Experimental
4.1. General methods
Optical rotations were determined at 25ꢁC with a Per-
kin–Elmer Model 241-Mc automatic polarimeter. 1H
NMR and 13C NMR spectra were recorded with
Bruker ARX 400 spectrometers (400MHz for 1H,
100MHz for 13C) for solutions in CDCl3 or D2O as indi-
cated. Chemical shifts are given in ppm downfield 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
mode. Thin-layer chromatography (TLC) was per-
formed 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 · 240mm, 18 · 300mm,
35 · 400mm) of silica gel (100–200 mesh) with EtOAc–
petroleum ether (60–90ꢁC) as the eluent. Solutions were
concentrated at <60ꢁC under reduced pressure.
1
[a]D +5.4 (c 1.0, CHCl3); H NMR (400Hz, CDCl3) d
8.11–7.23 (m, 10H, 2Ph), 5.69 (d, 1H, J3,4 = 3.2Hz, H-
4), 5.67 (m, 1H, CH2@CH–CH2O), 5.58 (dd, 1H,
J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 5.17–5.03 (m, 2H,
CH2@CH–CH2O), 4.75 (d, 1H, J1,2 = 8Hz, H-1), 4.08–
3.95 (m, 2H, CH2@CH–CH2O), 3.87 (dd, 1H,
J3,4 = 3.2, J2,3 = 10.4Hz, H-3), 3.79 (dd, 1H, J5,6 = 6.4,
J6,6 = 12.0Hz, H-6), 3.58 (dd, 1H, J5,6 = 6.4,
J6,6 = 12.0Hz, H-6), 3.23 (m, 1H, H-5). Anal. Calcd
for C26H30O7S: C, 64.17; H, 6.21. Found: C, 64.32; H,
6.19.
4.2. Isopropyl 3-O-allyl-2,4-di-O-benzoyl-1-thio-b-D-gal-
actopyranoside (6)
To a solution of 1,2,3,4,6-penta-O-acetyl-b-D-galacto-
pyranose (50.0g, 128mmol) in CH2Cl2 was added
Et2OÆBF3 (33.0mL) and iPrSH (17.0mL). The mixture
was stirred at rt for 1.5h, at the end of which time
TLC (2:1 petroleum ether–EtOAc) indicated that the
reaction was complete. The reaction mixture was neu-
tralized with dry Na2CO3, and then extracted with
CH2Cl2 (3 · 200mL). The combined extracts were con-
centrated to a syrup that was subjected to column chro-
matography with 3:1 petroleum ether–EtOAc as the
eluent to give compound 2 (40.5g, 75%) as a syrup.
To a solution of compound 2 (40.5g, 97.3mmol) in
CH3OH (200mL) was added 4.0M CH3ONa–CH3OH
solution dropwise to pH10. After stirring the mixture
at rt for 5h, TLC (5:1 EtOAc–CH3OH) indicated that
the reaction was complete. The reaction mixture was
neutralized with 1:10 HOAc–CH3OH, then the mixture
was concentrated, and the residue was purified by col-
umn chromatography (5:1 EtOAc–CH3OH) to give 3
(18.7g, 81%) as a syrup. To a solution of 3 (18.7g,
78.5mmol) in dry CH3OH (300mL) was added Bu2SnO
(22.9g, 91.9mmol), and the mixture was heated under
reflux for 2h, then concentrated to dryness. The residue
was diluted with toluene (300mL), and then allyl bro-
mide (87mL, 1.0mol), Bu4NI (28.9g, 78.5mol) were
added to the mixture. The reaction was carried out at
60ꢁC for 24h, at the end of which time TLC (EtOAc)
indicated that the reaction was complete. The reaction
mixture was concentrated, and the residue was purified
by column chromatography (1:1 petroleum ether–
EtOAc) to give 4 (17.1g, 79%) as a solid. A solution
of 4 (17.1g, 58.1mmol) and trityl chloride (17.8g,
63.9mmol) in pyridine (150mL) was stirred at 50ꢁC
4.3. Isopropyl 2,3,4,6-tetra-O-benzoyl-b-D-galactopyrano-
syl-(1!6)-3-O-allyl-2,4-di-O-benzoyl-1-thio-b-D-galacto-
pyranoside (8)
A solution of 6 (2.4g, 4.9mmol) and 2,3,4,6-tetra-O-
7
benzoyl-a-D-galactopyranosyl trichloroacetimidate
(4g, 5.4mmol) in dry CH2Cl2 (100mL) was stirred.
TMSOTf (40lL) was added dropwise at ꢀ20ꢁC with
nitrogen protection. The reaction mixture was stirred
for 2h, during which time the temperature gradually
raised to an ambient temperature. Then the mixture
was neutralized with triethylamine. Concentration of
the reaction mixture followed by purification on a silica
gel column with 3:1 petroleum ether–EtOAc as the elu-
ent gave 8 (4.8g, 85%) as a syrup. [a]D +13.4 (c 1.0,
CHCl3); 1H NMR (400Hz, CDCl3) d 8.11–7.23 (m,
30H, 6Ph), 5.94 (d, 1H, J3,4 = 3.2Hz, H-4), 5.80–5.68
(m, 2H, H-2, H-4), 5.68–5.58 (m, 1H, CH2@CH–
CH2O), 5.56 (dd, 1H, J2,3 = 10.4, J3,4 = 3.2Hz, H-3),
5.43 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 5.17–5.00
(m, 2H, CH2@CH–CH2O), 4.87 (d, 1H, J1,2 = 8.0Hz,
H-1), 4.67 (d, 1H, J1,2 = 8.0Hz, H-1), 4.43 (dd, 1H,
J5,6 = 6.0, J6,6 = 10.4Hz, H-6), 4.12–3.97 (m, 3H,
CH2@CH–CH2O, H-5), 3.87 (dd, 1H, J5,6 = 6.0,
J6,6 = 10.4Hz, H-6), 3.77 (dd, 1H, J3,4 = 3.2,
J2,3 = 10.4Hz, H-3), 3.05 (m, 1H, H-5). Anal. Calcd
for C60H56O16S: C, 67.65; H, 5.30. Found: C, 67.59;
H, 5.26.

846
A. Li, F. Kong / Bioorg. Med. Chem. 13 (2005) 839–853
4.4. 4-Methoxyphenyl 2,3,4,6-tetra-O-benzoyl-b-D-galac-
topyranosyl-(1!6)-3-O-allyl-2,4-di-O-benzoyl-b-D-galac-
topyranosyl-(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyr-
anosyl-(1!6)-2-O-acetyl-3,4-di-O-benzoyl-b-D-galacto-
pyranoside (10)
10.4Hz, H-3), 5.46 (dd, 1H, J3,4 = 3.4, J2,3 = 10.4Hz,
H-3), 5.35 (dd, 1H, J3,4 = 3.2, J2,3 10.4Hz, H-3), 5.13–
5.00 (m, 2H, CH2@CH–CH2O), 4.98 (d, 1H,
J1,2 = 8.0Hz, H-1), 4.77 (d, 1H, J1,2 = 8.0Hz, H-1),
4.57 (d, 1H, J1,2 = 8.0Hz, H-1), 4.37 (d, 1H,
J1,2 = 8.0Hz, H-1), 4.20 (dd, 1H, J5,6 = 5.4,
J6,6 = 11.2Hz, H-6), 4.10–3.93 (m, 8H, CH2@CH–
CH2O, H-2, H-5, 4H-6), 3.82 (s, 3H, CH3O), 3.60
(dd, 1H, J3,4 = 3.2, J2,3 = 10.4Hz, H-3); 13C
NMR (100MHz, CDCl3) d 165.8, 165.7, 165.6, 165.5,
165.4, 165.3, 165.3, 165.2, 165.2, 165.1, 165.0 (11C,
11COPh), 100.9, 100.9, 100.8, 100.6 (4C, 4C-1). Anal.
Calcd for C111H96O33: C, 68.09; H, 4.94. Found: C,
68.29; H, 4.72.
To a solution of 4-methoxyphenyl 2,3,4-tri-O-benzoyl-
b-D-galactopyranosyl-(1!6)-2-O-acetyl-3,4-di-O-benzoyl-
b-D-galactopyranoside (9, 1.9g, 1.88mmol) and 8 (2.0g,
1.88mmol) in dry CH2Cl2 (80mL) were added NIS
(635mg, 2.84mmol) and TMSOTf (169lL, 0.94mmol)
at ꢀ20ꢁC, the reaction mixture was stirred for 4h,
during which time the reaction temperature gradually
raised to ambient temperature. Then the reaction mix-
ture was worked up by conventional procedure, and
the product was purified on a silica gel column with
2:1 petroleum ether–EtOAc as the eluent to give 10
(3.45g, 92%) as a foamy solid. [a]D +42.3 (c 1.0, CHCl3);
1H NMR (400Hz, CDCl3) d 8.13–7.26 (m, 55H, 11Ph),
6.96 (d, 2H, J = 9.1Hz, CH3OC6H4O–), 6.83 (d, 2H,
J = 9.1Hz, CH3OC6H4O–), 5.88–5.86 (m, 2H, 2H-4),
5.83 (d, 1H, J3,4 = 3.2Hz, H-4), 5.70 (d, 1H,
J3,4 = 3.2Hz, H-4), 5.68 (dd, 1H, J1,2 = 8.0, J2,3
10.4Hz, H-2), 5.65–5.62 (m, 2H, H-2), 5.60–5.56 (m,
1H, CH2@CH–CH2O), 5.53 (dd, 1H, J3,4 = 3.2,
J2,3 = 10.4Hz, H-3), 5.46 (dd, 1H, J3,4 = 3.4,
J2,3 = 10.4Hz, H-3), 5.35 (dd, 1H, J3,4 = 3.2, J2,3
10.4Hz, H-3), 5.30 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz,
H-2), 5.13–5.00 (m, 2H, CH2@CH–CH2O), 4.98
(d, 1H, J1,2 = 8.0Hz, H-1), 4.77 (d, 1H, J1,2 = 8.0Hz,
H-1), 4.57 (d, 1H, J1,2 = 8.0Hz, H-1), 4.37 (d,
1H, J1,2 = 8.0Hz, H-1), 4.20 (dd, 1H, J5,6 = 5.4,
J6,6 = 11.2Hz, H-6), 4.11–3.95 (m, 7H, CH2@CH–
CH2O, 1H-5, 4H-6), 3.92 (s, 3H, CH3O), 3.60 (dd, 1H,
J3,4 = 3.2, J2,3 = 10.4Hz, H-3), 1.99 (s, 3H, CH3CO);
13C NMR (100MHz, CDCl3) d 170.0 (1C, 1CH3CO),
165.8, 165.7, 165.6, 165.5, 165.4, 165.3, 165.3, 165.2,
165.2, 165.1, 165.0 (11C, 11COPh), 100.9, 100.9, 100.8,
100.6 (4C, 4C-1). Anal. Calcd for C113H98O34: C,
67.86; H, 4.84. Found: C, 67.99; H, 4.80.
4.6. 4-Methoxyphenyl 2,3,4,6-tetra-O-benzoyl-b-D-galac-
topyranosyl-(1!6)-3-O-allyl-2,4-di-O-benzoyl-b-D-galac-
topyranosyl-(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyr-
anosyl-(1!6)-[2,3,5-tri-O-benzoyl-a-L-arabinofuranosyl-
(1!2)]-3,4-di-O-benzoyl-b-D-galactopyranoside (13)
Coupling of 11 (2.63g, 1.34mmol) and 12 (978mg,
1.61mmol) in anhyd CH2Cl2 (80mL) was carried out
by the same procedure as described in the coupling of
6 and 7. Purification by chromatography with 1.5:1
petroleum ether–EtOAc as the eluent gave 13 as a foamy
1
solid (2.8g, 87%). [a]D +53.4 (c 1.0, CHCl3); H NMR
(400Hz, CDCl3) d 8.13–7.23 (m, 70H, 14Ph), 6.92 (d,
2H, J = 9.1Hz, CH3OC6H4O–), 6.83 (d, 2H,
J = 9.1Hz, CH3OC6H4O–), 5.87–5.86 (m, 2H, 2H-4),
5.82 (d, 1H, J3,4 = 3.4Hz, H-4), 5.69 (d, 1H,
J3,4 = 3.4Hz, H-4), 5.64 (dd, 1H, J1,2 = 8.0, J2,3
=
10.4Hz, H-2), 5.63–5.57 (m, 2H, 1H-2, CH2@CH–
CH2O), 5.51 (s, 1H, Araf-H-1), 5.50–5.41 (m, 3H),
5.38 (d, 1H, J2,3 = 1.2Hz, Araf-H-2), 5.26 (dd, 1H,
J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 5.13–5.00 (m, 2H,
CH2@CH–CH2O), 4.97 (d, 1H, J1,2 = 8.0Hz, H-1),
4.77 (d, 1H, J1,2 = 8.0Hz, H-1), 4.53 (d, 1H,
J1,2 = 8.0Hz, H-1), 4.51 (dd, 1H, J1,2 = 8.0,
J2,3 = 10.4Hz, H-2), 4.37 (d, 1H, J1,2 = 8.0Hz, H-1),
4.17 (dd, 1H, J5,6 = 5.4, J6,6 = 11.2Hz, H-6), 4.10–3.70
(m, 11H, CH2@CH–CH2O, 2H-5, 7H-6), 3.68 (s, 3H,
CH3O), 3.60 (dd, 1H, J3,4 = 3.4, J2,3 = 10.4Hz, H-3);
13C NMR (100MHz, CDCl3) d 166.2, 165.8, 165.7,
165.6, 165.5, 165.4, 165.3, 165.2, 165.2, 165.1, 165.0,
165.0, 165.0, 164.9 (14C, 14COPh), 106.3 (Araf-C-1),
101.9, 101.8, 100.7, 100.6 (4Galp-C-1). Anal. Calcd for
C137H116O40: C, 68.49; H, 4.87. Found: C, 68.22; H,
4.73.
4.5. 4-Methoxyphenyl 2,3,4,6-tetra-O-benzoyl-b-D-galac-
topyranosyl-(1!6)-3-O-allyl-2,4-di-O-benzoyl-b-D-galac-
topyranosyl-(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyr-
anosyl-(1!6)-3,4-di-O-benzoyl-b-D-galactopyranoside
(11)
To a solution of 10 (3.45g, 1.72mmol) in CH3OH
(50mL)–CH2Cl2 (50mL) was added CH3COCl (3mL),
and the mixture was stirred at rt for 48h, at the end of
which time TLC (2:1 petroleum ether–EtOAc) indicated
that the reaction was complete. The mixture was neu-
tralized with triethylamine, and then concentrated, and
the residue was passed through a silica gel column with
2:1 petroleum ether–EtOAc as the eluent to give 11
(3.25g, 78%) as a foamy solid. [a]D +39.2 (c 1.0, CHCl3);
1H NMR (400Hz, CDCl3) d 8.14–7.23 (m, 55H, 11Ph),
6.96 (d, 2H, J = 9.1Hz, CH3OC6H4O–), 6.83 (d, 2H,
J = 9.1Hz, CH3OC6H4O–), 5.88–5.86 (m, 2H, 2H-4),
4.7. 4-Methoxyphenyl 2,3,4,6-tetra-O-benzoyl-b-D-galac-
topyranosyl-(1!6)-2,4-di-O-benzoyl-b-D-galactopyranos-
yl-(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyranosyl-
(1!6)-[2,3,5-tri-O-benzoyl-a-L-arabinofuranosyl-(1!2)]-
3,4-di-O-benzoyl-b-D-galactopyranoside (14)
To a solution of 13 (2.8g, 1.16mmol) in anhyd CH3OH
(50mL) was added PdCl2 (100mg), and the mixture was
stirred at rt for 5h, at the end of which time TLC (1:1
petroleum ether–EtOAc) indicated that the reaction
was complete. The mixture was filtered, and the filtrate
was concentrated. The residue was passed through a sil-
ica gel column with 1.5:1 petroleum ether–EtOAc as the
5.81 (d, 1H, J3,4 = 3.2Hz, H-4), 5.70 (d, 1H, J3,4
3.2Hz, H-4), 5.68 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz,
=
H-2), 5.65–5.62 (m, 2H, 2H-2), 5.60–5.56 (m, 1H,
CH2@CH–CH2O), 5.53 (dd, 1H, J3,4 = 3.2, J2,3
=

A. Li, F. Kong / Bioorg. Med. Chem. 13 (2005) 839–853
847
eluent to give 14 as a foamy solid (2.47g, 90%). [a]D
+69.6 (c 1.0, CHCl3); 1H NMR (400Hz, CDCl3) d
8.13–7.23 (m, 70H, 14Ph), 6.92 (d, 2H, J = 9.1Hz,
CH3OC6H4O–), 6.83 (d, 2H, J = 9.1Hz, CH3OC6H4O–),
5.86–5.83 (m, 3H, 3H-4), 5.66 (d, 1H, J3,4 = 3.4Hz, H-
4), 5.64–5.60 (m, 2H, H-2), 5.53 (s, 1H, Araf-H-1),
5.52–5.48 (m, 2H, 2H-3), 5.44 (dd, 1H, J3,4 = 3.4,
J2,3 = 10.4Hz, H-3), 5.38 (d, 1H, J2,3 = 1.2Hz, Araf-H-
2), 5.14 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 4.97
(d, 1H, J1,2 = 8.0Hz, H-1), 4.78 (d, 1H, J1,2 = 8.0Hz,
H-1), 4.53 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 4.51
(d, 1H, J1,2 = 8.0Hz, H-1), 4.45 (d, 1H, J1,2 = 8.0Hz,
H-1), 4.17 (dd, 1H, J5,6 = 5.4, J6,6 = 11.2Hz, H-6), 3.73
(s, 3H, CH3O); 13C NMR (100MHz, CDCl3) d 166.2,
165.8, 165.7, 165.6, 165.5, 165.4, 165.3, 165.2, 165.2,
165.1, 165.0, 165.0, 165.0, 164.9 (14C, 14COPh), 107.1
(Araf-C-1), 102.0, 101.9, 100.9, 100.7 (4Galp-C-1). Anal.
Calcd for C134H112O40: C, 68.13; H, 4.78. Found: C,
68.29; H, 4.70.
J = 9.1Hz, CH3OC6H4O–), 5.25 (s, 1H, Araf-H-1),
5.13 (s, 1H, Araf-H-1), 5.00 (d, 1H, J1,2 = 8.0Hz, H-1),
4.70 (d, 1H, J1,2 = 7.6Hz, H-1), 4.37 (d, 1H,
J1,2 = 7.6Hz, H-1), 4.34 (d, 1H, J1,2 = 7.6Hz, H-1); 13C
NMR (100MHz, D2O) d 109.3, 108.5 (2Araf-C-1),
103.4, 103.2, 103.1, 102.1 (4Galp-C-1). Anal. Calcd
for C41H64O30: C, 47.48; H, 6.22. Found: C, 47.63; H,
6.32.
4.10. Isopropyl 6-O-acetyl-2,3,4-tri-O-benzoyl-b-D-galac-
topyranosyl-(1!6)-3-O-allyl-2,4-di-O-benzoyl-1-thio-b-
D-galactopyranoside (18)
Coupling of 6 (3.0g, 6.17mmol) with 17 (4.6g,
6.79mmol) under the same conditions as described in
the coupling of 6 with 7 gave 18 as a foamy solid (puri-
fied with 3:1 petroleum ether–EtOAc, 5.1g, 83%). [a]D
+35.4 (c 1.0, CHCl3); 1H NMR (400Hz, CDCl3) d
8.11–7.23 (m, 25H, 5Ph), 5.83 (d, 1H, J3,4 = 3.2Hz, H-
4), 5.78 (m, 1H, J3,4 = 3.2Hz, H-4), 5.74 (dd, 1H,
J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 5.68–5.60 (m, 1H,
4.8. 4-Methoxyphenyl 2,3,4,6-tetra-O-benzoyl-b-D-galac-
topyranosyl-(1!6)-[2,3,5-tri-O-benzoyl-a-L-arabino-
furanosyl-(1!3)]-2,4-di-O-benzoyl-b-D-galactopyranosyl-
(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyranosyl-(1!6)-
[2,3,5-tri-O-benzoyl-a-L-arabinofuranosyl-(1!2)]-3,4-di-
O-benzoyl-b-D-galactopyranoside (15)
CH2@CH–CH2O), 5.47 (dd, 1H, J3,4 = 3.2, J2,3
=
10.4Hz, H-3), 5.43 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz,
H-2), 5.17–5.02 (m, 2H, CH2@CH–CH2O), 4.83
(d, 1H, J1,2 = 8.0Hz, H-1), 4.65 (d, 1H, J1,2 = 8.0Hz,
H-1), 4.14–4.05 (m, 4H, CH2@CH–CH2O, 2H-6), 3.82
(dd, 1H, J5,6 = 6.0, J6,6 = 10.4Hz, H-6), 3.77 (dd, 1H,
J3,4 = 3.2, J2,3 = 10.4Hz, H-3). Anal. Calcd for
C55H54O16S: C, 65.85; H, 5.43. Found: C, 65.79; H,
5.36.
Coupling of 12 (308mg, 0.51mmol) with 14 (1 g,
0.42mmol) in anhyd CH2Cl2 (50mL) was carried out
using the same procedure as described in the coupling
of 6 and 7, and 15 was obtained as a foamy solid (puri-
fied with 1.5:1 petroleum ether–EtOAc, 1.05g, 89%).
4.11. 4-Methoxyphenyl 6-O-acetyl-2,3,4-tri-O-benzoyl-b-
D-galactopyranosyl-(1!6)-3-O-allyl-2,4-di-O-benzoyl-b-
D-galactopyranosyl-(1!6)-2,3,4-tri-O-benzoyl-b-D-galac-
topyranoside (20)
1
[a]D +63.1 (c 1.0, CHCl3); H NMR (400Hz, CDCl3) d
8.09–7.21 (m, 85H, 17Ph), 6.92 (d, 2H, J = 9.1Hz,
CH3OC6H4O–), 6.83 (d, 2H, J = 9.1Hz, CH3OC6H4O–),
5.88 (d, 1H, J3,4 = 3.4Hz, H-4), 5.83 (d, 1H,
J3,4 = 3.4Hz, H-4), 5.79–5.75 (m, 2H, 2H-4), 5.68–5.59
(m, 3H, 3H-2), 5.53–5.42 (m, 4H, Araf-H-1, 3H-3),
5.38 (s, 1H, Araf-H-1), 5.27 (d, 1H, J2,3 = 1.2Hz,
Araf-H-2), 5.23 (d, 1H, J2,3 = 1.2Hz, Araf-H-2), 4.97
(d, 1H, J1,2 = 8.0Hz, H-1), 4.78 (d, 1H, J1,2 = 8.0Hz,
H-1), 4.52 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 4.51
(d, 1H, J1,2 = 8.0Hz, H-1), 4.33 (d, 1H, J1,2 = 8.0Hz,
H-1), 3.65 (s, 3H, CH3O); 13C NMR (100MHz, CDCl3)
d 166.2, 166.6, 165.9, 165.8, 165.7, 165.6, 165.5, 165.4,
165.3, 165.2, 165.2, 165.1, 165.1, 165.0, 164.9, 164.6,
163.2 (17C, 17COPh), 107.6, 106.3 (2Araf-C-1), 101.9,
101.1, 100.9, 100.6 (4Galp-C-1). Anal. Calcd for
C160H132O47: C, 68.46; H, 4.63. Found: C, 68.67; H,
4.70.
Coupling of 18 (8.0g, 8.0mmol) with 19 (4.0g,
6.7mmol) in anhyd CH2Cl2 (80mL) was carried out by
the same procedure as described in the coupling of 8
with 9. Purification by chromatography with 2:1 petro-
leum ether–EtOAc as the eluent gave 209b as a syrup
(8.8g, 87%). Deallylation of 20 followed by coupling
with 12 gave 22.9b
4.12. 6-O-Acetyl-2,3,4-tri-O-benzoyl-b-D-galactopyranos-
yl-(1!6)-[2,3,5-tri-O-benzoyl-a-L-arabinofuranosyl-
(1!3)]-2,4-di-O-benzoyl-b-D-galactopyranosyl-(1!6)-
2,3,4-tri-O-benzoyl-a-D-galactopyranosyl trichloroacet-
imidate (24)
To a solution of 22 (7.0g, 3.6mmol) in 4:1 CH3CN–H2O
(100mL) was added CAN (8.0g, 14.4mmol), and the
mixture was stirred at rt for 30min, at the end of which
time TLC (1:1 petroleum ether–EtOAc) indicated that
the reaction was complete. The mixture was extracted
with CH2Cl2 (5 · 50mL) and washed with water. The
organic layer was concentrated, and the crude hemi-
acetal was purified by column chromatography (2:1 petro-
leum ether–EtOAc) to afford a solid (5.7g, 3.1mmol).
To a solution of the solid in CH2Cl2 (80mL) were added
trichloroacetonitrile (1.0mL, 10mmol) and anhyd
potassium carbonate (1.7g, 12mmol). The reaction mix-
ture was stirred overnight at rt and then filtered, and the
4.9. 4-Methoxyphenyl b-D-galactopyranosyl-(1!6)-[a-L-
arabinofuranosyl-(1!3)]-b-D-galactopyranosyl-(1!6)-b-
D-galactopyranosyl-(1!6)-[a-L-arabinofuranosyl-(1!2)]-
b-D-galactopyranoside (16)
Compound 15 (300mg, 0.083mmol) was dissolved in a
satd solution of NH3 in MeOH (50mL). After a week
at rt, the reaction mixture was concentrated, and the resi-
due was purified by chromatography on Sephadex LH-
20 (MeOH) to afford 16 (99mg, 90%) as an amorphous
solid. [a]D +38.9 (c 1.0, H2O); 1H NMR (400MHz, D2O)
d 7.09 (d, 2H, J = 9.1Hz, CH3OC6H4O–), 6.91 (d, 2H,

848
A. Li, F. Kong / Bioorg. Med. Chem. 13 (2005) 839–853
filtrate was concentrated in vacuo. The residue was puri-
fied by column chromatography (2:1 petroleum ether–
EtOAc) to give 24 as a syrup (5.0g, 69% for two steps).
LH-20 (MeOH) to afford 27 (154mg, 85%) as an
amorphous solid. [a]D +24.9 (c 1.0, H2O); 1H NMR
(400MHz, D2O) d 7.08 (d, 2H, J = 9.1Hz, CH3O-
C6H4O–), 6.72 (d, 2H, J = 9.1Hz, CH3OC6H4O–), 5.17
(s, 1H, H-1, Araf-H-1), 5.09 (s, 1H, H-1, Araf-H-1),
4.87 (d, 1H, J1,2 = 7.6Hz, H-1), 4.70 (d, 1H,
J1,2 = 7.6Hz, H-1), 4.64 (d, 1H, J1,2 = 7.6Hz, H-1),
4.47 (d, 1H, J1,2 = 8.0Hz, H-1), 4.34 (d, 1H,
J1,2 = 7.6Hz, H-1), 4.26 (d, 1H, J1,2 = 7.6Hz, H-1); 13C
NMR (100MHz, D2O) d 109.3, 108.3 (2Araf-C-1),
103.4, 103.2, 103.2, 102.9, 102.1, 101.6 (6Galp-C-1).
Anal. Calcd for C53H84O40: C, 46.76; H, 6.22. Found:
C, 46.51; H, 6.39.
1
[a]D +61.4 (c 1.0, CHCl3); H NMR (400Hz, CDCl3) d
8.67 (s, 1H, NH), 8.07–7.21 (m, 55H, 11Ph), 6.73 (d,
1H, J1,2 = 3.6Hz, H-1), 6.05 (d, 1H, J3,4 = 3.6Hz, H-
4), 6.01–5.95 (m, 2H), 5.81 (d, 1H, J3,4 = 3.6Hz, H-4),
5.78 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 5.71 (d,
1H, J3,4 = 3.6Hz, H-4), 5.65 (dd, 1H, J2,3 = 10.4,
J3,4 = 3.6Hz, H-3), 5.61 (dd, 1H, J2,3 = 10.4, J3,4
=
3.6Hz, H-3), 5.58 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz,
H-2), 5.48–5.42 (m, 2H), 5.27 (s, 1H, Araf-H-1), 5.23
(d, 1H, J2,3 = 1.2Hz, Araf-H-2), 4.96 (d, 1H, J1,2
=
8.0Hz, H-1), 4.56 (d, 1H, J1,2 = 8.0Hz, H-1), 4.52 (d,
1H, J1,2 = 8.0Hz, H-1); 13C NMR (CDCl3, 100MHz):
d 171.6 (1C, CH3CO), 166.1, 165.8, 165.7, 165.5,
165.4, 165.3, 165.2, 165.2, 165.1, 164.9, 164.5 (11C,
11COPh), 107.6 (Araf-C-1), 101.5, 100.8, 100.5 (3Galp-
C-1). Anal. Calcd for C104H86Cl3NO32: C, 63.46; H,
4.40. Found: C, 64.22; H, 4.28.
4.15. 4-Methoxyphenyl 2,6-di-O-acetyl-3,4-di-O-benzoyl-
b-D-galactopyranosyl-(1!6)-2,3,4-tri-O-benzoyl-b-D-gal-
actopyranoside (29)
Coupling of 19 (6.0g, 10mmol) with 28 (7.4g,
12mmol) under the same conditions as described for
the coupling of 6 with 7 gave disaccharide 29 (9.4g,
1
89%) as a foamy solid. [a]D +57.6 (c 1.0, CHCl3); H
4.13. 4-Methoxyphenyl 2,3,4,6-tetra-O-benzoyl-b-D-
galactopyranosyl-(1!6)-[2,3,5-tri-O-benzoyl-a-L-arabino-
furanosyl-(1!2)]-3,4-di-O-benzoyl-b-D-galactopyranosyl-
(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyranosyl-(1!6)-
2,3,4-tri-O-benzoyl-b-D-galactopyranosyl-(1!6)-[2,3,5-
tri-O-benzoyl-a-L-arabinofuranosyl-(1!3)]-2,4-di-O-benz-
oyl-b-D-galactopyranosyl-(1!6)-2,3,4-tri-O-benzoyl-b-D-
galactopyranoside (26)
NMR (400MHz, CDCl3) d 8.12–7.26 (m, 25H, 5Ph),
7.02 (d, 2H, J = 9.2Hz, CH3OC6H4O–), 6.84 (d, 2H,
J = 9.2Hz, CH3OC6H4O–), 6.03 (dd, 1H, J2,1 = 8.0,
J2,3 = 10.4Hz, H-2), 5.97 (d, 1H, J3,4 = 3.6Hz, H-4),
5.79 (d, 1H, J3,4 = 3.6Hz, H-4), 5.62 (dd, 1H,
J2,3 = 10.4, J3,4 = 3.6Hz, H-3), 5.52 (dd, 1H, J2,1 = 8.0,
J2,3 = 10.4Hz, H-2), 5.33 (dd, 1H, J2,3 = 10.4, J3,4
=
3.6Hz, H-3), 5.27 (d, 1H, J1,2 = 8.0Hz, H-1), 4.73 (d,
1H, J1,2 = 8.0Hz, H-1), 3.97 (dd, 1H, J5,6 = 6.6,
J6,6 = 10.8Hz, H-6), 3.72 (s, 3H, OCH3), 2.00 (s,
3H, CH3CO), 1.86 (s, 3H, CH3CO). Anal. Calcd
for C58H52O19: C, 66.15; H, 4.98. Found: C, 66.27; H,
4.89.
Coupling of 23 (1.0g, 0.53mmol) with 25 (1.29g,
0.64mmol) under the same conditions as described for
the coupling of 6 with 7 gave octasaccharide 26
(1.65g, 81%) as a foamy solid. [a]D +43.6 (c 1.0, CHCl3);
1H NMR (400MHz, CDCl3) d 8.03–7.19 (m, 115H,
23Ph), 6.96 (d, 2H, J = 9.1Hz, CH3OC6H4O–), 6.86
(d, 2H, J = 9.1Hz, CH3OC6H4O–), 5.95–5.90 (m, 3H,
1H-2, 2H-4), 5.84–5.79 (m, 3H, 3H-4), 5.73 (d, 1H,
J3,4 = 3.6Hz, H-4), 5.62–5.47 (m, 10H), 5.42 (s, 1H,
Araf-H-1), 5.36 (d, 1H, J2,3 = 1.2Hz, Araf-H-2), 5.26
(s, 1H, Araf-H-1), 5.24 (d, 1H, J2,3 = 1.2Hz, Araf-H-
2), 5.10 (d, 1H, J1,2 = 8.0Hz, H-1), 4.74–4.68 (m, 3H),
4.54 (d, 1H, J1,2 = 8.0Hz, H-1), 4.15 (d, 1H,
J1,2 = 8.0Hz, H-1), 3.64 (s, 3H, OCH3); 13C NMR
(100MHz, CDCl3) d 166.2, 166.1, 166.0, 165.8, 165.7,
165.6, 165.6, 165.5, 165.4, 165.4, 165.3, 165.3, 165.2,
165.1, 165.0, 165.0, 164.9, 164.9, 164.8, 164.7, 164.7,
164.6, 164.6 (23C, 23COPh), 107.6, 106.5 (2Araf-C-1),
101.6, 101.5, 101.1, 100.9, 100.6, 100.5 (6Galp-C-1).
Anal. Calcd for C214H176O63: C, 68.43; H, 4.72. Found:
C, 68.37; H, 4.81.
4.16. 4-Methoxyphenyl 3,4-di-O-benzoyl-b-D-galactopyr-
anosyl-(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyranoside
(30)
To a solution of 29 (9.4g, 8.9mmol) in CH3OH
(50mL)–CH2Cl2 (50mL) was added CH3COCl (3mL),
and the mixture was stirred at rt for 48h, at the end of
which time TLC (1:1 petroleum ether–EtOAc) indicated
that the reaction was complete. The mixture was neu-
tralized with triethylamine, then concentrated, and the
residue was passed through a silica gel column with
2:1 petroleum ether–EtOAc as the eluent to give 30
(6.3g, 71%) as a foamy solid. [a]D +40.2 (c 1.0, CHCl3);
1H NMR (400MHz, CDCl3) d 8.06–7.25 (m, 25H, 5Ph),
7.01 (d, 2H, J = 9.2Hz, CH3OC6H4O–), 6.80 (d, 2H,
J = 9.2Hz, CH3OC6H4O–), 6.07 (d, 1H, J3,4 = 3.6Hz,
H-4), 6.01 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz, H-2),
5.67 (d, 1H, J3,4 = 3.6Hz, H-4), 5.64 (dd, 1H,
4.14. 4-Methoxyphenyl b-D-galactopyranosyl-(1!6)-[a-
L-arabinofuranosyl-(1!2)]-b-D-galactopyranosyl-(1!6)-
b-D-galactopyranosyl-(1!6)-b-D-galactopyranosyl-(1!
6)-[a-L-arabinofuranosyl-(1!3)]-b-D-galactopyranosyl-
(1!6)-b-D-galactopyranoside (27)
J2,3 = 10.4, J3,4 = 3.6Hz, H-3), 5.31 (dd, 1H, J2,3
=
10.4, J3,4 = 3.6Hz, H-3), 5.28 (d, 1H, J1,2 = 8.0Hz,
H-1), 4.56 (d, 1H, J1,2 = 8.0Hz, H-1), 4.16 (dd, 1H,
J5,6 = 6.4, J6,6 = 10.8Hz, H-6), 4.08 (dd, 1H, J1,2 = 8.0,
J2,3 = 10.4Hz, H-2), 3.71 (s, 3H, OCH3), 3.52 (dd,
1H, J5,6 = 6.8, J6,6 = 12Hz, H-6), 3.35 (dd, 1H,
J5,6 = 6.8, J6,6 = 12Hz, H-6). Anal. Calcd for
C54H48O17: C, 68.12; H, 4.81. Found: C, 68.27; H,
4.89.
Compound 26 (500mg, 0.13mmol) was dissolved in a
satd solution of NH3 in MeOH (50mL). After a week
at rt, the reaction mixture was concentrated, and the
residue was purified by chromatography on Sephadex

A. Li, F. Kong / Bioorg. Med. Chem. 13 (2005) 839–853
849
4.17. 4-Methoxyphenyl 6-O-acetyl-2,3,4-tri-O-benzoyl-b-
D-galactopyranosyl-(1!6)-3,4-di-O-benzoyl-b-D-galacto-
pyranosyl-(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyrano-
side (31)
mixture was treated by the same procedure as described
in the preparation of 24 to give 33 (5.0g, 70% for two
steps) as a syrup. [a]D +46.2 (c 1.0, CHCl3); H NMR
1
(400MHz, CDCl3) d 8.65 (s, 1H, NH), 8.26–7.17 (m,
55H, 11Ph), 6.71 (d, 1H, J1,2 = 3.6Hz, H-1), 6.04 (d,
1H, J3,4 = 3.6Hz, H-4), 5.87 (dd, 1H, J1,2 = 3.6,
J2,3 = 10.4Hz, H-2), 5.80 (d, 1H, J3,4 = 3.6Hz, H-4),
5.77 (d, 1H, J3,4 = 3.6Hz, H-4), 5.68 (dd, 1H,
J2,3 = 10.4, J3,4 = 3.6Hz, H-3), 5.56 (dd, 1H, J1,2 = 8.0,
J2,3 = 10.4Hz, H-2), 5.48 (s, 1H, Araf-H-1), 5.43–5.41
(m, 2H), 5.38 (d, 1H, J2,3 = 1.6Hz, Araf-H-2), 4.79 (d,
1H, J1,2 = 8.0Hz, H-1), 4.61 (d, 1H, J1,2 = 8.0Hz, H-
1), 4.31 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 2.00
(s, 3H, CH3CO); 13C NMR (100MHz, CDCl3) d 171.9
(1C, CH3CO), 166.1, 166.0, 165.7, 165.7, 165.5, 165.4,
165.3, 165.2, 165.2, 165.1, 165.0 (11C, 11COPh), 106.9
(Ara f-C-1), 101.5, 101.4, 101.0 (3Galp C-1). Anal.
Calcd for C104H86Cl3NO32: C, 63.46; H, 4.40. Found:
C, 63.22; H, 4.28.
Coupling of 30 (6.0g, 6.0mmol) with 17 (4.4g, 6.4mmol)
under the same conditions as described in the coupling of
6 with 7 gave 31 as a syrup (purified with 2:1 petroleum
ether–EtOAc, 7.1g, 81%). [a]D +67.4 (c 1.0, CHCl3); 1H
NMR (400Hz, CDCl3) d 8.11–7.25 (m, 40H, 8Ph), 7.00
(d, 2H, J = 9.2Hz, CH3OC6H4O–), 6.79 (d, 2H,
J = 9.2Hz, CH3OC6H4O–), 6.05 (dd, 1H, J1,2 = 8.0,
J2,3 = 10.4Hz, H-2), 6.01 (d, 1H, J3,4 = 3.2Hz, H-4),
5.90 (m, 1H, J3,4 = 3.2Hz, H-4), 5.78 (m, 1H,
J3,4 = 3.2Hz, H-4), 5.68 (dd, 1H, J1,2 = 8.0, J2,3
=
10.4Hz, H-2), 5.65 (dd, 1H, J3,4 = 3.2, J2,3 = 10.4Hz,
H-3), 5.52 (dd, 1H, J3,4 = 3.2, J2,3 = 10.4Hz, H-3), 5.28
(d, 1H, J1,2 = 8.0Hz, H-1), 5.21 (dd, 1H, J3,4 = 3.2,
J2,3 = 10.4Hz, H-3), 4.63 (d, 1H, J1,2 = 8.0Hz, H-1),
4.47 (d, 1H, J1,2 = 8.0Hz, H-1), 3.65 (s, 3H, OCH3),
1.98 (s, 3H, CH3CO); 13C NMR (100MHz, CDCl3) d
170.6 (1C, CH3CO), 166.1, 165.7, 165.6, 165.4, 165.3,
165.2, 165.1, 165.0 (8C, 8COPh), 100.9, 100.8, 100.3
(3C, 3C-1). Anal. Calcd for C83H72O26: C, 67.11; H,
4.89. Found: C, 67.29; H, 4.76.
4.20. 4-Methoxyphenyl 2,3,4-tri-O-benzoyl-b-D-galacto-
pyranosyl-(1!6)-[2,3,5-tri-O-benzoyl-a-L-arabinofurano-
syl-(1!2)]-3,4-di-O-benzoyl-b-D-galactopyranosyl-
(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyranoside (34)
To a solution of 32 (4.0g, 2.1mmol) in CH3OH
(50mL)–CH2Cl2 (50mL) was added CH3COCl (1mL),
and the mixture was treated by the same procedure as
described in the preparation of 11 to give 34 (3.3g,
4.18. 4-Methoxyphenyl 6-O-acetyl-2,3,4-tri-O-benzoyl-b-
D-galactopyranosyl-(1!6)-[2,3,5-tri-O-benzoyl-a-L-arab-
inofuranosyl-(1!2)]-3,4-di-O-benzoyl-b-D-galactopyrano-
syl-(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyranoside (32)
1
83%) as a syrup. [a]D +54.2 (c 1.0, CHCl3); H NMR
(400MHz, CDCl3) d 8.07–7.21 (m, 55H, 11Ph), 7.00
(d, 2H, J = 9.1Hz, CH3OC6H4O–), 6.80 (d, 2H,
J = 9.1Hz, CH3OC6H4O–), 6.03 (d, 1H, J3,4 = 3.6Hz,
H-4), 5.95 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 5.83
(d, 1H, J3,4 = 3.6Hz, H-4), 5.68–5.63 (m, 3H, H-4, H-
2, H-3), 5.48 (s, 1H, Araf-H-1), 5.38 (d, 1H,
J2,3 = 1.6Hz, Araf-H-2), 5.24 (d, 1H, J1,2 = 8.0Hz, H-
1), 4.74 (d, 1H, J1,2 = 8.0Hz, H-1), 4.49 (d, 1H,
Coupling of 31 (6.4g, 4.3mmol) with 12 (3.14g,
5.2mmol) under the same conditions as described for
the coupling of 6 with 7 gave tetrasaccharide 32 (7.4g,
1
89%) as a syrup. [a]D +33.2 (c 1.0, CHCl3); H NMR
(400MHz, CDCl3) d 8.04–7.22 (m, 55H, 11Ph), 7.01
(d, 2H, J = 9.1Hz, CH3OC6H4O–), 6.80 (d, 2H,
J = 9.1Hz, CH3OC6H4O–), 6.04 (d, 1H, J3,4 = 3.6Hz,
H-4), 5.98 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 5.79
(d, 1H, J3,4 = 3.6Hz, H-4), 5.75 (d, 1H, J3,4 = 3.6Hz,
H-4), 5.66 (dd, 1H, J2,3 = 10.4, J3,4 = 3.6Hz, H-3), 5.59
(dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 5.50 (s, 1H,
Araf-H-1), 5.44–5.40 (m, 2H, 2H-3), 5.39 (d, 1H,
J2,3 = 1.6Hz, Araf-H-2), 5.26 (d, 1H, J1,2 = 8.0Hz, H-
1), 4.76 (d, 1H, J1,2 = 8.0Hz, H-1), 4.51 (d, 1H,
J1,2 = 8.0Hz, H-1), 4.25 (dd, 1H, J1,2 = 8.0, J2,3
=
10.4Hz, H-2), 3.82 (dd, 1H, J5,6 = 6.4, J6,6 = 10.8Hz,
H-6), 3.69 (s, 3H, OCH3); 13C NMR (100MHz, CDCl3)
d 166.4, 166.0, 165.9, 165.7, 165.6, 165.4, 165.4, 165.2,
165.2, 165.1, 165.0 (11C, 11COPh), 107.3 (1Araf-C-1),
101.4, 101.3, 101.0 (3Galp-C-1). Anal. Calcd for
C107H90O32: C, 68.07; H, 4.80. Found: C, 68.27; H,
4.89.
J1,2 = 8.0Hz, H-1), 4.27 (dd, 1H, J1,2 = 8.0, J2,3
=
10.4Hz, H-2), 3.82 (dd, 1H, J5,6 = 6.4, J6,6 = 10.8Hz,
H-6), 3.69 (s, 3H, OCH3), 2.02 (s, 3H, CH3CO); 13C
NMR (100MHz, CDCl3) d 172.2 (1C, CH3CO), 166.2,
166.1, 165.7, 165.7, 165.5, 165.4, 165.3, 165.2, 165.2,
165.0, 165.0 (11C, 11COPh), 107.1 (1Araf-C-1), 101.5,
101.3, 101.0 (3Galp-C-1). Anal. Calcd for C109H92O33:
C, 67.83; H, 4.81. Found: C, 68.57; H, 4.89.
4.21. 4-Methoxyphenyl 6-O-acetyl-2,3,4-tri-O-benzoyl-b-
D-galactopyranosyl-(1!6)-[2,3,5-tri-O-benzoyl-a-L-arab-
inofuranosyl-(1!2)]-3,4-di-O-benzoyl-b-D-galactopyrano-
syl-(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyranosyl-
(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyranosyl-(1!6)-
[2,3,5-tri-O-benzoyl-a-L-arabinofuranosyl-(1!3)]-2,4-di-
O-benzoyl-b-D-galactopyranosyl-(1!6)-2,3,4-tri-O-benz-
oyl-b-D-galactopyranoside (35)
4.19. 6-O-Acetyl-2,3,4-tri-O-benzoyl-b-D-galactopyrano-
syl-(1!6)-[2,3,5-tri-O-benzoyl-a-L-arabinofuranosyl-
(1!2)]-3,4-di-O-benzoyl-b-D-galactopyranosyl-(1!6)-
2,3,4-tri-O-benzoyl-a-D-galactopyranosyl trichloroacet-
imidate (33)
Compounds 33 (1.87g, 0.94mmol) and 23 (1.5g,
0.79mmol) in dry CH2Cl2 (50mL) were coupled by the
same procedure as described in the preparation of 8 to
give 35 as a foamy solid (2.3g, 81%). [a]D +59.3 (c 1.0,
CHCl3); 1H NMR (400Hz, CDCl3) d 8.15–7.20 (m,
110H, 22PhH), 6.99 (d, 2H, J = 9.1Hz, CH3OC6H4O–),
To a solution of 32 (7.0g, 3.6mmol) in 4:1 CH3CN–H2O
(100mL) was added CAN (8.0g, 14.4mmol), and the

850
A. Li, F. Kong / Bioorg. Med. Chem. 13 (2005) 839–853
6.81 (d, 2H, J = 9.1Hz, CH3OC6H4O–), 6.02 (d, 1H,
J3,4 = 3.2Hz, H-4), 5.94 (dd, 1H, J1,2 = 8.0,
J2,3 = 10.4Hz, H-2), 5.84 (d, 1H, J3,4 = 3.2Hz, H-4),
5.79 (d, 1H, J3,4 = 3.6Hz, H-4), 5.76–5.74 (m, 2H),
5.67 (d, 1H, J3,4 = 4.0Hz, H-4), 5.64 (dd, 1H,
J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 5.60 (dd, 1H, J1,2 = 8.0,
J2,3 10.4 = Hz, H-2), 5.58–5.52 (m, 3H), 5.48 (s, 1H,
Araf-H-1), 5.46–5.42 (m, 6H), 5.40 (d, 1H,
J2,3 = 1.6Hz, Araf-H-2), 5.26 (s, 1H, Araf-H-1), 5.24
(d, 1H, J2,3 = 1.2Hz, Araf-H-2), 5.11 (d, 1H,
J1,2 = 8.0Hz, H-1), 4.72 (d, 1H, J1,2 = 8.0Hz, H-1),
4.36 (d, 1H, J1,2 = 8.0Hz, H-1), 4.34 (d, 1H,
J1,2 = 8.0Hz, H-1), 4.32 (d, 1H, J1,2 = 8.0Hz, H-1),
4.22 (dd, 1H, J1,2 = 8.0Hz, J2,3 10.4Hz, H-2), 4.14 (d,
1H, J1,2 = 8.0Hz, H-1), 4.04 (dd, 1H, J2,3 = 10.4,
J3,4 = 3.6Hz, H-3), 3.69 (s, 3H, CH3O), 1.80 (s, 3H,
CH3CO); 13C NMR (CDCl3, 100MHz): d 170.7 (1C,
CH3CO), 166.3, 166.2, 165.9, 165.6, 165.5, 165.5,
165.4, 165.4, 165.4, 165.3, 165.3, 165.1, 165.1, 165.0,
165.0, 165.0, 164.9, 164.9, 164.9, 164.8, 164.8, 164.5
(22C, 22COPh), 107.6, 106.8 (2Araf-C-1), 101.5, 100.8,
100.7, 100.6, 100.6, 100.4 (6Galp-C-1). Anal. Calcd for
C209H174O63: C, 67.96; H, 4.75. Found: C, 67.58; H,
4.87.
4.23. 4-Methoxyphenyl 6-O-acetyl-2,3,4-tri-O-benzoyl-b-
D-galactopyranosyl-(1!6)-[2,3,5-tri-O-benzoyl-a-L-arab-
inofuranosyl-(1!3)]-2,4-di-O-benzoyl-b-D-galactopyrano-
syl-(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyranosyl-
(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyranosyl-(1!6)-
[2,3,5-tri-O-benzoyl-a-L-arabinofuranosyl-(1!2)]-3,4-di-
O-benzoyl-b-D-galactopyranosyl-(1!6)-2,3,4-tri-O-benz-
oyl-b-D-galactopyranosyl-(1!6)-2,3,4-tri-O-benzoyl-b-D-
galactopyranosyl-(1!6)-[2,3,5-tri-O-benzoyl-a-L-arab-
inofuranosyl-(1!3)]-2,4-di-O-benzoyl-b-D-galactopyrano-
syl-(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyranoside
(37)
Compounds 24 (1.13g, 0.57mmol) and 36 (1.5g,
0.41mmol) in dry CH2Cl2 (50mL) were coupled by the
same procedure as described in the preparation of 8 to
give 37 as a foamy solid (1.68g, 75%). [a]D +101.5 (c
1.0, CHCl3); 1H NMR (400Hz, CDCl3) d 8.23–7.18
(m, 165H, 33PhH), 6.84 (dd, 4H, CH3OC6H4O–),
6.04–5.98 (m, 4H), 5.96 (d, 1H, J3,4 = 3.2Hz, H-4),
5.91 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 5.84 (d,
1H, J3,4 = 3.2Hz, H-4), 5.77 (d, 1H, J3,4 = 3.6Hz, H-
4), 5.74–5.70 (m, 2H), 5.58 (dd, 1H, J1,2 = 8.0,
J2,3 = 10.4Hz, H-2), 5.56 (dd, 1H, J2,3 = 10.4,
J3,4 = 3.6Hz, H-3), 5.55–5.53 (m, 8H), 5.52 (d, 1H,
J3,4 = 3.2Hz, H-4), 5.50 (dd, 1H, J1,2 = 8.0,
J2,3 = 10.4Hz, H-2), 5.49–5.44 (m, 7H), 5.43 (s, 1H,
Araf-H-1), 5.41 (d, 1H, J2,3 = 1.6Hz, Araf-H-2), 5.25
(s, 2H, 2Araf-H-1), 5.21 (d, 2H, J2,3 = 1.2Hz, 2Araf-
H-2), 5.10 (d, 1H, J1,2 = 8.0Hz, H-1), 4.61 (d, 1H,
J1,2 = 8.0Hz, H-1), 4.49 (d, 1H, J1,2 = 8.0Hz, H-1),
4.33 (d, 1H, J1,2 = 8.0Hz, H-1), 4.31 (d, 1H,
J1,2 = 8.0Hz, H-1), 4.03 (dd, 1H, J2,3 = 10.4Hz,
J3,4 = 3.6Hz, H-3), 3.71 (s, 3H, CH3O), 1.98 (s, 3H,
CH3CO); 13C NMR (CDCl3, 100MHz): d 169.9 (1C,
CH3CO), 166.5, 166.3, 166.3, 166.1, 166.1, 165.9,
165.9, 165.6, 165.6, 165.5, 165.5, 165.4, 165.4, 165.4,
165.3, 165.3, 165.2, 165.1, 165.1, 165.1, 165.0, 165.0,
165.0, 164.9, 164.9, 164.8, 164.8, 164.7, 164.7, 164.6,
164.6, 164.5, 164.5 (33C, 33COPh), 107.7, 107.7, 106.7
(3Araf-C-1), 101.7, 101.7, 101.1, 100.9, 100.7, 100.6,
100.5, 100.5, 100.2 (9Galp-C-1). Anal. Calcd for
C309H256O93: C, 68.00; H, 4.73. Found: C, 67.78; H,
4.94.
4.22. 4-Methoxyphenyl 2,3,4-tri-O-benzoyl-b-D-galacto-
pyranosyl-(1!6)-[2,3,5-tri-O-benzoyl-a-L-arabinofurano-
syl-(1!2)]-3,4-di-O-benzoyl-b-D-galactopyranosyl-
(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyranosyl-(1!6)-
2,3,4-tri-O-benzoyl-b-D-galactopyranosyl-(1!6)-[2,3,5-
tri-O-benzoyl-a-L-arabinofuranosyl-(1!3)]-2,4-di-O-benz-
oyl-b-D-galactopyranosyl-(1!6)-2,3,4-tri-O-benzoyl-b-D-
galactopyranoside (36)
To a solution of 35 (2.0g, 0.54mmol) in CH3OH
(25mL)–CH2Cl2 (25mL) was added CH3COCl
(0.5mL), and the mixture was treated by the same pro-
cedure as described in the preparation of 11 to give 36 as
a foamy solid (1.6g, 81%). [a]D +31.3 (c 1.0, CHCl3); 1H
NMR (400Hz, CDCl3) d 8.23–7.19 (m, 110H, 22PhH),
6.98 (d, 2H, J = 9.1Hz, CH3OC6H4O–), 6.80 (d, 2H,
J = 9.1Hz, CH3OC6H4O–), 6.01 (d, 1H, J3,4 = 3.2Hz,
H-4), 5.94 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 5.84
(d, 1H, J3,4 = 3.2Hz, H-4), 5.80–5.74 (m, 3H), 5.66 (d,
1H, J3,4 = 4.0Hz, H-4), 5.62–5.60 (m, 2H), 5.58–5.54
(m, 2H), 5.52 (dd, 1H, J2,3 = 10.4, J3,4 = 3.6Hz, H-3),
5.47 (s, 1H, Araf-H-1), 5.46–5.42 (m, 6H), 5.39 (d, 1H,
J2,3 = 1.6Hz, Araf-H-2), 5.26 (s, 1H, Araf-H-1), 5.24
(d, 1H, J2,3 = 1.2Hz, Araf-H-2), 5.12 (d, 1H,
J1,2 = 8.0Hz, H-1), 4.71 (d, 1H, J1,2 = 8.0Hz, H-1),
4.30 (d, 1H, J1,2 = 8.0Hz, H-1), 4.23 (dd, 1H,
J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 4.14 (d, 1H,
J1,2 = 8.0Hz, H-1), 3.69 (s, 3H, CH3O); 13C NMR
(CDCl3, 100MHz): d 167.1, 167.0, 166.3, 166.3, 166.2,
166.1, 166.0, 165.8, 165.7, 165.6, 165.6, 165.5, 165.4,
165.4, 165.3, 165.3, 165.2, 165.1, 165.0, 164.9, 164.7,
164.7 (22C, 22COPh), 107.5, 106.7 (2Araf-C-1), 101.5,
101.2, 101.0, 100.7, 100.6, 100.4 (6Galp-C-1). Anal.
Calcd for C207H172O62: C, 68.08; H, 4.75. Found: C,
68.40; H, 4.89.
4.24. 4-Methoxyphenyl 2,3,4-tri-O-benzoyl-b-D-galacto-
pyranosyl-(1!6)-[2,3,5-tri-O-benzoyl-a-L-arabinofurano-
syl-(1!3)]-2,4-di-O-benzoyl-b-D-galactopyranosyl-
(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyranosyl-(1!6)-
2,3,4-tri-O-benzoyl-b-D-galactopyranosyl-(1!6)-[2,3,5-
tri-O-benzoyl-a-L-arabinofuranosyl-(1!2)]-3,4-di-O-benz-
oyl-b-D-galactopyranosyl-(1!6)-2,3,4-tri-O-benzoyl-b-D-
galactopyranosyl-(1!6)-2,3,4-tri-O-benzoyl-b-D-galacto-
pyranosyl-(1!6)-[2,3,5-tri-O-benzoyl-a-L-arabino- furan-
osyl-(1!3)]-2,4-di-O-benzoyl-b-D-galactopyranosyl-
(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyranoside (38)
To a solution of 37 (1.5g, 0.27mmol) in CH3OH
(25mL)–CH2Cl2 (25mL) was added CH3COCl
(0.5mL), and the mixture was treated by the same pro-

A. Li, F. Kong / Bioorg. Med. Chem. 13 (2005) 839–853
851
cedure as described in the preparation of 11 to give 38 as
a foamy solid (1.05g, 71%). [a]D +89.2 (c 1.0, CHCl3);
1H NMR (400Hz, CDCl3) d 8.21–7.15 (m, 165H,
33PhH), 6.82 (dd, 4H, CH3OC6H4O–), 6.02 (d, 1H,
J3,4 = 3.2Hz, H-4), 6.00–5.96 (m, 3H), 5.93 (d, 1H,
J3,4 = 3.2Hz, H-4), 5.91 (dd, 1H, J1,2 = 8.0,
J2,3 = 10.4Hz, H-2), 5.84 (d, 1H, J3,4 = 3.2Hz, H-4),
5.82 (d, 1H, J3,4 = 3.6Hz, H-4), 5.78–5.71 (m, 3H),
5.63 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 5.59 (dd,
1H, J2,3 = 10.4, J3,4 = 3.6Hz, H-3), 5.57–5.53 (m, 8H),
5.50 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 5.48–5.46
(m, 6H), 5.45 (dd, 1H, J2,3 = 10.4, J3,4 = 3.6Hz, H-3),
5.41 (s, 1H, Araf-H-1), 5.39 (d, 1H, J2,3 = 1.6Hz,
Araf-H-2), 5.23 (s, 2H, 2Araf-H-1), 5.21 (d, 2H,
J2,3 = 1.2Hz, 2Araf-H-2), 5.13 (d, 1H, J1,2 = 8.0Hz,
H-1), 4.81 (d, 1H, J1,2 = 8.0Hz, H-1), 4.61 (d, 1H,
J1,2 = 8.0Hz, H-1), 4.48 (d, 1H, J1,2 = 8.0Hz, H-1),
4.33 (d, 1H, J1,2 = 8.0Hz, H-1), 4.31 (d, 1H,
J1,2 = 8.0Hz, H-1), 3.67 (s, 3H, CH3O); 13C NMR
(CDCl3, 100MHz): d 166.5, 166.5, 166.3, 166.3, 166.1,
166.0, 165.9, 165.9, 165.6, 165.6, 165.5, 165.5, 165.4,
165.4, 165.3, 165.3, 165.2, 165.2, 165.1, 165.1, 165.0,
165.0, 165.0, 164.9, 164.9, 164.8, 164.8, 164.8, 164.7,
164.6, 164.6, 164.5, 164.3 (33C, 33COPh), 107.8, 107.7,
106.9 (3Araf-C-1), 101.7, 101.1, 101.0, 100.9, 100.6,
100.5, 100.5, 100.4, 100.2 (9Galp-C-1). Anal. Calcd for
C307H254O92: C, 68.09; H, 4.73. Found: C, 68.45; H,
4.59.
100.7, 100.7, 100.6, 100.5, 100.5, 100.4, 100.4 (12Galp-
C-1). Anal. Calcd for C409H338O123: C, 68.03; H, 4.72.
Found: C, 68.32; H, 4.90.
4.26. Hexadecaoside acceptor 40
To a solution of 39 (946mg, 0.13mmol) in CH3OH
(20mL)–CH2Cl2 (20mL) was added CH3COCl
(0.4mL), and the mixture was treated by the same pro-
cedure as described in the preparation of 11 to give 40 as
a foamy solid (667mg, 71%). [a]D +75.1 (c 1.0, CHCl3);
1H NMR (400Hz, CDCl3) d 8.11–7.09 (m, 220H,
44PhH), 6.91 (dd, 4H, CH3OC6H4O–), 6.00 (d,
1H, J3,4 = 3.2Hz, H-4), 5.96–5.90 (7H), 5.89 (dd,
1H, J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 5.84 (d, 1H,
J3,4 = 3.2Hz, H-4), 5.77 (d, 1H, J3,4 = 3.6Hz, H-4),
5.73 (d, 1H, J3,4 = 4.0Hz, H-4), 5.70 (dd, 1H,
J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 5.68–5.60 (m, 8H), 5.58
(d, 1H, J3,4 = 3.2Hz, H-4), 5.56 (dd, 1H, J2,3 = 10.4,
J3,4 = 3.6Hz, H-3), 5.54 (dd, 1H, J1,2 = 8.0,
J2,3 = 10.4Hz, H-2), 5.53–5.50 (m, 3H), 5.51 (dd, 1H,
J2,3 = 10.4, J3,4 = 3.6Hz, H-3), 5.49–5.43 (m, 4H), 5.41
(s, 1H, Araf-H-1), 5.39 (d, 1H, J2,3 = 1.6Hz, Araf-H-
2), 5.35 (dd, 1H, J1,2 = 8.0, J2,3 10.4Hz, H-2), 5.30 (s,
1H, Araf-H-1), 5.28 (s, 2H, 2Araf-H-1), 5.24 (d, 1H,
J2,3 = 1.2Hz, Araf-H-2), 5.23–5.20 (m, 2H), 5.10 (d,
1H, J1,2 = 8.0Hz, H-1), 4.81 (d, 1H, J1,2 = 8.0Hz, H-
1), 4.60 (d, 1H, J1,2 = 8.0Hz, H-1), 4.44 (d, 1H,
J1,2 = 8.0Hz, H-1), 4.39 (d, 1H, J1,2 = 8.0Hz, H-1),
4.33 (d, 1H, J1,2 = 8.0Hz, H-1), 4.12 (d, 1H,
J1,2 = 8.0Hz, H-1), 3.65 (s, 3H, CH3O); 3C NMR
(CDCl3, 100MHz): d 167.1, 167.0, 166.5, 166.4, 166.3,
166.2, 166.2, 166.1, 166.1, 166.0, 165.0, 165.9, 165.9,
165.9, 165.8, 165.7, 165.7, 165.6, 165.6, 165.5, 165.5,
165.4, 165.4, 165.4, 165.4, 165.3, 165.3, 165.3, 165.2,
165.2, 165.1, 165.1, 165.0, 165.0, 165.0, 164.9, 164.9,
164.9, 164.8, 164.8, 164.8, 164.7, 164.6, 164.4 (44C,
44COPh), 107.7, 107.6, 107.4, 106.9 (4Araf-C-1),
101.7, 101.6, 101.1, 100.9, 100.8, 100.8, 100.7, 100.6,
100.5, 100.4, 100.4, 100.2 (12Galp-C-1). Anal. Calcd
for C407H336O122: C, 68.09; H, 4.72. Found: C, 68.37;
H, 4.58.
4.25. 4-Methoxyphenyl hexadecaoside 39
Coupling of 38 (1.0g, 0.18mmol) with 33 (508mg,
2.6mmol) under the same conditions as described for
the coupling of 6 with 7 gave compound 39 (946mg,
1
71%) as a foamy solid. [a]D +61.3 (c 1.0, CHCl3); H
NMR (400Hz, CDCl3) d 8.13–7.18 (m, 220H, 44PhH),
6.89 (dd, 4H, CH3OC6H4O–), 5.98 (d, 1H,
J3,4 = 3.2Hz, H-4), 5.94 (dd, 1H, J1,2 = 8.0,
J2,3 = 10.4Hz, H-2), 5.91–5.87 (7H), 5.84 (d, 1H,
J3,4 = 3.2Hz, H-4), 5.79 (d, 1H, J3,4 = 3.6Hz, H-4),
5.73 (d, 1H, J3,4 = 4.0Hz, H-4), 5.69–5.59 (m, 10H),
5.56 (dd, 1H, J2,3 = 10.4, J3,4 = 3.6Hz, H-3), 5.53 (dd,
1H, J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 5.50–5.43 (m, 8H),
5.42 (s, 1H, Araf-H-1), 5.40 (d, 1H, J2,3 = 1.6Hz,
Araf-H-2), 5.36 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz, H-
2), 5.30 (s, 1H, Araf-H-1), 5.28 (s, 2H, 2Araf-H-1),
5.24 (d, 1H, J2,3 = 1.2Hz, Araf-H-2), 5.23–5.20 (m,
2H), 5.12 (d, 1H, J1,2 = 8.0Hz, H-1), 4.81 (d, 1H,
J1,2 = 8.0Hz, H-1), 4.61 (d, 1H, J1,2 = 8.0Hz, H-1),
4.48 (d, 1H, J1,2 = 8.0Hz, H-1), 4.39 (d, 1H,
J1,2 = 8.0Hz, H-1), 4.14 (d, 1H, J1,2 = 8.0Hz, H-1),
3.68 (s, 3H, CH3O), 1.92 (s, 3H, CH3CO); 13C NMR
(CDCl3, 100MHz): d 171.0 (1C, CH3CO), 167.0,
166.9, 166.3, 166.2, 166.1, 166.1, 166.1, 166.0, 166.0,
166.0, 165.9, 165.9, 165.9, 165.9, 165.8, 165.7, 165.6,
165.6, 165.6, 165.5, 165.5, 165.4, 165.4, 165.4, 165.3,
165.3, 165.3, 165.2, 165.2, 165.2, 165.1, 165.1, 165.0,
165.0, 165.0, 164.9, 164.9, 164.9, 164.8, 164.8, 164.8,
164.7, 164.6, 164.5 (44C, 44COPh), 107.6, 107.6, 107.3,
106.8 (4Araf-C-1), 101.7, 101.6, 100.9, 100.9, 100.8,
4.27. 4-Methoxyphenyl twentyoside 41
Coupling of 40 (500mg, 0.069mmol) with 24 (205mg,
0.10mmol) under the same conditions as described for
the coupling of 6 with 7 gave compound 41 (404mg,
1
65%) as a foamy solid. [a]D +89.1 (c 1.0, CHCl3); H
NMR (400Hz, CDCl3) d 8.04–7.16 (m, 275H, 55PhH),
6.75 (dd, 4H, CH3OC6H4O–), 6.09 (d, 1H,
J3,4 = 3.2Hz, H-4), 5.91 (d, 1H, J3,4 = 3.2Hz, H-4),
5.90 (dd, 1H, J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 5.89–5.80
(13H), 5.78 (d, 1H, J3,4 = 3.2Hz, H-4), 5.76 (d, 1H,
J3,4 = 3.6Hz, H-4), 5.75–5.72 (m, 7H), 5.70 (d, 1H,
J3,4 = 4.0Hz, H-4), 5.60 (dd, 1H, J1,2 = 8.0,
J2,3 = 10.4Hz, H-2), 5.53 (dd, 1H, J2,3 = 10.4,
J3,4 = 3.6Hz, H-3), 5.51–5.43 (m, 15H), 5.41 (s, 2H,
Araf-H-1), 5.38 (d, 2H, Araf-H-2), 5.36–5.33 (m, 7H),
5.25 (s, 3H, 3Araf-H-1), 5.23 (d, 3H, 3Araf-H-2), 5.10

852
A. Li, F. Kong / Bioorg. Med. Chem. 13 (2005) 839–853
(d, 1H, J1,2 = 8.0Hz, H-1), 4.78 (d, 1H, J1,2 = 8.0Hz, H-
1), 4.61 (d, 1H, J1,2 = 8.0Hz, H-1), 4.46 (d, 1H,
J1,2 = 8.0Hz, H-1), 4.26 (d, 1H, J1,2 = 8.0Hz, H-1),
4.15 (d, 1H, J1,2 = 8.0Hz, H-1), 3.69 (s, 3H, CH3O),
2.00 (s, 3H, CH3CO); 13C NMR (CDCl3, 100MHz): d
171.2 (1C, CH3CO), 166.4, 166.4, 166.3, 166.3, 166.2,
166.2, 166.1, 166.1, 166.1, 166.0, 166.0, 166.0, 165.9,
165.9, 165.9, 165.9, 165.8, 165.8, 165.7, 165.7, 165.6,
165.6, 165.6, 165.5, 165.5, 165.5, 165.5, 165.4, 165.4,
165.4, 165.4, 165.3, 165.3, 165.3, 165.2, 165.2, 165.2,
165.1, 165.1, 165.0, 165.0, 165.0, 165.0, 164.9, 164.9,
164.9, 164.9, 164.8, 164.8, 164.8, 164.7, 164.7, 164.7,
164.6, 164.5 (55C, 55COPh), 107.7, 107.7, 107.6, 106.8,
106.3 (5Araf-C-1), 101.7, 101.0, 100.9, 100.9, 100.8,
100.7, 100.7, 100.6, 100.5, 100.5, 100.4, 100.4, 100.3,
100.2, 100.1 (15Galp-C-1). MALDI-TOF MS Calcd
for C509H420O153: 8984.5 [M]. Found: 9007 [M+Na+].
same procedure as described in the preparation of 8 to
give 43 as a foamy solid (2.5g, 81%). [a]D +61.4 (c 1.0,
CHCl3); 1H NMR (400Hz, CDCl3) d 8.11–7.15 (m,
110H, 22PhH), 6.97 (d, 2H, J = 9.1Hz, CH3OC6H4O–),
6.83 (d, 2H, J = 9.1Hz, CH3OC6H4O–), 6.00–5.92 (m,
3H, H-2, 2H-4), 5.83 (d, 1H, J3,4 = 3.2Hz, H-4), 5.79
(d, 1H, J3,4 = 3.6Hz, H-4), 5.76 (d, 1H, J3,4 = 3.2Hz,
H-4), 5.74 (d, 1H, J3,4 = 3.2Hz, H-4), 5.66 (d, 1H,
J3,4 = 4.0Hz, H-4), 5.64 (dd, 1H, J1,2 = 8.0,
J2,3 = 10.4Hz, H-2), 5.60–5.52 (m, 4H), 5.47 (s, 1H,
Araf-H-1), 5.42–5.39 (m, 5H), 5.41 (d, 1H,
J2,3 = 1.6Hz, Araf-H-2), 5.26 (s, 1H, Araf-H-1), 5.24
(d, 1H, J2,3 = 1.2Hz, Araf-H-2), 5.20 (d, 1H,
J1,2 = 8.0Hz, H-1), 4.73 (d, 1H, J1,2 = 8.0Hz, H-1),
4.38 (d, 1H, J1,2 = 8.0Hz, H-1), 4.34 (d, 1H,
J1,2 = 8.0Hz, H-1), 4.31 (d, 1H, J1,2 = 8.0Hz, H-1),
4.24 (dd, 1H, J1,2 = 8.0, J2,3 10.4Hz, H-2), 4.16 (d, 1H,
J1,2 = 8.0Hz, H-1), 4.06 (dd, 1H, J2,3 = 10.4,
J3,4 = 3.6Hz, H-3), 3.72 (s, 3H, CH3O), 1.96 (s, 3H,
CH3CO); 13C NMR (CDCl3, 100MHz): d 171.0 (1C,
CH3CO), 166.7, 166.4, 166.1, 166.0, 165.8, 165.7,
165.7, 165.6, 165.6, 165.6, 165.2, 165.1, 165.1, 165.0,
165.0, 165.0, 164.9, 164.9, 164.9, 164.8, 164.8, 164.6
(22C, 22COPh), 107.6, 106.9 (2Araf-C-1), 101.5, 100.9,
100.7, 100.7, 100.6, 100.5 (6Galp-C-1). Anal. Calcd for
C209H174O63: C, 67.96; H, 4.75. Found: C, 67.68; H,
4.87.
4.28. 4-Methoxyphenyl b-D-galactopyranosyl-(1!6)-[a-
L-arabinofuranosyl-(1!3)]-b-D-galactopyranosyl-(1!6)-
b-D-galactopyranosyl-(1!6)-b-D-galactopyranosyl-
(1!6)-[a-L-arabinofuranosyl-(1!2)]-b-D-galactopyrano-
syl-(1!6)-b-D-galactopyranosyl-(1!6)-b-D-galactopyran-
osyl-(1!6)-[a-L-arabinofuranosyl-(1!3)]-b-D-galacto-
pyranosyl-(1!6)-b-D-galactopyranosyl-(1!6)-b-D-
galactopyranosyl-(1!6)-[a-L-arabinofuranosyl-(1!2)]-b-
D-galactopyranosyl-(1!6)-b-D-galactopyranosyl-(1!6)-
b-D-galactopyranosyl-(1!6)-[a-L-arabinofuranosyl-
(1!3)]-b-D-galactopyranosyl-(1!6)-b-D-galactopyrano-
side (42)
4.30. 4-Methoxyphenyl 6-O-acetyl-2,3,4-tri-O-benzoyl-
b-D-galactopyranosyl-(1!6)-[2,3,5-tri-O-benzoyl-a-L-
arabinofuranosyl-(1!3)]-2,4-di-O-benzoyl-b-D-galacto-
pyranosyl-(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyrano-
syl-(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyranosyl-
(1!6)-[2,3,5-tri-O-benzoyl-a-L-arabinofuranosyl-(1!2)]-
3,4-di-O-benzoyl-b-D-galactopyranosyl-(1!6)-2,3,4-tri-
O-benzoyl-a-D-galactopyranosyl trichloroacetimidate
(44)
Compound 41 (400mg, 0.044mmol) was dissolved in a
satd solution of NH3 in MeOH (80mL). After a week
at rt, the reaction mixture was concentrated, and the resi-
due was purified by chromatography on Sephadex LH-
20 (MeOH) to afford 42 as an amorphous solid (120mg,
85%). [a]D +121.4 (c 1.0, H2O); 1H NMR (D2O,
400MHz) d 7.07 (dd, 4H, CH3OC6H4O–), 5.30 (s, 2H,
2Araf-H-1), 5.23 (s, 2H, 2Araf-H-1), 5.21 (s, 1H, Araf-
H-1), 5.10 (d, 1H, J1,2 = 8.0Hz, Gal-p-H-1), 4.98 (d,
To a solution of 43 (2.0g, 0.54mmol) in 4:1 CH3CN–
H2O (50mL) was added CAN (1.5g, 14.4mmol), and
the mixture was treated by the same procedure as de-
scribed in the preparation of 24 to give 44 (1.31g, 65%
for two steps) as a syrup. [a]D +70.7 (c 1.0, CHCl3);
1H NMR (400Hz, CDCl3) d 8.66 (s, 1H, NH), 8.06–
7.18 (m, 110H, 22PhH), 6.78 (d, 1H, J1,2 = 8.0Hz, H-
1), 6.04 (d, 1H, J3,4 = 3.2Hz, H-4), 5.94 (dd, 1H,
J1,2 = 8.0, J2,3 = 10.4Hz, H-2), 5.85 (d, 1H,
J3,4 = 3.2Hz, H-4), 5.77 (d, 1H, J3,4 = 3.6Hz, H-4),
5.76–5.74 (m, 2H, 2H-4), 5.68 (d, 1H, J3,4 = 4.0Hz, H-
4), 5.58–5.52 (m, 5H), 5.48 (s, 1H, Araf-H-1), 5.46 (d,
1H, J2,3 = 1.6Hz, Araf-H-2), 5.28 (s, 1H, Araf-H-1),
5.25 (d, 1H, J2,3 = 1.2Hz, Araf-H-2), 4.73 (d, 1H,
J1,2 = 8.0Hz, H-1), 4.37 (d, 1H, J1,2 = 8.0Hz, H-1),
1H, J1,2 = 8.0Hz, Gal-p-H-1), 4.80 (d, 1H, J1,2
=
7.6Hz, Galp-H-1), 4.61 (d, 3H, 3Galp-H-1), 4.51 (d,
1H, J1,2 = 8.0Hz, Gal-p-H-1), 4.48 (d, 3H, 3Galp-H-1),
4.38 (d, 1H, J1,2 = 7.2Hz, Galp-H-1), 4.32 (m, 2H,
2Galp-H-1), 4.25 (d, 1H, J1,2 = 8.0Hz, Gal-p-H-1),
4.21 (d, 1H, J1,2 = 8.0Hz, Gal-p-H-1); 13C NMR
(100MHz, D2O) d 109.3, 109.3, 109.1, 108.3, 108.3 (5
Araf-C-1), 103.4, 103.4, 103.4, 103.3, 103.3, 103.1,
102.9, 102.9, 102.8, 102.5, 102.4, 102.4, 102.1, 102.1,
101.7 (15Galp-C-1). MALDI-TOF MS Calcd for
C122H198O97: 3216.8 [M]. Found: 3237 [M+Na+].
4.29. 4-Methoxyphenyl 6-O-acetyl-2,3,4-tri-O-benzoyl-b-
D-galactopyranosyl-(1!6)-[2,3,5-tri-O-benzoyl-a-L-arab-
inofuranosyl-(1!3)]-2,4-di-O-benzoyl-b-D-galactopyran-
osyl-(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyranosyl-
(1!6)-2,3,4-tri-O-benzoyl-b-D-galactopyranosyl-(1!6)-
[2,3,5-tri-O-benzoyl-a-L-arabinofuranosyl-(1!2)]-3,4-di-
O-benzoyl-b-D-galactopyranosyl-(1!6)-2,3,4-tri-O-benz-
oyl-b-D-galactopyranoside (43)
4.35 (d, 1H, J1,2 = 8.0Hz, H-1), 4.30 (d, 1H, J1,2
=
8.0Hz, H-1), 4.22 (dd, 1H, J1,2 = 8.0Hz, J2,3 10.4Hz,
H-2), 4.19 (d, 1H, J1,2 = 8.0Hz, H-1), 4.03 (dd, 1H,
J2,3 = 10.4, J3,4 = 3.6Hz, H-3), 3.68 (s, 3H, CH3O),
1.92 (s, 3H, CH3CO); 13C NMR (CDCl3, 100MHz): d
170.7 (1C, CH3CO), 166.7, 166.3, 166.1, 166.0, 165.8,
165.8, 165.7, 165.7, 165.6, 165.6, 165.4, 165.3, 165.2,
165.1, 165.0, 165.0, 164.9, 164.9, 164.8, 164.8, 164.7,
164.5 (22C, 22COPh), 107.8, 106.6 (2Araf-C-1), 101.7,
101.3, 101.0, 100.9, 100.8, 100.6 (6Galp-C-1). Anal.
Compounds 24 (1.87g, 0.94mmol) and 34 (1.5g,
0.79mmol) in dry CH2Cl2 (50mL) were coupled by the

A. Li, F. Kong / Bioorg. Med. Chem. 13 (2005) 839–853
853
18, 921–924; (c) Koeners, H. J.; Verhoeven, J.; van Boom,
´ ´
Calcd for C204H168Cl3NO62: C, 65.65; H, 4.54. Found:
C, 65.28; H, 4.77.
J. H. Tetrahedron Lett. 1980, 21, 381–382; (d) Csavas, M.;
´
Borbas, A.; Janossy, L.; Liptak, A. Tetrahedron Lett.
2003, 44, 631–635.
´
´
´ ´
´
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8. (a) Csavas, M.; Borbas, A.; Szilagyi, L.; Liptak, A. Synlett
2002, 887–890; (b) Koeners, H. J.; Verdegaal, C. H. M.;
van Boom, J. H. Recl. Trav. Chim. Pays-Bas 1981, 100,
118–122; (c) Timmers, C. M.; Wigchert, S. C. M.;
Leeuwenburgh, M. A.; van der Marel, G. A.; van Boom,
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).
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