Synthesis of the rhamnosyl trisaccharide repeating unit to mimic the antigen determinant of Pseudomonas syringae lipopolysaccharide

Article abstract of DOI:10.1055/s-2007-965995

The trisaccharide 2,3,4-O-tribenzyl-α-L-rhamnosyl-(1→3)-4-O- acetyl-2-O-benzoyl-(1→2)-4-O-acetyl-3-O-benzoyl-α-L-rhamnosyl-1-(4- tolyl)thio-α-L-rhamnopyranoside was prepared from the thio-sugar 1-(4-tolyl)thio-α,β-L-rhamnopyranoside from the nonreducing e

Full text of DOI:10.1055/s-2007-965995

1412
PAPER
Synthesis of the Rhamnosyl Trisaccharide Repeating Unit To Mimic the
Antigen Determinant of Pseudomonas syringae Lipopolysaccharide
S
ynthesis of Rha
h
nosyl Trisa
u
ccharide ng-Shan Yu,* Heng-Yen Wang, Li-Wu Chiang, Kai Pei
Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu, No. 101 sec. 2,
Guang-Fu Rd., 300 Taiwan, Taiwan
Fax +886(3)5718649; E-mail: csyu@mx.nthu.edu.tw
Received 15 January 2007; revised 26 February 2007
has become an emerging interest in recent glycobiology
field. The synthesis of such molecules, with characteris-
tics that could initiate immuno-recognition, is of critical
importance for the study of possible cancer vaccines. For
Abstract: The trisaccharide 2,3,4-O-tribenzyl-a-L-rhamnosyl-
(1→3)-4-O-acetyl-2-O-benzoyl-(1→2)-4-O-acetyl-3-O-benzoyl-
a-L-rhamnosyl-1-(4-tolyl)thio-a-L-rhamnopyranoside was pre-
pared from the thio-sugar 1-(4-tolyl)thio-a,b-L-rhamnopyranoside
from the nonreducing end to the reducing end. The two acceptors example, the synthetic alpha-gal ceramide has been exten-
possessing 2- and 3-OH groups for the construction of the trisaccha-
sively investigated for its ability to induce prominent im-
ride were obtained from a 2,3-benzylidine-protected thio-sugar in a
mune response of natural killer T cells, mediated by
one-pot deprotection manner in a respective ratio of 1:2.5. As do-
signaling CD1d molecules.4,5
nors for glycosylation, the thio-sugars of both mono- and disaccha-
Among these glycoconjugates, the repeating units are
thought to play a central role in tuning the immune speci-
ficity. We are interested in the development of glycocer-
amide derivatives and have focused especially on the
assembly of the glyco portion of the trisaccharide moiety
of rhamnose. While rhamnose has been reported to be a
rare sugar component found in natural LPS or in some
herbs such as Reishi,6 some strains of bacteria, such as
Pseudomonas syringae pv. coronafaciens IMV 9030 and
atrofaciens IMV 8281 were found to possess this specific
sequence of a-L-rha(1→3)a-L-rha(1→2)a-L-rha.7,8 Fur-
thermore, a tetrasaccharide comprising these three rham-
nose residues has been recognized as the antigen
determinant responsible for the toxin of Bacillus anthra-
cis.9,10
rides were converted to trichloroacetimido rhamnosides. Through
this chemoselective strategy, a trisaccharide was obtained that re-
tained an anomeric thio group for coupling with ceramide moieties.
Bioassays are in progress.
Key words: cancer vaccine, imidate, rhamnose, trisaccharide, gly-
cosylation
Lipopolysaccharide (LPS), also called endotoxin, is found
in Gram-negative bacteria in which it forms the major an-
choring component of the membrane surface.1 LPS is
comprised of two components, namely, lipid A and
polysaccharide.2 The exterior polysaccharide portion is
composed of three types of saccharide moieties termed the
inner core, outer core and O-specific chain. Of these, the
O-specific chain is an invariant repeating unit of oligosac-
charides. When mammalians ingest a small amount of
LPS, their immune system will respond to this foreign
molecule by stimulating slight inflammatory effects, the
symptoms of which are negligible, however, in cases
when large amounts of LPS is taken in, this may result in
high fever, septic shock or even death. The saccharide
portion has been recognized to be a key player in trigger-
ing this immune response. Through the recent study of
this specific glycan–glycan interaction between patho-
gens and their hosts, glycoconjugates have acquired a new
terminology: glycosynapse.3
Herein, we report the facile preparation of a trisaccharide
of rhamnose 26 bearing a thio group ready for subsequent
glycosylation with ceramide.11 As the ceramide moiety
was synthesized via a multi-step synthesis, our trisaccha-
ride portion 1 was assembled first. The retrosynthetic
analysis of this trisaccharide moiety is shown in
Scheme 1.
Encouraged by the recent success of constructing oligo-
sialic acids via chemoselective glycosylation with alter-
nate thio and phosphite glycosides,12 we attempted to
assemble the trisaccharide unit from the nonreducing end
to the reducing end. Due to the importance of protecting
groups with respect to tuning the reactivity of glycosyla-
tion, we initially synthesized and compared both ether-
and ester-type protecting groups. Preparation of the three
thio donors 8, 10 and 11 was achieved via peracetylation13
of the four hydroxyl groups of rhamnose 6, introduction of
a 4-thiotolyl group,14 deprotection of the hydroxyl
groups14 and, finally, protection with benzyl15 and ben-
zoyl groups (Scheme 2).
LPS was believed to exert its damaging bioactivity
through a two-step process: inducing a general immune
response by the lipid A portion, and targeting cells ex-
pressing biomolecules bearing a structural resemblance to
the saccharide portion of LPS. Thus, modification of the
structure of LPS to redirect the intrinsic immune respons-
es specifically against some diseases such as cancer cells
After removal of the thio groups, the three hemiacetals
12,13,16 1317 and 14,18 were obtained in high yields. Upon
introduction of the trichloroacetamido groups, the three
SYNTHESIS 2007, No. 9, pp 1412–1420
Advanced online publication: 23.03.2007
DOI: 10.1055/s-2007-965995; Art ID: Z01307SS
© Georg Thieme Verlag Stuttgart · New York
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x
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x
x
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PAPER
Synthesis of Rhamnosyl Trisaccharide
1413
Cer
O
STol
OH
Me
O
Me
O
RO
RO
a
RO
RO
OR
OR
R = Ac
10 R = Bn
11 R = Bz
Me
HO
O
HO
12 R = Ac, 95%
13 R = Bn, 91%
14 R = Bz, 93%
STol
8
O
Me
O
NH
Cl
Me
HO
AcO
O
Cl
Cl
BzO
O
O
O
OH
b
Me
O
Me
HO
O
Me
O
O
AcO
RO
HO
O
RO
OBz
O
OR
Me
BnO
1
15 R = Ac, 73%
R = Bn, 81%
16 R = Bz, 86%, α + β
BnO
5
OBn
26
NH
Cl
STol
Scheme 3 Reagents and conditions: (a) NBS, acetone–H2O, r.t., 1
h, 90%; (b) CH2Cl2, r.t.; (i) for Ac: K2CO3 (1.1 equiv), CCl3CN (20
equiv), 2.5 h; (ii) for Bn: NaH (1.1 equiv), CCl3CN (10 equiv), 2.5 h;
(iii) for Bz: DBU (0.5 equiv), CCl3CN (10 equiv), 2 h.
Cl
Cl
R =
Me
AcO
O
BzO
2
OH
STol
+
OR
trolling the stereoselectivity of the imidates in benzyl-pro-
tected rhamnose.17a For example, a- and b-imidates could
be independently prepared by using either a strong base
(e.g. NaH) or a weak base (e.g. K2CO3), respectively.
However, no analogous rules for either acetyl- or benzoyl-
protected rhamnose could be found in the literature. Com-
mon bases used for the preparation of acetyl- and benzoyl-
protected imidates have been cesium carbonate or a com-
bination of potassium carbonate and 1,8-diazabicy-
clo[5.4.0]undec-7-ene (DBU), respectively. The a-
configurational assignments of the three imidates 15, 5
and 16 were made on the basis of empirical data.16c,19,20
Me
O
Me
AcO
O
O
O
AcO
O
HO
OBz
OBz
OR
4
Me
BnO
BnO
Me
BnO
OBn
3
BnO
OBn
5
Scheme 1 Retrosynthetic analysis of the preparation of the rhamno-
se trisaccharide repeating unit; Cer = ceramide.
While an efficient preparation of an acceptor bearing a 3-
OH group has been reported, a corresponding, facile pro-
cedure for the preparation of the 2-OH isomer remains a
challenge.21,22 The typical four-step synthesis of the 2-OH
acceptor, starting from acetyl-protected 1-bromorham-
noside via reaction with sym-collidine and subsequent
deprotection, was relatively lengthy and low-yielding
(24%). Our preparation of both acceptors 19 and 20, si-
multaneously, was achieved in three steps (Scheme 4).
imidates 5,16c 15,17a and 16,19 were obtained (Scheme 3).
Though no NMR spectrum was available for compound
16, the presence of a sole a-anomer was suggested by the
observation of a single spot by TLC analysis. Adjusting of
the basicity of the system is a common method for con-
Me
OAc
Me
O
OH
O
AcO
HO
a
AcO
Attempts at coupling the donor 5 with acceptor 19 failed
to provide the corresponding disaccharide due to the pro-
pensity of the p-methoxyphenyl (PMB) group to be elim-
inated. This group was therefore replaced by a more stable
ester-type protecting group. For convenience, a mixture of
compounds 19 and 20 was protected with the benzoyl
group to provide a mixture of 21 and 22; however, these
compounds could not be separated by column chromatog-
raphy. Following deprotection with cerium(IV) ammoni-
um nitrate (CAN), the mixture of compounds 4 and 2
obtained could only be partially (~30%) purified by chro-
matography. For analytical purposes, further purification
HO
OAc
OH
7
6
b
STol
STol
Me
O
Me
O
AcO
RO
c
AcO
RO
OAc
OR
8
9
R = H
d
10 R = Bn
11 R = Bz
e
Scheme 2 Reagents and conditions: (a) Ac2O, DMAP, pyridine, 30 of samples of the isolated compounds 4 and 2 by HPLC
min, 95%; (b) p-thiocresol, BF3·Et2O, CH2Cl2, 0 °C→r.t., 1 h, 81%;
(c) MeONa, MeOH, H+, 20 min, 99%; (d) NaH, 0 °C, 20 min, BnBr,
r.t., 1 h, 89%; (e) BzCl, DMAP, pyridine, 30 min, 95%.
was performed. Due to the problems with purification, the
two isomers were chromatographically separated at an
earlier stage of the preparation; taking advantage of the
Synthesis 2007, No. 9, 1412–1420 © Thieme Stuttgart · New York

1414
C.-S. Yu et al.
PAPER
STol
O
NH
STol
Me
O
H
Cl
Cl
AcO
HO
RO
a
STol
O
HO
O
OH
O
Me
Cl
+
Me
O
O
9
MeOPh
BnO
HO
BnO
OBz
OBn
17α,β R = H
18α,β R = Ac
4
b
5
STol
Tol = C6H4Me
Me
O
c
O
(a)
STol
AcO
O
Me
O
STol
OBz
AcO
Me
Me
RO
O
BnO
OBz
21 R = PMB
AcO
BnO
PMBO
OBn
OH
e
19
23
d
4
R = H
66%
Scheme 5 Reagents and conditions: (a) 4Å MS, CH2Cl2, TMSOTf,
0 °C (30 min)→r.t., 78%.
+
STol
+
Me
O
STol
AcO
e
BzO
Me
O
R
OR
AcO
Me
O
HO
22 R = PMB
STol
OPMB
26%
AcO
20
2
R = H
O
Me
+
O
OBz
AcO
Me
O
Scheme 4 Reagents and conditions: (a) CSA, DMF, p-anisaldehyde
dimethyl acetal, 78%; (b) DMAP, pyridine, Ac2O, 97% (18a–18b,
2:3); (c) Na2CNBH3, 4Å MS, CH2Cl2, TFA, r.t., 16 h, 92% (from
18a); (d) DMAP, pyridine, BzCl, r.t., 30 min, 97% (21–22, 2.5:1), ob-
tained from a mixture of 19,20; (e) CAN, MeCN–H2O (9:1), r.t., 1 h,
72% (4–2, 2.5:1), obtained from a mixture of 21,22.
BzO
BnO
OH
BnO
2
OBn
23 R = STol
a
b
c
24 R = OH (α,β)
25 R = OC=NHCCl3
STol
Me
O
AcO
subtle Rf differences (6%), compounds 19 and 20 could be
separated by chromatography. As indicated in Table 1, the
glycosylation yield of the three donors was satisfactory,
particularly in the case of the ester-protected sugar 15.
BzO
O
Me
O
O
AcO
O
OBz
Disaccharide 23 was also obtained (Scheme 5) which,
through application of the method shown in Scheme 2,
was used to form the imidate of disaccharide 25 (76%
yield from 23; Scheme 6). Coupling of 25 with the 2-OH
acceptor 2 gave the trisaccharide 26 in high yield.
Me
BnO
BnO
OBn
26
Scheme 6 Reagents and conditions: (a) NBS, acetone–H2O, r.t., 1
h, 92%; (b) DBU (0.5 equiv), CCl3CN (10 equiv), CH2Cl2, 1.5 h,
83%; (c) 4Å MS, CH2Cl2, TMSOTf, 0 °C (15 min)→r.t., 84%.
Table 1 Effect of Protecting Groups on Glycosylation Yielda
Donor
Acceptor TMSOTf Yield
(1 equiv)
(2 equiv) (equiv)
(%)
In brief, the current method provides a facile route for the
preparation of two acceptors 4 and 2, simultaneously,
which can be easily separated by column chromatogra-
phy. The glycosylation yield was improved when more re-
active, ester-protected donors 15 and 16 were added. The
glycosylation of trisaccharide donor 26 with ceramide ac-
ceptors is in progress.
NH
Cl
Cl
Cl
OH
O
Me
RO
O
RO
OR
5 (R = Bn)
16 (R = Bz)
15 (R = Ac)
0.3
0.2
0.3
70
80
90
NMR spectroscopy was performed at the department of chemistry
of National Tsing-Hua University (NTHU). 1H NMR and 13C NMR
spectra (including DEPT-135) were recorded using 500 MHz Vari-
an Unity INOVA instruments. ESI-QTOF mass spectroscopy was
performed at the department of applied chemistry of the National
Chiao Tung University (NCTU). ESI-MS spectra were recorded us-
ing a Micromass Q-Tof liquid chromatograph tandem mass spec-
trometer. Analytical TLC was performed using Macherey–Nagel
a In CH2Cl2 at –20 °C.
Synthesis 2007, No. 9, 1412–1420 © Thieme Stuttgart · New York

PAPER
Synthesis of Rhamnosyl Trisaccharide
1415
silica gel 60 F254 precoated plates, which were examined by UV
absorption at 254 nm and visualized by staining with a solution pre-
pared from 5% p-anisaldehyde, sulfuric acid, acetic acid and EtOH
under heating. Column chromatography employed Merck Geduran
Si 60 silica gel (230–400 mesh). Solvents of either industrial grade
or reagent grade (EtOAc, acetone and n-hexane) were distilled prior
to column chromatography. Solvents of reagent grade were dried
before use. DMF was distilled over CaH2 under reduced pressure
and stored over 4Å MS. CH2Cl2 and pyridine were distilled over
CaH2. THF was distilled over Na after repeated treatment with
FeSO4 and KOH for the removal of peroxide. MeOH was distilled
over Mg. Normal-phase HPLC (Agilent 1100) was equipped with a
sample loop (500 mL) and a semipreparative column (9.4 × 250 mm
ZORBAX SIL, 5 mm material). Constant conditions were used [n-
hexane–EtOAc, 3:1; flow rate 3 mL/min; UV detection (260 nm)].
1H NMR (500 MHz, CD3OD): d = 1.26 (d, J6,5 = 6.5 Hz, 3 H, H-6),
2.31 (s, 3 H, SPhCH3), 3.44 (dd, J4,3 = 10.0 Hz, J4,5 = 9.5 Hz, 1 H,
H-4), 3.64 (dd, J3,4 = 10.0 Hz, J3,2 = 3.5 Hz, 1 H, H-3), 4.05 (dq,
J5,4 = 9.5 Hz, J5,6 = 6.0 Hz, 1 H, H-5), 4.56 (dd, J2,3 = 3.5 Hz,
J2,1 = 1.0 Hz, 1 H, H-2), 5.28 (d, J1,2 = 1.0 Hz, 1 H, H-1), 7.13 (d,
J = 8.5 Hz, 2 H, Harom), 7.34 (d, J = 8.5 Hz, 2 H, Harom).
13C NMR (125 MHz, CD3OD): d = 17.83 (C-6), 21.08 (SPhCH3),
70.88 (CH), 72.91 (CH), 73.82 (CH), 74.17 (CH), 90.56 (C-1),
130.78 (arom., 2 × C), 132.22 (arom.), 133.28 (arom., 2 × C),
138.85 (arom.).
MS (ESI+Q-TOF): m/z = 541.2 [2 × M + H]+, 293.1 [M + Na]+,
271.1 [M + H]+.
2,3-O-Di(4-methoxy)benzylidene-1-(4-tolyl)thio-a,b-L-rham-
nopyranoside (17a,b)
A mixture of compounds 9 (0.67 g, 2.48 mmole), CSA (175 mg,
0.74 mmol), DMF (8 mL) and p-anisaldehyde dimethyl acetal (0.5
mL, 3 mmol) was stirred at 50 °C under N2 for 3 h. The starting ma-
terials 9 (Rf = 0.13 and Rf = 0.06) were consumed, while products
17 (Rf = 0.44) were detected on TLC (n-hexane–EtOAc, 1:1). After
removal of the volatile solvents, the residue was partitioned be-
tween EtOAc (10 mL) and sat. aq NaHCO3 (3 mL) and NaCl (3 mL)
sequentially. The organic layer was dried (Na2SO4), filtered and
concentrated to give a residue which was purified by column chro-
matography on silica gel (n-hexane–EtOAc, 1:1) to give 17.
2,3,4-Tri-O-acetyl-1-(4-tolyl)thio-a-L-rhamnopyranoside (8)
A mixture of L-rhamnose (7.6 g, 22.8 mmol), DMAP (0.55 g, 4.5
mmol) and pyridine (40 mL) was stirred at r.t. under N2 for 10 min.
Ac2O (23 mL) was added and the mixture was stirred for 30 min.
The reaction was followed by monitoring formation of the product
1,2,3,4-O-tetraacetyl-a,b-L-rhamnopyranoside (7; Rf = 0.86) by
TLC (n-hexane–EtOAc, 1:1). Upon completion, the solvent was re-
moved under reduced pressure and the crude mixture was purified
by column chromatography (n-hexane–EtOAc, 1:1) to provide a
mixture of the products in 95% yield (14.3 g). A portion of this mix-
ture (2.42 g, 7.27 mmol) and p-thiocresol (1.24 g, 8.42 mmol) was
dissolved in CH2Cl2 (5 mL) and the solution was cooled to 0 °C. To
the solution was added BF3·Et2O (2.06 mL, 14.6 mmol) slowly un-
der N2. The reaction mixture was warmed to r.t. and stirred for 60
min until the starting material (Rf = 0.22; n-hexane–EtOAc, 7:3)
was consumed and the products 8 (Rf = 0.55 and Rf = 0.45) were
formed. After the removal of the volatile solvents, the residue was
partitioned between CH2Cl2 (30 mL) and sat. aq solutions of
NaHCO3 (15 mL), NaCl (15 mL) and H2O (10 mL) sequentially.
The organic layer was then dried (Na2SO4), concentrated and the
residue was purified by column chromatography on silica gel (n-
hexane–EtOAc, 3:1) to give 8.
Yield: 78% (755 mg).
1H NMR (500 MHz, benzene-d6): d = 1.22 (d, J6,5 = 6.5 Hz, 3 H, H-
6), 1.29 (d, J5,6 = 6.0 Hz, 3 H, H-6), 1.99 (s, 3 H, SPhCH3), 3.26 (s,
3 H, PhOCH3), 3.29 (s, 3 H, PhOCH3), 3.47 (dq, J5,6 = 6.5 Hz,
J5,4 = 7.5 Hz, 1 H, H-5), 3.56 (dq, J5,6 = 6.0 Hz, J5,4 = 7.5 Hz, 1 H,
H-5), 4.16 (dd, J4,3 = 7.5 Hz, J4,5 = 7.5 Hz, 1 H, H-4), 4.24 (d,
J2,3 = 6.0 Hz, 1 H, H-2), 4.27 (dd, J4,3 = 7.0 Hz, J4,5 = 7.5 Hz, 1 H,
H-4), 4.27 (dd, J3,2 = 6.0 Hz, J3,4 = 7.0 Hz, 1 H, H-3), 4.33 (dd,
J3,2 = 5.5 Hz, J3,4 = 7.0 Hz, 1 H, H-3), 4.41 (d, J2,3 = 5.5 Hz, 1 H,
H2), 4.49 (dd, J3,4 = 7.5 Hz, J3,2 = 5.0 Hz, 1 H, H-3), 5.76 (s, 1 H,
O2CHPh or H-1), 5.94 (s, 1 H, O2CHPh or H-1), 6.00 (s, 1 H,
O2CHPh or H-1), 6.10 (s, 1 H, O2CHPh or H-1), 6.73 (d, J = 9.0 Hz,
2 H, Harom), 6.84 (d, J = 8.0 Hz, 2 H, Harom), 7.30 (d, J = 8.0 Hz, 2 H,
Harom), 7.33 (d, J = 7.5 Hz, 2 H, Harom).
13C NMR (125 MHz, CDCl3): d = 17.05 (C-6), 17.07 (C-6), 21.01
(SPhCH3), 55.16 (O2CHPhOCH3), 55.45 (O2CHPhOCH3), 66.91
(O2CHPhOCH3), 69.10 (C-4), 71.97 (C-3), 72.10, 72.39, 75.43,
76.01 (C-2), 76.43 (C-2), 77.00, 86.02 (C-1), 129.36 (arom.),
129.95 (arom., 2 × C), 132.45 (arom., 2 × C), 138.21 (arom.),
169.93 (OCCH3), 170.01 (OCCH3), 170.03 (OCCH3).
Yield: 81% (2.33 g).
1H NMR (500 MHz, CDCl3): d = 1.22 (d, J5,6 = 6.0 Hz, 3 H, H-6),
1.99 (s, 3 H, CH3), 2.06 (s, 3 H, CH3), 2.11 (s, 3 H, CH3), 2.31 (s,
3 H, SPhCH3), 4.35 (dq, J5,4 = 9.5 Hz, J5,6 = 6.0 Hz, 1 H, H-5), 5.11
(dd, J4,3 = 10.5 Hz, J4,5 = 9.5 Hz, 1 H, H-4), 5.27 (dd, J3,4 = 10.5 Hz,
J3,2 = 3.5 Hz, 1 H, H-3), 5.30 (br s, 1 H, H-1), 5.46 (dq, J2,3 = 3.5
Hz, J2,1 = 1.5 Hz, 1 H, H-2), 7.10 (d, J = 8.0 Hz, 2 H, Harom), 7.33 (d,
J = 8.0 Hz, 2 H, Harom).
13C NMR (125 MHz, CDCl3): d = 17.30 (C-6), 20.68 (OCCH3),
20.81 (OCCH3), 20.91 (OCCH3), 21.11 (SPhCH3), 67.67 (CH),
69.36 (CH), 71.18 (CH), 71.28 (CH), 86.02 (CH), 129.36 (arom.,
SPhCH3), 129.95 (arom., SPhCH3), 132.45 (arom., SPhCH3),
138.21 (arom., SPhCH3), 169.93 (OCCH3), 170.01 (OCCH3)
170.03 (OCCH3).
MS (ESI+Q-TOF): m/z = 389.2 [M + H]+.
2,3-O-Di(4-methoxy)benzylidene-4-O-acetyl-1-(4-tolyl)thio-a-
L-rhamnopyranoside (18a)
A mixture of compound 17a,b (157 mg, 0.4 mmol), DMAP (13.8
mg, 0.1 mmol) and pyridine (0.8 mL) was stirred for 20 min. Ac2O
(0.5 mL) was added and the reaction was stirred at r.t. for 30 min.
Products 18a and 18b (both Rf = 0.61) were detected on TLC (n-
hexane–EtOAc, 7:3). After removal of the volatile solvents, the
crude product was purified by column chromatography on silica gel
(n-hexane–EtOAc, 4:1) to give a mixture of 18a and 18b in 97%
yield (147 mg) in a ratio of 2:3 respectively. An analytical sample
was further purified with normal phase HPLC to provide pure 18a
and 18b.
1H NMR (500 MHz, benzene-d6): d = 1.19 (d, J6,5 = 6.5 Hz, 3 H, H-
6), 1.68 (s, 3 H, CH3), 2.00 (s, 3 H, SPhCH3), 3.24 (s, 3 H,
PhOCH3), 4.38 (dq, J5,4 = 10.0 Hz, J5,6 = 6.5 Hz, 1 H, H-5), 4.45 (d,
J2,3 = 5.0 Hz, 1 H, H-2), 4.49 (dd, J3,4 = 7.5 Hz, J3,2 = 5.0 Hz, 1 H,
H-3), 5.46 (dd, J4,5 = 10.0 Hz, J4,3 = 8.5 Hz, 1 H, H-4), 5.94 (s, 1 H,
O2CHPh or H-1), 6.31 (s, 1 H, H-1 or O2CHPh), 6.73 (d, J = 9.0 Hz,
MS (ESI+Q-TOF): m/z = 419.1 [M + Na]+, 273.1 [M – SPhCH3 +
H].
1-(4-Tolyl)thio-a-L-rhamnopyranoside (9)
A mixture of compounds 8 (2.64 g, 9.8 mmol), MeONa (0.36 g, 9.8
mmol) and MeOH (20 mL) was stirred at r.t. for 20 min. The prod-
ucts 9 (Rf = 0.13 and Rf = 0.06) were detected on TLC (n-hexane–
EtOAc, 1:1). After completion of the reaction, the reaction mixture
was treated with Amberlite IR-120 (H+ form) and filtered. After
concentration, the residue was purified by column chromatography
on silica gel (n-hexane–EtOAc, 3:7) to give 9.
Yield: 99% (1.8 g).
Synthesis 2007, No. 9, 1412–1420 © Thieme Stuttgart · New York

1416
C.-S. Yu et al.
PAPER
2 H, Harom), 6.84 (d, J = 8.5 Hz, 2 H, Harom), 7.30 (d, J = 8.5 Hz, 2 H,
arom), 7.33 (d, J = 8.5 Hz, 2 H, Harom).
1 H, H-5), 4.49 (d, Jgem = 12.5 Hz, 1 H, OCH2Ph), 4.58 (d,
Jgem = 11.5 Hz, 1 H, OCH2Ph), 5.05 (dd, J4,3 = 9.5 Hz, J4,5 = 9.5 Hz,
1 H, H-4), 5.45 (d, J1,2 = 1.0 Hz, 1 H, H-1), 6.88 (d, J = 8.5 Hz, 2 H,
Harom), 7.10 (d, J = 7.5 Hz, 2 H, Harom), 7.22 (d, J = 8.5 Hz, 2 H,
H
13C NMR (125 MHz, benzene-d6): d = 17.21 (C-6), 20.40 (OCCH3),
20.94 (SPhCH3), 54.71 (O2CHPhOCH3), 65.60 (CH), 72.07 (CH),
76.69 (CH), 77.21 (CH), 84.94 (C-1), 103.70 (O2CHPhOCH3),
113.94 (arom., CH, 2 × C), 128.29 (arom., CH, 2 × C), 130.09
(arom., CH, 2 × C), 131.32 (arom.), 132.92 (arom., CH, 2 × C),
137.87 (arom.), 160.76 (arom.), 169.59 (OCCH3).
Harom), 7.31 (d, J = 8.5 Hz, 2 H, Harom).
13C NMR (125 MHz, CDCl3): d = 17.25 (C-6), 20.98 (OCCH3),
21.07 (SPhCH3), 55.28 (PhOCH3), 67.43 (CH), 69.66 (CH), 71.46
(OCH2Ph), 72.53 (CH), 76.46 (CH), 85.10 (C-1), 113.96 (arom.,
2 × C), 129.45 (arom.), 129.49 (arom., 2 × C), 129.87 (arom.,
2 × C), 129.89 (arom.), 131.93 (arom., 2 × C), 137.73 (arom.),
159.52 (arom.), 170.05 (OCCH3).
4-O-Acetyl-2,3-O-di-(4-methoxybenzylidene)-1-(4-tolyl)thio-b-
L-rhamnopyranoside (18b)
1H NMR (500 MHz, benzene-d6): d = 1.13 (d, J6,5 = 6.0 Hz, 3 H, H-
6), 1.64 (s, 3 H, HAc), 2.00 (s, 3 H, SPhCH3), 3.20 (s, 3 H, PhOCH3),
4.25 (d, J2,3 = 5.5 Hz, 1 H, H-2), 4.33 (dd, J3,4 = 7.0 Hz, J3,2 = 5.5
Hz, 1 H, H-3), 4.35 (dq, J5,4 = 10.0 Hz, J5,6 = 6.0 Hz, 1 H, H-5), 5.44
(dd, J4,5 = 10.0 Hz, J4,3 = 7.5 Hz, 1 H, H-4), 5.76 (s, 1 H, H-1 or
O2CHPh), 5.97 (s, 1 H, O2CHPh or H-1), 6.81 (d, J = 9.0 Hz, 2 H,
MS (ESI+Q-TOF): m/z = 887.4 [2 × M + Na]+, 455.1 [M + Na]+,
433.2 [M + H]+.
2,3,4-O-Tribenzyl-1-(4-tolyl)thio-a-L-rhamnopyranoside (10a)
A mixture of compounds 19 (218 mg, 0.8 mmol), DMF (4 mL),
THF (4 mL) and NaH (60 % in oil; 114 mg, 2.83 mmol) was stirred
under N2 for 20 min and then cooled to 0 °C. BnBr (317 mL, 2.7
mmol) was added and the reaction mixture was warmed to r.t. and
stirred for 1 h. The starting materials (Rf = 0.06) was consumed,
while the products 10a (Rf = 0.67) was formed [monitored by TLC
(n-hexane–EtOAc, 1:1)]. The reaction was quenched with MeOH (1
mL) and, after removal of the volatile solvents, the crude product
was purified by column chromatography on silica gel (n-hexane–
EtOAc, 9:1→4:1) to give 10a (89%, 388 mg).
H
H
arom), 6.84 (d, J = 8.0 Hz, 2 H, Harom), 7.35 (d, J = 8.0 Hz, 2 H,
arom), 7.66 (d, J = 8.5 Hz, 2 H, Harom).
13C NMR (125 MHz, benzene-d6): d = 17.17 (C-6), 20.44 (OCCH3),
20.93 (SPhCH3), 54.67 (O2CHPhOCH3), 66.00 (CH), 75.46 (CH),
75.77 (CH), 78.91 (CH), 84.21 (C-1), 105.07 (O2CHPhOCH3),
114.17 (arom., 2 × C), 128.87 (arom., 2 × C), 129.41 (arom.),
130.04 (arom.), 130.11 (arom., 2 × C), 132.92 (arom., 2 × C),
137.93 (arom.), 161.09 (arom.), 169.41 (OCCH3).
1H NMR (500 MHz, CDCl3): d = 1.33 (d, J6,5 = 6.0 Hz, 3 H, H-6),
2.31 (s, 3 H, SPhCH3), 3.66 (dd, J4,3 = 9.5 Hz, J4,5 = 9.5 Hz, 1 H, H-
4), 3.82 (dd, J3,4 = 9.5 Hz, J3,2 = 3.0 Hz, 1 H, H-3), 3.95 (dd,
J2,3 = 3.0 Hz, J2,1 = 1.5 Hz, 1 H, H-2), 4.13 (dq, J5,4 = 9.5 Hz,
J5,6 = 6.0 Hz, 1 H, H-5), 4.56 (d, Jgem = 12.5 Hz, 1 H, OCH2Ph),
4.59 (d, Jgem = 12.5 Hz, 1 H, OCH2Ph), 4.62 (d, Jgem = 12.0 Hz, 1 H,
OCH2Ph), 4.63 (d, Jgem = 11.0 Hz, 1 H, OCH2Ph), 4.69 (d,
Jgem = 12.5 Hz, 1 H, OCH2Ph), 4.95 (d, Jgem = 10.5 Hz, 1 H,
OCH2Ph), 5.40 (d, J1,2 = 1.5 Hz, 1 H, H-1), 7.07 (d, J = 8.5 Hz,
2 H), 7.21–7.39 (m, 17 H, Harom).
13C NMR (125 MHz, CDCl3): d = 17.88 (C-6), 21.09 (SPhCH3),
69.221 (CH), 72.02 (OCH2Ph), 72.05 (OCH2Ph), 75.45 (OCH2Ph),
76.37 (CH), 79.95 (CH), 80.51 (CH), 86.07 (C-1), 127.66 (arom.,
2 × C), 127.73 (arom.), 127.78 (arom.), 127.80 (arom., 2 × C),
128.00 (arom., 4 × C), 128.37 (arom., 4 × C), 128.50 (arom.),
129.79 (OCH2Ph, 2 × C), 130.78 (arom.), 131.93 (OCH2Ph, 2 × C),
137.51 (arom.), 137.89 (arom.), 138.22 (arom.), 138.52 (arom.).
4-O-Acetyl-3-O-(4-methoxy)benzyl-1-(4-tolyl)thio-a-L-rham-
nopyranoside (19)
A mixture of compound 16a (42 mg, 0.1 mmol), 4Å molecular
sieves (128 mg) and CH2Cl2 (4 mL) was stirred for 20 min. To the
solution was added sodium cyanoborohydride (81 mg, 1 mmol),
THF (3 mL) and TFA (0.15 mL, 1.92 mmol) sequentially and the
reaction was stirred at r.t. for 16 h. The starting material 18a
(Rf = 0.61) was consumed, while the products 19 (Rf = 0.31) and 20
(Rf = 0.25) were formed [monitored by TLC (n-hexane–EtOAc,
7:3)]. After the removal of the volatile solvents, the residue was par-
titioned between CH2Cl2 (10 mL) and sat. aq NaHCO3 (3 mL), NaCl
(3 mL) and H2O (3 mL) sequentially. The organic layer was then
dried (Na2SO4), filtered and concentration to give a residue which
was purified by column chromatography on silica gel (n-hexane–
EtOAc, 4:1) to give 19 (66%, 28 mg) and 20 (26%, 11 mg).
1H NMR (500 MHz, CDCl3): d = 1.18 (d, J6,5 = 6.5 Hz, 3 H, H-6),
2.10 (s, 3 H, OCCH3), 2.32 (s, 3 H, SPhCH3), 3.79 (s, 3 H,
PhOCH3), 3.80 (dd, J3,4 = 10.0 Hz, J3,2 = 4.0 Hz, 1 H, H-3), 3.95
(dd, J2,3 = 4.0 Hz, J2,1 = 1.0 Hz, 1 H, H-2), 4.20 (dq, J5,4 = 10.0 Hz,
J5,6 = 6.5 Hz, 1 H, H-5), 4.43 (d, Jgem = 12.5 Hz, 1 H, OCH2Ph),
4.63 (d, Jgem = 11.5 Hz, 1 H, OCH2Ph), 4.89 (dd, J4,3 = 10.0 Hz,
J4,5 = 10.0 Hz, 1 H, H-4), 5.41 (br s, 1 H, H-1), 6.85 (d, J = 8.5 Hz,
2 H, Harom), 7.10 (d, J = 7.5 Hz, 2 H, Harom), 7.21 (d, J = 8.5 Hz, 2 H,
MS (ESI+Q-TOF): m/z = 563.1 [M + Na]+, 417.1 [M – SPhCH3 +
H].
2,3,4-O-Tribenzoyl-1-(4-tolyl)thio-a-L-rhamnopyranoside
(11a)
A mixture of compounds 9 (96 mg, 0.35 mmol), DMAP (17 mg,
0.14 mmol) and pyridine (1 mL) was stirred for 10 min. BzCl (185
mL, 1.32 mmol) was then added and the reaction was stirred at r.t.
under N2 for 30 min. The products 11a (Rf = 0.73) was detected by
TLC (n-hexane–EtOAc. 7:3). After the removal of the volatile sol-
vents, the residue was partitioned between EtOAc (10 mL) and sat.
aq NaCl (5 mL) and H2O (5 mL) sequentially. The organic layer
was then dried (Na2SO4), filtered and, after concentration, the resi-
due was purified by column chromatography on silica gel (n-hex-
ane–EtOAc, 4:1) to give 11a (95%, 197 mg).
1H NMR (500 MHz, CDCl3): d = 1.37 (d, J6,5 = 6.0 Hz, 3 H, H-6),
2.32 (s, 3 H, SPhCH3), 4.68 (dq, J5,4 = 10.0 Hz, J5,6 = 6.0 Hz, 1 H,
H-5), 5.60 (d, J1,2 = 1.5 Hz, 1 H, H-1), 5.72 (dd, J4,3 = 10.0 Hz,
J4,5 = 10.0 Hz, 1 H, H-4), 5.80 (dd, J3,4 = 10.0 Hz, J3,2 = 3.0 Hz, 1 H,
H-3), 5.90 (dq, J2,3 = 3.0 Hz, J2,1 = 1.5 Hz, 1 H, H-2), 7.14 (d,
J = 8.5 Hz, 2 H, Harom), 7.26 (d, J = 8.0 Hz, 2 H, Harom), 7.36–7.48
(m, 7 H, Harom), 7.52 (d, J = 7.5 Hz, 1 H, Harom), 7.58 (d, J = 7.5 Hz,
Harom), 7.29 (d, J = 8.5 Hz, 2 H, Harom).
13C NMR (125 MHz, CDCl3): d = 17.28 (C-6), 21.06 (OCCH3),
21.10 (SPhCH3), 55.27 (PhOCH3), 67.17 (CH), 70.00 (CH), 72.10
(OCH2Ph), 74.98 (CH), 79.25 (CH), 85.37 (C-1), 114.02 (arom.,
2 × C), 129.19 (arom.), 129.73 (arom., 2 × C), 129.88 (arom.,
2 × C), 130.21 (arom.), 132.12 (arom., 2 × C), 137.83 (arom.),
159.56 (arom.), 170.99 (OCCH3).
MS (ESI+Q-TOF): m/z = 887.4 [2 × M + Na]+, 455.1 [M + Na]+,
433.2 [M + H]+.
4-O-Acetyl-2-O-(4-methoxy)benzyl-1-(4-tolyl)thio-a-L-rham-
nopyranoside (20)
1H NMR (500 MHz, CDCl3): d = 1.16 (d, J6,5 = 7.0 Hz, 3 H, H-6),
2.03 (s, 3 H, CH3), 2.31 (s, 3 H, SPhCH3), 3.72 (dd, J3,4 = 9.5 Hz,
J3,2 = 4.0 Hz, 1 H, H-3), 3.80 (s, 3 H, PhOCH3), 4.18 (dd, J2,3 = 4.0
Hz, J2,1 = 1.0 Hz, 1 H, H-2), 4.20 (dq, J5,4 = 9.5 Hz, J5,6 = 7.0 Hz,
Synthesis 2007, No. 9, 1412–1420 © Thieme Stuttgart · New York

PAPER
Synthesis of Rhamnosyl Trisaccharide
1417
1 H, Harom), 7.82 (d, J = 7.5 Hz, 2 H, Harom), 7.99 (d, J = 7.0 Hz, 2 H,
product 16 (Rf = 0.6; n-hexane–EtOAc, 3:7) was formed. After the
removal of the volatile solvents, the crude residue was purified by
column chromatography on silica gel (n-hexane–EtOAc, 7:3) to
give 16 (86%, 84 mg).
Harom), 8.06 (d, J = 7.5 Hz, 2 H, Harom).
MS (ESI+Q-TOF): m/z = 583.1 [M + H+], 459.1 [M – SPhCH3 + H].
2,3,4-O-Tribenzyl-L-rhamnopyranoside (13a,b)
MS (ESI+Q-TOF): m/z = 459.2 [M – imidate – H + H].
A mixture of compounds 10a (844 mg, 1.6 mmol), NBS (565 mg,
3.2 mmol) and acetone–H2O (1:1, 10 mL) was stirred at r.t. for 1 h.
The reaction was monitored by TLC (n-hexane–EtOAc, 7:3). NBS
(282 mg, 1.6 mmol) was added and the solution was stirred for a fur-
ther 1 h. The starting material (Rf = 0.67) was consumed, while the
products 10a,b (Rf = 0.32) formed. After the removal of the volatile
solvents, the crude product was purified by column chromatography
on silica gel (n-hexane–EtOAc, 1:3) to give 10a,b (91%, 620 mg).
2,3,4-O-Triacetyl-1-O-trichloroacetimido-a-L-rhamnopyran-
oside (15)
A mixture of compound 12 (27 mg, 0.1 mmol), K2CO3 (148 mg, 1.1
mmol) and CH2Cl2 (2 mL) was vigorously stirred for 30 min. After
addition of CCl3CN (190 mL, 1.9 mmol), the mixture was stirred for
2 h. After removal of the volatile solvents, the crude residue was pu-
rified by column chromatography on silica gel (n-hexane–EtOAc,
9:2) to give 15.
MS (ESI+Q-TOF): m/z = 457.1 [M + Na]+.
Yield: 73% (30 mg); Rf = 0.6 (n-hexane–EtOAc, 6:4).
2,3,4-O-Tribenzoyl-a,b-L-rhamnopyranoside (14a,b)
A mixture of compounds 11a,b (169 mg, 0.29 mmol), NBS (107
mg, 0.6 mmol) and acetone–H2O (1:2, 4 mL) was stirred at r.t. for 1
h. The reaction was monitored by TLC (n-hexane–EtOAc, 7:3).
NBS (51 mg, 0.29 mmol) was added and stirring was continued for
1 h. The starting material (Rf = 0.72) was consumed, while the prod-
ucts 14a,b (Rf = 0.36) was formed. After the removal of the volatile
solvents, the crude products were purified by column chromatogra-
phy on silica gel (n-hexane–EtOAc, 9:2) to give 14a,b (93%, 129
mg).
1H NMR (500 MHz, benzene-d6): d = 1.23 (d, J6,5 = 6.0 Hz, 3 H, H-
6), 1.55 (s, 3 H, OCCH3), 1.62 (s, 3 H, OCCH3), 1.71 (s, 3 H,
OCCH3), 4.32 (dq, J5,4 = 9.5 Hz, J5,6 = 6.5 Hz, 1 H, H-5), 5.60 (dd,
J4,3 = 10.5 Hz, J4,5 = 9.5 Hz, 1 H, H-4), 5.79 (dd, J3,4 = 10.5 Hz,
J3,2 = 3.5 Hz, 1 H, H-3), 5.85 (dd, J2,3 = 3.5 Hz, J2,1 = 2.5 Hz, 1 H,
H-2), 6.50 (d, J2,1 = 2.5 Hz, 1 H, H-1), 8.47 (s, 1 H, NH).
13C NMR (125 MHz, benzene-d6): d = 17.60 (C-6), 19.99 (OCCH3),
20.17 (OCCH3), 20.23 (OCCH3), 68.38 (CH), 69.48 (CH), 69.96
(CH), 70.59 (CH), 95.55 (C-1), 159.86 (OCNHCCl3), 169.31
(OCNHCCl3), 169.36 (OCNHCCl3), 169.51 (OCNHCCl3).
MS (ESI+Q-TOF): m/z = 499.1 [M + Na]+.
4-O-Acetyl-2-O-benzoyl-3-O-(4-methoxy)benzyl-1-(4-
tolyl)thio-a-L-rhamnopyranoside (21)
2,3,4-O-Triacetyl-a,b-L-rhamnopyranoside (12)
Compound 12 was prepared using the procedure described above.
Compound 8 (144 mg, 0.4 mmol), NBS (108 mg, 0.6 mmol) and
acetone–H2O (9:1, 6 mL) were employed. Purification by column
chromatography (n-hexane–EtOAc, 7:4) gave pure 12.
A mixture of compounds 19 and 20 (134 mg, 0.31 mmol), DMAP
(23 mg, 0.19 mmol) and pyridine (4 mL) was stirred for 10 min. To
the solution was added BzCl (45 mL, 0.32 mmol) and the reaction
mixture was stirred at r.t. under N2 for 30 min. The products 21 and
22 (both Rf = 0.53) were detected by TLC (n-hexane–EtOAc, 7:3).
After removal of the volatile solvents, the residue was partitioned
between EtOAc (10 mL) and sat. aq NaCl (5 mL) and H2O (5 mL),
sequentially. The organic layer was dried (Na2SO4) and filtered. Af-
ter concentration, the residue was purified by column chromatogra-
phy on silica gel (n-hexane–EtOAc, 9:1) to give 21 and 22 (total
yield: 97%, 161 mg) in a ratio of 2.5:1. No further purification with
HPLC was pursued. The peaks corresponding to compound 21 in
the NMR spectra of the mixture was elucidated and could be as-
signed as follows.
1H NMR (500 MHz, CDCl3): d = 1.24 (d, J6,5 = 6.5 Hz, 3 H, H-6),
2.04 (s, 3 H, OCCH3), 2.30 (s, 3 H, SPhCH3), 3.78 (s, 3 H,
PhOCH3), 3.86 (dd, J3,4 = 9.5 Hz, J3,2 = 3.0 Hz, 1 H, H-3), 4.28 (dq,
J5,4 = 10.0 Hz, J5,6 = 6.0 Hz, 1 H, H-5), 4.42 (d, Jgem = 12.0 Hz, 1 H,
OCH2Ph), 4.61 (d, Jgem = 12.0 Hz, 1 H, OCH2Ph), 5.18 (dd,
J4,3 = 9.5 Hz, J4,5 = 10.0 Hz, 1 H, H-4), 5.47 (d, J1,2 = 1.5 Hz, 1 H,
H-1), 5.75 (dd, J2,3 = 2.5 Hz, J2,1 = 1.5 Hz, 1 H, H-2), 6.83 (d,
J = 8.5 Hz, 2 H, Harom), 7.10 (d, J = 7.5 Hz, 2 H, Harom), 7.19 (d,
J = 8.0 Hz, 2 H, Harom), 7.34 (d, J = 8.5 Hz, 2 H, Harom), 7.43 (d,
J = 7.5 Hz, 2 H, Harom), 7.54 (d, J = 8.0 Hz, 1 H, Harom), 8.05 (d,
J = 7.5 Hz, 2 H, Harom).
Yield: 95% (100 mg); Rf = 0.2 (n-hexane–EtOAc, 3:7).
MS (ESI+Q-TOF): m/z = 313.3 [M + Na]+.
2,3,4-O-Tribenzyl-1-O-trichloroacetimido-a-L-rhamnopyrano-
side (5)
A mixture of compounds 13a,b (100 mg, 0.23 mmol) and CH2Cl2 (2
mL) was stirred under N2 for 20 min. After addition of NaH (60%
in oil; 11 mg, 0.27 mmol) the solution was stirred for 30 min then
CCl3CN (235 mL, 2.3 mmol) was added. The reaction mixture was
stirred at r.t. for 1.5 h, during which the product 5 (Rf = 0.57) was
detected on TLC (n-hexane–EtOAc, 7:3). After the removal of the
volatile solvents, the crude residue was purified by column chroma-
tography on silica gel (n-hexane–EtOAc, 9:1) to give 5 (81%, 108
mg).
1H NMR (500 MHz, benzene-d6): d = 1.37 (d, J6,5 = 6.5 Hz, 3 H, H-
6), 3.93 (dd, J4,3 = 9.0 Hz, J4,5 = 9.0 Hz, 1 H, H-4), 3.98 (dd,
J2,3 = 3.5 Hz, J2,1 = 2.0 Hz, 1 H, H-2), 4.09 (dd, J3,4 = 9.0 Hz,
J3,2 = 3.0 Hz, 1 H, H-3), 4.21 (dq, J5,4 = 10.0 Hz, J5,6 = 6.0 Hz, 1 H,
H-5), 4.49 (br s, 2 H, OCH2Ph), 4.50 (d, J = 11.5 Hz, 1 H,
OCH2Ph), 4.60 (br s, 2 H, OCH2Ph), 4.96 (d, J = 11.5 Hz, 1 H,
OCH2Ph), 6.67 (d, J1,2 = 2.0 Hz, 1 H, H-1), 7.04–7.19 (m, 9 H,
Harom), 7.28 (d, J = 7.0 Hz, 4 H, Harom), 7.39 (d, J = 7.2 Hz, 2 H,
MS (ESI+Q-TOF): m/z = 1095.4 [2 × M + Na]+, 559.1 [M + Na]+.
Harom), 8.43 (s, 1 H, NH).
4-O-Acetyl-3-O-benzoyl-2-O-(4-methoxy)benzyl-1-(4-
tolyl)thio-a-L-rhamnopyranoside (22)
MS (ESI+Q-TOF): m/z = 595.2 [M + NH4]+, 417.2 [M – imidate –
H + H].
1H NMR (500 MHz, CDCl3): d = 1.26 (d, J6,5 = 6.5 Hz, 3 H, H-6),
1.97 (s, 3 H, OCCH3), 2.33 (s, 3 H, SPhCH3), 3.67 (s, 3 H,
PhOCH3), 4.21 (dd, J2,3 = 3.0 Hz, J2,1 = 1.5 Hz, 1 H, H-2), 4.34 (dq,
J5,4 = 10.0 Hz, J5,6 = 6.5 Hz, 1 H, H-5), 4.40 (d, Jgem = 12.0 Hz, 1 H,
OCH2Ph), 4.55 (d, Jgem = 12.5 Hz, 1 H, OCH2Ph), 5.31 (dd,
J3,4 = 10.0 Hz, J3,2 = 3.0 Hz, 1 H, H-3), 5.41 (s, 1 H, H-1), 5.43 (dd,
J4,3 = 10.0 Hz, J4,5 = 10.0 Hz, 1 H, H-4), 6.58 (d, J = 8.0 Hz, 2 H,
2,3,4-O-Tribenzoyl-1-O-trichloroacetimido-a-L-rhamnopyran-
oside (16)
A mixture of compounds 14a,b (75 mg, 0.16 mmol) and CH2Cl2 (3
mL) was stirred for 20 min. To the solution was added CCl3CN
(0.18 mL, 1.79 mmol) and the mixture was vigorously stirred for 30
min. A catalytic amount of DBU (11.8 mL, 0.08 mmol) was added
and the reaction mixture was stirred at r.t. under N2 for 1 h. The
Harom), 7.08 (d, J = 8.5 Hz, 2 H, Harom), 7.11 (d, J = 8.5 Hz, 2 H,
Synthesis 2007, No. 9, 1412–1420 © Thieme Stuttgart · New York

1418
C.-S. Yu et al.
PAPER
Harom), 7.33 (d, J = 8.0 Hz, 2 H, Harom), 7.45 (d, J = 7.0 Hz, 2 H,
2,3,4-O-Tribenzyl-a-L-rhamnosyl-(1→3)-4-O-acetyl-2-O-ben-
zoyl-1-(4-tolyl)thio-a-L-rhamnopyranoside (23)
Harom), 7.56 (d, J = 7.0 Hz, 1 H, Harom), 7.98 (d, J = 7.0 Hz, 2 H,
Harom).
A mixture of compound 4 (90 mg, 0.22 mmol), 4 Å molecular
sieves (220 mg) and compound 5 (130 mg, 0.23 mmol) in CH2Cl2
(5 mL) was stirred at r.t. for 30 min then cooled to 0 °C. TMSOTf
(19 mL, 0.11 mmol) was added and the reaction mixture was stirred
for 30 min and then warmed to r.t.. The product 21 (Rf = 0.65) was
detected on TLC (n-hexane–EtOAc, 7:3). After completion of the
reaction, the reaction mixture was quenched with Et3N (0.5 mL), di-
luted with CH2Cl2 (15 mL) and filtered. After concentration, the res-
idue was purified by column chromatography on silica gel (n-
hexane–EtOAc, 9:2) to give 21 (78%, 64 mg).
1H NMR (500 MHz, CDCl3): d = 1.18 (d, J6,5 = 6.0 Hz, 3 H, H-6),
1.21 (d, J6¢,5¢ = 6.0 Hz, 3 H, H-6¢), 1.88 (s, 3 H, OCCH3), 2.30 (s,
3 H, SPhCH3), 3.51 (dd, J4¢,5¢ = 9.0 Hz, J4¢,3¢ = 9.0 Hz, 1 H, H-4¢),
3.59 (dd, J2¢,3¢ = 3.0 Hz, J2¢,1¢ = 2.0 Hz, 1 H, H-2¢), 3.63 (dq,
13C NMR (125 MHz, CDCl3): d = 17.41 (C-6), 17.52 (C-6), 20.81
(OCCH3), 20.97 (OCCH3), 21.09 (SPhCH3), 55.07 (PhOCH3),
55.24 (PhOCH3), 67.76 (CH), 67.86 (CH), 70.622 (CH), 70.773
(OCH2Ph), 71.30 (CH), 72.14 (OCH2Ph), 72.26 (CH), 72.72 (CH),
74.23 (CH), 76.22 (CH), 85.99 (C-1), 86.47 (C-1), 113.65, 113.78
(arom., 2 × C), 128.44, 129.31, 129.52, 129.58 (arom.), 129.63
(arom.), 129.74 (arom.), 129.81, 129.88, 129.94, 131.97, 132.28,
133.29, 138.08 (arom.), 159.32 (arom.), 165.74 (OCPh), 169.96
(OCCH3).
4-O-Acetyl-2-O-benzoyl-1-(4-tolyl)thio-a-L-rhamnopyranoside
(4)
A mixture of compounds 22, 21 (158 mg, 0.29 mmol) and CAN
(327 mg, 0.6 mmol) in MeCN–H2O (9:1, 4 mL) was stirred for 60
min. To the solution was added CAN (122 mg, 0.22 mmol) and the
reaction mixture was stirred at r.t. for 1 h. The products 4 (Rf = 0.41)
and 2 (Rf = 0.39) were detected by TLC (n-hexane–EtOAc, 7:3).
After the removal of the volatile solvents, the residue was parti-
tioned between EtOAc (10 mL) and sat. aq Na2CO3 (5 mL) and H2O
(5 mL), sequentially. The organic layer was dried (Na2SO4) and fil-
tered. After concentration, the residue was purified by column chro-
matography on silica gel (n-hexane–EtOAc, 7:3) to give 4 (52%, 64
mg) and 2 (20%, 25 mg). For analytical purposes, a small amount
of each sample was further purified with HPLC (n-hexane–EtOAc,
7:3).
1H NMR (500 MHz, CDCl3): d = 1.26 (d, J6,5 = 6.0 Hz, 3 H, H-6),
2.16 (s, 3 H, OCCH3), 2.30 (s, 3 H, SPhCH3), 4.36 (dd, J3,4 = 9.5
Hz, J3,2 = 3.0 Hz, 1 H, H-3), 4.38 (dq, J5,4 = 9.5 Hz, J5,6 = 6.0 Hz,
1 H, H-5), 5.04 (dd, J4,3 = 9.5 Hz, J4,5 = 9.5 Hz, 1 H, H-4), 5.51 (d,
J1,2 = 1.5 Hz, 1 H, H-1), 5.75 (d, J2,1 = 1.5 Hz, 1 H, H-2), 7.10 (d,
J = 8.0 Hz, 2 H, Harom), 7.36 (d, J = 8.0 Hz, 2 H, Harom), 7.45 (d,
J = 7.0 Hz, 2 H, Harom), 8.04 (d, J = 7.5 Hz, 2 H, Harom), 8.08 (d,
J = 7.0 Hz, 1 H, Harom).
J
J
5¢,4¢ = 9.0 Hz, J5¢,6¢ = 6.5 Hz, 1 H, H-5¢), 3.64 (dd, J3¢,4¢ = 9.0 Hz,
3¢,2¢ = 3.0 Hz, 1 H, H-3¢), 4.12 (dd, J3,4 = 10.0 Hz, J3,2 = 3.5 Hz, 1 H,
H-3), 4.30 (dq, J5,4 = 9.5 Hz, J5,6 = 6.0 Hz, 1 H, H-5), 4.45 (d,
Jgem = 11.5 Hz, 1 H, OCH2Ph), 4.48 (d, Jgem = 11.5 Hz, 1 H,
OCH2Ph), 4.48 (d, Jgem = 12.0 Hz, 1 H, OCH2Ph), 4.63 (d,
Jgem = 13.0 Hz, 1 H, OCH2Ph), 4.69 (d, Jgem = 12.5 Hz, 1 H,
OCH2Ph), 4.73 (d, Jgem = 12.0 Hz, 1 H, OCH2Ph), 4.91 (d,
J1¢,2¢ = 1.5 Hz, 1 H, H-1¢), 5.18 (dd, J4,5 = 9.5 Hz, J4,3 = 9.5 Hz, 1 H,
H-4), 5.48 (d, J1,2 = 1.5 Hz, 1 H, H-1), 5.58 (d, J2,3 = 2.5 Hz, 1 H, H-
2), 7.10 (d, J = 8.0 Hz, 2 H, Harom), 7.13 (d, J = 8.5 Hz, 2 H), 7.20–
7.32 (m, 13 H, Harom), 7.35 (d, J = 8.5 Hz, 2 H, Harom), 7.41 (dd,
J = 8.0 Hz, J = 8.0 Hz, 2 H, Harom), 7.54 (dd, J = 8.0 Hz, J = 8.0 Hz,
1 H, Harom), 8.03 (d, J = 7.0 Hz, 2 H, Harom).
13C NMR (125 MHz, CDCl3): d = 17.48 (C-6), 17.87 (C-6¢), 20.76
(OCCH3), 21.11 (SPhCH3), 67.78 (CH), 69.04 (CH), 72.51
(OCH2Ph), 72.79 (OCH2Ph), 73.15 (CH), 73.89 (CH), 74.16
(OCH2Ph), 74.83 (CH), 76.74 (CH), 77.25 (CH), 79.25 (CH), 85.90
(C-1), 100.42 (C-1¢), 127.29 (arom.), 127.48 (arom., 3 × C), 127.68
(arom., 3 × C), 127.76 (arom., 2 × C), 128.13 (arom., 2 × C),
128.29 (arom., 2 × C), 128.39 (arom., 2 × C), 128.50 (arom.,
2 × C), 129.52 (arom.), 129.60 (arom.), 129.89 (arom., 2 × C),
129.92 (arom., 2 × C), 132.41 (arom., 2 × C), 133.34 (arom.),
138.10 (arom.), 138.24 (arom.), 138.44 (arom.), 138.68 (arom.),
165.70 (OCPh), 169.75 (OCCH3).
13C NMR (125 MHz, CDCl3): d = 17.42 (C-6), 21.04 (OCCH3),
21.10 (SPhCH3), 67.29 (CH), 69.56 (CH), 74.77 (CH), 76.74 (CH),
86.14 (C-1), 128.56 (arom., 2 × C), 129.26 (arom.), 129.64 (arom.),
129.87 (arom., 2 × C), 129.94 (arom., 2 × C), 130.16 (arom.),
132.38 (arom., 2 × C), 133.57 (arom.), 138.13 (arom.), 165.90
(OCPh), 171.65 (OCCH3).
MS (ESI+Q-TOF): m/z = 833.5 [M + H]+, 856.5 [M + Na]+, 709.4
[M – SPhCH3 + H].
MS (ESI+Q-TOF): m/z = 855.4 [2 × M + Na]+, 439.2 [M + Na]+,
2,3,4-O-Tribenzyl-a-L-rhamnosyl-(1→3)-4-O-acetyl-2-O-ben-
zoyl-a,b-L-rhamnopyranoside (24a,b)
317.1 [M – SPhCH3 + Na]+, 295.2 [M – SPhCH3 + H]+.
A mixture of compound 23 (86 mg, 0.1 mmol) and NBS (29 mg, 0.2
mmol) in acetone–H2O (1:1, 8 mL) was stirred at r.t. for 1 h. NBS
(33 mg, 0.18 mmol) was added and stirring was continued for 1 h.
The products 24a,b (Rf = 0.25) were detected on TLC (n-hexane–
EtOAc, 7:3). After concentration, the crude residue was purified by
column chromatography on silica gel (n-hexane–EtOAc, 7:3) to
give 24a,b (92%, 69 mg).
4-O-Acetyl-3-O-benzoyl-1-(4-tolyl)thio-a-L-rhamnopyranoside
(2)
1H NMR (500 MHz, CDCl3): d = 1.26 (d, J6,5 = 6.0 Hz, 3 H, H-6),
1.98 (s, 3 H, OCCH3), 2.32 (s, 3 H, SPhCH3), 4.43 (dq, J5,4 = 9.5
Hz, J5,6 = 6.0 Hz, 1 H, H-5), 4.47 (dd, J2,3 = 2.5 Hz, J2,1 = 1.5 Hz,
1 H, H-2), 5.36 (dd, J4,3 = 10.0 Hz, J4,5 = 9.5 Hz, 1 H, H-4), 5.40
(dd, J3,4 = 10.0 Hz, J3,2 = 2.5 Hz, 1 H, H-3), 5.44 (d, J1,2 = 1.5 Hz,
1 H, H-1), 7.12 (d, J = 7.5 Hz, 2 H, Harom), 7.37 (d, J = 8.5 Hz, 2 H,
1H NMR (500 MHz, CDCl3): d = 1.16 (d, J5,6 = 6.0 Hz, 3 H, H-6),
1.19 (d, J5¢,6¢ = 6.0 Hz, 3 H, H-6¢), 1.85 (s, 3 H, OCCH3), 3.49 (dd,
Harom), 7.44 (d, J = 8.0 Hz, 2 H, Harom), 7.57 (d, J = 7.0 Hz, 1 H,
Harom), 8.01 (d, J = 7.0 Hz, 2 H, Harom).
J
J
4¢,5¢ = 9.0 Hz, J4¢,3¢ = 9.0 Hz, 1 H, H-4¢), 3.58 (dd, J2¢,3¢ = 2.5 Hz,
2¢,1¢ = 2.5 Hz, 1 H, H-2¢), 3.64 (dd, J3¢,4¢ = 9.0 Hz, J3¢,2¢ = 2.5 Hz,
13C NMR (125 MHz, CDCl3): d = 17.33 (C-6), 20.79 (OCCH3),
21.12 (SPhCH3), 67.63 (CH), 70.87 (CH), 71.05 (CH), 72.77 (CH),
87.85 (C-1), 128.63 (arom., 2 × C), 129.23 (arom.), 129.82 (arom.,
3 × C), 129.96 (arom., 2 × C), 132.16 (arom., 2 × C), 133.54
(arom.), 137.97 (arom.), 165.57 (OCPh), 170.11 (OCCH3).
1 H, H-3¢), 3.65 (dq, J5¢,4¢ = 9.0 Hz, J5¢,6¢ = 6.0 Hz, 1 H, H-5¢), 4.05
(dq, J5,4 = 10.0 Hz, J5,6 = 6.0 Hz, 1 H, H-5), 4.21 (dd, J3,4 = 9.5 Hz,
J3,2 = 3.5 Hz, 1 H, H-3), 4.43 (d, Jgem = 11.5 Hz, 1 H, OCH2Ph),
4.47 (d, Jgem = 11.5 Hz, 1 H, OCH2Ph), 4.48(d, Jgem = 11.5 Hz, 1 H,
OCH2Ph), 4.62 (d, Jgem = 12.0 Hz, 1 H, OCH2Ph), 4.68 (d,
Jgem = 12.5 Hz, 1 H, OCH2Ph), 4.73 (d, Jgem = 11.5 Hz, 1 H,
OCH2Ph), 4.90 (d, J1¢,2¢ = 2.0 Hz, 1 H, H-1¢), 5.13 (dd, J4,5 = 9.0 Hz,
J4,3 = 9.0 Hz, 1 H, H-4), 5.30 (br s, 1 H, H-1), 5.37 (dd, J2,3 = 3.5
Hz, J2,3 = 2.5 Hz, 1 H, H-2), 7.12 (d, J = 8.0 Hz, 2 H, Harom), 7.14–
MS (ESI+Q-TOF): m/z = 855.4 [2 × M + Na]+, 439.2 [M + Na]+,
317.1 [M – SPhCH3 + H + Na]+, 295.2 [M – SPhCH3 + 2H]+.
Synthesis 2007, No. 9, 1412–1420 © Thieme Stuttgart · New York

PAPER
Synthesis of Rhamnosyl Trisaccharide
1419
7.34 (m, 14 Harom), 7.42 (dd, J = 8.0 Hz, J = 8.0 Hz, 2 H, Harom),
7.55 (dd, J = 7.5 Hz, 2 H, Harom), 7.55 (d, J = 6.5 Hz, 2 H, Harom).
MS (ESI+Q-TOF): m/z = 749.3 [M + Na]+.
was monitored by TLC (Rf = 0.5; n-hexane–EtOAc, 7:3). The mix-
ture was quenched with Et3N (0.5 mL), diluted with CH2Cl2 (10
mL) and filtered. After removal of the volatile solvents, the crude
residue was purified by column chromatography on silica gel (n-
hexane–EtOAc, 8:3) to give 26 (84%, 15 mg).
2,3,4-O-Tribenzyl-a-L-rhamnosyl-(1→3)-4-O-acetyl-2-O-ben-
zoyl-1-O-trichloroacetimido-a-L-rhamnopyranoside (25)
A mixture of compound 24a,b (47 mg, 0.07 mmol), CH2Cl2 (2 mL)
and CCl3CN (65 mL, 0.65 mmol) was stirred at r.t. for 20 min. A so-
lution of DBU [0.72 mL, 0.01 mmol; taken from a stock solution of
DBU (0.1 mL) in CH2Cl2 (1 mL)] was added and the stirring was
continued for 1 h. The product 25 (Rf = 0.69) was detected on TLC
(n-hexane–EtOAc, 3:2). After the removal of the volatile solvents,
the crude residue was purified by column chromatography on silica
gel (n-hexane–EtOAc, 4:1) to give 25 (83%, 47 mg).
1H NMR (500 MHz, CDCl3): d = 1.08 (d, J6,5 = 7.0 Hz, 3 H, H-6),
1.17 (d, J6¢,5¢ = 6.0 Hz, 3 H, H-6¢), 1.29 (d, J6¢¢,5¢¢ = 6.0 Hz, 3 H, H-
6¢¢), 1.86 (s, 3 H, OCCH3, HAc¢), 1.96 (s, 3 H, OCCH3, HAc), 2.32 (s,
3 H, SPhCH3), 3.50 (dd, J4¢¢,5¢¢ = 8.5 Hz, J4¢¢,3¢¢ = 9.0 Hz, 1 H, H-4¢¢),
3.58 (br s, 1 H, H-2¢¢), 3.63 (dd, J3¢¢,4¢¢ = 9.0 Hz, J3¢¢,2¢¢ = 3.0 Hz, 1 H,
H-3¢¢), 3.67 (dq, J5¢¢,4¢¢ = 8.5 Hz, J5¢¢,6¢¢ = 6.0 Hz, 1 H, H-5¢¢), 3.91 (dq,
J5,4 = 9.0 Hz, J5,6 = 6.0 Hz, 1 H, H-5), 4.23 (dd, J3,4 = 9.5 Hz,
J3,2 = 3.5 Hz, 1 H, H-3¢), 4.40 (dq, J5¢,4¢ = 9.5 Hz, J5¢,6¢ = 6.5 Hz, 1 H,
H-5¢), 4.40 (d, J2,3 = 3.5 Hz, 1 H, H-2), 4.41 (d, Jgem = 11.0 Hz, 1 H,
OCH2Ph), 4.43 (d, Jgem = 11.5 Hz, 1 H, OCH2Ph), 4.49 (d,
Jgem = 11.5 Hz, 1 H, OCH2Ph), 4.63 (d, Jgem = 13.0 Hz, 1 H,
OCH2Ph), 4.67 (d, Jgem = 12.5 Hz, 1 H, OCH2Ph), 4.75 (d,
Jgem = 11.5 Hz, 1 H, OCH2Ph), 4.96 (br s, 1 H, H-1¢¢), 5.00 (d,
1H NMR (500 MHz, CDCl3): d = 1.16 (d, J6,5 = 6.0 Hz, 3 H, H-6),
1.24 (d, J6¢,5¢ = 6.0 Hz, 3 H, H-6¢), 1.90 (s, 3 H, OCCH3), 3.50 (dd,
J
J
4¢,5¢ = 9.0 Hz, J4¢,3¢ = 9.0 Hz, 1 H, H-4¢), 3.61 (dd, J2¢,3¢ = 2.5 Hz,
2¢,1¢ = 2.5 Hz, 1 H, H-2¢), 3.65 (dd, J3¢,4¢ = 9.0 Hz, J3¢,2¢ = 2.5 Hz,
J1¢,2¢ = 1.0 Hz, 1 H, H-1¢), 5.09 (dd, J4¢,5¢ = 9.5 Hz, J4¢,3¢ = 9.5 Hz,
1 H, H-3¢), 3.69 (dq, J5¢,4¢ = 9.0 Hz, J5¢,6¢ = 6.0 Hz, 1 H, H-5¢), 4.02
(dq, J5,4 = 9.5 Hz, J5,6 = 6.0 Hz, 1 H, H-5), 4.27 (dd, J3,4 = 9.5 Hz,
J3,2 = 3.0 Hz, 1 H, H-3), 4.45 (d, Jgem = 12.0 Hz, 1 H, OCH2Ph),
4.50 (d, Jgem = 11.5 Hz, 2 H, OCH2Ph), 4.61 (d, Jgem = 12.0 Hz, 1 H,
OCH2Ph), 4.68 (d, Jgem = 12.0 Hz, 1 H, OCH2Ph), 4.69 (d,
Jgem = 11.0 Hz, 1 H, OCH2Ph), 4.92 (d, J1¢,2¢ = 2.5 Hz, 1 H, H-1¢),
5.23 (dd, J4,5 = 9.5 Hz, J4,3 = 9.5 Hz, 1 H, H-4), 5.53 (dd, J2,3 = 3.0
Hz, J2,1 = 1.5 Hz, 1 H, H-2), 6.34 (d, J1,2 = 1.5 Hz, 1 H, H-1), 7.16
(d, J = 6.5 Hz, 2 H, Harom), 7.20–7.31 (m, 13 H, Harom), 7.45 (dd,
J = 7.5 Hz, J = 7.5 Hz, 2 H, Harom), 7.58 (dd, J = 8.0 Hz, J = 8.0 Hz,
1 H, Harom), 8.07 (d, J = 7.0 Hz, 2 H, Harom), 8.73 (s, 1 H, NH).
1 H, H-4¢), 5.33 (dd, J4,5 = 9.5 Hz, J4,3 = 9.5 Hz, 1 H, H-4), 5.44 (br
s, 1 H, H-2¢), 5.48 (br s, 1 H, H-1), 5.53 (dd, J3,4 = 9.5 Hz, J3,2 = 3.5
Hz, 1 H, H-3), 7.12 (d, J = 8.0 Hz, 2 H, Harom), 7.14 (d, J = 7.5 Hz,
2 H, Harom), 7.18–7.42 (m, 19 H, Harom), 7.45 (dd, J = 7.0 Hz, J = 7.0
Hz, 1 H, Harom), 7.51 (dd, J = 7.5 Hz, J = 7.5 Hz, 1 H, Harom), 7.96
(d, J = 7.0 Hz, 2 H, Harom), 8.03 (d, J = 7.0 Hz, 2 H, Harom).
13C NMR (125 MHz, CDCl3): d = 17.45 (C-6), 17.48 (C-6¢), 17.76
(C-6¢¢), 20.76 (OCCH3), 20.76 (OCCH3), 21.13 (SPhCH3), 67.35
(CH), 67.97 (CH), 68.99 (CH), 71.08 (CH), 71.44 (CH), 72.02
(CH), 72.44 (OCH2Ph), 72.68 (OCH2Ph), 72.93 (CH), 73.56 (CH),
74.11 (OCH2Ph), 75.38 (CH), 78.43 (CH), 79.53 (CH), 80.23 (CH),
87.49 (C-1), 99.34 (C-1¢¢), 99.93 (C-1¢), 127.22 (arom.), 127.49
(arom., 3 × C), 127.63 (arom., 3 × C), 127.74 (arom., 2 × C),
128.09 (arom., 2 × C), 128.25 (arom., 2 × C), 128.35 (arom.,
2 × C), 128.43 (arom., 2 × C), 128.66 (arom., 2 × C), 128.98
(arom.), 129.50 (arom.), 129.84 (arom., 2 × C), 130.03 (arom., 2 ×
C), 130.19 (arom.), 132.34 (arom., 2 × C), 133.19 (arom.), 133.40
(arom.), 138.12 (arom.), 138.32 (arom.), 138.52 (arom.), 138.86
(arom.), 165.71 (OCPh), 165.71 (OCPh), 169.70 (OCCH3).
1H NMR (500 MHz, benzene-d6): d = 1.29 (d, J6,5 = 6.0 Hz, 3 H, H-
6), 1.39 (d, J6¢,5¢ = 6.5 Hz, 3 H, H-6¢), 1.61 (s, 3 H, OCCH3), 3.80
(dd, J4¢,5¢ = 9.0 Hz, J4¢,3¢ = 9.0 Hz, 1 H, H-4¢), 3.81 (dd, J2¢,3¢ = 3.0 Hz,
J2¢,1¢ = 2.0 Hz, 1 H, H-2¢), 3.99 (dd, J3¢,4¢ = 9.0 Hz, J3¢,2¢ = 3.0 Hz,
1 H, H-3¢), 4.20 (dq, J5¢,4¢ = 9.0 Hz, J5¢,6¢ = 6.0 Hz, 1 H, H-5¢), 4.32
(dq, J5,4 = 10.0 Hz, J5,6 = 6.5 Hz, 1 H, H-5), 4.34 (d, Jgem = 12.0 Hz,
1 H, OCH2Ph), 4.42 (d, Jgem = 11.0 Hz, 1 H, OCH2Ph), 4.45 (d,
Jgem = 11.0 Hz, 1 H, OCH2Ph), 4.54 (d, Jgem = 12.0 Hz, 1 H,
OCH2Ph), 4.65 (d, Jgem = 12.0 Hz, 1 H, OCH2Ph), 4.68 (dd,
J3,4 = 10.0 Hz, J3,2 = 3.5 Hz, 1 H, H-3), 4.82 (d, Jgem = 11.5 Hz, 1 H,
OCH2Ph), 5.26 (d, J1¢,2¢ = 2.0 Hz, 1 H, H-1¢), 5.75 (dd, J4,5 = 10.0
Hz, J4,3 = 10.0 Hz, 1 H, H-4), 6.10 (dd, J2,1 = 2.0 Hz, J2,3 = 3.5 Hz,
1 H, H-2), 6.79 (d, J1,2 = 2.0 Hz, 1 H, H-1), 6.92 (dd, J = 7.5 Hz,
J = 7.5 Hz, 2 H, Harom), 7.00–7.20 (m, 12 H, Harom), 7.24 (d, J = 7.5
Hz, 2 H, Harom), 7.32 (d, J = 8.0 Hz, 2 H, Harom), 8.21 (d, J = 7.0 Hz,
2 H, Harom), 8.57 (s, 1 H, NH).
MS (ESI+Q-TOF): m/z = 1125.7 [M + H]+, 1147.7 [M + Na]+.
Acknowledgment
We thank the National Science Council of Taiwan and National
Tsing-Hua University for providing financial support (NSC-95-
2113-M-007-039) and for funding WCRC.
13C NMR (125 MHz, benzene-d6): d = 17.79 (C-6), 18.41 (C-6¢),
20.35 (OCCH3), 69.85 (CH), 69.97 (CH), 71.204 (CH), 72.63
(OCH2Ph), 73.06 (CH), 73.34 (OCH2Ph), 73.86 (CH), 74.45
(OCH2Ph), 76.77 (CH), 80.24 (CH), 80.73 (CH), 95.49 (C-1),
100.91 (C-1¢), 127.34, 127.58, 127.70, 127.73, 127.87, 127.91,
128.28, 128.32, 128.46, 128.54, 128.71, 130.26, 133.35, 139.05
(OCNHCCl3), 139.25 (OCNHCCl3), 139.50 (OCNHCCl3), 159.78
(OCNHCCl3), 165.63 (OCPh), 169.25 (OCCH3).
References
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MS (ESI+Q-TOF): m/z = 749.4 [M – imidate + OH + Na]+.
2,3,4-O-Tribenzyl-a-L-rhamnosyl-(1→3)-4-O-acetyl-2-O-ben-
zoyl-(1→2)-4-O-acetyl-3-O-benzoyl-a-L-rhamnosyl-1-(4-
tolyl)thio-a-L-rhamnopyranoside (26)
A mixture of compound 25 (23 mg, 0.03 mmol), CH2Cl2 (3 mL),
compound 2 (7 mg, 0.02) and 4 Å molecular sieves (30 mg) was
stirred at r.t. for 30 min then cooled to 0 °C. To the solution was
added TMSOTf (0.3 mL, 0.01 mmol), prepared by the addition of
TMSOTf (100 mL) to CH2Cl2 (5 mL). After stirring at 0 °C for 15
min, the mixture was warmed to r.t. and formation of the product 26
Synthesis 2007, No. 9, 1412–1420 © Thieme Stuttgart · New York

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C.-S. Yu et al.
PAPER
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