Synthesis of tetra- and hexasaccharide fragments corresponding to the O-antigenic polysaccharide of Klebsiella pneumoniae

Article abstract of DOI:10.1016/j.tet.2012.03.074

The preparation of linear tetra- (1) and hexasaccharides (2), containing the repeating unit [→3)-β-Galf-(1→3)-α-Galp-(1→] present in the O-polysaccharide of the lipopolysaccharide of Klebsiella pneumoniae is described. The key step in their synthesis is the α-selective galactopyranosylation of 3-OH di- and tetrasaccharide acceptors (20 and 22) with a disaccharide trichloroacetimidate donor 19 in the presence of trimethylsilyl triflate in a diethyl ether-CH₂Cl ₂ mixture as solvent.

Full text of DOI:10.1016/j.tet.2012.03.074

Tetrahedron 68 (2012) 3795e3802
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of tetra- and hexasaccharide fragments corresponding
to the O-antigenic polysaccharide of Klebsiella pneumoniae
*
San-Yong Zhu, Jin-Song Yang
Key Laboratory of Drug Targeting and Delivery Systems, Ministry of Education, and Department of Chemistry of Medicinal Natural Products, West China School of Pharmacy,
Sichuan University, Chengdu 610041, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 January 2012
Received in revised form 10 March 2012
Accepted 20 March 2012
Available online 28 March 2012
The preparation of linear tetra- (1) and hexasaccharides (2), containing the repeating unit [/3)-b-Galf-
(1/3)-
a
-Galp-(1/] present in the O-polysaccharide of the lipopolysaccharide of Klebsiella pneumoniae
-selective galactopyranosylation of 3-OH di- and
is described. The key step in their synthesis is the
a
tetrasaccharide acceptors (20 and 22) with a disaccharide trichloroacetimidate donor 19 in the presence
of trimethylsilyl triflate in a diethyl ethereCH2Cl2 mixture as solvent.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Klebsiella pneumoniae
Lipopolysaccharide
Synthesis
Trichloroacetimidate
1. Introduction
hexasaccharides (2) as their p-methoxyphenyl glycosides (Scheme
1), which represent two and three consecutive D-galactan I motifs
Pathogenic Gram-negative bacteria are a major public health
concern because they are the causative agents of several life-
threatening diseases. Of particular importance to us is Klebsiella
pneumoniae, which is responsible for several infections, including
pneumonia, bacteremia, and urinary tract infections with high in-
cidence and mortality.1 Previous work has shown that two-surface
carbohydrate components of K. pneumoniae, its capsular poly-
saccharide (CPS), and the O-antigen portion of its lipopolysaccha-
ride (LPS), are important virulence determinants.2 The O-antigens
of K. pneumoniae represent a family of molecules composed of re-
peating carbohydrate subunits linked to the core region of LPS. In
the case of serotype O1, one of the most clinically prevalent sero-
types, O-antigenic glycan is built up from two disaccharide re-
from the O-chain of K. pneumoniae.
2. Results and discussion
According to our retrosynthetic analysis (Scheme 1), di-
saccharide block 3, a properly functionalized form of -galactan I is
D
a key precursor for the construction of 1 and 2. First, it can be easily
switched to a disaccharyl trichloroacetimidate donor after removal
of the p-methoxyphenyl (PMP) aglycon. Second, the site of the
chain elongation can be liberated by a minimal protecting group
manipulation only involving selective removal of the O-levulinoyl
(Lev) group. Third, a nonparticipating substituent, O-benzyl group
was incorporated at C-2 of the galactopyranose unit to facilitate the
construction of the challenging a-galactopyranosyl linkages. Com-
pound 3 would be synthesized through the coupling of p-methyl-
phenyl (Tol) thioglycoside donor 4 with 3-OH acceptor 5. So far,
peating units,
galactan II [/3)-
the distal end of the O chains.
D
-galactan I [/3)-
b
a
-Galf-(1/3)-
a
-Galp-(1/] and
D-
b-Galp-(1/3)-
-Galp-(1/].3
D-Galactan II forms
D
-Galactan I disaccharide motif is also
found in other K. pneumoniae serotypes, e.g., O2a and O2a,c. In view
of developing potential anti-K. pneumoniae vaccines and studying
structureebioactivity relationship of carbohydrates, synthetic
studies on these antigenic O-polysaccharides are of considerable
interests.4 Herein, we report efficient synthesis of tetra- (1) and
several examples for the synthesis of
been found in the literature. Both the Marino group5 and Ning
group6 applied a similar indirect method, i.e., the formation of a
D-galactan I derivatives have
b
-
(1/3)-linked digalactofuranose framework followed by the con-
version of the reducing-end Galf unit into the expected Galp moi-
ety. This disaccharide structure was also prepared by the Kim7 and
Hanashima8 groups employing
a
20-carboxybenzyl (CB) gal-
actofuranoside and a thioglycoside methodology, respectively, to be
used as a building block for the synthesis of glycosphingolipid
agelagalastatin and ganglioside AG2 pentasaccharide.
* Corresponding author. Tel./fax: þ86 28 85503723; e-mail address: yjs@scu.edu.cn
(J.-S. Yang).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.03.074

3796
S.-Y. Zhu, J.-S. Yang / Tetrahedron 68 (2012) 3795e3802
Scheme 1. Chemical structures and retrosynthetic analysis of the target oligosaccharides (1 and 2).
Scheme 2 displays the preparation of the galactofuranose de-
rivative 4. Reaction of -galactose with methanol following the
protocol of Lubineau et al.9 gave an
mixture of methyl -gal-
actofuranosides (6). This mixture, either purified or crude, was next
converted to the known p-methylphenylthio -galactofuranoside
acetonide 16 (85%), whose O-benzylation of the remaining C2 OH
D
afforded an excellent yield of 17. Further elaboration of the re-
sultant 17 to 5 involved (i) release of 3,4,6-tri-OHs in acidic medium
to 2-O-benzyl intermediate 18,16 and (ii) 4,6-O-benzylidene acetal
formation of 18 with PhCH(OMe)2 in dimethyl formamide (DMF) to
the requisite product.
a/
b
D
b-D
(7).10 Subsequent 5,6-O-acetonide protection of 7 provided diol 8
(88%),11 which underwent a regioselective monosilylation reaction
with 1.2 equiv of tert-butyldiphenylsilyl chloride (TBDPSCl) to af-
ford 2-O- and 3-O-TBDPS ethers 9 and 10 as a chromatographically
separable mixture (9/10, ca. 5:1).7,12 The major product, 9, was then
acylated conventionally with excess chloroacetyl chloride or levu-
linic acid (LevOH) to give chloroacetate 11 and levulinate 12 in 80%
and quantitative yields, respectively. However, treatment of 11 with
n-tetrabutylammonium fluoride (TBAF) in tetrahydrofuran (THF)
failed to reveal the expected O-desilylation product. Instead, si-
multaneous cleavage of the TBDPS and the chloroacetyl groups was
observed by TLC analysis. Gratifyingly, exposure of the Lev-
protected counterpart 12 at 0e10 ꢀC to TBAF proved to be feasible
and thus furnished the corresponding alcohol 13 in 86% yield. Fi-
nally, installation of a benzoyl group, which is required to ensure
neighboring group participation13 in later glycosylation at the 2-
position of 13 finished the preparation of the thioglycoside 4.
Scheme 3. Synthesis of the galactopyranose acceptor 5. Reagents and conditions: (a)
TrCl, pyridine, 68 ꢀC, 98%; (b) Me2C(OMe)2, acetone, p-TsOH (cat.), 85%; (c) BnBr, NaH,
DMFeTHF, 0 ꢀC/rt, 98%; (d) H2SO4, MeOH, 82%; (e) PhCH(OMe)2, p-TsOH, DMF, 60 ꢀC,
80%.
The coupling of the
D-galactofuranosyl donor 4 with the D-gal-
actopyranosyl acceptor 5 in the presence of N-iodosuccinimide
(NIS)eanhydrous silver triflate (AgOTf) promoter system generated
solely the
NMR spectrum of 3, the anomeric proton of the
ring appeared as a singlet at dH 5.44 ppm, indicating a trans re-
lationship for H-1 and H-2 and hence a
configuration.17 Further-
more, the 13C NMR spectrum of 3 showed the resonance at dC
103.1 ppm for C-1 -furanosidic center, also characteristic of the
b
-linked disaccharide 3 in 88% yield (Scheme 3). In the 1H
D-galactofuranose
b
b
b-
Galf linkage.18 Oxidative cleavage of the p-methoxyphenyl (PMP)
group at the anomeric carbon of 3 using ceric ammonium nitrate
(CAN) in aqueous acetonitrile at 0 ꢀC yielded an intermediate
hemiacetal. It is worth noting that temperature is critical to this
CAN-mediated oxidation process, as higher temperatures (e.g.,
25 ꢀC) led to undesired cleavage of both the PMP and the iso-
propylidene moieties. Activation of the obtained crude hemiacetal
for glycoside formation was performed by treatment with tri-
chloroacetonitrile (CCl3CN) and 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU), thereby giving the trichloroacetimidate 19 as a single di-
astereomer (88%, two steps from 3). However, imidate 19 could not
be isolated pure because it suffered from minor degradation during
chromatographic purification on a silica gel support. In parallel,
Scheme 2. Synthesis of the galactofuranose thioglycoside donor 4. Reagents and
conditions: (a) acetone, CuSO4, H2SO4, 88%; (b) TBDPSCl, imidazole, DMAP, CH2Cl2, for
9: 60%, for 10: 12%; (c) for 11: chloroacetyl chloride, py, CH2Cl2, 80% from 9, for 12:
LevOH, DCC, DMAP, CH2Cl2, quant. yield from 9; (d) TBAF, THF, 0/10 ꢀC, 3 h, 86% from
12; (e) BzCl, py, 85%.
The synthesis of galactopyranose building block 5, began with
the known p-methoxyphenyl
b
-D
-galactopyranoside (14), which is
after delevulinoylation of 3 using hydrazine monoacetate
readily available from
D
-galactose by published procedures
(N2H4$HOAc) at ambient temperature, disaccharide alcohol ac-
ceptor 20 was obtained in nearly quantitative yield. The benzoate
ester bond of 3 was stable under these mild hydrolysis conditions.
(Scheme 3).14 Selective substitution of the primary C6 OH in 14 with
a trityl (Tr) group easily provided 1515 in very good yield. Triol 15
was then protected with 2,2-dimethoxypropane to form the
1
The H NMR of 20 clearly indicated an upfield shift of the H-30

S.-Y. Zhu, J.-S. Yang / Tetrahedron 68 (2012) 3795e3802
3797
signal from dH 5.12 ppm in the 1H NMR spectrum of compound 3 to
dH 4.09 ppm caused by removal of the Lev substituent at this
position.
With the useful disaccharide glycosylating agents 19 and 20 in
hand, we went on with the assembly of the target protected tetra-
and hexasaccharides. Schmidt’s glycosylation19 of the glycosyl
imidate 19 with the acceptor 20 activated by a catalytic amount of
trimethylsilyl triflate (TMSOTf) in a mixed solvent system of diethyl
etheredichloromethane (v/v, 6:1) at ꢁ78 ꢀC produced the desired
a
-galactopyranosyl tetrasaccharide 21 in an excellent isolated yield
of 92%. Remarkably, no
reaction mixture. The
b
-tetrasaccharide was detected at all in the
a
-stereochemistry at the newly generated
anomeric center of 21 could be easily established on the basis of its
13
1H and C NMR spectral data, especially of the observed H10eH20
0
0
coupling constant (JH1 ꢁH2 ¼3.6 Hz) and the anomeric carbon shift
at dC 99.7 ppm of the -galactopyranose ring. Then, the synthesis of
a
the higher hexasaccharide was proceeding. Selective removal of the
Lev protection on the non-reducing terminal galactofuranosyl
residue of 21 again with N2H4$HOAc exposed the site of chain ex-
tension and yielded tetrasaccharide nucleophile 22 almost in
quantitative yield. Finally, through the same trichloroacetimidate
glycosylation method described above, substrate 22 was efficiently
condensed with the key disaccharyl donor 19 to deliver the cor-
responding hexasaccharide adduct 23 in an equally excellent yield
Scheme 5. Deprotection and completion of synthesis of 1 and 2. Reagents and condi-
tions: (a) NaOMe, MeOH, CH2Cl2, rt, 1 d, for 24: 90% from 21, for 25: 98% from 23; (b) (i)
CF3CO2H, CH2Cl2, rt; (ii) H2 (40 atm), 10% PdeC, MeOH, 45 ꢀC, 20 h, for 1: 74%, two steps
from 24, for 2: 76%, two steps from 25.
deprotection sequence (Scheme 3). The target molecules 1 and 2
were carefully purified by gel filtration chromatography, and their
NMR and HR ESIMS data are in agreement with the desired struc-
tures as homogeneous entity. Full characterizations are provided in
Supplementary data.
0
0
(94%) and with complete
99.5 ppm of the newly formed
Global deprotection of 21 and 23 was not entirely straightfor-
a
-stereoselectivity (JH1 eH2 ¼3.2 Hz and dC
a
-galactopyranosidic linkage).
ꢀ
3. Conclusion
ward (Schemes 4 and 5). Methanolysis of 21 and 23 under Zemplen
conditions20 cleanly cleaved the benzoate and levulinoylate ester
functionalities, giving alcohols 24 and 25, respectively, as foams in
excellent yields. Our next attempts for extensive removal of all the
O-isopropylidene and O-benzylidene acetals and the benzylic pro-
tecting groups present in 24 by employing acidic hydrogenolysis
conditions (e.g., H2, PdeC, 10% HCleMeOH), led to a complex
mixture of products as a result of cleavage of the interglycosidic
linkages. We therefore turned to an alternative two-step depro-
tection approach. Thus, milder acidic hydrolysis of 24 (20% CF3CO2H
in CH2Cl2) followed by catalytic hydrogenation of the formed tet-
rasaccharide alcohol (H2, PdeC, MeOH) secured successfully the
desired free p-methoxyphenyl glycoside 1 in a satisfactory 74%
yield for two steps, with the isopropylidene ketals, the benzylidene
acetals, and the benzyl ethers being cleaved. Likewise, the homo-
logue of 1, the hexasaccharide substance 2, was obtained readily
from the corresponding precursor 25 by means of a similar
We have carried out the high-yielding synthesis of the oligo-
saccharides 1 and 2 structurally related to the repeating unit D-
galactan I found in the O-antigens of K. pneumoniae. The combined
use of the 2-O-Bn ether equipped trichloroacetimidate 19 as donor
and a mixture of diethyl ethereCH2Cl2 as solvent realized the
completely stereoselective creation of the challenging 1,2-cis gal-
actopyranosidic bonds.
4. Experimental section
4.1. General methods
All non-aqueous reactions were performed under a nitrogen
atmosphere and monitored by thin layer chromatography (TLC)
using Silica Gel GF254 plates with detection by charring with 10% (v/
Scheme 4. Synthesis of protected tetra- and hexasaccharides (21 and 23). Reagents and conditions: (a) NIS, AgOTf, 4 A molecular sieves, CH2Cl2, ꢁ40/ꢁ20 ꢀC, 88%; (b) (i)
ꢁ
Ce(NH4)2(NO3)6, MeCN, H2O, 0 ꢀC, 1 h; (ii) CCl3CN, DBU, CH2Cl2, 0 ꢀC/rt, 88%, two steps; (c) N2H4$HOAc, CH2Cl2, MeOH, rt, 98%; (d) TMSOTf, ꢁ78/0 ꢀC, 4 A molecular sieves,
ꢁ
Et2OeCH2Cl2¼6:1, 2 h, 92%; (e) N2H4$HOAc, CH2Cl2, MeOH, 98%; (f) 19, TMSOTf, ꢁ78/0 ꢀC, 4 A molecular sieves, Et2OeCH2Cl2¼6:1, 2 h, 94%.
ꢁ

3798
S.-Y. Zhu, J.-S. Yang / Tetrahedron 68 (2012) 3795e3802
v) H2SO4 in EtOH or by UV detection. Solvents used in the reactions
were distilled from appropriate drying agents prior to use. Silica gel
(200e300 mesh) was used for column chromatography. Optical
rotations were measured with a PE-314 automatic polarimeter at
20ꢂ1 ꢀC for solutions in a 1.0 dm cell. HR ESIMS spectra were ac-
quired on Agilent 6210 TOF LC/MS instrument. 1H and 13C NMR
spectra were obtained on Bruker AC-E 200 or Varian INOVA-400/54
spectrometer in CDCl3 with tetramethylsilane (TMS) as internal
J¼8.0 Hz), 3.33 (t,1H, J¼7.6 Hz), 2.36 (s, 3H),1.33 (s, 3H),1.26 (s, 3H),
1.20 (s, 9H); 13C NMR (100 Hz, CDCl3):
19.2, 21.1, 25.5, 25.7, 26.85
(2C), 26.9, 65.5, 75.2, 80.3, 81.9, 85.0, 96.2 (C-1), 109.7, 127.96 (2C),
128.0 (2C), 129.7 (2C), 130.16, 130.2, 131.3 (2C), 132.8, 133.1, 133.5,
135.8 (2C), 136.1 (2C), 136.8; HR ESIMS: calcd for C32H40O5SiS
[MþNa]þ 587.2264, found m/z 587.2258.
d
4.4. p-Tolyl 2-O-tert-butyldiphenylsilyl-3-O-chloroacetyl-5,6-
reference. Chemical shifts (
d) are expressed in parts per million
O-isopropylidene-1-thio-b-D-galactofuranoside (11)
downfield from the internal TMS absorption. Standard splitting
patterns are abbreviated: s (singlet), d (doublet), t (triplet), q
(quartet), m (multiplet). J values are given in hertz.
To a solution of 9 (256 mg, 0.45 mmol) in pyridineeCH2Cl2
(1:10, v/v, 4.4 mL) was added chloroacetyl chloride (72.1 L,
m
0.91 mmol) at 0 ꢀC. The mixture was stirred for 5 h at room tem-
perature, and then was quenched with ice water and extracted with
CH2Cl2 (10 mLꢃ3). The combined organic extracts were washed
with water (10 mLꢃ3) and brine (10 mL), dried over anhydrous
Na2SO4, and concentrated. The residue was purified by column
chromatography (15:1, petroleum ethereEtOAc) to afford com-
4.2. p-Tolyl 5,6-O-isopropylidene-1-thio-b-D-
galactofuranoside (8)
To a solution of 7 (5.5 g, 19.2 mmol) in acetone (340 mL) were
added CuSO4 (684 mg, 4.29 mmol) and H2SO4 (6 mL). The reaction
mixture was stirred for 1 d at room temperature. Then it was
neutralized with triethylamine and filtered. The combined filtrates
were concentrated in vacuo to give a residue, which was purified by
column chromatography (1:1, petroleum ethereEtOAc) to afford
pound 11 as a colorless syrup (233 mg, 80%). Rf 0.50 (7:1, petroleum
20
ethereEtOAc). [
a
]
ꢁ23.08 (c 0.98, CHCl3); 1H NMR (400 MHz,
D
CDCl3):
d
7.67e7.61 (m, 4H), 7.48e7.37 (m, 6H), 7.17, 7.04 (each 2H,
J¼8.0 Hz), 5.29 (d, 1H, J¼2.8 Hz, H-1), 5.18 (dd, 1H, J¼2.4, 4.0 Hz),
4.44 (dd, 1H, J¼2.4, 11.6 Hz), 4.30 (t, 1H, J¼2.4 Hz), 4.13 (t, 1H,
J¼4.4 Hz), 4.03 (dd, 1H, J¼6.4, 8.4 Hz), 3.96 (dd, 1H, J¼6.4, 8.4 Hz),
3.87 (d, 1H, J¼15.2 Hz), 3.87 (d, 1H, J¼12.0 Hz), 2.31 (s, 3H), 1.42 (s,
compound 8 as a colorless syrup (5.52 g, 88%). Rf 0.40 (1:1, petro-
20
leum ethereEtOAc).
(400 MHz, CDCl3):
[a
]
ꢁ138.02 (c 0.7, CHCl3); 1H NMR
D
d
7.39 (d, 2H, J¼8.0 Hz), 7.15 (d, 2H, J¼8.0 Hz),
5.47 (s, 1H, H-1), 4.38 (t, 1H, J¼7.2 Hz), 4.22 (d, 1H, J¼7.2 Hz), 4.17 (d,
1H, J¼6.8 Hz), 4.10e4.07 (m, 2H), 4.01 (t, 1H, J¼8.0 Hz), 2.78 (d, 1H,
J¼8.0 Hz), 2.35 (s, 3H), 1.63 (d, 1H, J¼8.0 Hz), 1.40 (s, 3H), 1.39 (s,
3H), 1.38 (s, 3H), 1.08 (m, 9H); 13C NMR (100 Hz, CDCl3):
d 19.0, 21.1,
25.2, 26.3, 26.8 (3C), 40.5, 65.5, 75.2, 81.3, 81.5, 82.4, 93.7 (C-1),
109.9, 127.8 (2C), 127.9 (2C), 129.6 (2C), 129.9, 130.1, 130.12, 132.4,
132.5, 132.7 (2C), 135.9 (2C), 135.94 (2C), 137.7, 166.3; HR ESIMS:
calcd for C34H41O8SiSCl [MþNa]þ 663.1980, found m/z 663.1991.
3H); 13C NMR (100 Hz, CDCl3):
d 21.1, 25.6 (2C), 65.5, 75.7, 79.3, 80.9,
84.5, 93.5 (C-1), 110.1, 129.9 (2C), 132.6 (2C), 136.9, 138.0; HR ESIMS:
calcd for C16H22O5S [MþNa]þ 349.1086, found m/z 349.1090.
4.5. p-Tolyl 2-O-tert-butyldiphenylsilyl-3-O-levulinoyl-5,6-O-
4.3. p-Tolyl 2-O-tert-butyldiphenylsilyl-5,6-O-isopropylidene-
isopropylidene-1-thio-b-D-galactofuranoside (12)
1-thio-b-D-galactofuranoside (9) and p-tolyl 3-O-tert-
butyldiphenylsilyl-5,6-O-isopropylidene-1-thio-
galactofuranoside (10)
b
-
D
-
To a solution of 9 (227 mg, 0.4 mmol) in CH2Cl2 (3.6 mL) were
added DCC (580 mg, 2.82 mmol), DMAP (9.8 mg, 0.08 mmol), and
levulinic acid (93.24 mg, 0.8 mmol). The reaction mixture was
stirred for 3 h at room temperature. Then it was filtered and the
filtrate was concentrated in vacuo to give a residue, which was
purified by column chromatography (5:1, petroleum ethereEtOAc)
to afford compound 12 as a colorless syrup (266 mg, quant.). Rf 0.40
To a mixture of 8 (2.52 g, 7.73 mmol), imidazole (1.05 g,
15.46 mmol), and DMAP (280 mg, 2.32 mmol) in CH2Cl2 (41.8 mL)
at 0 ꢀC was added TBDPSCl (2.18 mL, 9.28 mmol) dropwise. After
being stirred at room temperature for overnight, the reaction was
quenched with saturated aqueous NH4Cl (30 mL) and extracted
with EtOAc (2ꢃ30 mL). The combined organic layer was washed
with saturated aqueous NaHCO3 (50 mL) and brine (50 mL), dried
over anhydrous Na2SO4, and concentrated. The residue was purified
by silica gel flash column chromatography (15:1, petroleum ether-
eEtOAc) to afford compound 9 (2.62 g, 4.64 mmol, 60%) and com-
pound 10 (524 mg, 0.93 mmol, 12%).
(3:1, petroleum ethereEtOAc). [
a
]
20 ꢁ47.06 (c 1.7, CHCl3); 1H NMR
D
(400 MHz, CDCl3):
d
7.62e7.67 (m, 4H), 7.36e7.47 (m, 6H), 7.16 (d,
2H, J¼8.0 Hz), 7.04 (d, 2H, J¼8.0 Hz), 5.26 (d,1H, J¼2.4 Hz, H-1), 5.10
(dd, 1H, J¼2.4, 3.6 Hz), 4.44 (dd, 1H, J¼6.4, 12.4 Hz), 4.32 (t, 1H,
J¼2.4 Hz), 4.12 (dd, 1H, J¼4.0, 5.6 Hz), 4.04 (dd, 1H, J¼6.8, 8.4 Hz),
3.95 (dd, 1H, J¼6.8, 8.4 Hz), 2.69e2.64 (m, 2H), 2.45e2.42 (m, 1H),
2.36e2.32 (m, 1H), 2.31 (s, 3H), 2.16 (s, 3H), 1.43 (s, 3H), 1.39 (s, 3H),
1.08 (s, 9H); 13C NMR (100 Hz, CDCl3):
d 19.0, 21.0, 25.2, 26.3, 26.7
4.3.1. Compound 9. Colorless syrup. Rf 0.55 (3:1, petroleum ether-
(3C), 27.7, 29.7, 37.7, 65.6, 75.5, 79.8, 81.5, 83.1, 94.0 (C-1), 109.7,
127.7 (2C), 127.8 (2C), 129.5 (2C), 129.9, 130.0, 130.2, 132.45, 132.5,
132.6 (2C), 135.78 (2C), 135.83 (2C), 139.4, 171.4, 206.0; HR ESIMS:
calcd for C37H46O7SiS [MþNa]þ 685.2632, found m/z 685.2617.
20
eEtOAc). [
a]
ꢁ43.08 (c 1.2, CHCl3); 1H NMR (400 MHz, CDCl3):
D
d
7.71e7.68 (m, 4H), 7.51e7.40 (m, 6H), 7.26 (d, 2H, J¼8.0 Hz), 7.08
(d, 2H, J¼8.0 Hz), 5.35 (d, 1H, J¼2.4 Hz, H-1), 4.34 (dd, 1H, J¼5.2,
10.4 Hz), 4.23 (t, 1H, J¼2.8 Hz), 4.04e4.01 (m, 3H), 3.98 (dd, 1H,
J¼6.8, 8.4 Hz), 2.33 (s, 3H), 1.75 (d, 1H, J¼5.6 Hz), 1.46 (s, 3H), 1.40 (s,
4.6. p-Tolyl 3-O-levulinoyl-5,6-O-isopropylidene-1-thio-b-D-
galactofuranoside (13)
3H), 1.11 (s, 9H); 13C NMR (100 Hz, CDCl3):
d
19.1, 21.2, 25.3, 26.5,
26.9 (2C), 27.0, 65.4, 75.4, 79.1, 83.87, 83.9, 92.9 (C-1), 109.7, 128.0
(2C), 128.1 (2C), 129.7 (2C), 130.1, 130.2, 132.6, 132.9 (2C), 133.2,
135.8 (2C), 135.9 (2C), 136.2, 137.8; HR ESIMS: calcd for C32H40O5SiS
[MþNa]þ 587.2264, found m/z 587.2259.
To a solution of 12 (510 mg, 0.77 mmol) in THF (6.6 mL) was
added TBAF (0.46 mL, 1.0 M in THF, 0.46 mmol) dropwise at 0 ꢀC
and the resulting mixture was stirred for 3 h at the same temper-
ature. After the solvent was removed under reduced pressure, the
crude material was dissolved with CH2Cl2 (20 mL). The resulting
organic solution was washed with saturated aqueous NH4Cl
(10 mLꢃ3) and brine (10 mL), dried over anhydrous Na2SO4, and
concentrated. The residue was purified by column chromatography
(4:1, petroleum ethereEtOAc) to afford compound 13 as a colorless
4.3.2. Compound 10. Colorless syrup. Rf 0.65 (3:1, petroleum
20
ethereEtOAc). [
a
]
ꢁ104.67 (c 0.9, CHCl3); 1H NMR (400 MHz,
D
CDCl3):
d
7.79e7.70 (m, 4H), 7.51e7.41 (m, 8H), 7.16 (d, 2H,
J¼7.6 Hz), 5.52 (s, 1H, H-1), 4.40 (d, 1H, J¼11.2 Hz), 4.24 (s, 1H), 4.12
(s, 1H), 4.00 (d, 1H, J¼11.6 Hz), 3.86 (t, 1H, J¼8.0 Hz), 3.77 (t, 1H,

S.-Y. Zhu, J.-S. Yang / Tetrahedron 68 (2012) 3795e3802
3799
20
syrup (281 mg, 86%). Rf 0.50 (2:1, petroleum ethereEtOAc). [
a
]
NMR (100 Hz, CDCl3):
d
26.4, 28.2, 55.6, 63.0, 73.0, 73.4, 73.8, 79.0,
D
ꢁ141.84 (c 1.25, CHCl3); 1H NMR (400 MHz, CDCl3):
d
7.39, 7.13
86.8, 101.9 (C-1), 110.4, 114.5 (2C), 118.7 (2C), 127.1 (3C), 127.9 (6C),
128.8 (6C), 143.9 (3C), 151.3, 155.4; HR ESIMS: calcd for C35H36O7
[MþNa]þ 591.2359, found m/z 591.2345.
(each 2H, J¼8.4 Hz), 5.47 (s,1H, H-1), 4.99 (d,1H, J¼2.0 Hz), 4.48 (dt,
1H, J¼1.6, 7.6 Hz), 4.28e4.26 (m, 2H), 4.18 (d, 1H, J¼10.4 Hz), 4.08
(d, 1H, J¼6.8 Hz), 3.99 (t, 1H, J¼8.0 Hz), 2.85e2.80 (m, 2H), 2.63 (t,
2H, J¼6.4 Hz), 2.33 (s, 3H), 2.20 (s, 3H), 1.39 (s, 3H), 1.38 (s, 3H); 13C
4.10. p-Methoxyphenyl 2-O-benzyl-3,4-O-isopropylidene-6-O-
NMR (100 Hz, CDCl3):
d 21.0, 25.4, 25.6, 27.9, 29.6, 37.8, 65.3, 75.4,
trityl-
b-D
-galactopyranoside (17)
79.3, 80.7, 81.9, 95.1 (C-1), 109.9, 129.7 (2C), 130.9, 132.0 (2C), 137.4,
172.2, 206.4; HR ESIMS: calcd for C21H28O7S [MþNa]þ 447.1454,
found m/z 447.1444.
A
mixture of 16 (1.36 g, 2.39 mmol) and NaH (458 mg,
19.1 mmol) in DMFeTHF (1:1, v/v,18.0 mL) was stirred for 30 min at
0 ꢀC. Then to the mixture was added BnBr (566.7
m
l, 4.78 mmol) at
4.7. p-Tolyl 2-O-benzoyl-3-O-levulinoyl-5,6-O-isopropylidene-
the same temperature. After being stirred at room temperature for
4 h, the reaction was quenched with ice water (20 mL) and
extracted with EtOAc (2ꢃ30 mL). The combined organic layer was
washed with brine (30 mL), dried over anhydrous Na2SO4, and
concentrated. The residue was purified by silica gel flash column
chromatography (5:1, petroleum ethereEtOAc) to afford the title
compound 17 as white solid (1.54 g, 0.43 mmol, 98%). Rf 0.55 (3:1,
1-thio-b-D-galactofuranoside (4)
To a solution of 13 (347 mg, 0.82 mmol) in pyridine (5.78 mL)
was added BzCl (189
L, 1.64 mmol) dropwise at 0 ꢀC. The mixture
m
was stirred for 5 h at room temperature, and then was quenched
with ice water and extracted with CH2Cl2 (10 mLꢃ3). The combined
organic extracts were washed with water (10 mLꢃ3) and brine
(10 mL), dried over anhydrous Na2SO4, and concentrated. The res-
idue was purified by column chromatography (8:1, petroleum
20
petroleum ethereEtOAc). [
(400 MHz, CDCl3):
a]
þ18.25 (c 1.26, CHCl3); 1H NMR
D
d
7.59 (d, 6H, J¼8.0 Hz), 7.54 (d, 2H, J¼7.2 Hz),
7.44e7.29 (m, 12H), 7.24, 6.91 (each 2H, J¼8.8 Hz), 5.06 (d, 1H,
J¼11.2 Hz), 5.00 (d, 1H, J¼11.2 Hz), 4.88 (d, 1H, J¼8.0 Hz, H-1), 4.30
(dd, 1H, J¼6.0, 6.4 Hz), 4.16 (dd, 1H, J¼1.6, 5.2 Hz), 3.86 (dd, 1H,
J¼2.0, 2.4 Hz), 3.81 (s, 3H), 3.77 (d, 1H, J¼8.4 Hz), 3.75 (d, 1H,
J¼7.2 Hz), 3.48 (dd, 1H, J¼4.0, 10.0 Hz), 1.47 (s, 3H), 1.39 (s, 3H); 13C
ethereEtOAc) to afford compound 4 as a colorless syrup (367 mg,
20
85%). Rf 0.50 (3:1, petroleum ethereEtOAc). [
a
]
ꢁ88.1 (c 1.27,
D
CHCl3); 1H NMR (400 MHz, CDCl3):
d
8.04 (d, 2H, J¼7.2 Hz), 7.60 (t,
1H, J¼7.2 Hz), 7.46e7.42 (m, 4H), 7.14 (d, 2H, J¼8.0 Hz), 5.62 (d, 1H,
J¼2.0 Hz, H-1), 5.46 (d, 1H, J¼2.0 Hz), 5.33 (dd, 1H, J¼1.6, 4.8 Hz),
4.46 (dt, 1H, J¼4.8, 11.2 Hz), 4.37 (t, 1H, J¼4.4 Hz), 4.09 (dd, 1H,
J¼6.8, 8.8 Hz), 3.96 (dd, 1H, J¼6.8, 8.8 Hz), 2.88e2.75 (m, 2H),
2.73e2.58 (m, 2H), 2.33 (s, 3H), 2.20 (s, 3H), 1.41 (s, 3H), 1.38 (s, 3H);
NMR (100 Hz, CDCl3):
d 26.5, 27.9, 55.6, 63.1, 72.7, 73.8, 73.9, 79.3,
79.5, 86.9, 102.2 (C-1), 110.2, 114.5 (2C), 118.6 (2C), 127.1 (3C), 127.7,
127.9 (6C), 128.3 (2C), 128.4 (2C), 128.8 (6C), 138.3, 144.0 (3C), 151.6,
155.3; HR ESIMS: calcd for C42H42O7 [MþNa]þ 691.2829, found m/z
691.2815.
13C NMR (100 Hz, CDCl3):
d 21.1, 25.3, 26.2, 27.9, 29.7, 37.8, 65.5, 75.1,
77.7, 81.8, 82.2, 91.4 (C-1), 109.8, 128.4 (2C), 129.0, 129.5, 129.8 (2C),
129.84 (2C), 133.0 (2C), 133.5, 138.1, 165.2, 171.8, 206.2; HR ESIMS:
calcd for C28H32O8S [MþNa]þ 551.1716, found m/z 551.1702.
4.11. p-Methoxyphenyl 2-O-benzyl-b-D-galactopyranoside (18)
To a solution of 17 (1.7 g, 0.98 mmol) in CH3OH (25.5 mL) was
added slowly H2SO4 (1.13 mL) and the resulting mixture was stirred
for 3 h at room temperature. After the solvent was removed under
reduced pressure, the residue was purified by column chromatog-
raphy (1:1, petroleum ethereEtOAc) to afford compound 18 as
4.8. p-Methoxyphenyl 6-O-trityl-b-D-galactopyranoside (15)
To a solution of 14 (888 mg, 3.1 mmol) in pyridine (20 mL) was
added TrCl (1.30 g, 4.7 mmol). The mixture was stirred for 1 d at
60 ꢀC. After the solvent was removed under reduced pressure, the
residue was purified by column chromatography (1:1, petroleum
ethereEtOAc) to afford compound 15 as a white solid (1.61 g, 98%).
a white solid (797 mg, 82%). Rf 0.50 (8:1, CH2Cl2eCH3OH). [
a
]
20 ꢁ8.8
D
(c 1.58, CH3OH); 1H NMR (400 MHz, CDCl3):
d
7.38e7.31 (m, 5H),
Rf 0.50 (9:1, CH2Cl2eCH3OH). [
(400 MHz, CDCl3):
a
]
20 ꢁ23.33 (c 1.08, CHCl3); 1H NMR
7.03, 6.86 (each 2H, J¼8.8 Hz), 5.08 (d, 1H, J¼11.2 Hz), 4.93 (d, 1H,
J¼8.0 Hz, H-1), 4.79 (d, 1H, J¼11.2 Hz), 4.05 (s, 1H), 4.01 (dd, 1H,
J¼5.6, 11.6 Hz), 3.90e3.84 (m, 1H), 3.81e3.77 (m, 1H), 3.79 (s, 3H),
3.71e3.67 (m, 1H), 3.65 (t, 1H, J¼5.2 Hz), 2.80 (s, 1H), 2.59 (d, 1H,
J¼3.6 Hz), 2.21 (dd, 1H, J¼4.8, 8.0 Hz); 13C NMR (100 Hz, DMSO):
D
d
7.43 (d, 6H, J¼7.6 Hz), 7.24 (t, 6H, J¼7.6 Hz),
7.20 (s, 1H), 7.19 (s, 1H), 7.17 (s, 1H), 7.07, 6.74 (each 2H, J¼8.8 Hz),
4.69 (d, 1H, J¼7.6 Hz, H-1), 3.91 (t, 1H, J¼8.8 Hz), 3.85e3.80 (m, 3H),
3.70 (s, 3H), 3.59 (t,1H, J¼4.0 Hz), 3.52 (s,1H), 3.49 (d,1H, J¼6.0 Hz),
3.27 (d, 1H, J¼8.4 Hz), 3.07 (s, 1H); 13C NMR (100 Hz, CDCl3):
d
55.5,
d
55.6, 60.5, 68.6, 73.0, 74.0, 75.5, 79.4, 102.0 (C-1), 114.7 (2C), 117.6
(2C), 127.4, 127.8 (2C), 128.2 (2C), 139.4, 151.6, 154.5; HR ESIMS:
63.0, 69.3, 71.2, 73.5, 74.0, 86.9, 102.3 (C-1), 114.4 (2C), 118.6 (2C),
127.1 (3C), 127.9 (6C), 128.6 (6C), 143.6 (3C), 151.1, 155.3; HR ESIMS:
calcd for C32H32O7 [MþNa]þ 551.2046, found m/z 551.2035.
calcd for C20H24O7 [MþNa]þ 399.1420, found m/z 399.1411.
4.12. p-Methoxyphenyl 2-O-benzyl-5,6-O-benzylidene-b-D-
4.9. p-Methoxyphenyl 3,4-O-isopropylidene-6-O-trityl-
b-
D-
galactopyranoside (5)
galactopyranoside (16)
To a solution of 18 (1.72 g, 4.58 mmol) in DMF (24.0 mL) were
added p-TsOH (118 mg, 0.69 mmol) and PhCH(OMe)2 (1.37 mL,
9.16 mmol). After being stirred for overnight at 60 ꢀC, the reaction
mixture was poured into petroleum ethereice water (1:1, v/v,
200 mL), and the suspension was filtered to afford 5 as a white solid
To a solution of 15 (2.0 g, 3.79 mmol) in acetone (41.0 mL) were
added p-TsOH (65 mg, 0.53 mmol) and Me2C(OMe)2 (1.16 mL,
9.47 mmol). The reaction mixture was stirred at room temperature
for 8 h. After the solvent was removed under reduced pressure, the
resulting residue was purified by column chromatography (3:1,
petroleum ethereEtOAc) to afford 16 as a white solid (1.83 g, 85%).
(1.7 g, 80%). Rf 0.50 (50:1, CH2Cl2eCH3OH). [
a
]
20 ꢁ9.8 (c 1.1, CHCl3);
D
1H NMR (400 MHz, CDCl3):
d
7.55e7.53 (m, 2H), 7.40e7.26 (m, 8H),
Rf 0.53 (1:1, petroleum ethereEtOAc). [
a
]
20 ꢁ13.33 (c 0.9, CHCl3); 1H
7.07, 6.84 (each 2H, J¼9.2 Hz), 5.58 (s, 1H), 5.07 (d, 1H, J¼11.2 Hz),
4.90 (d, 1H, J¼7.6 Hz, H-1), 4.83 (d, 1H, J¼11.2 Hz), 4.37 (d, 1H,
J¼12.4 Hz), 4.26 (d, 1H, J¼1.6 Hz), 4.10 (d, 1H, J¼12.0 Hz), 3.90 (d,
1H, J¼7.6 Hz), 3.88 (d,1H, J¼7.6 Hz), 3.78 (s, 3H), 3.53 (s, 1H), 2.57 (s,
D
NMR (400 MHz, CDCl3):
d
7.55 (d, 6H, J¼8.0 Hz), 7.34 (t, 6H,
J¼7.6 Hz), 7.29 (s, 1H), 7.28 (s, 1H), 7.26 (s, 1H), 7.18, 6.86 (each 2H,
J¼8.8 Hz), 4.69 (d, 1H, J¼8.0 Hz, H-1), 4.18e4.13 (m, 2H), 3.88e3.84
(m, 2H), 3.77 (s, 3H), 3.71 (dd, 1H, J¼7.6, 10.0 Hz), 3.44 (dd, 1H,
J¼4.0, 10.0 Hz), 3.14 (d, 1H, J¼2.8 Hz), 1.55 (s, 3H), 1.37 (s, 3H); 13C
1H); 13C NMR (100 Hz, CDCl3):
d 55.6, 66.6, 69.1, 72.4, 75.1, 75.3,
79.0, 101.4, 103.0 (C-1), 114.5 (2C), 118.8 (2C), 126.5 (2C), 127.8, 128.1

3800
S.-Y. Zhu, J.-S. Yang / Tetrahedron 68 (2012) 3795e3802
(2C), 128.3 (2C), 128.4 (2C), 129.3, 137.5, 138.4, 151.5, 155.4; HR
(2C), 128.4 (2C), 129.0, 129.8 (2C), 130.6, 133.4, 137.7, 138.1, 161.1,
164.9, 171.8, 206.1. Attempts to further purify this compound for
HRMS analysis were unsuccessful.
ESIMS: calcd for C27H28O7 [MþNa]þ 487.1733, found m/z 487.1734.
4.13. p-Methoxyphenyl 2-O-benzoyl-3-O-levulinoyl-5,6-O-
isopropylidene- -galactofuranosyl-(1/3)-2-O-benzyl-5,6-
O-benzylidene-b-D-galactopyranoside (3)
b
-
D
4.15. p-Methoxyphenyl 2-O-benzoyl-5,6-O-isopropylidene-
-galactofuranosyl-(1/3)-2-O-benzyl-5,6-O-benzylidene-
galactopyranoside (20)
b-
b-D-
D
A mixture of donor 4 (311 mg, 0.59 mmol), acceptor 5 (228 mg,
ꢁ
0.49 mmol), and 4 A molecular sieves (780 mg) in CH2Cl2 (12.0 mL)
To a solution of 3 (65 mg, 0.075 mmol) in CH3OHeCH2Cl2 (1:1, v/
v, 2.0 mL) was added hydrazine acetate (14 mg, 0.15 mmol). The
mixture was stirred for overnight at room temperature, and then
was quenched with aqueous NaHCO3 (10 mL) and extracted with
CH2Cl2 (10 mLꢃ3). The combined organic extracts was washed with
brine (10 mL), dried over anhydrous Na2SO4, and concentrated. The
residue was purified by column chromatography (2:1, petroleum
was stirred for 10 min at room temperature and cooled to ꢁ40 ꢀC.
To the resulting mixture were added NIS (199 mg, 0.74 mmol) and
AgOTf (37.8 mg, 0.12 mmol). The reaction mixture was allowed to
warm to ꢁ20 ꢀC and stirred for 1 h at the same temperature,
quenched with triethylamine, and filtered. The combined filtrates
were concentrated in vacuo to give a residue, which was purified by
column chromatography (2:1, petroleum ethereEtOAc) to afford 3
ethereEtOAc) to afford compound 20 as a colorless syrup (57 mg,
as a pale yellow syrup (375 mg, 88%). Rf 0.55 (1:1, petroleum
20
98%). Rf 0.55 (1:1, petroleum ethereEtOAc). [
a
]
ꢁ23.9 (c 1.08,
D
20
ethereEtOAc). [
a
]
ꢁ4.38 (c 1.05, CHCl3); 1H NMR (400 MHz,
D
CHCl3); 1H NMR (400 MHz, CDCl3):
d
8.00 (d, 2H, J¼7.6 Hz),
CDCl3):
d
8.03 (d, 2H, J¼7.6 Hz), 7.59 (d, 2H, J¼7.6 Hz), 7.47 (t, 3H,
7.63e7.55 (m, 3H), 7.48e7.36 (m, 7H), 7.29e7.16 (m, 3H), 7.08, 6.84
(each 2H, J¼8.8 Hz), 5.60 (s, 1H), 5.59 (s, 1H), 5.19 (d, 1H, J¼1.2 Hz,
H-1A), 4.98 (d, 1H, J¼10.8 Hz), 4.91 (d, 1H, J¼8.0 Hz, H-1B), 4.81 (d,
1H, J¼10.8 Hz), 4.43 (d, 1H, J¼3.2 Hz), 4.39 (d, 1H, J¼12.0 Hz), 4.24
(dd, 1H, J¼6.4, 14.4 Hz), 4.16e4.07 (m, 3H), 4.01 (d, 1H, J¼8.0 Hz),
3.94 (d, 1H, J¼3.6 Hz), 3.91e3.87 (m, 2H), 3.78 (s, 3H), 3.55 (s, 1H),
3.53 (d, 1H, J¼8.0 Hz), 1.47 (s, 3H), 1.40 (s, 3H); 13C NMR (100 Hz,
J¼7.6 Hz), 7.41e7.35 (m, 5H), 7.24e7.18 (m, 3H), 7.16, 7.06 (each 2H,
J¼8.0 Hz), 5.59 (s, 1H), 5.53 (s, 1H), 5.44 (s, 1H, H-1A), 5.12 (d, 1H,
J¼4.8 Hz), 4.97 (d, 1H, J¼10.8 Hz), 4.91 (d, 1H, J¼8.0 Hz, H-1B), 4.81
(d, 1H, J¼11.2 Hz), 4.41 (d, 1H, J¼3.6 Hz), 4.38 (d, 1H, J¼6.0 Hz), 4.35
(d, 1H, J¼6.8 Hz), 4.27 (t, 1H, J¼6.8 Hz), 4.13e4.04 (m, 3H), 3.91 (dd,
1H, J¼3.6, 9.6 Hz), 3.84 (dd, 1H, J¼6.8, 8.4 Hz), 3.78 (s, 3H), 3.53 (s,
1H), 2.67e2.61 (m, 1H), 2.48e2.34 (m, 3H), 2.08 (s, 3H), 1.43 (s, 3H),
CDCl3): d 25.3, 26.7, 55.6, 65.6, 66.3, 69.0, 75.4, 75.9, 76.4, 77.3 (2C),
1.39 (s, 3H); 13C NMR (100 Hz, CDCl3):
d 25.3, 26.5, 27.7, 29.7, 37.6,
78.4, 84.3, 86.4, 101.3, 103.0 (C-1B), 107.2 (C-1A), 110.0, 114.4 (2C),
118.9 (2C), 126.3 (2C), 127.7, 128.1 (2C), 128.2 (2C), 128.3 (2C), 128.6
(2C), 128.8, 129.1, 129.8 (2C), 133.7, 137.4, 138.3, 151.5, 155.3, 166.0;
HR ESIMS: calcd for C43H46O13 [MþNa]þ 793.2836, found m/z
793.2830.
55.6, 65.6, 66.4, 69.0, 75.4, 75.8, 76.1, 77.3, 77.4, 78.6, 81.5, 83.5,
101.2, 103.1 (C-1B), 107.7 (C-1A), 110.0, 114.4 (2C), 118.9 (2C), 126.4
(2C), 127.6, 128.1 (2C), 128.2 (2C), 128.3 (2C), 128.4 (2C), 129.01,
129.03, 129.8 (2C), 133.5, 137.9, 138.3, 151.5, 155.3, 164.9, 171.8,
206.2; HR ESIMS: calcd for C48H52O15 [MþNa]þ 891.3204, found m/z
891.3188.
4.16. p-Methoxyphenyl 2-O-benzoyl-3-O-levulinoyl-5,6-O-
4.14. 2-O-Benzoyl-3-O-levulinoyl-5,6-O-isopropylidene-
galactofuranosyl-(1/3)-2-O-benzyl-5,6-O- benzylidene-
galactopyranosyl trichloroacetimidate (19)
b
-
-
D
-
-
isopropylidene-
O-benzylidene-
O-isopropylidene-
5,6-O-benzylidene-
b
-
D
-galactofuranosyl-(1/3)-2-O-benzyl-5,6-
-galactopyranosyl-(1/3)-2-O-benzoyl-5,6-
-galactofuranosyl-(1/3)-2-O-benzyl-
-galactopyranoside (21)
a
D
a-D
b-D
b-D
To a solution of 3 (130 mg, 0.15 mmol) in CH3CNeH2O (4:1, v/v,
5.0 mL) was added CAN (244 mg, 0.45 mmol) at 0 ꢀC. The mixture
was stirred for 1 h at the same temperature, and then was
quenched with aqueous NaHCO3 and extracted with EtOAc
(10 mLꢃ3). The combined organic extracts was washed with water
(10 mLꢃ2), aqueous NaHCO3 (10 mLꢃ3) and brine (10 mL), dried
over anhydrous Na2SO4, and concentrated. The obtained residue
was purified by column chromatography (2:1, petroleum ether-
eEtOAc) to afford the desired lactol as a pale yellow syrup, which
was directly used for the next step. To a solution of the obtained
lactol (111 mg, 0.15 mmol) in CH2Cl2 (3.0 mL) were added CCl3CN
A mixture of donor 19 (101 mg, 0.11 mmol), acceptor 20 (43 mg,
0.055 mmol), and 4 A molecular sieves (150 mg) in Et2OeCH2Cl2
ꢁ
(6:1, v/v, 2.0 mL) was stirred for 10 min at room temperature and
cooled to ꢁ78 ꢀC. To the resulting mixture was added a solution of
TMSOTf (4.04 mL, 0.01 mmol) in CH2Cl2 (0.5 mL) and stirred at
ꢁ78 ꢀC for 1 h. The reaction mixture was allowed to warm to 0 ꢀC
over 1 h, then quenched with triethylamine and filtered. The
combined filtrates were concentrated in vacuo to give a residue,
which was purified by column chromatography (3:1, petroleum
ethereEtOAc) to afford 21 as a colorless syrup (79 mg, 92%). Rf 0.50
20
(73
m
L, 0.73 mmol) and DBU (one drop) at 0 ꢀC. The mixture was
(1.5:1, petroleum ethereEtOAc). [
(400 MHz, CDCl3):
a]
þ17.2 (c 1.1, CHCl3); 1H NMR
D
stirred for 4 h during which time it was gradually warmed to am-
bient temperature, and then concentrated to give a residue. Puri-
fication by column chromatography (3:1, petroleum ethereEtOAc)
afforded 19 as a colorless syrup (119 mg, 88% over two steps) that
d
8.03 (d, 2H, J¼7.6 Hz), 7.99 (d, 2H, J¼7.6 Hz),
7.61e7.57 (m, 4H), 7.48e7.09 (m, 22H), 7.08, 6.84 (each 2H,
J¼8.8 Hz), 5.68 (s, 1H), 5.58 (s, 1H), 5.51 (s, 1H), 5.49 (s, 1H), 5.41 (s,
1H, H-1A), 5.20 (s, 1H, H-1C), 5.16 (d, 1H, J¼3.6 Hz, H-1B), 5.14 (d, 1H,
J¼4.8 Hz), 4.96 (d, 1H, J¼10.8 Hz), 4.91 (d, 1H, J¼7.6 Hz, H-1D), 4.83
(d, 2H, J¼10.8 Hz), 4.62 (d, 1H, J¼12.0 Hz), 4.40e4.24 (m, 5H), 4.19
(dd, 1H, J¼6.8, 13.2 Hz), 4.11e3.99 (m, 6H), 3.973e.80 (m, 7H), 3.78
(s, 3H), 3.60 (d, 1H, J¼12.4 Hz), 3.52 (s, 1H), 2.69e2.62 (m, 1H),
2.51e2.540 (m, 3H), 2.08 (s, 3H), 1.43 (s, 6H), 1.40 (s, 3H), 1.35 (s,
contained a minor impurity. Rf 0.50 (2.5:1, petroleum ether-
20
eEtOAc). [
d
a
]
þ37.11 (c 1.5, CHCl3); 1H NMR (400 MHz, CDCl3):
D
8.60 (s, 1H), 8.00 (d, 2H, J¼7.6 Hz), 7.60e7.53 (m, 3H), 7.45e7.29
(m, 7H), 7.25 (t, 2H, J¼7.6 Hz), 7.18 (d, 1H, J¼7.2 Hz), 6.61 (d, 1H,
J¼3.2 Hz, H-1B), 5.57 (s, 1H), 5.56 (s, 1H), 5.42 (s, 1H, H-1A), 5.10 (d,
1H, J¼4.4 Hz), 4.79 (d, 1H, J¼12.0 Hz), 4.73 (d, 1H, J¼12.0 Hz), 4.54
(d, 1H, J¼2.8 Hz), 4.38e4.25 (m, 4H), 4.21 (dd, 1H, J¼3.6, 10.0 Hz),
4.10e4.04 (m, 2H), 3.95 (s, 1H), 3.83 (t, 1H, J¼7.6 Hz), 2.70e2.62 (m,
1H), 2.51e2.40 (m, 3H), 2.08 (s, 3H), 1.44 (s, 3H), 1.39 (s, 3H); 13C
3H); 13C NMR (100 Hz, CDCl3):
d 25.3 (2C), 26.5, 26.54, 27.7, 29.7,
37.6, 55.6, 63.0, 65.6, 65.7, 66.4, 69.0, 69.04, 73.8, 75.0, 75.3, 75.5,
75.8, 75.9, 76.2, 76.23, 77.3, 77.9, 78.0, 81.1, 81.5, 82.9, 83.4, 85.4,
99.7,100.4,101.3 (C-1B),103.2 (C-1D),107.3 (C-1C),108.1 (C-1A),110.0
(2C), 114.4 (2C), 118.9 (2C), 126.2 (2C), 126.7 (2C), 127.6, 127.7, 128.0
(2C), 128.1 (2C), 128.2 (4C), 128.3 (2C), 128.4 (2C), 128.5 (4C), 128.8,
129.1, 129.2, 129.3, 129.8 (2C), 129.9 (2C), 133.47, 133.5, 138.0, 138.1,
NMR (100 Hz, CDCl3):
d 25.2, 26.5, 27.7, 29.6, 37.6, 64.7, 65.6, 69.0,
73.2, 74.0, 75.2, 75.8, 77.3 (2C), 81.5, 83.5, 91.5, 95.4 (C-1B), 100.9,
107.6 (C-1A), 109.9, 126.2 (2C), 127.4, 127.5 (2C), 128.1 (2C), 128.2

S.-Y. Zhu, J.-S. Yang / Tetrahedron 68 (2012) 3795e3802
3801
138.14, 138.4, 151.6, 155.3, 164.95, 165.0, 171.9, 206.1; HR ESIMS:
4.19. p-Methoxyphenyl 5,6-O-isopropylidene-
osyl-(1/3)-2-O-benzyl-5,6-O-benzylidene-
syl-(1/3)-5,6-O-isopropylidene- -galactofuranosyl-(1/3)-2-
O-benzyl-5,6-O-benzylidene- -galactopyranoside (24)
b
-
D
-galactofuran
calcd for C84H90O26 [MþNa]þ 1537.5618, found m/z 1537.5632.
a-D-galactopyrano
b-D
4.17. p-Methoxyphenyl 2-O-benzoyl-5,6-O-isopropylidene-
-galactofuranosyl-(1/3)-2-O-benzyl-5,6-O-benzylidene-
galactopyranosyl-(1/3)-2-O-benzoyl-5,6-O-isopropylidene-
-galactofuranosyl-(1/3)-2-O-benzyl-5,6-O-benzylidene-
-galactopyranoside (22)
b
-
b-D
D
a-D-
To a solution of 21 (96 mg, 0.06 mmol) in CH2Cl2eCH3OH (1:10, v/
v, 3.0 mL) was added NaOCH3 (29 mg, 0.54 mmol) at 0 ꢀC. After being
stirred for overnight at room temperature, the reactionwas quenched
with acetic acid and the resulting mixture was concentrated to dry-
ness. The crude material was purified by column chromatography
b
-
D
b-
D
Compound 22 was obtained as a colorless syrup from 21 (83 mg,
0.055 mmol) as described for the preparation of 20, yielding 76 mg
(1:1, petroleum ethereEtOAc) to afford compound 24 as a white foam
20
20
(98%). Rf 0.51 (1.5:1, petroleum ethereEtOAc). [
a
]
þ6.9 (c 1.02,
(70.5 mg, 92%). Rf 0.45 (EtOAc). [
a
]
þ5.61 (c 1.3, CHCl3); 1H NMR
D
D
CHCl3); 1H NMR (400 MHz, CDCl3):
d
7.98 (d, 4H, J¼8.0 Hz),
(400 MHz, CDCl3): d 7.59e7.58 (m, 2H), 7.44e7.26 (m, 18H), 7.10, 6.85
7.65e7.58 (m, 4H), 7.47e7.16 (m, 20H), 7.12e7.08 (m, 2H), 7.09, 6.84
(each 2H, J¼8.8 Hz), 5.67 (d, 1H, J¼1.6 Hz), 5.60 (s, 2H), 5.53 (s, 1H),
5.21 (d,1H, J¼4.0 Hz, H-1B), 5.20 (s,1H, H-1A), 5.11 (s,1H, H-1C), 4.98
(d, 1H, J¼10.8 Hz), 4.92 (d, 1H, J¼7.6 Hz, H-1D), 4.82 (d, 1H,
J¼10.8 Hz), 4.75 (d,1H, J¼11.6 Hz), 4.59 (d,1H, J¼11.6 Hz), 4.35e4.05
(m, 10H), 3.99 (d, 1H, J¼3.6 Hz), 3.94e3.86 (m, 8H), 3.81 (s, 1H), 3.78
(s, 3H), 3.56 (d,1H, J¼8.4 Hz), 3.54 (s,1H), 3.48 (d,1H, J¼11.6 Hz),1.45
(s, 3H),1.44 (s, 3H),1.40 (s, 3H),1.36 (s, 3H); 13C NMR (100 Hz, CDCl3):
(each 2H, J¼8.8 Hz), 5.54 (s,1H), 5.39 (s,1H), 5.32 (s,1H, H-1A), 4.99 (s,
1H, H-1C), 4.99 (d,1H, J¼12.4 Hz), 4.95 (d,1H, J¼4.4 Hz, H-1B), 4.94 (d,
1H, J¼8.0 Hz, H-1D), 4.77 (d, 1H, J¼10.4 Hz), 4.71 (d, 1H, J¼12.0 Hz),
4.52 (d, 1H, J¼12.0 Hz), 4.39 (t, 1H, J¼6.8 Hz), 4.34 (s, 1H), 4.32 (d, 1H,
J¼5.2 Hz), 4.26 (d, 1H, J¼2.8 Hz), 4.21 (d, 1H, J¼4.8 Hz), 4.18 (d, 1H,
J¼3.2 Hz), 4.15 (d, 1H, J¼7.2 Hz), 4.10 (s, 1H), 4.07 (s, 1H), 4.04 (s, 1H),
4.02e3.93 (m, 8H), 3.90 (s,1H), 3.87 (d,1H, J¼2.8 Hz), 3.83 (s,1H), 3.79
(s, 3H), 3.74 (s, 2H), 3.54 (s, 1H), 3.51 (d, 2H, J¼12.4 Hz), 3.06 (d, 1H,
J¼8.4 Hz), 1.46 (s, 3H), 1.41 (s, 6H), 1.39 (s, 3H); 13C NMR (100 Hz,
d
25.3 (2C), 26.5, 26.7, 55.6, 62.7, 65.5, 65.9, 66.4, 68.89, 68.92, 73.7,
74.5, 75.2, 75.4, 75.9, 75.94, 76.1, 76.5, 77.1, 77.7, 77.9, 80.8, 83.3, 83.7,
85.3, 86.8, 99.1, 100.4, 101.3 (C-1B), 103.2 (C-1D), 106.7 (C-1C), 108.1
(C-1A),110.0,110.1,114.4 (2C),118.9 (2C),126.0 (2C),126.9 (2C),127.6,
127.7, 127.8 (2C), 128.1 (2C), 128.2 (5C), 128.3 (2C), 128.4 (2C), 128.5
(2C), 128.6 (2C), 128.9, 129.1, 129.4, 129.8 (4C), 133.5, 133.7, 138.6,
138.0, 138.2 (2C), 151.6, 155.3, 164.9, 165.9; HR ESIMS: calcd for
C79H84O24 [MþNa]þ 1439.5251, found m/z 1439.5231.
CDCl3): d 25.5, 25.6, 25.7, 26.1, 55.6, 62.6, 65.6, 65.8, 66.4, 68.9, 69.0,
73.7, 73.8, 75.2, 75.3, 75.6, 75.7, 76.2, 76.4, 77.3, 77.6, 78.1, 78.4, 78.6,
81.9, 86.7, 88.4, 99.2,100.4,101.4(C-1B),103.4(C-1D),109.4,109.3,110.4
(C-1A), 110.8 (C-1C),114.5 (2C), 119.0 (2C), 125.9 (2C),127.0 (2C), 127.6,
128.9 (2C), 128.1, 128.2 (2C), 128.35 (2C), 128.4 (2C), 128.5 (2C), 128.6
(2C),129.0,129.6,137.3,138.1 (2C),138.3,151.5,155.4; HR ESIMS: calcd
for C65H76O22 [MþNa]þ 1231.4726, found m/z 1231.4711.
4.18. p-Methoxyphenyl 2-O-benzoyl-3-O-levulinoyl-5,6-O-
4.20. p-Methoxyphenyl
b-D-galactofuranosyl-(1/3)-a-D-galact
isopropylidene-
O-benzylidene-
O-isopropylidene-
5,6-O-benzylidene-
5,6-O-isopropylidene-
benzyl-5,6-O-benzylidene-
b
-
D
D
-galactofuranosyl-(1/3)-2-O-benzyl-5,6-
-galactopyranosyl-(1/3)-2-O-benzoyl-5,6-
-galactofuranosyl-(1/3)-2-O-benzyl-
-galactopyranosyl-(1/3)e2-O-benzoyl-
-galactofuranosyl-(1/3)-2-O-
-galactopyranoside (23)
opyranosyl-(1/3)-
anoside (1)
b
-
D
-galactofuranosyl-(1/3)- -galactopyr
b-D
a-
b-D
a-
D
To a solution of 24 (42 mg, 0.035 mmol) in CH2Cl2 (2.4 mL) was
added TFA (0.6 mL) and the resulting mixture was stirred for 7 h at
room temperature. After the solvent was removed under reduced
pressure, the obtained residue was dissolved in CH3OH (3.0 mL). To
the solution was added 10% Pd/C (45 mg) and the reaction mixture
was stirred under a hydrogen atmosphere of 40 atm for 20 h at 45 ꢀC.
The reaction mixture was filtered and the filtrate was concentrated in
vacuo to give a residue, which was purified by column chromatog-
raphy on Sephadex LH-20 (CH3OH) to afford compound 1 as a white
foam (20 mg, 74% over two steps). Rf 0.70 (1:1, CH3OHeH2O, RP-18
b-D
b-D
Compound 23 was obtained as a colorless syrup from 19 (85 mg,
0.06 mmol) and 22 (109 mg, 0.12 mmol) as described for the
preparation of 21, yielding 122 mg (94%). Rf 0.55 (1:1, petroleum
20
ethereEtOAc). [
CDCl3):
a
]
D
þ18.53 (c 1.7, CHCl3); 1H NMR (400 MHz,
d
8.03 (d, 2H, J¼8.0 Hz), 7.99 (s, 2H), 7.97 (s, 2H), 7.62e7.58
(m, 5H), 7.48e7.07 (m, 34H), 7.09, 6.85 (each 2H, J¼9.2 Hz), 5.69 (d,
1H, J¼2.4 Hz), 5.67 (d,1H, J¼1.6 Hz), 5.58 (s,1H), 5.51 (s, 2H), 5.48 (s,
1H), 5.42 (s, 1H, H-1A), 5.19 (s, 1H, H-1C), 5.17 (s, 1H, H-1E), 5.17 (d,
1H, J¼3.6 Hz, H-1B), 5.15 (d, 1H, J¼3.2 Hz, H-1D), 5.14 (d, 1H,
J¼4.8 Hz), 4.96 (d, 1H, J¼10.4 Hz), 4.91 (d, 1H, J¼8.0 Hz, H-1F), 4.83
(d, 2H, J¼10.4 Hz), 4.81 (d, 1H, J¼10.8 Hz), 4.78 (d, 1H, J¼10.8 Hz),
4.61 (d, 1H, J¼11.6 Hz), 4.57 (d, 1H, J¼11.6 Hz), 4.39 (dd, 1H, J¼6.8,
13.2 Hz), 4.34e4.328 (m, 4H), 4.25e4.21 (m, 2H), 4.16 (dd, 1H,
J¼6.8, 13.2 Hz), 4.12e4.04 (m, 5H), 3.99e3.90 (m, 8H), 3.89e3.83
(m, 6H), 3.79 (s, 5H), 3.55 (s, 1H), 3.53 (s,1H), 3.52 (s, 1H), 2.66e2.63
(m,1H), 2.50e2.40 (m, 3H), 2.09 (s, 3H),1.43 (s, 9H),1.41 (s, 3H),1.38
plate). [
a
]
20 ꢁ12.83 (c 1.2, CH3OH); 1H NMR (400 MHz, D2O):
d 7.16,
D
7.01 (each 2H, J¼8.8 Hz), 5.29 (s, 1H, H-1C), 5.22 (s, 1H, H-1A), 5.11 (s,
1H, H-1B), 5.04 (d, 1H, J¼7.2 Hz, H-1D), 4.48 (s, 1H), 4.30 (t, 1H,
J¼4.8 Hz), 4.21e4.18 (m, 4H), 4.14e4.07 (m, 3H), 3.98 (s, 2H),
3.89e3.85 (m, 4H), 3.83 (s, 3H), 3.79e3.64 (m, 9H); 13C NMR (100 Hz,
D2O):
d 58.0, 62.9, 63.4, 64.86, 64.9, 69.5, 70.6, 71.5, 71.9, 72.9 (2C),
73.4, 77.5, 79.0, 79.2, 81.9, 82.4, 83.7, 84.1, 84.9, 86.6,101.7 (C-1B),103.7
(C-1D),111.3 (C-1A),111.7 (C-1C),117.2 (2C),120.4 (2C),153.1,156.9; HR
ESIMS: calcd for C31H48O22 [MþNa]þ 795.2535, found m/z 795.2548.
(s, 3H), 1.35 (s, 3H); 13C NMR (100 Hz, CDCl3):
d
25.3 (3C), 26.5 (3C),
4.21. p-Methoxyphenyl 5,6-O-isopropylidene-
syl-(1/3)-2-O-benzyl-5,6-O-benzylidene- -galactopyranosyl-
(1/3)-5,6-O-isopropylidene- -galactofuranosyl-(1/3)-2-O-
benzyl-5,6-O-benzylidene- -galactopyranosyl-(1/3)-5,6-O-
isopropylidene- -galactofuranosyl-(1/3)-2-O-benzyl-5,6-O-
benzylidene- -galactopyranoside (25)
b-D-galactofurano
27.7, 29.7, 37.6, 55.6, 63.0, 63.1, 65.5, 65.6, 66.4, 68.9 (2C), 73.7 (2C),
73.8 (2C), 74.9 (2C), 75.2, 75.4, 75.5, 75.7 (2C), 75.8 (2C), 76.1, 76.2,
76.3, 77.9 (2C), 81.0, 81.2, 81.5, 82.7, 82.9, 83.3, 85.1, 85.3, 99.5 (2C),
100.4, 100.7 (C-1D), 101.3 (C-1B), 103.2 (C-1F), 107.2 (C-1E), 107.8 (C-
1C), 108.1 (C-1A), 109.9 (3C), 114.4 (2C), 118.9 (2C), 126.1 (4C), 126.5
(2C), 126.8 (2C), 127.55, 127.58, 127.6, 127.8 (2C), 127.9 (2C), 128.0
(2C), 128.2 (6C), 128.25 (2C), 128.3 (2C), 128.35 (2C), 128.44 (6C),
128.8, 129.09, 129.11, 129.16, 129.2, 129.4, 129.8 (4C), 129.9 (2C),
133.4, 138.0, 138.05, 138.1, 138.13, 138.2, 138.3, 151.6, 155.3, 164.9,
165.0 (2C), 171.9, 206.0; HR ESIMS: calcd for C120H128O37 [MþNa]þ
2183.8032, found m/z 2183.7996.
a-D
b-D
a-D
b-D
b-D
Compound 25 was obtained as a white solid from 23 (65 mg,
0.03 mmol) as described for the preparation of 24, yielding 49 mg
(94%). Rf 0.50 (1:10, petroleum ethereEtOAc). [
CHCl3); 1H NMR (400 MHz, CDCl3):
(m, 3H), 7.40e7.27 (m, 25H), 7.11, 6.86 (each 2H, J¼8.8 Hz), 5.57 (s,1H),
20
a]
D
þ4.88 (c 0.8,
d
7.65 (d, 2H, J¼7.2 Hz), 7.59e7.51

3802
S.-Y. Zhu, J.-S. Yang / Tetrahedron 68 (2012) 3795e3802
5.54 (s,1H), 5.43 (s,1H), 5.37 (s,1H, H-1A), 5.03 (d,1H, J¼2.8 Hz, H-1C),
4.98 (s,1H, H-1E), 4.96 (d,1H, J¼4.0 Hz, H-1B), 4.95 (d,1H, J¼8.0 Hz, H-
1F), 4.93 (d, 1H, J¼3.6 Hz, H-1D), 4.80 (d, 1H, J¼12.4 Hz), 4.77 (d, 1H,
J¼10.4 Hz), 4.70 (d, 1H, J¼12.0 Hz), 4.68 (d,1H, J¼11.6 Hz), 4.53 (d,1H,
J¼12.0 Hz), 4.51 (d, 1H, J¼11.6 Hz), 4.46e4.41 (m, 2H), 4.34e4.18 (m,
8H), 4.12e3.95 (m, 12H), 3.92 (d, 1H, J¼2.8 Hz), 3.89 (d, 2H, J¼2.8 Hz),
3.86 (s, 2H), 3.83 (d, 2H, J¼3.2 Hz), 3.79 (s, 3H), 3.76 (d, 2H, J¼2.4 Hz),
3.73 (d, 2H, J¼3.6 Hz), 3.54 (d, 2H, J¼12.8 Hz), 3.43 (d, 1H, J¼12.8 Hz),
3.39 (d, 1H, J¼2.8 Hz), 3.35 (s, 1H), 3.28 (d, 1H, J¼9.6 Hz), 3.04 (d, 1H,
J¼7.6 Hz),1.47 (s, 3H),1.46 (s, 3H),1.43 (s, 3H),1.41 (s, 3H),1.39 (s, 6H);
of Education (NCET-08-0377, 20100181110082), and Sichuan Prov-
ince (08ZQ026-029) of China for financial support.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2012.03.074. These data in-
clude MOL files and InChiKeys of the most important compounds
described in this article.
13C NMR (100 Hz, CDCl3):
d 25.3, 25.5, 25.65, 25.7, 25.9, 26.2, 55.6, 62.5,
63.0, 65.59, 65.63, 65.8, 66.4, 68.8, 68.9, 73.2, 73.4, 73.7, 74.0, 75.1, 75.3,
75.6, 75.7, 76.0, 76.2, 76.23, 76.4, 76.5, 76.9, 77.5, 78.1, 78.2, 78.5, 78.6,
82.3, 82.6, 85.6, 86.7, 88.0, 88.5, 99.2 (2C),100.3,100.8 (C-1D),101.5 (C-
1B), 103.4 (C-1F), 109.6, 110.0 (2C), 110.3 (C-1A), 110.5 (C-1E), 110.9 (C-
1C), 114.5 (2C), 119.0 (2C), 125.8 (2C), 126.7 (2C), 127.4 (2C), 127.9 (5C),
128.1 (2C), 128.2 (2C), 128.4 (4C), 128.45 (2C), 128.5 (2C), 128.6 (2C),
128.7 (2C), 129.1, 129.5, 129.7, 137.3, 138.0, 138.1, 138.11, 138.4, 138.5,
151.5, 155.4; HR ESIMS: calcd for C94H110O32 [MþNa]þ 1773.6878,
found m/z 1773.6864.
References and notes
1. Sherris Medical Microbiology, 4th ed.; Ryan, K. J., Ray, C. G., Eds.; McGraw Hill:
New York, NY, 2004.
2. (a) Alberti, S.; Alvarez, D.; Merino, S.; Casado, M.; Vivanco, F.; Tomas, J.;
Benedi, V. Infect. Immun. 1996, 64, 4726e4732; (b) Alberti, S.; Marques, G.;
Hernandez-Alles, S.; Rubires, X.; Tomas, J.; Vivanco, F.; Benedi, V. Infect.
Immun. 1996, 64, 4719e4725; (c) Shankar-Sinha, S.; Valencia, G. A.; Janes,
B. K.; Rosenberg, J. K.; Whitfield, C.; Bender, R. A.; Standiford, T. J.;
Younger, J. G. Infect. Immun. 2004, 72, 1423e1430 and references cited
therein.
3. (a) Kol, O.; Wieruszeski, J.; Strecker, G.; Fournet, B.; Zalisz, R.; Smets, P. Car-
bohydr. Res. 1992, 236, 339e344; (b) Whitfield, C.; Richards, J.; Perry, M.; Clarke,
B.; MacLean, L. J. Bacteriol. 1991, 173, 1420e1431; (c) Vinogradov, E.; Frirdich, E.;
MacLean, L. L.; Perry, M. B.; Petersen, B. O.; Duus, J. é; Whitfield, C. J. Biol. Chem.
2002, 277, 25070e25081.
4. For reviews on bacterial polysaccharide-based vaccines, see: (a) Lucas, A.
H.; Apicella, M. A.; Taylor, C. E. Clin. Infect. Dis. 2005, 41, 705e712; (b) Roy,
R. Drug Discov. Today 2004, 1, 327e336; (c) Kuberan, B.; Linhardt, R. J. Curr.
Org. Chem. 2000, 4, 653e677; (d) Pozsgay, V. Adv. Carbohydr. Chem. Biochem.
2000, 56, 153e199; (e) Jennings, H. J. Adv. Carbohydr. Chem. Biochem. 1983,
41, 155e208.
5. Baldoni, L.; Marino, C. J. Org. Chem. 2009, 74, 1994e2003.
6. Wang, H.-R.; Zhang, G.-H.; Ning, J. Carbohydr. Res. 2003, 338, 1033e1037.
7. Lee, Y. J.; Lee, B.-Y.; Jeon, H. B.; Kim, K. S. Org. Lett. 2006, 8, 3971e3974.
8. Hanashima, S.; Yamaguchi, Y.; Ito, Y.; Sato, K. Tetrahedron Lett. 2009, 50,
6150e6153.
9. Lubineau, A.; Fischer, J. C. Synth. Commun. 1991, 21, 815e818.
10. Completo, G. C.; Lowary, T. L. J. Org. Chem. 2008, 73, 4513e4525.
11. Bai, Y.; Lowary, T. L. J. Org. Chem. 2006, 71, 9658e9671.
12. Gandolfi-Donadio, L.; Gallo-Rodriguez, C.; de Lederkremer, R. M. J. Org. Chem.
2002, 67, 4430e4435.
13. Paulsen, H. Angew. Chem., Int. Ed. Engl. 1982, 21, 155e173.
14. Zhang, Z. Y.; Magnusson, G. Carbohydr. Res. 1996, 295, 41e55.
15. Qin, Z.-H.; Liu, H.; Li, H.; Cai, M.-S.; Li, Z.-J. Carbohydr. Res. 2002, 337,
621e628.
16. Barili, P. L.; Berti, G.; Catelani, G.; Colonna, F.; Marra, A. Tetrahedron Lett. 1986,
27, 2307e2310.
17. (a) Bundle, D. R.; Lemieux, R. U. Methods Carbohydr. Chem. 1976, 7, 79e86; (b) de
Oliveira, M. T.; Hughes, D. L.; Nepogodiev, S. A.; Field, R. A. Carbohydr. Res. 2008,
343, 211e220 and references cited therein.
4.22. p-Methoxyphenyl
pyranosyl-(1/3)- -galactofuranosyl-(1/3)-
-galactofuranosyl-(1/3)- -galactopyrano
b-D-galactofuranosyl-(1/3)-a-D-galacto
b-D
a-D-galactopyr
anosyl-(1/3)-
b-D
b-D
side (2)
Compound 2 was obtained as a white foam from 25 (55 mg,
0.032 mmol) as described for the preparation of 1, yielding 26 mg
20
(76% over two steps). Rf 0.55 (1:2, CH3OHeH2O, RP-18 plate). [
a
]
D
ꢁ11.6 (c 0.8, CH3OH); 1H NMR (400 MHz, D2O):
d 7.11, 6.96 (each 2H,
J¼8.8 Hz), 5.24 (s, 1H, H-1C), 5.20 (s, 1H, H-1E), 5.15 (s, 1H, H-1A),
5.06 (s, 2H, H-1B, H-1D), 5.00 (d, 1H, J¼7.2 Hz, H-1F), 4.43 (s, 1H),
4.40 (s, 1H), 4.28e4.21 (m, 2H), 4.15e4.12 (m, 6H), 4.05e4.01 (m,
4H), 3.92 (s, 4H), 3.85e3.80 (m, 6H), 3.78 (s, 3H), 3.76e3.70 (m, 6H),
3.69e3.62 (m, 6H); 13C NMR (100 Hz, D2O):
d 58.2, 63.1, 63.5 (2C),
65.0 (2C), 65.1 (2C), 69.5, 69.6, 70.8, 71.6, 71.7, 72.1, 73.3 (2C), 73.6,
73.7, 77.4, 77.6, 79.2, 79.4, 79.42, 82.1, 82.6, 83.8, 84.2, 84.3, 85.1,
86.8 (2C), 101.8 (C-1D), 101.9 (C-1B), 103.9 (C-1F), 111.5 (C-1A), 111.77
(C-1E), 111.8 (C-1C), 117.4 (2C), 120.6 (2C), 153.3, 157.1; HR ESIMS:
calcd for C43H68O32 [MþNa]þ 1119.3592, found m/z 1119.3573.
Acknowledgements
18. Bock, K.; Pedersen, C. Adv. Carbohydr. Chem. 1983, 41, 27e66.
19. Schmidt, R. R. Angew. Chem., Int. Ed. Engl. 1986, 25, 212e235.
20. McAuliffe, J. C.; Hindsgaul, O. J. Org. Chem. 1997, 62, 1234e1239.
We appreciate NSFC (21172156, 21021001), the National Basic
Research Program of China (973 Program, 2010CB833202), Ministry