Synthesis of the pentasaccharide moiety of thornasterside A

Article abstract of DOI:10.1002/ejoc.201300575

The synthesis of the pentasaccharide moiety of thornasteroside A, the first asterosaponin isolated from starfish in 1978 has been achieved for the first time. Initially, a [3+2] convergent strategy was attempted, but the β(1→4) glycosidic linkage between

Full text of DOI:10.1002/ejoc.201300575

FULL PAPER
DOI: 10.1002/ejoc.201300575
Synthesis of the Pentasaccharide Moiety of Thornasterside A
Junlong Xiong,[a] Zhichao Lu,[a] Ning Ding,[a] Sumei Ren,[a] and Yingxia Li*[a]
Keywords: Synthesis design / Natural products / Carbohydrates / Oligosaccharides / Glycosylation
The synthesis of the pentasaccharide moiety of thornastero-
side A, the first asterosaponin isolated from starfish in 1978
lactopyranosyl donor (18) equipped with a neighboring par-
ticipating Lev (levulinoyl) group at the 2-position was first
has been achieved for the first time. Initially, a [3+2] conver- coupled with a trisaccharide acceptor to construct the β(1Ǟ4)
gent strategy was attempted, but the β(1Ǟ4) glycosidic link-
age between galactopyranose (sugar IV) and xylopyranose
(sugar II) was formed with a low stereoselectivity and in low
yield. Subsequently, a [3+1+1] strategy was adopted. A ga-
glycosidic bond. Then the Lev group was selectively re-
moved, and subsequent glycosylation with a perbenzoylated
D-fucopyranosyl Schmidt donor efficiently gave the desired
pentasaccharide.
Introduction
Over the last few decades, many secondary metabolites
with unusual chemical structures and interesting pharmaco-
logical properties have been isolated from marine plants
and animals. Steroidal glycosides, the predominant second-
ary metabolites in starfish, are considered to be responsible
for the general toxicity of starfish,[1] and these steroidal gly-
cosides show a broad spectrum of pharmacological activi-
ties.[2–4] The structures of steroidal glycosides seem to be
quite peculiar in terms of both their carbohydrate and agly-
con moieties. They are usually divided into three substruc-
tural types: asterosaponin (sulfated steroidal glycosides),
steroidal cyclic glycosides, and polyhydroxysteroidal glycos-
ides.[5] Thornasteroside A (Figure 1), the first asterosaponin
isolated from Acanthaster planci L. in 1978,[6,7] has the typi-
cal structural features of asterosaponin: an aglycon with a
Δ9(11)-3β,6α-diol structure with a sulfated 3-OH, and an oli-
gosaccharide residue attached to the 6-OH of the aglycon.
The total synthesis of thornasteroside A is a challenge.
One of the obstacles to its synthesis is the presence of the
20-OH group β to a carbonyl group in the aglycon. The
great instability of this 20-OH group means that a straight-
forward synthesis in which the sugar residues are attached
one by one to the aglycon cannot be achieved efficiently,
because the repeated glycosylations and protection/depro-
tection steps will frequently involve acidic or basic condi-
Figure 1. The structure of thornasterside A.
tions.[8,9] A convergent strategy, in which a preconstructed
oligosaccharide donor is coupled with the aglycon under
neutral conditions, could address the issue. The carbo-
hydrate portion of thornasteroside A is a pentasaccharide
with the sequence: [β-d-Quip-(1Ǟ2)]-[β-d-Fucp-(1Ǟ2)-β-d-
Galp-(1Ǟ4)]-β-d-Xylp-(1Ǟ3)-β-d-Quip, which is the typi-
cal oligosaccharide sequence of asterosaponins. Of the five
monosaccharide components, three are 6-deoxypyranoses
and one is a five-carbon pyranose (xylose). These monosac-
charides are unusual as components of natural glycosides,
and as a result, the selective protection of a given hydroxy
group is more complicated in these monosaccharides.[10]
Therefore, the efficient synthesis of the oligosaccharide
chain is not a trivial task. As part of our work towards the
total synthesis of thornasteroside A, in this paper, we report
the efficient synthesis of the pentasaccharide residue.
[a] School of Pharmacy, Fudan University,
826 Zhangheng Rd., 201203 Shanghai, P. R. China
E-mail: liyx417@fudan.edu.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300575.
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Synthesis of the Pentasaccharide Moiety of Thornasterside A
Synthesis of Trisaccharide Acceptor 3
Results and Discussion
The synthesis of trisaccharide acceptor 3 is shown in
Scheme 1. The glycosylation between building blocks 4 and
5 promoted by TMSOTf gave disaccharide 10 in a low yield
of 47%. We rationalized that the low reactivity of the 3-OH
group of 4, resulting from the presence of two neighboring
electron-withdrawing benzoyl groups, should be responsible
for the low coupling yield. Therefore, the more reactive benz-
ylated acceptor 9 was selected. To our delight, the glycosyl-
ation between 5 and 9 promoted by TMSOTf gave disac-
charide 11 in a satisfactory 82% yield. Removal of the Lev
group from 11 gave 12. As expected, coupling of monosac-
charide donor 6 with acceptor 12 occurred smoothly to give
trisaccharide 13 in 78% yield.
[3+2] Coupling Strategy
Pentasaccharide 1, with an OMP (4-methoxyphenol)
group at the reducing end of the sugar chain, was selected
as the target. The OMP glycoside could easily be trans-
formed into an ortho-alkynylbenzoate donor, which could
be coupled with the aglycon under neutral conditions, cata-
lyzed by
a
gold(I) complex (e.g., Ph3PAuOTf or
Ph3PAuNTf2).[11]
Initially, we designed a [3+2] convergent strategy to ef-
ficiently construct the pentasaccharide (Figure 2). The key
points in this approach were to achieve the stereoselectivity
(β-linkage) and regioselectivity (glycosylation of the 4-OH
of sugar II) during the glycosylation reaction between ac-
We tried to remove the two acetyl groups from 13 to
ceptor 3 and donor 2. By using the new method of palla- obtain diol 3, which would serve as the acceptor in the re-
dium-mediated β-selective glycosylation,[12,13] a β(1Ǟ4) gly- gioselective coupling with disaccharide donor 2. The reac-
cosidic bond would be formed with a nonparticipating tion was attempted under mildly acidic condition
group at the 2-OH of donor 2 (i.e., in sugar V). The regiose- [CH3COCl/CH3OH/CH2Cl2 (1:25:25)] so that the benzoyl
lectivity of the glycosylation at the 4-OH of xylopyranose groups in 13 would not be affected during the deacetylation.
(sugar II) in the presence of the 3-OH would be achieved When 13 was treated under these conditions at room tem-
because of the reactivity difference between the 4-OH and perature for 8 h, only 40% of the intended di-deacetyl-
the 3-OH groups (4-OH Ͼ 3-OH).[14]
ated product (i.e., 3) was formed, along with more than 50%
Trisaccharide acceptor 3 and disaccharide donor 2 could of the mono-deacetylated product (i.e., 14). Obviously, unex-
be constructed using monosaccharide building blocks 4–6 pected product 14 would be a more suitable acceptor than 3
and 7–8, respectively. As all the glycosidic bonds in penta- in the next glycosylation reaction. To our delight, under
saccharide 1 have the β configuration, the required milder conditions [CH3COCl/CH3OH/CH2Cl2 (1:50:50)], 14
monosaccharide building blocks 4–8 were all equipped with could be obtained cleanly in an excellent yield of 82%. The
participating benzoyl or levulinoyl (Lev) groups at the 2- structure of 14 was confirmed by careful interpretation of
1
OH.
1H, H–1H COSY, HMQC, and HMBC spectra.
Figure 2. [3+2] coupling strategy.
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Scheme 1. Synthesis of trisaccharide acceptors 3 and 14. Reagents and conditions: a) molecular sieves (4 Å), TMSOTf (TMS = trimethyl-
silyl; 0.2 equiv.), CH2Cl2, –78 °C, 47% for 10, 82% for 11; b) AcOH·NH2NH2, CH3OH/CH2Cl2 (1:4), 92%; c) molecular sieves (4 Å),
TMSOTf (0.2 equiv.), CH2Cl2, –78 °C, 78%; d) CH3COCl/CH3OH/CH2Cl2 (1:50:50), 82% for 14, 10% for 3.
Synthesis of Disaccharide Donor 2
tween 2 and 14 were investigated. The results are shown in
Table 1. Based on Nguyen’s method for palladium-mediated
β-selective glycosylation in the absence of a traditional C-
2-ester neighboring group,[12,13] we used Pd(CH3CN)4-
(BF4)2 to catalyze the glycosylation between disaccharide
donor 2 and trisaccharide acceptor 14. The reactions were
performed with 2mol-% or 5mol-% Pd(CH3CN)4(BF4)2 at
different temperatures (Table 1, entries 1–8). Unfortunately,
in all cases, donor-derived decomposition products were
isolated as the major products, and trisaccharide acceptor
14 remained almost unreacted. These results show that this
method is not suitable for directing β glycosidic bond for-
mation between 2 and 14.
The synthetic route to 2 is shown in Scheme 2. Building
block 7 was coupled with trichloroacetimidate 8[15] in the
presence of TMSOTf to smoothly give disaccharide 15. Di-
saccharide 15 was converted into trichloroacetimidate do-
nor 2 in a two-step procedure in 78% yield. The synthesis
of building blocks 4 (9), 5, 6, and 7 is described in detail in
the Supporting Information.
When the reaction was conducted under normal condi-
tions [TMSOTf (0.2 equiv.), anhydrous CH2Cl2, –78 °C],
only the undesired α-linked (J1(IV)-H,2(IV)-H = 3.2 Hz) penta-
saccharide (i.e., 16) was obtained in a high 85% yield. Next,
we used acetonitrile as the solvent for the glycosylation, ex-
pecting a β glycosidic bond between the xylopyranose
(sugar II) and galactopyranose (sugar IV) to be formed due
to the solvent effect of acetonitrile.[16–18] The expected β-
linked pentasaccharide (i.e., 17) was detected this time, but
the yield was quite low (15%), and it was formed along
with 10% of the α-linked pentasaccharide (i.e., 16). Further
attempts to vary the solvents and temperatures in the
TMSOTf-catalyzed glycosylation did not result in improved
Scheme 2. Synthesis of donor 2. Reagents and conditions: a) mo-
lecular sieves (4 Å), TMSOTf (0.2 equiv.), CH2Cl2, –78 °C, 83%;
b) NBS (N-bromosuccinimide), acetone/H2O (9:1), 0 °C;
c) CCl3CN, DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), CH2Cl2,
78% (2 steps).
Coupling of Disaccharide Donor with Trisaccharide
Acceptor
Having synthesized disaccharide donor 2 and trisac- selectivity and yield (See Table S1 in the Supporting Infor-
charide acceptor 14, conditions for the glycosylation be- mation).
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Synthesis of the Pentasaccharide Moiety of Thornasterside A
Table 1. Glycosylation of 14 and 2[a] promoted by Pd(CH3CN)4(BF4)2.
Entry
CH2Cl2/CH3CN (v/v) Amount [mol-%] of Pd(CH3CN)4(BF4)2
T [°C]
Yield of 16
Yield of 17
[b]
[b]
1
2
3
4
5
6
7
8
1:0
1:0
1:0
1:0
1:0
0:1
0:1
1:1
2
2
2
5
5
5
5
5
–78
0
25
–78
0
–40
0
0
–
–
–
–
–
–
–
–
–
[b]
[b]
–
[b]
[b]
–
[b]
[b]
–
[b]
[b]
–
[b]
[b]
–
[b]
[b]
–
[b]
[b]
–
[a] In all the entries, 1.2 equiv. donor 2 and 1.0 equiv. acceptor 14 were used. [b] Undefined products with unreacted 14, as judged by
TLC.
[3+1+1] Coupling Strategy
After the construction of the pentasaccharide by the
[3+2] approach with satisfactory stereoselectivity and yield
had failed, we then turned our attention to a [3+1+1] strat-
egy (Figure 3). Building block 18, equipped with a partici-
pating Lev group at the 2-position ensured a β configura-
tion for the glycosidic bond formed in the glycosylation be-
tween 14 and 18. The Lev group could be selectively re-
moved to give a tetrasaccharide acceptor, which would be
coupled with building block 8 to give the desired pentasac-
charide (i.e., 17).
We conducted glycosylation trials between trichloroaceti-
midate donor 18 and acceptor 14 to give tetrasaccharide 17.
The proportions of donor/acceptor were varied, as was the
amount of TMSOTf, as shown in Table 2. The desired tet-
Figure 3. [3+1+1] coupling strategy.
rasaccharide (i.e., 19) was not detected when the reaction
was conducted with 1.2 equiv. of donor 18 and catalyzed by
0.2 equiv. of TMSOTf (Table 2, entry 1). When the amount
of donor 18 was increased to 4.0 equiv., the desired tetrasac-
charide 19 was formed in an isolated yield of 27%. To en-
hance the yield, a “reverse addition” approach was tried,
but no improvement was observed over the normal addition
method (Table 2, entry 3). Further increasing the amount
of donor 18 to 6.0 equiv. led to a slight improvement in the
than 1.0 equiv. (with respect to the amount of acceptor 14),
the glycosylation proceeded smoothly to give the desired
product. For instance, the glycosylation between 18
(1.2 equiv.) and 14 (1.0 equiv.) activated by 1.0 equiv. of
TMSOTf gave tetrasaccharide 19 in a good 68% yield
(Table 2, entry 5).
Having synthesized 19, the Lev group was removed to
yield (to 30%, Table 2, entry 4). Further study showed that smoothly give tetrasaccharide acceptor 20 (Scheme 3).
the amount of TMSOTf had a great impact on the glycosyl- TMSOTf-mediated coupling of 20 with monosaccharide 8
ation. When the amount of TMSOTf was increased to more gave pentasaccharide 17 in a satisfactory 83% yield. Global
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Table 2. Glycosylation of 14 with monosaccharide donor 19.[a,b]
Entry
Donor 18 (equiv.)
TMSOTf (equiv.)
Yield of 19 [%]
1
2
3
4
5
6
7
1.2
4.0
0.2
0.2
0.2
0.2
1.0
1.0
2.0
0
27
25
30
68
72
71
4.0[c]
6.0
1.2
4.0
4.0
[a] Molar equivalents of the donor and promoters are based on the amount of acceptor (1.0 equiv.). [b] All the reactions were conducted
in dry CH2Cl2 in the presence of molecular sieves (4 Å) at –78 °C. [c] Reverse addition approach.
Scheme 3. Synthesis of the pentasaccharide by a [3+1+1] strategy. Reagents and conditions: a) AcOH·N2H4, CH3OH/CH2Cl2 (1:4), 93%;
b) molecular sieves (4 Å), TMSOTf, CH2Cl2, –78 °C, 83%. c) Pd(OH)2/C, H2, CH3OH/EtOAc (1:1), 98%; d) CH3ONa, CH3OH, 88%.
deprotection of pentasaccharide 17 was achieved by hydro- asterosaponin isolated from Acanthaster planci L. in 1978.
genolysis of the benzyl ethers over Pd(OH)2/C, followed by Initially, a [3+2] convergent strategy was attempted, but the
deacylation to remove the benzoyl and acetyl groups and β-glycosidic bond between the xylopyranose (sugar II) and
give target pentasaccharide 1. The structure of 1 was con- galactopyranose (sugar IV) could only be constructed with
firmed by NMR spectroscopy. The five anomeric proton a low stereoselectivity and in a low 15% yield. Sub-
1
signals in the H NMR spectrum appear at δ = 5.53 (d, J sequently, a [3+1+1] strategy was adopted. Galactopyrano-
= 3.75 Hz, H-1I), 4.75 (d, J = 7.33 Hz), 4.74 (d, J = syl donor 18, equipped with a neighboring participating
7.94 Hz), 4.63 (d, J = 7.33 Hz), and 4.61 (d, J = 7.33 Hz) Lev group at the 2-position, was first coupled with a trisac-
ppm, and the five anomeric carbon signals appear at δ = charide acceptor to construct the β-glycosidic bond
104.03, 103.81, 102.77, 100.71, 97.36 (C-1I) ppm.
smoothly. Then the Lev group was selectively removed, and
subsequent glycosylation with a perbenzoylated d-fucopyr-
anosyl Schmidt donor gave the desired pentasaccharide ef-
ficiently. The work reported here significantly facilitates the
total synthesis of the whole thornasteroside A molecule and
Conclusion
In summary, we have accomplished the first synthesis of also of other structurally related oligosaccharides isolated
the pentasaccharide of thornasteroside A, which is the first from starfish and other marine organisms.
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Synthesis of the Pentasaccharide Moiety of Thornasterside A
H), 3.30 (dd, J = 12.0, 7.1 Hz, 1 H, 5II-H), 3.21 (d, J = 4.6 Hz, 1
H, OH), 2.90 (t, J = 9.2 Hz, 1 H, 4III-H), 2.49 (d, J = 5.5 Hz, 1 H,
OH), 1.33 (d, J = 6.1 Hz, 3 H, CH3), 1.17 (d, J = 6.2 Hz, 3 H,
CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 165.87, 165.38,
165.36, 154.91, 150.71, 138.05, 138.00, 133.44, 133.22, 129.77,
129.74, 129.68, 129.22, 129.01, 128.79, 128.66, 128.54, 128.45,
128.37, 128.32, 128.28, 128.16, 127.80, 117.92, 114.48, 100.89,
95.41, 81.74, 80.46, 79.57, 77.79, 74.63, 73.50, 72.83, 72.77, 72.21,
70.72, 69.54, 67.01, 63.65, 55.60, 17.98, 17.70 ppm. HRMS (ESI):
calcd. for C59H60O17Na [M + Na]+ 1063.3720; found 1063.3722.
Experimental Section
General Methods: All chemicals used were reagent grade. Chemicals
were used as supplied except where noted. Dichloromethane and
methanol were heated at reflux over calcium hydride and distilled
prior to use. Acetonitrile was heated at reflux over phosphorus
pentoxide and distilled prior to use. Analytical thin-layer
chromatography was performed on silica gel HF254, and plates were
visualized by charring with H2SO4 (5% v/v in CH3OH) or by UV
detection. Column chromatography was conducted by elution of a
column of silica gel (200–300 mesh) with EtOAc/petroleum ether
(b.p. 60–90 °C) as the eluent. 1H NMR spectra were obtained with
a Bruker 400 (400 MHz) instrument, and chemical shifts are re-
ported on the δ scale. CHCl3 (δ = 7.26 ppm) or TMS (δ = 0.00 ppm)
were used as internal references. 13C NMR spectra were obtained
with a Bruker 400 (100 MHz) instrument, and chemical shifts are
reported on the δ scale. CDCl3 (δ = 77.0 ppm) or TMS (δ =
0.00 ppm) were used as internal references. COSY, HMQC, and
HMBC experiments were routinely used to definitively assign the
1
Data for 14: [α]2D0 = +25.1 (c = 0.5, CHCl3). H NMR (400 MHz,
CDCl3): δ = 7.95–7.79 (m, 6 H, ArH), 7.52–7.50 (m, 2 H, ArH),
7.47–7.23 (m, 17 H, ArH), 6.92 (d, J = 9.1 Hz, 2 H, ArH), 6.80 (d,
J = 9.1 Hz, 2 H, ArH), 5.76 (t, J = 9.6 Hz, 1 H, 3I-H), 5.46 (dd, J
= 9.6, 3.3 Hz, 1 H, 2I-H), 5.32 (d, J = 3.3 Hz, 1 H, 1I-H), 5.29 (t,
J = 9.6 Hz, 1 H, 3II-H), 5.22 (d, J = 7.2 Hz, 1 H, 1II-H), 5.15–5.04
(m, 2 H, 1III-H, 3II-H), 4.96 (dd, J = 16.1, 9.5 Hz, 2 H, CH2Ph),
4.82–4.80 (m, 1 H, 4II-H), 4.75 (d, J = 11.4 Hz, 1 H, CH2Ph), 4.63
(d, J = 10.9 Hz, 1 H, CH2Ph), 4.45 (t, J = 9.3 Hz, 1 H, 3III-H),
4.05 (dd, J = 11.6, 3.6 Hz, 1 H, 5II-H), 4.00–3.88 (m, 2 H, 2II-H,
5III-H), 3.74 (s, 3 H, OCH3Ph), 3.73–3.65 (m, 2 H, 5I-H, 4II-H),
3.35 (dd, J = 11.6, 6.4 Hz, 1 H, 5II-H), 3.10 (t, J = 9.4 Hz, 1 H),
2.72 (1 H, OH), 2.06 (s, 3 H, OAc), 1.31 (d, J = 4.8 Hz, 3 H, CH3),
1.21 (d, J = 5.4 Hz, 3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3):
δ = 171.26, 165.93, 165.40, 165.30, 154.95, 150.89, 138.14, 137.98,
133.39, 133.18, 129.76, 129.71, 129.44, 129.11, 128.89, 128.64,
128.57, 128.45, 128.37, 128.33, 128.28, 128.15, 127.82, 117.97,
114.53, 100.70, 100.21, 95.69, 82.27, 81.02, 75.38, 74.78, 73.90,
73.74, 73.18, 72.91, 72.56, 70.59, 68.16, 67.11, 63.11, 55.63, 21.14,
17.98, 17.65 ppm. HRMS (ESI): calcd. for C61H62O18Na [M +
Na]+ 1105.3833; found 1105.3804.
1
signals of H NMR and 13C NMR spectra. Optical rotations were
recorded with a Perkin–Elmer 343 polarimeter.
2,3,4-Tri-O-benzoyl-6-deoxy-β-
D-galactopyranosyl-(1Ǟ2)-3,4,6-tri-
O-acetyl-α- -galactopyranosyl Trichloroacetimidate (2): NBS
D
(0.99 g, 5.58 mmol) was added to a stirred solution of compound
15 (1.62 g, 1.86 mmol) in acetone/H2O (9:1, 40 mL), and the mix-
ture was stirred at 0 °C for 1 h. After this time, TLC (petroleum
ether/EtOAc, 3:1) showed complete conversion of the starting ma-
terial into a more slowly moving component. The mixture was dis-
solved in EtOAc (200 mL) and washed with NaHCO3 (10% aq.;
20 mL). The organic phase was dried with Na2SO4 and then con-
centrated to a syrup. The crude product was dissolved in dry
CH2Cl2 (40 mL), and CCl3CN (0.93 mL, 9.30 mmol) and then
DBU (0.13 mL, 0.93 mmol) were added at 0 °C. The solution was
stirred at room temperature for 6 h. The solution was concentrated
in vacuo, and the crude product was purified by flash chromatog-
raphy (petroleum ether/EtOAc, 5:1) to give pure compound 2
(1.31 g, 78%) as a white foam. Since glycosyl trichloroacetimidates
are not stable, this compound was used for further reaction without
detailed characterization.
p-Methoxyphenyl 3,4-Di-O-acetyl-2-O-levulinoyl-β-
D-xylopyran-
osyl-(1Ǟ3)-2,4-di-O-benzyl-6-deoxy-α- -glucopyranoside (11): A
D
mixture of compound 9 (1.17 g, 2.59 mmol), compound 5 (1.36 g,
3.11 mmol), and molecular sieves (4 Å; 400 mg) in dry CH2Cl2
(50 mL) was stirred under nitrogen for 30 min. The mixture was
cooled to –78 °C, and TMSOTf (94 μL, 0.52 mmol) was added. The
mixture was stirred for 45 min, after which time TLC showed com-
plete consumption of acceptor 9. The mixture was filtered through
a pad of Celite, and the filtrate was washed successively with
NaHCO3 (10 mL) and brine (20 mL). The organic phase was sepa-
rated and dried (Na2SO4), and the solvents were evaporated in
vacuo. The residue was purified by silica gel column chromatog-
raphy (petroleum ether/EtOAc, 3:1) to give pure disaccharide 11
p-Methoxyphenyl 2,3,4-Tri-O-benzoyl-6-deoxy-β-
(1Ǟ2)-β- -xylopyranosyl-(1Ǟ3)-2,4-di-O-benzyl-6-deoxy-α-
pyranoside (3) and p-Methoxyphenyl 2,3,4-Tri-O-benzoyl-6-deoxy-β-
-glucopyranosyl-(1Ǟ2)-3-O-acetyl-β- -xylopyranosyl-(1Ǟ3)-2,4-
di-O-benzyl-6-deoxy-α- -glucopyranoside (14): CH3COCl (0.5 mL)
D
-glucopyranosyl-
D
D-gluco-
D
D
D
was added to a solution of 13 (1.20 g, 1.07 mmol) in dry CH3OH/
CH2Cl2 (25 mL/25 mL). The mixture was stirred at room tempera-
ture for 12 h, after which time TLC (petroleum ether/EtOAc, 2:1)
indicated that the reaction was complete. The reaction mixture was
then neutralized with Et3N. The mixture was concentrated, passed
through a silica gel column (petroleum ether/EtOAc, 3:1) to give
14 (0.95 g, 82%) and 3 (0.11 g, 10%).
1
(1.62 g, 82%) as a white foam. [α]2D0 = –67.8 (c = 0.80, CHCl3). H
NMR (400 MHz, CDCl3): δ = 7.40–7.26 (m, 10 H, ArH), 6.88 (d,
J = 7.8 Hz, 2 H, ArH), 6.79 (d, J = 7.8 Hz, 2 H, ArH), 5.23 (d, J
= 9.2 Hz, 1 H, 3II-H), 5.18 (d, J = 3.5 Hz, 1 H, 1I-H), 5.15 (d, J =
7.6 Hz, 1 H, 1II-H), 5.12–5.06 (m, 1 H, 5I-H), 5.03–5.00 (m, 1 H,
4I-H), 4.98 (d, J = 10.8, Hz, 1 H, CH2Ph), 4.79 (d, J = 11.5 Hz, 1
H, CH2Ph), 4.59 (d, J = 10.8, Hz, 1 H, CH2Ph), 4.57 (d, J =
Data for 3: H NMR (400 MHz, CDCl3): δ = 7.95 (t, J = 7.2 Hz, 11.6 Hz, 1 H, CH2Ph), 4.41 (t, J = 9.2 Hz, 1 H, 2II-H), 4.09 (t, J
1
4 H, ArH), 7.81 (d, J = 7.3 Hz, 2 H, ArH), 7.53 (d, J = 7.3 Hz, 2
H, ArH), 7.47–7.26 (m, 17 H, ArH), 6.92 (d, J = 9.1 Hz, 2 H,
= 9.2 Hz, 1 H, 4I-H), 3.85 (dd, J = 9.6, 6.2 Hz, 1 H, 5II-H), 3.76
(s, 3 H, OCH3Ph), 3.67 (dd, J = 9.6, 3.5 Hz, 1 H, 2I-H), 3.31 (t, J
ArH), 6.79 (d, J = 9.1 Hz, 2 H, ArH), 5.76 (t, J = 10.0 Hz, 1 H, = 10.0 Hz, 1 H, 5II-H), 3.14 (t, J = 9.2 Hz, 1 H, 3I-H), 2.74–2.70
3I-H), 5.51 (dd, J = 9.6, 3.4 Hz, 1 H, 2I-H), 5.30 (t, J = 9.6 Hz, 1
H, 4I-H), 5.24 (d, J = 3.5 Hz, 1 H, 1I-H), 5.21 (d, J = 5.6 Hz, 1 H,
1II-H), 4.90 (d, J = 8.1 Hz, 1 H, 1III-H), 4.87 (d, J = 10.6 Hz, 1 H,
(m, 2 H, COCH2CH2), 2.59–2.55 (m, 2 H, COCH2CH2), 2.18 (s, 3
H, OAc), 2.10 (s, 3 H, OAc), 2.05 (s, 3 H, OAc), 1.16 (d, J = 6.2 Hz,
3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 205.90, 171.40,
CH2Ph), 4.81 (d, J = 11.2 Hz, 1 H, CH2Ph), 4.68 (d, J = 11.4 Hz, 170.34, 169.92, 154.88, 150.52, 138.08, 137.75, 128.61, 128.51,
1 H, CH2Ph), 4.58 (d, J = 10.5 Hz, 1 H, CH2Ph), 4.37 (t, J =
128.30, 128.10, 127.73, 117.93, 114.41, 100.75 (C-1II), 95.45 (C-1I),
9.2 Hz, 1 H, 3III-H), 4.08 (dd, J = 12.0, 3.8 Hz, 1 H, 5II-H), 3.86 81.48, 80.72, 78.16, 75.23, 73.32, 72.06, 69.23, 67.12, 62.35, 55.55,
(dd, J = 9.7, 6.3 Hz, 1 H, 2II-H), 3.76 (s, 3 H, OCH3Ph), 3.67 (t, J
= 6.4 Hz, 1 H, 2II-H), 3.59–3.52 (m, 4 H, 5-H, 3II-H, 4II-H, 5III
37.53, 29.73, 27.84, 20.75, 20.73, 17.83 ppm. HRMS (ESI): calcd.
-
for C41H48O14Na [M + Na]+ 787.2942; found 787.2936.
Eur. J. Org. Chem. 2013, 6158–6166
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6163

J. Xiong, Z. Lu, N. Ding, S. Ren, Y. Li
FULL PAPER
p-Methoxyphenyl 3,4-Di-O-acetyl-β-
D
-xylopyranosyl-(1Ǟ3)-2,4-di-
stirred under nitrogen for 30 min. The mixture was cooled to 0 °C,
and TMSOTf (104 μL, 0.58 mmol) was added. The mixture was
stirred for 30 min, after which time TLC showed complete con-
O-benzyl-6-deoxy-α-
D-glucopyranoside (12): Compound 11 (1.62 g,
2.12 mmol) was dissolved in dry CH3OH/CH2Cl2 (10 mL/40 mL),
and AcOH·NH2NH2 (1.95 g, 21.2 mmol) was added. The reaction sumption of acceptor 7. The mixture was filtered through a pad of
mixture was stirred overnight at room temperature, then the mix-
ture was concentrated in vacuo. The residue was purified by
chromatography (petroleum ether/EtOAc, 5:1) to give pure com-
pound 12 (1.15 g, 92%) as a white foam. [α]2D0 = –36.8 (c = 0.50,
Celite, and the filtrate was washed successively with NaHCO3
(10 mL) and brine (20 mL). The organic phase was separated and
dried with Na2SO4, and the solvents were evaporated in vacuo. The
residue was purified by flash chromatography (petroleum ether/
CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.36–7.26 (m, 10 H, EtOAc, 3:1) to give pure compound 15 (2.16 g, 83%) as a white
ArH), 6.92 (d, J = 8.8 Hz, 2 H, ArH), 6.80 (d, J = 8.8 Hz, 2 H,
foam. [α]2D0 = +102 (c = 1.20, CHCl3). 1H NMR (400 MHz,
ArH), 5.23 (d, J = 3.3 Hz, 1 H, 1I-H), 5.11 (t, J = 9.5 Hz, 1 H, 3II- CDCl3): δ = 8.13 (d, J = 7.3 Hz, 2 H, ArH), 7.84 (d, J = 7.3 Hz, 2
H), 5.03–4.91 (m, 2 H, 4II-H, PhCH2), 4.72 (d, J = 7.2 Hz, 1 H,
H, ArH), 7.79 (d, J = 7.3 Hz, 2 H, ArH), 7.61 (t, J = 7.4 Hz, 1 H,
1II-H), 4.69–4.58 (m, 3 H, PhCH2), 4.37 (t, J = 9.4 Hz, 1 H, 3I-H), ArH), 7.53–7.34 (m, 8 H, ArH), 7.30–7.21 (m, 3 H, ArH), 7.16 (d,
3.97 (dd, J = 11.5, 5.6 Hz, 1 H, 5II-H), 3.91–3.83 (m, 1 H, 5I-H), J = 8.0 Hz, 2 H, ArH), 5.77–5.65 (m, 2 H, 2II-H, 4II-H), 5.50 (dd,
3.80 (s, 1 H, OH), 3.77 (s, 3 H, PhOCH3), 3.66 (dd, J = 9.8, 3.4 Hz,
J = 10.4, 3.3 Hz, 1 H, 3II-H), 5.31 (d, J = 3.0 Hz, 1 H, 4I-H), 5.14
1 H, 2I-H), 3.55 (t, J = 8.3 Hz, 1 H, 2II-H), 3.17 (m, 2 H, 4I-H, 5II- (d, J = 7.8 Hz, 1 H, 1II-H), 4.93 (dd, J = 9.8, 3.2 Hz, 1 H, 5I-H),
H), 2.10 (s, 3 H, COCH3), 2.06 (s, 3 H, COCH3), 1.21 (d, J =
4.70 (d, J = 9.6 Hz, 1 H, 1I-H), 4.17–4.08 (m, 3 H, 2I-H, 6I-H, 5II-
H), 4.04 (dd, J = 11.3, 6.3 Hz, 1 H, 6I-H), 3.82 (t, J = 6.6 Hz, 1 H,
6.2 Hz, 3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.54,
170.10, 155.04, 150.68, 138.21, 136.74, 128.69, 128.41, 128.35, 3I-H), 2.37 (s, 3 H, -CH3Ph), 1.99 (s, 3 H, OAc), 1.96 (s, 3 H, OAc),
127.90, 127.72, 117.82, 114.55, 105.42 (C-1II), 95.15 (C-1I), 83.02, 1.86 (s, 3 H, OAc), 1.38 (d, J = 6.4 Hz, 3 H, CH3) ppm. 13C NMR
80.95, 79.02, 75.18, 73.85, 73.61, 72.79, 69.03, 67.37, 63.01, 55.63,
20.91, 20.76, 17.82 ppm. HRMS (ESI): calcd. for C36H42O12Na [M
+ Na]+ 689.2574; found 689.2572.
(100 MHz, CDCl3): δ = 170.33, 170.02, 169.57, 165.90, 165.73,
165.10, 138.04, 133.40, 133.21, 130.01, 129.70, 129.56, 129.50,
129.41, 129.28, 129.21, 128.77, 128.53, 128.31, 128.25, 100.22,
87.14, 74.00, 72.48, 72.31, 70.86, 70.61, 69.88, 67.35, 61.51, 29.65,
21.14, 20.60, 20.51, 20.47, 16.30 ppm. HRMS (ESI): calcd. for
C46H46O15SNa [M + Na]+ 893.2455; found 893.2457.
p-Methoxyphenyl 2,3,4-Tri-O-benzoyl-6-deoxy-β-
(1Ǟ2)-3,4-di-O-acetyl-β- -xylopyranosyl-(1Ǟ3)-2,4-di-O-benzyl-
6-deoxy-α- -glucopyranoside (13): A mixture of compound 12
D-glucopyranosyl-
D
D
(1.02 g, 1.53 mmol), compound 6 (1.14 g, 1.84 mmol), and molecu-
lar sieves (4 Å; 200 mg) in dry CH2Cl2 (30 mL) was stirred under
nitrogen for 30 min. The mixture was cooled to 0 °C, and TMSOTf
(56 μL, 0.31 mmol) was added. The mixture was stirred for 30 min,
after which time TLC showed complete consumption of acceptor
12. Then, the mixture was filtered through a pad of Celite, and the
filtrate was washed successively with NaHCO3 (5 mL) and brine
(10 mL). The organic phase was separated and dried with Na2SO4,
and the solvents were evaporated in vacuo. The residue was purified
by flash chromatography (petroleum ether/EtOAc, 3:1) to give pure
compound 13 (1.29 g, 78%) as a white foam. [α]2D0 = +8.2 (c = 0.5,
CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.96–7.94 (m, 2 H,
ArH), 7.85–7.83 (m, 2 H, ArH), 7.79–7.77 (m, 2 H, ArH), 7.55–
7.22 (m, 19 H, ArH), 6.93 (d, J = 8.0 Hz, 2 H, ArH), 6.81 (d, J =
8.0 Hz, 2 H, ArH), 5.78 (t, J = 9.7 Hz, 1 H, 3I-H), 5.49 (dd, J =
9.6, 3.4 Hz, 1 H, 2II-H), 5.34 (t, J = 9.6 Hz, 1 H, 4I-H), 5.28 (d, J
= 3.2 Hz, 1 H, 1I-H), 5.25 (d, J = 6.4 Hz, 1 H, 1II-H), 5.10–4.99
(m, 2 H, 1III-H, 3II-H), 4.93 (dd, J = 16.1, 9.5 Hz, 2 H, CH2Ph),
4.84–4.82 (m, 1 H, 4II-H), 4.70 (d, J = 11.1 Hz, 1 H, CH2Ph), 4.61
(d, J = 10.6 Hz, 1 H, CH2Ph), 4.42 (t, J = 9.1 Hz, 1 H, 3III-H),
4.03 (dd, J = 11.8, 5.0 Hz, 1 H, 5II-H), 3.96–3.83 (m, 2 H, 2II-H,
5III-H), 3.77 (s, 3 H, OCH3Ph), 3.76–3.69 (m, 2 H, 5I-H, 2III-H),
3.32 (dd, J = 11.8, 8.8 Hz, 1 H, 5II-H), 3.11 (t, J = 9.3 Hz, 1 H,
4III-H), 1.92 (s, 3 H, OAc), 1.91 (s, 3 H, OAc), 1.38 (d, J = 4.8 Hz,
3 H, CH3), 1.21 (d, J = 5.5 Hz, 3 H, CH3) ppm. 13C NMR
(100 MHz, CDCl3): δ = 170.23, 169.37, 165.91, 165.42, 165.00,
154.85, 150.70, 138.15, 137.95, 133.38, 133.13, 129.73, 129.64,
129.40, 129.02, 128.86, 128.78, 128.62, 128.48, 128.41, 128.34,
128.22, 128.11, 127.81, 117.74, 114.43, 101.29, 100.84, 95.63, 81.92,
80.97, 77.95, 77.70, 75.01, 73.73, 73.60, 73.04, 72.92, 72.52, 70.49,
69.22, 66.90, 61.67, 55.57, 20.83, 20.65, 17.92, 17.75 ppm. HRMS
(ESI): calcd. for C63H64O19Na [M + Na]+ 1147.3939; found
1147.3936.
p-Methoxyphenyl 2,3,4-Tri-O-benzoyl-6-deoxy-β-
osyl-(1Ǟ2)-3,4,6-tri-O-acetyl-α- -galactopyranosyl-(1Ǟ4)-[2,3,4-
tri-O-benzoyl-6-deoxy-β- -glucopyranosyl-(1Ǟ2)]-3-O-acetyl-β-
xylopyranosyl-(1Ǟ3)-2,4-di-O-benzyl-6-deoxy-α- -glucopyranoside
D-galactopyran-
D
D
D-
D
(16): A mixture of compound 14 (0.23 g, 0.21 mmol), compound 2
(0.22 g, 0.25 mmol), and molecular sieves (4 Å; 200 mg) in dry
CH2Cl2 (20 mL) was stirred under nitrogen for 30 min. The mixture
was cooled to –78 °C, and TMSOTf (7.6 μL, 0.042 mmol) was
added. The mixture was stirred for 30 min, after which time TLC
showed complete consumption of acceptor 14. The mixture was
filtered through a pad of Celite, and the filtrate was washed suc-
cessively with NaHCO3 (5 mL) and brine (10 mL). The organic
phase was separated and dried with Na2SO4, and the solvents were
evaporated in vacuo. The residue was purified by flash chromatog-
raphy (petroleum ether/EtOAc, 4:1) to give pure compound 16
1
(0.33 g, 85%) as a white foam. H NMR (400 MHz, CDCl3): δ =
8.19 (d, J = 7.2 Hz, 2 H, ArH), 8.00–7.95 (m, 2 H, ArH), 7.94–
7.84 (m, 5 H, ArH), 7.84–7.79 (m, 4 H, ArH), 7.78–7.73 (m, 2 H,
ArH), 7.68 (t, J = 7.8 Hz, 1 H, ArH), 7.60–7.46 (m, 4 H, ArH),
7.42–7.40 (m, 4 H, ArH), 7.38–7.35 (m, 7 H, ArH), 7.34–7.18 (m,
9 H, ArH), 6.92 (d, J = 9.2 Hz, 2 H, ArH), 6.80 (d, J = 9.2 Hz, 2
H, ArH), 5.89 (t, J = 9.7 Hz, 1 H), 5.77–5.65 (m, 2 H), 5.60–5.46
(m, 2 H), 5.37 (t, J = 9.6 Hz, 1 H), 5.28 (d, J = 3.6 Hz, 1I-H), 5.24
(d, J = 3.2 Hz, 1IV-H), 5.23–5.20 (m, 2 H), 5.19 (d, J = 7.5 Hz, 1
H, 1II-H), 5.04 (d, J = 8.0 Hz, 1V-H), 5.00–4.95 (m, 2 H), 4.93 (d,
J = 10.8 Hz, 1 H, CH2Ph), 4.84 (d, J = 7.9 Hz, 1 H, 1III-H), 4.72
(d, J = 11.0 Hz, 1 H, CH2Ph), 4.53–4.37 (m, 2 H), 4.21–4.04 (m, 3
H), 4.03–3.91 (m, 2 H), 3.91–3.78 (m, 3 H), 3.77 (s, 3 H, CH3Ph),
3.69 (dd, J = 9.6, 7.6 Hz, 1 H), 3.57 (dd, J = 9.6, 6.2 Hz, 1 H), 3.28
(t, J = 9.2 Hz, 1 H), 3.01 (t, J = 9.2 Hz, 1 H), 2.07 (s, 3 H, OAc),
2.06 (s, 3 H, OAc), 2.01 (s, 3 H, OAc), 1.34 (d, J = 6.1 Hz, 3 H,
CH3), 1.26 (d, J = 6.2 Hz, 3 H, CH3), 1.21 (s, 3 H, OAc), 1.15 (d,
J = 6.2 Hz, 3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ =
170.46, 169.83, 169.70, 169.25, 166.11, 165.73, 165.63, 165.49,
165.13, 164.73, 154.92, 150.87, 138.48, 138.07, 133.87, 133.43,
133.32, 133.18, 130.05, 129.76, 129.72, 129.47, 129.29, 129.20,
128.89, 128.85, 128.72, 128.69, 128.49, 128.42, 128.32, 128.28,
p-Tolyl 2,3,4-Tri-O-benzoyl-6-deoxy-β-
D-galactopyranosyl-(1Ǟ2)-
3,4,6-tri-O-acetyl-1-thio-β- -galactopyranoside (15): A mixture of
D
compound 7 (1.21 g, 2.93 mmol), compound 8 (2.18 g, 3.52 mmol),
and molecular sieves (4 Å; 400 mg) in dry CH2Cl2 (60 mL) was
6164
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 6158–6166

Synthesis of the Pentasaccharide Moiety of Thornasterside A
128.21, 128.13, 128.04, 127.56, 118.10, 102.76 (C-1III), 101.02 (C- flash chromatography (petroleum ether/EtOAc, 3:1) to give pure
1II, C-1V), 98.82 (C-1IV), 95.79 (C-1I), 81.85, 81.07, 78.89, 78.14,
74.72, 73.98, 73.87, 73.75, 73.07, 72.55, 72.11, 70.97, 70.40, 69.69,
69.34, 68.31, 67.85, 66.93, 66.77, 63.95, 61.55, 55.63, 20.82, 20.73,
20.62, 19.52, 18.01, 17.91, 16.45 ppm. HRMS (MALDI-DHB):
calcd. for C100H100O33Na [M + Na]+ 1851.6044; found 1851.6039.
compound 19 (0.26 g, 68%) as a white foam. [α]2D0 = –29.8 (c =
0.50, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J =
7.3 Hz, 2 H, ArH), 7.84 (d, J = 7.4 Hz, 2 H, ArH), 7.78 (d, J =
7.4 Hz, 2 H, ArH), 7.54–7.24 (m, 19 H, ArH), 6.94 (d, J = 9.0 Hz,
2 H, ArH), 6.81 (d, J = 9.1 Hz, 2 H, ArH), 5.84 (t, J = 9.7 Hz, 1
H), 5.56–5.45 (m, 1 H), 5.38 (t, J = 9.6 Hz, 1 H), 5.33 (s, 1 H), 5.25
(d, J = 3.5 Hz, 1 H, 1I-H), 5.16 (d, J = 7.4 Hz, 1 H, 1IV-H), 5.09–
5.03 (m, 2 H), 5.01 (d, J = 7.0 Hz, 1 H, 1II-H), 4.95 (apparent t, J
= 9.9 Hz, 3 H), 4.68 (d, J = 10.9 Hz, 1 H, CH2Ph), 4.63 (d, J =
11.0 Hz, 1 H, CH2Ph), 4.43 (t, J = 9.1 Hz, 1 H), 4.34 (d, J = 7.1 Hz,
1 H, 1III-H), 4.10–3.99 (m, 2 H), 3.93–3.78 (m, 5 H), 3.78 (s, 3 H,
OCH3Ph), 3.73–3.64 (m, 1 H), 3.20 (t, J = 11.0 Hz, 1 H), 3.12 (t,
J = 9.2 Hz, 1 H), 2.83–2.75 (m, 1 H), 2.64–2.50 (m, 2 H), 2.36–
2.29 (m, 1 H), 2.14 (s, 3 H, CH3Ph), 2.11 (s, 3 H, CH3CO), 2.04
(s, 3 H, OAc), 2.00 (s, 3 H, OAc), 1.89 (s, 3 H, OAc), 1.40 (d, J =
6.1 Hz, 3 H, CH3), 1.17 (d, J = 6.2 Hz, 3 H, CH3) ppm. 13C NMR
(100 MHz, CDCl3): δ = 205.84, 170.75, 170.36, 170.34, 170.18,
169.12, 166.01, 165.52, 165.07, 155.02, 150.89, 138.63, 138.03,
133.41, 133.16, 133.04, 129.82, 129.80, 129.70, 129.65, 129.16,
128.96, 128.92, 128.65, 128.46, 128.42, 128.31, 128.26, 128.16,
128.07, 127.75, 118.23, 114.55, 101.11, 101.02, 100.92, 95.92, 81.88,
81.17, 78.42, 77.54, 74.87, 73.95, 73.81, 73.27, 72.77, 70.80, 70.65,
68.88, 66.93, 66.87, 63.08, 61.07, 55.65, 37.68, 29.69, 27.69, 20.84,
20.67, 20.63, 20.51, 18.02, 17.92 ppm. HRMS (MALDI-TOF):
calcd. for C78H84O28Na [M + Na]+ 1491.5046; found 1491.5042.
p-Methoxyphenyl 2,3,4-Tri-O-benzoyl-6-deoxy-β-
osyl-(1Ǟ2)-3,4,6-tri-O-acetyl-β- -galactopyranosyl-(1Ǟ4)-[2,3,4-
tri-O-benzoyl-6-deoxy-β- -glucopyranosyl-(1Ǟ2)]-3-O-acetyl-β-
-xylopyranosyl-(1Ǟ3)-2,4-di-O-benzyl-6-deoxy-α- -gluco-
D-galactopyran-
D
D
D
D
pyranoside (17): A mixture of compound 20 (102 mg, 0.074 mmol),
compound 8 (60 mg, 0.097 mmol), and molecular sieves (4 Å;
30 mg) in dry CH2Cl2 (15 mL) was stirred under nitrogen for
30 min. The mixture was cooled to –78 °C, and TMSOTf (17.6 μL,
0.097 mmol) was added. The mixture was stirred for 30 min, after
which time TLC showed complete consumption of acceptor 20.
The mixture was filtered through a pad of Celite, and the filtrate
was washed successively with NaHCO3 (5 mL) and brine (10 mL).
The organic phase was separated and dried with Na2SO4, and the
solvents were evaporated in vacuo. The residue was purified by
flash chromatography (petroleum ether/EtOAc, 3:1) to give pure
compound 17 (113 mg, 83%) as a white foam. [α]2D0 = –12.3 (c =
0.50, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 8.05 (d, J =
7.2 Hz, 2 H, ArH), 7.98–7.91 (m, 6 H, ArH), 7.79 (t, J = 7.4 Hz,
4 H, ArH), 7.54 (t, J = 6.6 Hz, 4 H, ArH), 7.49–7.46 (m, 5 H,
ArH), 7.43–7.40 (m, 6 H, ArH), 7.39–7.34 (m, 10 H, ArH), 7.23–
7.20 (m, 3 H), 6.91 (d, J = 9.1 Hz, 2 H, ArH), 6.80 (d, J = 9.1 Hz,
p-Methoxyphenyl 3,4,6-Tri-O-acetyl-β-
-glucopyranosyl-(1Ǟ2)]-3-O-
-xylopyranosyl-(1Ǟ3)-2,4-di-O-benzyl-6-deoxy-α-D-
D-galactopyranosyl-(1Ǟ4)-
2 H, ArH), 5.86 (t, J = 9.7 Hz, 1 H), 5.63–5.54 (m, 3 H), 5.45 (d, [2,3,4-tri-O-benzoyl-6-deoxy-β-
D
J = 9.6 Hz, 1 H), 5.38 (dd, J = 10.4, 3.4 Hz, 1 H), 5.34 (d, J =
3.9 Hz, 1 H, 1I-H), 5.32–5.30 (m, 1 H), 5.28 (d, J = 7.6 Hz, 1 H,
1IV-H), 5.20 (d, J = 3.3 Hz, 1 H), 5.10–5.05 (m, 2 H), 5.03 (d, J =
7.9 Hz, 1 H, 1II-H), 4.98 (d, J = 7.9 Hz, 1 H, 1V-H), 4.88 (d, J =
10.4 Hz, 1 H, CH2Ph), 4.81 (dd, J = 10.4, 3.4 Hz, 1 H), 4.66 (appar-
ent d, J = 11.1 Hz, 2 H, CH2Ph), 4.45 (t, J = 9.0 Hz, 1 H), 4.37
acetyl-β-
D
glucopyranoside (20): Compound 19 (182 mg, 0.124 mmol) was dis-
solved in dry CH3OH/CH2Cl2 (5 mL/20 mL), and AcOH·N2H4
(114 mg, 1.24 mmol) was added. The reaction mixture was stirred
overnight at room temperature, then the mixture was concentrated
in vacuo. The residue was purified by flash chromatography (petro-
(d, J = 7.6 Hz, 1 H, 1III-H), 4.21–4.14 (m, 1 H), 4.02 (dd, J = 11.0, leum ether/EtOAc, 3:1) to give pure compound 20 (158 mg, 93%)
6.2 Hz, 1 H), 3.98–3.87 (m, 3 H), 3.85–3.79 (m, 4 H), 3.77 (s, 3 H,
CH3Ph), 3.73 (d, J = 7.2 Hz, 2 H), 3.33 (t, J = 9.2 Hz, 1 H), 3.17
as a white foam. [α]2D0 = –18.2 (c = 0.20, CHCl3). 1H NMR
(400 MHz, CDCl3): δ = 7.95 (d, J = 7.3 Hz, 2 H, ArH), 7.82 (d, J
(t, J = 9.2 Hz, 1 H), 1.99 (s, 3 H, OAc), 1.98 (s, 3 H, OAc), 1.71 = 7.4 Hz, 2 H, ArH), 7.76 (d, J = 7.4 Hz, 2 H, ArH), 7.54–7.24
(s, 3 H, OAc), 1.65 (s, 3 H, OAc), 1.42 (d, J = 6.1 Hz, 3 H, CH3), (m, 19 H, ArH), 6.94 (d, J = 9.0 Hz, 2 H, ArH), 6.81 (d, J = 9.1 Hz,
1.22 (d, J = 6.2 Hz, 3 H, CH3), 1.15 (d, J = 6.3 Hz, 3 H, CH3) 2 H, ArH), 5.84 (t, J = 9.7 Hz, 1 H), 5.47 (t, J = 8.8 Hz, 1 H),
ppm. 13C NMR (100 MHz, CDCl3): δ = 170.30, 170.04, 169.80, 5.38–5.32 (m, 2 H, 1IV-H), 5.30–5.22 (m, 2 H, 1I-H), 5.02–4.96 (m,
169.39, 165.97, 165.88, 165.46, 165.41, 165.04, 165.01, 154.89, 3 H, 1II-H), 4.89–4.83 (m, 2 H), 4.65 (d, J = 10.9 Hz, 1 H, PhCH2),
150.90, 138.51, 137.98, 133.42, 133.38, 133.19, 133.15, 133.08, 4.63 (d, J = 11.0 Hz, 1 H, PhCH2), 4.43 (t, J = 9.1 Hz, 1 H), 4.34
130.11, 129.88, 129.82, 129.76, 129.71, 129.59, 129.53, 129.18, (d, J = 7.1 Hz, 1 H, 1III-H), 4.10–3.95 (m, 3 H), 3.93–3.78 (m, 1
129.12, 128.98, 128.83, 128.65, 128.62, 128.44, 128.38, 128.32, H), 3.78–3.70 (m, 8 H), 3.58 (t, J = 7.8 Hz, 1 H), 3.40–3.30 (m, 1
128.23, 128.20, 127.73, 117.99, 114.49, 101.73, 101.41, 101.05, H), 3.12 (t, J = 9.2 Hz, 1 H), 2.64 (s, 1 H, OH), 2.33 (s, 3 H, OAc),
100.76, 95.61, 81.80, 81.26, 78.11, 77.61, 75.49, 74.90, 74.11, 73.86,
73.39, 73.12, 72.72, 72.29, 71.48, 71.18, 70.78, 70.65, 70.26, 69.92,
66.87, 66.69, 62.78, 60.80, 55.60, 21.05, 20.62, 20.13, 20.05, 18.04,
17. 90, 16.32 ppm. HRMS (MALDI-DHB): calcd. for
2.18 (s, 3 H, OAc), 2.04 (s, 3 H, OAc), 2.00 (s, 3 H, OAc), 1.89 (s,
3 H, CH3), 1.40 (d, J = 6.1 Hz, 3 H, CH3), 1.17 (d, J = 6.2 Hz, 3
H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.36, 170.30,
170.08, 169.80, 165.93, 165.43, 165.14, 154.90, 150.79, 138.40,
137.93, 133.40, 133.17, 133.10, 133.40, 133.17, 133.10, 129.75,
129.66, 129.48, 129.06, 128.85, 128.62, 128.44, 128.31, 128.26,
128.20, 128.10, 127.76, 118.03, 114.48, 101.21, 101.06, 100.83,
95.64, 81.91, 77.71, 77.60, 74.70, 74.42, 73.76, 73.48, 73.19, 73.02,
72.67, 72.17, 70.63, 70.53, 68.65, 66.92, 66.87, 61.02, 55.61, 29.68,
20.96, 20.74, 20.67, 20.59, 17.99, 17.79 ppm. HRMS (MALDI-
TOF): calcd. for C73H78O26Na [M + Na]+ 1393.4679; found
1393.4673.
C
100H100O33Na [M + Na]+ 1851.6044; found 1851.6037.
p-Methoxyphenyl 3,4,6-Tri-O-acetyl-2-O-levulinoyl-β-
anosyl-(1Ǟ4)-[2,3,4-tri-O-benzoyl-6-deoxy-β- -glucopyranosyl-
(1Ǟ2)]-3-O-acetyl-β- -xylopyranosyl-(1Ǟ3)-2,4-di-O-benzyl-6-
deoxy-α- -glucopyranoside (19): A mixture of compound 14
D
-galactopyr-
D
D
D
(0.28 g, 0.26 mmol), compound 18 (0.29 g, 0.52 mmol), and molec-
ular sieves (4 Å; 100 mg) in dry CH2Cl2 (20 mL) was stirred under
nitrogen for 30 min. The mixture was cooled to –78 °C, and
TMSOTf (47 μL, 0.26 mmol) was added. The mixture was stirred
for 30 min, then it was filtered through a pad of Celite. The filtrate
was washed successively with NaHCO3 (5 mL) and brine (10 mL). tri-O-benzoyl-6-deoxy-β-
The organic phase was separated and dried with Na2SO4, and the
solvents were evaporated in vacuo. The residue was purified by
p-Methoxyphenyl 2,3,4-Tri-O-benzoyl-6-deoxy-β-
osyl-(1Ǟ2)-3,4,6-tri-O-acetyl-β- -galactopyranosyl-(1Ǟ4)-[2,3,4-
-glucopyranosyl-(1Ǟ2)]-3-O-acetyl-β-
-xylopyranosyl-(1Ǟ3)-6-deoxy-α- -glucopyranoside (21): Pd-
(OH)2/C (20wt.-%; 19 mg) was added to a solution of compound
D-galactopyran-
D
D
D
D
Eur. J. Org. Chem. 2013, 6158–6166
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6165

J. Xiong, Z. Lu, N. Ding, S. Ren, Y. Li
FULL PAPER
17 (95 mg, 0.052 mmol) in EtOAc (20 mL) and methanol (20 mL).
The resulting suspension was vigourously stirred under H2 (g) at
room temperature and atmospheric pressure for 24 h. The reaction
mixture was filtered through Celite. The filtrate was concentrated
to dryness to give, without further purification, compound 21
(79 mg, 98%) as a pale yellow foam. [α]2D0 = –5.7 (c = 0.20, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 8.08 (d, J = 7.5 Hz, 2 H, ArH),
7.95–7.89 (m, 5 H, ArH), 7.78 (d, J = 7.7 Hz, 4 H, ArH), 7.58–
7.51 (m, 7 H, ArH), 7.45–7.39 (m, 7 H, ArH), 7.28–7.22 (m, 5 H,
ArH), 7.11 (d, J = 7.7 Hz, 2 H, ArH), 6.88 (d, J = 7.8 Hz, 2 H,
ArH), 5.90 (t, J = 9.7 Hz, 1 H), 5.69 (s, 1 H), 5.59–5.48 (m, 4 H,
1I-H), 5.39 (t, J = 9.5 Hz, 1 H), 5.21 (s, 1 H), 5.13 (t, J = 9.6 Hz,
1 H), 5.00 (d, J = 8.0 Hz, 1 H, 1IV-H), 4.92 (d, J = 8.0 Hz, 1 H,
1II-H), 4.79 (d, J = 10.5 Hz, 1 H), 4.69 (d, J = 7.5 Hz, 1 H, 1V-H),
4.40 (d, J = 7.1 Hz, 1 H, 1III-H), 4.29–4.20 (m, 2 H), 4.12–4.01 (m,
2 H), 3.98–3.89 (m, 3 H), 3.87–3.78 (m, 7 H), 3.70 (t, J = 8.8 Hz,
1 H), 3.50 (t, J = 10.9 Hz, 1 H), 3.27 (t, J = 8.9 Hz, 1 H), 2.02 (s,
3 H, OAc), 1.81 (s, 3 H, OAc), 1.78 (s, 3 H, OAc), 1.71 (s, 3 H,
OAc), 1.48 (d, J = 5.6 Hz, 3 H, CH3), 1.37 (d, J = 6.1 Hz, 3 H,
CH3), 1.32 (d, J = 5.7 Hz, 3 H, CH3) ppm. 13C NMR (100 MHz,
CDCl3): δ = 170.24, 169.78, 169.72, 168.92, 165.88, 165.76, 165.46,
165.04, 165.00, 164.97, 154.89, 150.62, 133.36, 133.22, 133.15,
129.76, 129.69, 129.63, 129.59, 129.42, 129.34, 129.08, 128.84,
128.77, 128.66, 128.50, 128.36, 128.24, 128.19, 128.12, 127.26,
118.06, 114.43, 103.20, 102.05, 101.59, 100.96, 97.23, 87.36, 79.65,
75.39, 75.17, 74.05, 73.85, 73.30, 72.60, 72.36, 72.03, 71.83, 71.06,
70.84, 70.68, 70.34, 69.83, 68.22, 66.54, 63.20, 60.83, 55.55, 29.62,
20.66, 20.57, 20.14, 17.68, 17.10, 16.54 ppm. HRMS (MALDI-
DHB): calcd. for C86H88O33Na [M + Na]+ 1671.5105; found
1671.5107.
δ = 154.90, 149.99, 119.07, 115.25, 104.03 (C-1), 103.81 (C-1),
102.77 (C-1), 100.71 (C-1), 97.36 (C-1I), 83.95, 81.85, 80.08, 76.90,
75.31, 75.17, 74.84, 74.25, 74.11, 73.53, 72.69, 72.46, 71.99, 71.40,
71.34, 70.65, 68.77, 68.63, 63.13, 61.15, 55.90, 16.73, 16.67,
15.83 ppm. HRMS (MALDI-DHB): calcd. for C36H56O23Na [M +
Na]+ 879.3096; found 879.3104.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details, 1H and 13C NMR spectra for all new
compounds.
Acknowledgments
The authors thank the National Nature Science Foundation of
China (NSFC) (grant numbers 21002014 and 81072525) for finan-
cial support.
[1] J.-M. Kornprobst, G. Barnathan, Comp. Biochem. Physiol.
1998, 119, 1–51.
[2] Ikegami, J. Exp. Zool. 1976, 198, 359–366.
[3] M. M. Anisimov, N. G. Prokofieva, L. Y. Korotkikh, I. I. Ka-
pustina, V. A. Stonik, Toxicon 1980, 18, 221–223.
[4] H.-F. Tang, Y.-H. Yi, L. Li, P. Sun, S.-Q. Zhang, Y.-P. Zhao,
Fitoterapia 2006, 77, 28–34.
[5] L. Minale, C. Pizza, R. Riccio, F. Zollo, Pure Appl. Chem.
1982, 54, 1935–950.
[6] I. Kitagawa, M. Kobayashi, Chem. Pharm. Bull. 1978, 26,
1864–1873.
[7] V. D’Auria, L. Minale, R. Riccio, Chem. Rev. 1993, 93, 1839–
1895.
[8] Alexei V. Demchenko (Ed.), Handbook of Chemical Glycosyl-
ation, Wiley-VCH, Germany, 2008, p. 1–21.
[9] P. J. Garegg, in: Adv. Carbohydr. Chem. Biochem., vol. 59, Aca-
demic Press, 2004, p. 69–134.
[10] J. Robertson, P. M. Stafford, in: Carbohydrates (Ed.: H. M. I.
Osborn), Academic Press, Oxford, UK, 2003, p. 9–68.
[11] Y. Li, X. Yang, Y. Liu, C. Zhu, Y. Yang, B. Yu, Chem. Eur. J.
2010, 16, 1871–1882.
[12] J. Yang, C. Cooper-Vanosdell, E. A. Mensah, H. M. Nguyen,
J. Org. Chem. 2008, 73, 794–800.
[13] E. A. Mensah, J. M. Azzarelli, H. M. Nguyen, J. Org. Chem.
2009, 74, 1650–1657.
[14] X. Lv, S. Yu, J. Wang, Y. Du, Carbohydr. Res. 2011, 346, 1786–
1791.
[15] L. M. Lerner, Carbohydr. Res. 1993, 241, 291–294.
[16] R. R. Schmidt, M. Behrendt, A. Toepfer, Synlett 1990, 694–
696.
p-Methoxyphenyl 6-Deoxy-β-
lactopyranosyl-(1Ǟ4)-[6-deoxy-β-
xylopyranosyl-(1Ǟ3)-6-deoxy-α- -glucopyranoside (1): Compound
D
-galactopyranosyl-(1Ǟ2)-β-
D-ga-
D
-glucopyranosyl-(1Ǟ2)]-β-D-
D
21 (62 mg, 0.0376 mmol) was dissolved in dry MeOH (10 mL), and
NaOMe was added until a pH of 11 was reached. The reaction
mixture was stirred for 6 h at 60 °C. The solution was neutralized
with DOWEX 50W H+ resin, and then it was filtered. The filtrate
was concentrated, and the residue was purified on a Sephadex LH-
20 column (MeOH/H2O, 10:1) to give compound 1 (28 mg, 88%)
as a white solid. 1H NMR (400 MHz, D2O): δ = 7.11 (d, J =
8.86 Hz, 2 H, ArH), 6.97 (d, J = 8.17 Hz, 2 H, ArH), 5.52 (d, J =
3.75 Hz, 1 H, 1I-H), 4.76 (d, J = 7.33 Hz, 1 H, 1-H), 4.74 (d, J =
7.94 Hz, 1 H, 1-H), 4.63 (d, J = 7.33 Hz, 1 H, 1-H), 4.60 (d, J =
7.33 Hz, 1 H, 1-H), 4.18 (dd, J = 11.9, 4.9 Hz, 1 H), 3.94–3.89 (m,
5 H), 3.86–3.82 (m, 5 H), 3.82–3.79 (m, 4 H), 3.78–3.75 (m, 3 H),
3.73–3.51 (m, 5 H), 3.40–3.29 (m, 2 H), 3.24 (t, J = 9.3 Hz, 1 H),
1.34 (d, J = 6.1 Hz, 3 H, CH3), 1.28 (d, J = 6.4 Hz, 3 H, CH3),
1.24 (d, J = 6.2 Hz, 3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3):
[17] A. Marra, J. Esnault, A. Veyrieres, P. Sinaÿ, J. Am. Chem. Soc.
1992, 114, 6354–6360.
[18] D. Crich, M. Patel, Carbohydr. Res. 2006, 341, 1467–1475.
Received: June 4, 2013
Published Online: August 6, 2013
6166
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 6158–6166