Facile synthesis of tumor-associated carbohydrate antigen ganglioside GM3 from sialic acid, lactose, and serine

Article abstract of DOI:10.1002/ejoc.200900778

Ganglioside GM₃ [α-Neu5Ac-(2,3)-β-Gal-(1,4)-β- Glc-(1,1)Cer; 1] is considered as an important: tumor-associated carbohydrate antigen, which, can be used in the development of tumor vaccine, In this study, a facile and convergent synthetic strat

Full text of DOI:10.1002/ejoc.200900778

FULL PAPER
DOI: 10.1002/ejoc.200900778
Facile Synthesis of Tumor-Associated Carbohydrate Antigen Ganglioside GM3
from Sialic Acid, Lactose, and Serine
Guo-wen Xing,*[a] Li Chen,[a] and Fen-fen Liang[a]
Keywords: Carbohydrates / Amino acids / Sialic acids / Antitumor agents / Antigens / Sphingolipids
Ganglioside GM3 [α-Neu5Ac-(2,3)-β-Gal-(1,4)-β-Glc-(1,1)-
Cer; 1] is considered as an important tumor-associated carbo-
hydrate antigen, which can be used in the development of
tumor vaccine. In this study, a facile and convergent syn-
thetic strategy for GM3 was developed, and the preparation
thesized from lactose in 7 steps with 25% yield. With novel
N-acetyl-5-N,4-O-oxazolidinone protected p-toluenethio-
sialoside 15 as donor, which was developed by our group,
the sialylation of benzoyl-protected lactosyl ceramide diol 23
was successfully accomplished in 54% yield. Our strategy
of three building blocks started from the most readily avail- here provides a shorter linear total synthesis of GM3 in five
able compounds sialic acid, lactose, and
L
-serine. Ceramide
steps and with 26% overall yield.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
aglycon 9 was constructed from -serine in 13 steps with 6%
L
overall yield, and lactosyl trichloroacetimidate 14 was syn-
be overexpressed in some tumor tissues of small-cell lung
cancer, human breast cancer, melanomas, and so on, but
Introduction
Gangliosides, bearing neuraminic residues in their struc- had a more restricted distribution in normal tissues.[3] As a
tures, comprise a big family of glycosphingolipids. It is good target for cancer-active immunotherapy, the GM3-
found that gangliosides widely exist in vertebrate cells, espe- based vaccine has been efficiently developed for preclinical/
cially in central nervous system cells, which are the essential clinical study by several research groups.[4] In addition,
building blocks of the plasma membrane. Many biological GM3 is not only the precursor to deacetyl-, lyso-, or deace-
studies illustrate the significance of gangliosides in cell re- tyl-lyso-GM3 derivatives,[5] but it is also the key intermedi-
cognition, signal transduction, immunological modulation, ate to further achieve more complex ganglioside analogues
and so on, which are involved in many aspects of cell physi- such as GM1, GM2, GD3, and so on,[1a] which are also
ological events.[1]
crucial tumor-associated carbohydrate agents.
Ganglioside GM3 [α-Neu5Ac-(2,3)-β-Gal-(1,4)-β-Glc-
However, one of the bottlenecks to prepare GM3-based
(1,1)-Cer] (1, Scheme 1) was first isolated from horse eryth- vaccine for biological activity assay is the limited supply of
rocyte in 1952.[2] It is composed of a trisaccharide carbo- chemically pure GM3. Although there have been reports to
hydrate moiety and a long-chain ceramide tail. In recent synthesize GM3 by chemical or chemoenzymatic strate-
years, GM3 has attracted great attention as an important gies[6] since the first GM3 synthesis in 1985 by Ogawa et
tumor-associated carbohydrate antigen, as it was found to al.,[6i] many of these procedures suffer from drawbacks:
Scheme 1. Structure of ganglioside GM3.
(i) The chemoenzymatic preparation of GM3 has generally
been carried out on smaller scales. (ii) Despite the signifi-
cant progress made in the syntheses of various sialic acid
containing oligosaccharides, the chemical approaches to
GM3 are usually met with low regio- and stereoselectivity
[a] Department of Chemistry, Beijing Normal University,
Beijing 100875, P. R. China
Fax: +86-10-58802075
E-mail: gwxing@bnu.edu.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200900778.
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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G.-w. Xing, L. Chen, F.-f. Liang
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due to the harsher sialylation. (iii) The synthetic route is using TBDPS (tert-butyldiphenylsilyl) and cleavage of the
usually long owing to complicated protecting group manip- Boc group with TFA produced amine 7. Then, condensa-
ulations. (iv) It is worth noting that the de novo synthesis tion of the 3-NH2 in 7 with stearic acid in the presence
of GM3 has not yet been reported with sialic acid, lactose, of HBTU and Hünig’s base, and removal of the TBDPS
and serine as the most readily available starting materials. protection by treatment with TBAF afforded building block
On the basis of our previous studies on sialylation[7] and 9 in good yield.
glycolipid synthesis,[8,9] and as a part of our efforts to de-
velop novel GM3-protein complex vaccine, we are interested
in developing a general and facile strategy for the synthesis
of GM3 and its related structures.
Results and Discussion
The retrosynthetic analysis of GM3 is shown in
Scheme 2. Our facile convergent synthesis starts from sialic
acid, lactose, and -serine, three relatively cheap and simple
starting materials, which contain all the necessary stereo-
chemical information located in GM3. In order to avoid
laborious and time-consuming protection–deprotection
steps and to shorten the synthetic route, only acetyl or
benzoyl groups were chosen for building blocks 9, 14, and
15. There are two key steps for the total synthetic strategy:
one involves formation of the glycosidic bond between the
trisaccharide and ceramide and the other involves sialyl-
ation of lactose. To accomplish the former coupling, lacto-
syl trichloroacetamidate 14 was utilized in this study. For
the latter glycosylation, N-acetyl-5-N,4-O-oxazolidinone-
protected p-toluenethiosialoside 15,[7] which was developed
Scheme 3. Synthesis of ceramide building block 9.
by our group, was selected as the sialyl donor.
Firstly, ceramide building block 9 was constructed from
-serine (Scheme 3). According to our previous study[8] and
Secondly, lactose building block 14 was prepared from
related works,[10,11] alcohol 5 was prepared in nine steps lactose (Scheme 4). Thioglycoside 10[12] was treated with
with 10% yield. Protection of the 1-OH in compound 5 by 2,2-dimethoxypropane containing 10-camphorsulfonic acid
Scheme 2. Retrosynthetic analysis of GM3.
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Synthesis of Tumor-Associated Carbohydrate Antigen Ganglioside GM3
Scheme 4. Synthesis of lactose building block 14.
(CSA) under reflux, followed by neutralization with trieth-
ylamine and concentration. The resulting mixture was dis-
solved in 10:1 methanol/water and then boiled for 6 h[13] to
afford β-lactosyl p-toluenethioside 11. Because it is possible
to obtain 2,3-, 2Ј,3Ј-, or 4Ј,6Ј-acetal at the same time during
the reaction, it is necessary to carefully identify the struc-
ture of 11. In the previous study,[12] its structure was deter-
mined only by NMR spectroscopic analysis. Considering
the crystal of 11 was not good enough for X-ray diffraction,
herein we identified the structure of the product by X-ray
crystallographic analysis of its derivative. Thus, benzo-
ylation of 11 with the use of BzCl in pyridine, followed by
removal[14] of the p-toluenethio group with NBS in acetone/
water provided compound 13. The solid-state structure of
13 was confirmed by single-crystal X-ray diffraction (Fig-
ure 1),[15] which illustrated that the desired 3Ј,4Ј-O-iso-
propylidene lactoside 11 had been successfully synthesized.
Then, by using a routine procedure, compound 13 was
easily converted into lactosyl trichloroacetamidate 14 in
high yield (98%).
To efficiently build an α-Neu5Ac-(2,3)-Gal glycosidic
bond is the critical point of the total synthesis of GM3.
Among many contributions to this issue, the galactose ac-
Figure 1. X-ray crystallographic structure of 13.
ceptor was commonly protected by a benzyl group. With
various leaving groups such as halides,[6j,16] phos-
phates,[6d,6e,6h,17,18] xanthates,[6l,17] and so on, the corre- with 2,6,6Ј-tri-O-pivaloylthiolactoside and no β-product
sponding sialylation was furnished in different yield (25– was observed,[6a] the reaction temperature is higher (60 °C),
61%) and α-selectivity (α/β = 1:1.2 to Ͼ9.0:1) depending which is seldom used in glycosylation reactions.
on different research groups. However, it is worth noting
Generally, if acyl (benzoyl) was used for the protection
that there are only few publications detailing the use of an of galactose/lactose, followed by sialylation, the whole syn-
acyl protecting group for the galactose acceptors. The sial- thetic route for GM3 could become shorter than if benzyl
ylation efficiency is altered with a change in the acyl type. was used as a protecting group. Because there is a double
In the case of a benzoyl protecting group, a lower glycosyl- bond in the ceramide aglycon of GM3, it is unfeasible to use
ation yield (16%) was obtained with diethyl sialyl phos- hydrogenation conditions to remove the benzyl protecting
phate.[6h] Although a higher sialylation yield (72%) was groups in the galactose/lactose unit during the final depro-
achieved with 2β-chloro-3β-phenylthio sialylate coupled tection step. Considering the benzoyl lactose derivative has
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G.-w. Xing, L. Chen, F.-f. Liang
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a relatively low reactivity for glycosylation, it is therefore
important to find new suitable sialyl donors to overcome
this problem.
Recently, we successfully designed and synthesized a
novel sialic acid donor N-acetyl-5-N,4-O-oxazolidinone-
protected p-toluenethiosialoside 15,[7] which can be readily
prepared from sialic acid and p-toluenethiol (Scheme 5). It
was demonstrated that 15 could be successfully applied to
various sialylations with good yields and stereoselectivities
at –40 °C with CH2Cl2/MeCN (2:1) as reaction media. To
further broaden its substrate adaptability, we found donor
15 could be efficiently coupled not only with benzyl-pro-
tected methyl galactoside diol 16, but also with benzoyl-
protected methyl galactoside diol 17 with α/β = 1.6–2.0, and
the corresponding sialylation products 19 and 20 were af-
forded in high yields (72–89%).[7,12] On the basis of these
results, a methyl glycoside of ganglioside GM3 trisaccharide
21 was successfully synthesized from compound 15 as do-
nor and methyl 2,3,6,2Ј,6Ј-penta-O-benzoyl-β-lactoside (18)
as acceptor in a 68% yield and α/β = 1.6:1 (Figure 2).[12]
Figure 2. Structures of galactose/lactose acceptors and their sialyl-
ation products.
As mentioned above, ganglioside GM3 trisaccharide de-
rivative 21 was prepared from p-toluenethiosialoside 15 as
donor. The sialylation occurred at the more reactive 3-OH
of acceptor 18 and no glycosylation product with 1Ǟ4 link-
age was observed. The anomeric stereochemistry of 21 was
assigned on the basis of the chemical shifts of the sialic
Scheme 5. Synthesis of sialyl donor 15.
3
acid 3eq-H[21] and the JC-1,3ax-H coupling constant.[22] For
3
Inspired by the above results, and with building blocks anomer 21α, JC-1,3ax-H = 6.0 Hz, 3eq-H = 2.74 ppm com-
9, 14, and 15 in hand, a facile linear synthesis of GM3 was pared with that of 21β (3eq-H = 2.62 ppm).[12] On the basis
carried out (Scheme 6). Condensation of 3-O-benzyl cer- of the study of the model reaction, we finally performed the
amide 9 with 3Ј,4Ј-O-isopropylidene-2,3,6,2Ј,6Ј-penta-O- key sialylation between donor 15 and acceptor 23. Similarly,
benzoyl-1-O-α-lactosyl trichloroacetimidate (14) by using GM3 precursor 24 was successfully produced in 54% yield
the promoter TMSOTf in CH2Cl2, afforded glycolipid 22 in and α/β = 4:1. For anomer 24α, 3eq-H = 2.74 ppm and for
60% yield.[19] With the participation of the neighboring 24β 3eq-H = 2.58 ppm. Global deprotection of all the acyl
group (OBz) during the glycosylation step, the newly groups with sodium methoxide and saponification of the
formed glycosidic bond of 22 was shown to be 1,2-trans on methyl ester with LiOH in THF/H2O generated the ganglios-
1
the basis of its H NMR spectra (J1Ј-H,2Ј-H = 7.6 Hz). Re- ide GM3 in 97% yield. The physical data of synthetic 1
moval of the isopropylidene group of 22 led to 3Ј,4Ј-O-un- were in good agreement with those reported for the natural
protected lactosyl ceramide acceptor 23 in 84% yield.
product.
Scheme 6. Linear synthesis of GM3 1.
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Synthesis of Tumor-Associated Carbohydrate Antigen Ganglioside GM3
(2S,3R,E)-2-Amino-3-O-benzoyl-1-(tert-butyldiphenylsilyloxy)-4-
octadecene-1,3-diol (7): Anisole (1 mL) was added to a solution of
compound 6 (470 mg,0.63 mmol) in anhydrous DCM (2 mL). TFA
was slowly dropped into the reaction mixture at 0 °C. The reaction
mixture was stirred at 0 °C for 10 min, warmed to room tempera-
ture, and stirred for an additional 0.5 h. After complete consump-
tion of the starting material (TLC monitoring), anhydrous ether
(20 mL) was added and the solvent was evaporated, which was re-
peated for three times. Then, toluene (20 mL) was added and co-
evaporated to completely remove the remaining TFA. Crude prod-
uct 7 was directly used in the next step without further purification.
Conclusions
In summary, our strategy provides the facile and conver-
gent total synthesis of GM3 in a shorter linear sequence of
five steps and 26% overall yield. With N-acetyl-5-N,4-O-
oxazolidinone protected p-toluenethiosialoside 15 as donor,
the sialylation on benzoyl protected lactosyl ceramide diol
23 was successfully accomplished. The results of this study
should be value to synthesize more complex sialylated gly-
colipids. The preparation of GM3-protein conjugate for de-
veloping tumor vaccine is currently being investigated and
will be reported in due course.
(2S,3R,E)-3-O-Benzoyl-1-(tert-butyldiphenylsilyloxy)-2-octadecan-
amido-4-octadecene-1,3-diol (8): To a solution of stearic acid
(272 mg,0.96 mmol) in DCM/1,4-dioxane (2:1, 4 mL) was added O-
benzotriazole N,N,NЈ,NЈ-tetramethyluronium hexafluorophosphate
(HBTU; 315 mg,083 mmol) and N-ethyldiisopropylamine (DIEA;
165 mg,0.22 mL,1.28 mmol). After stirring for 10 min, above crude
amine was added to the mixture. The reaction was allowed to stir
overnight. After complete consumption of the starting material
(TLC monitoring), the solution was diluted with EtOAc (100 mL),
washed with saturated sodium hydrogen carbonate solution
(3ϫ20 mL) and brine (2ϫ30 mL), and dried with sodium sulfate.
After removal of the solvent, the residue was purified by column
chromatography (hexanes/EtOAc, 35:1) to give 8 (394 mg,
Experimental Section
General: All chemicals were purchased as reagent grade and used
without further purification. All glycosylation reactions were per-
formed in flame-dried glassware under an inert argon atmosphere.
Dichloromethane (DCM) or acetonitrile (MeCN) were distilled
from calcium hydride, and tetrahydrofuran (THF) was distilled
from sodium/benzophenone. Reactions were monitored with ana-
lytical thin-layer chromatography (TLC) on silica gel F254 glass
plates and visualized under UV light (254 nm) and/or by staining
with acidic ceric ammonium molybdate. Flash column chromatog-
1
0.43 mmol, 68%) as a white solid. H NMR (500 MHz, CDCl3): δ
= 0.91 (t, J = 6.9 Hz, 6 H, CH3), 1.08 [s, 9 H, SiC(CH3)3], 1.26–
1.33 (m, 50 H, CH2), 1.60–1.63 (m, 2 H, CH2), 2.02–2.04 (m, 2 H,
6-H), 2.14–2.18 (m, 2 H, CH2), 3.74 (dd, J = 10.5, 3.9 Hz, 1 H, 1a-
H), 3.92 (dd, J = 10.5, 3.3 Hz, 1 H, 1b-H), 4.45–4.46 (m, 1 H, 2-
H), 5.52 (dd, J = 15.4, 7.6 Hz, 1 H, 4-H), 5.69 (t, J = 7.5 Hz, 1 H,
3-H), 5.77 (d, J = 9.4 Hz, 1 H, NH), 5.91 (dt, J = 15.4, 7.3 Hz, 1
H, 5-H), 7.21–8.02 (m, 15 H, ArH) ppm. 13C NMR (125 MHz,
CDCl3): δ = 172.5 (OC=O), 165.3 (NC=O), 137.2 (C-5), 135.5,
135.4, 133.0, 132.9, 132.6, 130.4, 129.9, 129.8, 129.7, 128.4, 127.8,
127.7, 125.1 (C-4), 74.1 (C-3), 62.4 (C-1), 52.2 (C-2), 37.0, 32.4,
31.9, 29.7 (2 C), 29.6, 29.5 (2 C), 29.4, 29.3, 29.2, 29.0, 26.9 (3 C),
25.8, 22.7, 19.3, 14.1 (CH3) ppm. HRMS (ESI): calcd. for
C59H93NO4NaSi [M + Na]+ 930.6772; found 930.6792.
1
raphy was performed on silica gel (200–300 mesh). H NMR spec-
tra were recorded with a 400 or 500 MHz NMR spectrometer at
20 °C. Chemical shifts (in ppm) were determined relative to tet-
ramethylsilane (δ = 0 ppm) in deuterated solvents. Coupling con-
stant(s) in Hertz (Hz) were measured from 1D spectra. 13C At-
tached Proton Test (C-APT) spectra were obtained with at either
100 or 125 MHz and are calibrated with CDCl3 (δ = 77.23 ppm).
ESI and high-resolution mass spectra were recorded with a Bruker
Apex IV FTMS or Waters LCT Premier XE mass spectrometer.
Optical rotations were measured at 589 nm with a Perkin–Elmer
343 polarimeter by using a 10-cm microcell.
(2S,3R,E)-3-O-Benzoyl-2-(tert-butoxycarbonyl)amido-1-(tert-butyl-
diphenylsilyloxy)-4-octadecene-1,3-diol (6): To a solution of 5 (2S,3R,E)-3-O-Benzoyl-2-octadecanamido-4-octadecene-1,3-diol (9):
(370 mg, 0.73 mmol) in DCM was added TBDPSCl (305 mg,
0.29 mL), Et3N (0.13 mL), and DMAP (27 mg). The reaction mix-
ture was stirred at room temperature for 6 h. The reaction was
quenched by adding MeOH (0.2 mL) at 0 °C. After stirring for
10 min, the mixture was then diluted with DCM (150 mL), washed
with saturated sodium hydrogen carbonate solution (3ϫ30 mL)
and brine (3ϫ30 mL), and dried with sodium sulfate. After re-
moval of the solvent, the mixture was purified by column
To a solution of compound 8 (340 mg,0.37 mmol) in THF (6 mL)
cooled to 0 °C was added a solution of TBAF (1.13  in THF,
1 mL) within 5 min. After stirring for 10 min, the mixture was
warmed to room temperature and stirred for an additional 30 min.
After complete consumption of the starting material (TLC moni-
toring), the reaction was quenched with saturated sodium hydrogen
carbonate solution (10 mL) and diluted with DCM (150 mL),
washed with saturated sodium hydrogen carbonate solution
(3ϫ50 mL) and brine (3ϫ50 mL), and dried with sodium sulfate.
chromatography (hexanes/EtOAc, 40:1) to give 6 (523 mg,
1
0.70 mmol, 96%) as a thick oil. H NMR (400 MHz, CDCl3): δ = After removal of the solvent, the remainder was purified by column
0.88 (t, J = 6.9 Hz, 3 H, CH3), 1.05 [s, 9 H, SiC(CH3)3], 1.23–1.25
(m, 22 H, CH2), 1.45 [s, 9 H, OC(CH3)3], 1.98–2.03 (m, 2 H, 6-H), 0.34 mmol, 92%) as a white solid. H NMR (400 MHz CDCl3): δ
3.73 (dd, J = 10.1, 3.6 Hz, 1 H, 1a-H), 3.80 (dd, J = 10.2, 3.5 Hz, = 0.88 (t, J = 7.0 Hz, 6 H, CH3), 1.25 (m, 50 H, CH2), 1.58–1.65
1 H, 1b-H), 4.07–4.11 (m, 1 H, 2-H), 4.78 (d, J = 9.7 Hz, 1 H, (m, 2 H, CH2), 2.02–2.07 (m, 2 H, 6-H), 2.13–2.23 (m, 2 H, CH2),
NH), 5.47 (dd, J = 15.6, 7.6 Hz, 1 H, 4-H), 5.62 (t, J = 7.2 Hz, 1 3.68 (dd, J = 12.0, 2.9 Hz, 1 H, 1a-H), 3.74 (dd, J = 12.0, 3.5 Hz,
H, 3-H), 5.88 (dt, J = 15.4, 7.1 Hz, 1 H, 5-H), 7.20–7.43 (m, 8 H, 1 H, 1b-H), 4.24–4.31 (m, 1 H, 2-H), 5.52 (t, J = 7.6 Hz, 1 H, 3-
chromatography (hexanes/EtOAc, 6:1) to yield 9 (226 mg,
1
ArH), 7.54–7.65 (m, 5 H, ArH), 7.97–7.98 (m, 2 H, ArH) ppm. 13
NMR (100 MHz, CDCl3): δ = 165.3 (OC=O), 155.3 (NC=O),
C
H), 5.61 (dd, J = 15.2, 7.6 Hz, 1 H, 4-H), 5.85 (dt, J = 14.9, 6.8 Hz,
1 H, 5-H), 6.07 (d, J = 8.4 Hz, 1 H, NH), 7.45–8.05 (m, 5 H, ArH)
137.2 (C-5), 135.6 (2 C), 134.8, 133.1, 132.8 (2 C), 130.5, 129.8, ppm. 13C NMR (100 MHz, CDCl3): δ = 173.4 (NC=O), 166.6
129.7 (2 C), 129.6 (2 C), 128.3, 127.8, 127.7, 124.7 (C-4), 79.4
[OC(CH3)3], 74.5 (C-3), 62.7 (C-1), 54.2 (C-2), 32.4, 32.0, 29.7, 4), 74.7 (C-3), 61.9 (C-1), 53.5 (C-2), 36.9, 32.3, 32.0, 29.7 (3C),
29.6, 29.5, 29.4, 29.3, 28.9, 28.4, 28.3 (2 C), 26.9, 26.8, 26.6, 22.7, 29.6, 29.5 (2C), 29.4 (2C), 29.3 (2C), 28.9, 25.8, 22.7, 14.1 (CH3)
(OC=O), 137.5 (C-5), 133.5, 129.8, 129.7, 128.9, 124.9, 124.7 (C-
19.3, 14.2 (CH3) ppm. HRMS (ESI): calcd. for C46H67NO5SiNa ppm. HRMS (ESI): calcd. for C43H76NO4 [M + 1]+ 670.5774;
[M + Na]+ 764.4686; found 764.4663.
found 670.5757.
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2,3,6,2Ј,6Ј-Penta-O-benzoyl-3Ј,4Ј-O-isopropylidene-1-O-β-lactose
(13): To a solution of 12[12] (1.0 g, 0.99 mmol) in 90 % acetone
aqueous solution (20 mL) was added N-bromosuccinimide (0.72 g,
4.0 mmol), and the solution was stirred for 1 h at room tempera-
ture. After complete consumption of the starting material (TLC
monitoring), the reaction was quenched with saturated sodium hy-
drogen carbonate solution (2 mL) and diluted with DCM
(150 mL), washed with saturated sodium bisulfite (3ϫ30 mL), so-
dium hydrogen carbonate solution (3 ϫ 30 mL), and brine
(3ϫ30 mL), and dried with sodium sulfate. After removal of the
solvent, the crude product was recrystallized (hexanes/EtOAc, 6:1)
to afford 13 (0.78 g, 0.86 mmol, 87%) as granular-crystalline. M.p.
δ = 0.88 (t, J = 6.9 Hz, 6 H, CH3), 1.20–1.25 (m, 50 H), 1.60–1.82
(m, 4 H, CH2), 1.91–1.94 (m, 2 H, 6-H), 3.52 (dd, J = 9.7, 3.4 Hz,
1 H, 1a-H), 3.71–3.76 (m, 3 H, 1b-H, 6aЈЈ-H, 6bЈЈ-H), 4.06–4.41
(m, 8 H, 2-H, 2Ј-H, 4Ј-H, 5Ј-H, 6aЈ-H, 6bЈ-H, 3ЈЈ-H, 5ЈЈ-H), 4.55
(d, J = 7.6 Hz, 1 H, 1Ј-H), 4.59 (d, J = 7.8 Hz, 1 H, 1ЈЈ-H), 5.12
(t, J = 7.2 Hz, 1 H, 2ЈЈ-H), 5.36–5.43 (m, 2 H, 4-H, 4ЈЈ-H), 5.47 (t,
J = 7.5 Hz, 1 H, 3-H), 5.61 (d, J = 9.1 Hz, 1 H, NH), 5.70–5.80
(m, 2 H, 5-H, 3Ј-H), 7.28–7.64 (m, 18 H, ArH), 7.88–8.08 (m, 12
H, ArH) ppm. 13C NMR (100 MHz CDCl3): δ = 172.6 (NC=O),
165.9, 165.8, 165.5, 165.3, 165.1, 164.9 (6 ϫ C=O), 137.3 (C-5),
133.3, 133.2, 133.1, 133.0, 132.9, 132.8, 130.9, 130.2, 129.9, 129.8,
129.3, 129.1, 128.8, 128.6, 124.9 (C-4), 110.8 [C(Me)2], 101.0 (C-
1ЈЈ), 100.2 (C-1Ј), 77.0, 75.2, 74.1, 73.5, 72.3, 67.7 (C-1), 62.9 (C-
6Ј), 62.5 (C-6ЈЈ), 50.5 (C-2), 36.5, 32.3, 32.0, 29.7, 29.6 (2 C), 29.5
1
188–190 °C. [α]2D0 = +80.5 (c = 0.6, CH2Cl2). H NMR (400 MHz
CDCl3): δ = 1.26 (s, 3 H, CH3), 1.52 (s, 3 H, CH3), 2.74 (s, 1 H,
OH), 3.85–3.91 (m, 2 H, 6aЈ-H, 6bЈ-H), 4.12 (d, J = 5.6 Hz, 1 H, (2 C), 29.4, 29.2, 29.1, 28.9, 27.9, 26.8, 25.5, 22.7, 14.3 (CH3) ppm.
5Ј-H), 4.20 (t, J = 9.7 Hz, 1 H, 4-H), 4.27 (t, J = 6.9 Hz, 1 H, 3Ј-
HRMS (ESI): calcd. for C93H119NO19Na [M + Na]+ 1576.8274;
H), 4.33 (m, 1 H, 5-H), 4.39 (d, J = 9.7 Hz, 1 H, 1-H), 4.52 (d, J found 1576.8259.
= 12.2 Hz, 1 H, 6a-H), 4.61 (d, J = 12.3 Hz, 1 H, 6b-H), 4.70 (d,
J = 7.6 Hz, 1 H, 1Ј-H), 5.15–5.20 (m, 2 H, 2-H, 2Ј-H), 5.58 (br. s,
(2,6-Di-O-Benzoyl-β-
oyl-β-D-glucopyranosyl)-(1Ǟ1)-(2S,3R,E)-3-O-benzoyl-2-octadecan-
D
-galactopyranosyl)-(1Ǟ4)-(2,3,6-tri-O-benz-
1 H, 4Ј-H), 6.08 (t, J = 9.8 Hz, 1 H, 3-H), 7.30–7.62 (m, 15 H,
ArH), 7.96–8.09 (m, 10 H, ArH) ppm. 13C NMR (100 MHz
CDCl3): δ = 166.1, 166.0, 165.9, 165.6, 165.0 (C=O ϫ5), 133.4,
133.3, 133.2, 133.1, 132.9, 130.2, 130.0, 129.9, 129.8, 129.7, 129.6,
129.5, 129.4, 129.1, 128.7, 128.6, 128.5, 128.4, 128.3, 128.2, 110.9
[C(Me)2], 100.1 (C-1Ј), 90.4 (C-1), 77.2, 75.5, 73.7, 73.2, 72.3, 71.4,
69.6, 68.7, 63.1 (C-6), 62.6 (C-6Ј), 27.4 (CH3), 26.2 (CH3) ppm.
HRMS (ESI): calcd. for C50H47O16 [M + 1]+ 903.2864; found
903.2874.
amido-4-octadecene-1,3-diol (23): A solution of 22 (80 mg,
0.051 mmol) in AcOH/H2O (80%, 2 mL) was heated to 70 °C for
5 h. After complete consumption of the starting material (TLC
monitoring), the solvent was evaporated, and the residue was puri-
fied by column chromatography on silica gel (hexanes/EtOAc, 2:1)
to provide 23 (65 mg, 0.043 mmol, 84%) as a white solid. 1H NMR
(400 MHz CDCl3): δ = 0.88 (t, J = 6.7 Hz, 6 H, CH3), 1.20–1.25
(m, 52 H), 1.75–1.78 (m, 2 H, CH2), 1.91–1.96 (m, 2 H, 6-H), 3.45
(t, J = 6.2 Hz, 1 H, 3ЈЈ-H), 3.54 (dd, J = 9.7, 3.2 Hz, 1 H, 1a-H),
3.58–3.63 (m, 1 H, 5Ј-H), 3.66 (dd, J = 9.4, 1.9 Hz, 1 H, 1b-H),
3.72–3.78 (m, 2 H, 6aЈЈ-H, 6bЈЈ-H), 3.97–4.01 (m, 1 H, 5ЈЈ-H), 4.07–
4.12 (m, 2 H, 6aЈ-H, 6bЈ-H), 4.32–4.42 (m, 3 H, 2-H, 1Ј-H, 1ЈЈ-H),
4.54–4.58 (m, 2 H, 2Ј-H, 4Ј-H), 5.21–5.26 (m, 1 H, 2ЈЈ-H), 5.37–
5.42 (m, 2 H, 4-H, 4ЈЈ-H), 5.47 (t, J = 7.4 Hz, 1 H, 3-H), 5.61–5.68
(m, 2 H, 3Ј-H, NH), 5.77 (dt, J = 15.2, 7.1 Hz, 1 H, 5-H), 7.28–
7.62 (m, 18 H, ArH), 7.88–8.05 (m, 12 H, ArH) ppm. 13C NMR
2,3,6,2Ј,6Ј-Penta-O-benzoyl-3Ј,4Ј-O-isopropylidene-1-O-α-lactosyl
trichloroacetimidate (14): To a solution of 13 (0.70 g, 0.77 mmol)
dissolved in anhydrous DCM (6 mL) was added CCl3CN (0.8 mL,
7.7 mmol) and DBU (56 µL, 0.39 mmol). After 1 h at room tem-
perature, the dark solution was concentrated and then purified by
flash chromatography (hexanes/EtOAc/DCM, 6:1:1, containing 1%
triethylamine) to yield 14 (0.80 g, 0.76 mmol, 98%) as a white solid.
1H NMR (400 MHz CDCl3): δ = 1.25 (s, 3 H, CH3), 1.49 (s, 3 H, (100 MHz, CDCl3): δ = 172.6 (NC=O), 166.3, 166.0, 165.8, 165.7,
CH3), 3.77–3.82 (m, 2 H, 6aЈ-H, 6bЈ-H), 4.10–4.15 (m, 1 H, 5Ј-H), 165.3, 165.1 (6ϫC=O), 137.4 (C-5), 133.5, 133.4, 133.3, 133.2,
4.23–4.34 (m, 4 H, 2-H, 4-H, 5-H, 3Ј-H), 4.51 (dd, J = 12.3, 1.5 Hz, 132.8, 130.1, 129.9, 129.8 (2 C), 129.7, 129.6 (2 C), 129.5 (2 C),
1 H, 6a-H), 4.58 (d, J = 12.7 Hz, 1 H, 6b-H), 4.69 (d, J = 7.3 Hz, 129.4, 129.1, 129.0, 128.6, 128.5 (2 C), 128.4, 128.2, 124.7 (C-4),
1 H, 1Ј-H), 5.16 (t, J = 6.8 Hz, 1 H, 2Ј-H), 5.49 (dd, J = 10.0, 100.8 (C-1ЈЈ), 100.7 (C-1Ј), 75.8, 74.0, 73.5, 73.0, 72.6 (2 C), 72.0,
3.4 Hz, 1 H, 4Ј-H), 6.09 (t, J = 8.7 Hz, 1 H, 3-H), 6.69 (d, J = 68.6, 67.6 (C-1), 62.5 (C-6Ј), 61.9 (C-6ЈЈ), 50.4 (C-2), 36.5, 32.3,
3.1 Hz, 1 H, 1Ј-H), 7.30–7.65 (m, 15 H, ArH), 7.92–8.08 (m, 10 H,
31.9, 29.7 (2 C), 29.6 (2 C), 29.5, 29.4, 29.3, 29.2, 28.9, 25.5, 22.7,
14.2 (CH3) ppm. HRMS (ESI): calcd. for C90H115NO19Na [M +
ArH), 8.54 (s, 1 H, Cl3C-C=NH) ppm. 13C NMR (100 MHz
CDCl3): δ = 165.9, 165.7, 165.5, 165.3, 165.0 (C=O ϫ5), 160.7 Na]+ 1536.7961; found 1536.7893.
(C=N), 133.6, 133.5, 133.4, 133.3 (2 C), 133.1, 133.0, 129.9, 129.8,
(Methyl 5-Acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl-3,5-dide-
oxy- -glycero-α- -galacto-2-nonulopyranosylonate)-(2Ǟ3)-(2,6-di-
O-benzoyl-β- -galactopyranosyl)-(1Ǟ4)-(2,3,6-tri-O-benzoyl-β-
129.7, 129.5 (2 C), 129.3, 128.6 (2 C), 128.5, 128.4 (2 C), 110.8
[C(Me)2], 100.7 (C-1Ј), 93.1 (C-1), 77.0, 75.1, 73.7, 73.0, 71.4, 71.3,
70.6, 70.1, 62.8 (C-6), 62.1 (C-6Ј), 27.3 (CH3), 26.1 (CH3) ppm.
D
D
D
D-
glucopyranosyl)-(1Ǟ1)-(2S,3R,E)-3-O-benzoyl-2-octadecanamido-
4-octadecene-1,3-diol (24): A solution of sialyl donor 15 (21 mg,
0.036 mmol) and 23 (36 mg,0.024 mmol) in DCM (2 mL) and
MeCN (1 mL) was added over freshly dried powdered 4 Å molecu-
lar sieves (100 mg). The resulting mixture was stirred for 0.5 h at
room temperature under an argon atmosphere and then cooled to
–50 °C and stirred for an additional 0.5 h, followed by addition of
NIS (12.5 mg,0.053 mmol). After 5 min, TfOH (2 µL,0.024 mmol)
was added through a syringe. The reaction was stirred at –50 °C
for 2 h. After complete consumption of the starting material (TLC
monitoring), the reaction was quenched by addition of Et3N
(0.1 mL), and the mixture was diluted with DCM and filtered
through Celite. The organic layer was washed with 20% aqueous
NaS2O3 solution and brine, dried with sodium sulfate, and concen-
trated. The residue was purified by column chromatography on sil-
ica gel (hexanes/EtOAc, 2:1) to give 24 (25 mg, 0.013 mmol, 54%,
(2,6-Di-O-Benzoyl-3,4-O-isopropylidene-β-
D-galactopyranosyl)-
(1Ǟ4)-(2,3,6-tri-O-benzoyl-β- -glucopyranosyl)-(1Ǟ1)-(2S,3R,E)-
D
3-O-benzoyl-2-octadecanamido-4-octadecene-1,3-diol (22): A solu-
tion of trichloroacetimidate 14 (160 mg, 0.15 mmol) and ceramide
derivative 9 (67 mg, 0.10 mmol) in anhydrous DCM (8 mL) was
added over freshly dried powdered 4 Å molecular sieves and cooled
to –20 °C. TMSOTf (7.2 µL, 0.04 mmol) was slowly added to the
solution, and the mixture was stirred at –20 °C for 1.5 h. The reac-
tion was quenched by addition of Et3N (0.1 mL), and the mixture
was diluted with DCM and filtered through Celite. The organic
layer was washed with brine (3ϫ30 mL) and dried with sodium
sulfate and concentrated. The residue was purified by column
chromatography on silica gel (hexanes/EtOAc, 6:1) to furnish 22
(80 mg, 0.051 mmol, 60% based on consumed acceptor 9) as a
white solid, and recovered 9 (10 mg). 1H NMR (400 MHz CDCl3):
5968
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Eur. J. Org. Chem. 2009, 5963–5970

Synthesis of Tumor-Associated Carbohydrate Antigen Ganglioside GM3
α/β = 4:1) as a glassy solid. Data for the α-anomer: 1H NMR
[4]
a) Y. Azuma, Y. Ishikawa, S. Kawai, T. Tsunenari, H. Tsunoda,
T. Igawa, S. Iida, M. Nanami, M. Suzuki, R. F. Irie, M. Tsu-
chiya, H. Yamada-Okabe, Clin. Cancer Res. 2007, 13, 2745–
2750; b) R. J. Bitton, M. D. Guthmann, M. R. Gabri, A. J.
Carnero, D. F. Alonso, L. Fainboim, D. E. Gomez, Oncol. Rep.
2002, 9, 267–276; c) Y. Diaz, A. Gonzalez, A. Lopez, R. Perez,
A. M. Vazquez, E. Montero, Cancer Immunol. Immunother.
2009, 58, 1117–1128; d) L. E. Fernandez, D. F. Alonso, D. E.
Gomez, A. M. Vazquez, Expert Rev. Vaccines 2003, 2, 89–95;
e) M. R. Gabri, Z. Mazorra, G. V. Ripoll, C. Mesa, L. E. Fer-
nandez, D. E. Gomez, D. F. Alonso, Clin. Cancer Res. 2006,
12, 7092–7098; f) J. P. Oliva, Z. Valdes, A. Casaco, G. Pimentel,
J. Gonzalez, I. Alvarez, M. Osorio, M. Velazco, M. Figueroa,
R. Ortiz, X. Escobar, M. Orozco, J. Cruz, S. Franco, M. Diaz,
L. Roque, A. Carr, A. M. Vazquez, C. Mateos, M. C. Rubio,
R. Perez, L. E. Fernandez, Breast Cancer Res. Treat. 2006, 96,
115–121; g) A. M. Bada, A. Casaco, A. Mancebo, D. Fuentes,
B. Gonzalez, O. Hernandez, N. Subiros, M. Artega, J. Hernan-
dez, A. Carr, L. E. Fernandez, Pak. J. Biol. Sci. 2005, 8, 1045–
1050.
(400 MHz CDCl3): δ = 0.88 (t, J = 6.6 Hz, 6 H, CH3), 1.07–1.36
(m, 50 H, CH2), 1.53 (s, 3 H, Ac), 1.68–1.75 (m, 4 H, CH2), 1.91
(s, 3 H, Ac), 1.93 (s, 3 H, Ac), 2.00–2.06 (m, 3 H, CH2, 3axЈЈЈ-H),
2.41 (s, 3 H, Ac), 2.74 (dd, J = 12.4, 3.2 Hz, 1 H, 3eqЈЈЈ-H), 3.46–
4.07 (m, 13 H, 1a-H, 1b-H, 4Ј-H, 5Ј-H, 6aЈ-H, 6bЈ-H, 2ЈЈ-H, 4ЈЈЈ-
H, 5ЈЈЈ-H, 8ЈЈЈ-H, OCH3), 4.11–4.16 (m, 1 H, 3ЈЈ-H), 4.37–4.58 (m,
8 H, 2-H, 3Ј-H, 1ЈЈ-H, 6aЈЈ-H, 6bЈЈ-H, 6ЈЈЈ-H, 9aЈЈЈ-H, 9bЈЈЈ-H),
4.74 (d, J = 7.9 Hz, 1 H, 1Ј-H), 5.29–5.47 (m, 5 H, 3-H, 4-H, 2Ј-
H, 5ЈЈ-H, 7ЈЈЈ-H), 5.62 (d, J = 8.8 Hz, 1 H, NH), 5.66–5.78 (m, 2
H, 5-H, 4ЈЈ-H), 7.26–7.58 (m, 18 H, ArH), 7.87–8.13 (m, 12 H,
ArH) ppm. 13C NMR (100 MHz CDCl3): δ = 171.6 (NC=O),
170.6, 169.7, 169.0, 168.9 (4ϫMeC=O), 167.5 (C=OOMe), 164.8,
164.7, 164.4, 164.3, 164.1, 163.7 (6ϫPhC=O), 152.3 (NC=OO),
136.2 (C-5), 132.3, 131.9, 131.7, 129.2, 129.1, 129.0, 128.9, 128.8 (2
C), 128.7, 128.6, 128.5 (2 C), 128.4, 128.1, 127.5, 127.4, 127.3,
127.2, 123.8 (C-4), 99.8 (C-1ЈЈ), 99.6 (C-1Ј), 96.2 (C-2ЈЈЈ), 74.3,
74.2, 73.8, 73.1, 72.9, 72.2, 71.6, 71.1, 70.8, 70.3, 69.5, 67.2, 66.5
[5]
a) G. A. Nores, N. Hanai, S. B. Levery, H. L. Eaton, E. K. Sa-
lyan, S. Hakomori, Carbohydr. Res. 1988, 179, 393–410; b) O.
Valiente, L. Mauri, R. Casellato, L. E. Fernandez, S. Sonnino,
J. Lipid Res. 2001, 42, 1318–1324.
(C-1), 65.6, 62.2 (C-9ЈЈЈ), 61.5 (C-6Ј), 61.2 (C-6ЈЈ), 57.7, 52.1, 49.4,
35.4, 34.8, 31.2, 30.9, 28.7, 28.6, 28.5 (3 C), 28.3 (2 C), 28.2 (2 C),
27.9, 24.5, 23.5, 21.7, 19.9, 19.7, 19.2, 13.1 (CH3) ppm. MS (ESI):
m/z = 1994 [M + Na]+.
[6]
a) T. Tomoo, T. Kondo, H. Abe, S. Tsukamoto, M. Isobe, T.
Goto, Carbohydr. Res. 1996, 284, 207–222; b) Y. Liu, X. Ruan,
X. Li, Y. Li, J. Org. Chem. 2008, 73, 4287–4290; c) U. Zehavi,
A. Tuchinsky, Glycoconj. J. 1998, 15, 657–662; d) T. J. Martin,
R. Brescello, A. Toepfer, R. R. Schmidt, Glycoconj. J. 1993, 10,
16–25; e) R. I. Duclos Jr, Carbohydr. Res. 2000, 328, 489–507;
f) M. Numata, M. Sugimoto, S. Shibayama, T. Ogawa, Car-
bohydr. Res. 1988, 174, 73–85; g) K. K. C. Liu, S. J. Danishef-
sky, J. Am. Chem. Soc. 1993, 115, 4933–4934; h) H. Sakamoto,
S. Nakamura, T. Tsuda, S. Hashimoto, Tetrahedron Lett. 2000,
41, 7691–7695; i) M. Sugimoto, T. Ogawa, Glycoconj. J. 1985,
2, 5–9; j) M. Numata, M. Sugimoto, S. Shibayama, T. Ogawa,
Carbohydr. Res. 1988, 174, 73–85; k) T. J. Martin, R. Brescello,
A. Toepfer, R. R. Schmidt, Glycoconj. J. 1993, 10, 16–25; l)
Z. Y. Zhu, Y. M. Zhang, Acta Chim. Sinica 2007, 65, 2009–
2916; m) L. F. Tietze, D. Gretzke, Eur. J. Org. Chem. 1998,
1895–1899.
F. F. Liang, L. Chen, G. W. Xing, Synlett 2009, 425–428.
D. Wu, G. W. Xing, M. A. Poles, A. Horowitz, Y. Kinjo, B.
Sullivan, V. Bodmer-Narkevitch, O. Plettenburg, M. Kro-
nenberg, M. Tsuji, D. D. Ho, C. H. Wong, Proc. Natl. Acad.
Sci. USA 2005, 102, 1351–1356.
G. W. Xing, D. Wu, M. A. Poles, A. Horowitz, M. Tsuji, D. D.
Ho, C. H. Wong, Bioorg. Med. Chem. 2005, 13, 2907–2916.
a) W. R. Roush, J. A. Hunt, J. Org. Chem. 1995, 60, 798–806;
b) P. Garner, J. M. Park, J. Org. Chem. 1987, 52, 2361–2364; c)
L. Williams, Z. Zhang, F. Shao, P. J. Carroll, M. M. Joullie,
Tetrahedron 1996, 52, 11673–11694.
(5-Acetamido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyran-
osylicacid)-(2Ǟ3)-β-galactopyranosyl-(1Ǟ4)-β-glucopyranosyl-
(1Ǟ1)-(2S,3R,E)-2-octadecanamido-4-octadecene-1,3-diol (1): To a
solution of 24α (7 mg, 3.5 µmol) in anhydrous methanol (0.5 mL)
was dropwise added a solution of sodium methoxide (5 mg NaOMe
in 1 mL MeOH) in an ice bath, and this mixture was stirred at 0 °C
for 2 h. Then, the reaction was warmed to room temperature and
stirred overnight. Dowex (H+) resin was added to neutralize the
base. The resin was filtered off and washed several times sequen-
tially with methanol and MeOH/DCM (1:1). The combined filtrate
was concentrated, and the resultant residue was dissolved in THF/
H2O (3:1, 2 mL) at 0 °C. To this solution was added LiOH·H2O
(5 mg). After stirring at 0 °C for 30 min, the mixture was neutral-
ized with Dowex (H+) resin. Following removal of the resin, the
filtrate was concentrated under reduced pressure. The crude prod-
uct was purified by column chromatography (CHCl3/MeOH/H2O,
[7]
[8]
65:35:5) to obtain 1 (4 mg, 3.5 µmol, 97%) as a white solid. [α]2D0
=
+2.7 (c = 0.2; CHCl3/MeOH, 1:1) {ref.[6h] [α]2D0 = +1.9 (c = 0.2;
CHCl3/MeOH, 1:1)}. The 1H NMR spectroscopic data of the com-
pound were in agreement with those reported in Ref.[20]
[9]
Supporting Information (see also the footnote on the first page of
[10]
1
this article): H and 13C NMR spectra of all the new compounds.
[11]
[12]
I. Ojima, E. S. Vidal, J. Org. Chem. 1998, 63, 7999–8003.
L. Chen, F. F. Liang, M. F. Xu, G. W. Xing, Z. W. Deng, Acta
Chim. Sinica 2009, 67, 1355–1362.
Acknowledgments
[13]
[14]
[15]
G. Catelani, F. Colonna, A. Marra, Carbohydr. Res. 1988, 182,
The project was financially supported by the National Natural Sci-
ence Foundation of China (20502002) and the Beijing Municipal
Commission of Education. The authors are grateful to Prof. Guo-
fu Zi for helpful discussions on X-ray crystallography.
297–300.
M. S. Motawia, J. Marcussen, B. L. Moller, J. Carbohydr.
Chem. 1995, 14, 1279–1294.
CCDC-739785 (for 13) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
H. Paulsen, U. Von Deessen, Carbohydr. Res. 1986, 146, 147–
153.
U. Greilich, R. Brescello, K. H. Jung, R. R. Schmidt, Liebigs
Ann. 1996, 663–672.
[1] a) T. Kolter, K. Sandhoff, Angew. Chem. Int. Ed. 1999, 38,
1532–1568; b) C. L. M. Stults, C. C. Sweeley, B. A. Matcher,
Methods Enzymol. 1989, 179, 167–214.
[2] T. Yamakawa, S. J. Suzuki, Biochemistry 1951, 38, 199–212.
[3] a) R. Fuentes, R. Allman, M. D. Mason, Lung Cancer 1997,
18, 21–33; b) G. Ritter, P. O. Livingston, Semin. Cancer Biol.
1991, 2, 401–409; c) P. Hersey, Cancer Treat. Res. 1991, 54,
137–151.
[16]
[17]
[18]
J. C. Castro-Palomino, G. Ritter, S. R. Fortunato, S. Reinhardt,
L. J. Old, R. R. Schmidt, Angew. Chem. Int. Ed. Engl. 1997, 36,
1998–2001.
Eur. J. Org. Chem. 2009, 5963–5970
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5969

G.-w. Xing, L. Chen, F.-f. Liang
FULL PAPER
[19]
[21] G. J. Boons, A. V. Demchenko, Chem. Rev. 2000, 100, 4539–
4565.
[22] H. Hori, T. Nakajima, Y. Nishida, H. Ohrui, H. Meguro, Tetra-
hedron Lett. 1988, 29, 6317–6320.
A recent review on the glycosylation of ceramide see: J. A. Mo-
rales-Serna, O. Boutureira, Y. Diaz, M. I. Matheu, S. Castillon,
Carbohydr. Res. 2007, 342, 1595–1612.
[20] T. A. W. Koerner Jr, J. H. Prestegard, P. C. Demou, R. K. Yu,
Received: July 13, 2009
Published Online: October 13, 2009
Biochemistry 1983, 22, 2676–2678.
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Eur. J. Org. Chem. 2009, 5963–5970