A cyclic glucosyl ceramide acceptor as a versatile building block for complex ganglioside synthesis

Article abstract of DOI:10.1016/j.tetlet.2009.12.121

A cyclic glucosyl ceramide (GlcCer) acceptor has been developed as a versatile building block for the synthesis of complex ganglioside. A macrocyclic GlcCer acceptor, which was the product of intramolecular glycosylation between glucose and ceramide, exhibited high reactivity during the coupling reactions with a variety of complex oligosaccharyl donors, thereby furnishing the corresponding ganglioside frameworks in high yields.

Full text of DOI:10.1016/j.tetlet.2009.12.121

Tetrahedron Letters 51 (2010) 1126–1130
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A cyclic glucosyl ceramide acceptor as a versatile building block
for complex ganglioside synthesis
Kohki Fujikawa a,b, Tomohiro Nohara a, Akihiro Imamura a,b, Hiromune Ando a,b, Hideharu Ishida a,
,
*
Makoto Kiso a,b,
*
a Department of Applied Bioorganic Chemistry, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
b Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Yoshida Ushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A cyclic glucosyl ceramide (GlcCer) acceptor has been developed as a versatile building block for the syn-
thesis of complex ganglioside. A macrocyclic GlcCer acceptor, which was the product of intramolecular
glycosylation between glucose and ceramide, exhibited high reactivity during the coupling reactions with
a variety of complex oligosaccharyl donors, thereby furnishing the corresponding ganglioside frame-
works in high yields.
Received 24 November 2009
Revised 21 December 2009
Accepted 22 December 2009
Available online 28 December 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Ganglioside
Intramolecular glycosylation
Glucosyl ceramide
Sialic acid
Among glycolipids, which cover the surface of animal cells, gan-
gliosides are distinguished by the one or more sialic acid residues
that are positioned at the termini of their glycan chains. It is well
known that gangliosides function as receptors for toxins, viruses
and bacteria and mediate the targeting of lymphocytes to inflam-
matory tissue.1,2 Furthermore, gangliosides involved in raft such
as GM3 and GM1 are considered to be important mediators in
the signal transduction.3 In addition, many gangliosides have been
reported to be tumor-specific antigens.4 Therefore, the elucidation
and medicinal application of the biological functions of ganglio-
sides have been intensively investigated. However, gangliosides
are only a minor constituent of glycolipids, which has been an
impediment to functional research into gangliosides; thus, a large
and readily available supply of pure gangliosides is highly
desirable.
glioside framework was not always satisfactory in terms of total
yield, and required considerable effort and expertise, which pre-
vented a large supply of fine gangliosides from being produced.
In this context, direct coupling of the full-length glycan and cera-
mide segments effectively reduces the total steps required for
the synthesis of the final structure. However, the yield of the direct
coupling tends to diminish as the length of the oligosaccharide
increases.9
Recently, we have proposed a new strategy for the synthesis of
gangliosides that uses cyclic glucosyl ceramide as a key building
block. In this approach, saturated phytoceramide was used instead
of unsaturated ceramide.10 In the present Letter, we demonstrate
the power of this new strategy by presenting representative exam-
ples of the efficient assembly of complex ganglioside frameworks
using a cyclic glucosyl ceramide acceptor.
To date, our group has completed the first syntheses of various
gangliosides including sialyl Lewis X,5 sialyl Lewis A,6 and GQ1b.7
However, to advance the biological and medicinal application of
gangliosides, we must approach the synthesis of gangliosides sys-
tematically and on large scale. In our previous syntheses of gan-
gliosides, a fully assembled glycan segment was coupled with
azide-sphingosine to construct the glycolipid framework. This
was followed by the reduction of the azide group and amide forma-
tion via reaction with fatty acid such as stearic acid, yielding the
protected ganglioside.5–8 However, the final assembly of the gan-
In this new strategy, ganglioside is disconnected at the b(1,4)-
linkage between the Gal-Glc sequence, which is
a common
sequence in all mammalian gangliosides, thus providing an oli-
gosaccharyl galactosyl donor and a glucosyl ceramide (GlcCer)
acceptor. Glucose is first glycosidated with the C1 hydroxyl group
of ceramide, and then the GlcCer unit serves as a common coupling
partner for oligosaccharide donors (Scheme 1). To accept a variety
of branched and complex oligosaccharide donors, the C4 hydroxyl
group of the GlcCer acceptor is required to be highly reactive. In
addition, the efficiency of the ceramide introduction, which is gen-
erally low even in the case of glucose, should be further improved
with respect to total efficiency. To meet these criteria, we have
envisaged the intramolecular glycosidation11 of glucose and cera-
* Corresponding authors. Tel./fax: +81 58 293 2918 (H.I.).
E-mail address: ishida@gifu-u.ac.jp (H. Ishida).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.12.121

K. Fujikawa et al. / Tetrahedron Letters 51 (2010) 1126–1130
1127
Table 1
Common sequence
of
Examination of intramolecular glycosidation
gangliosides
O
Oligosaccharide
O
O
OH
O
O
O
OH
O
OH
O
O
HO
O
Promoter
HO
O
C13H2
O
6
O
MPMO
C13H27
C17H35
7
Oligosaccharide
CH2Cl2
MS4Å
0°C
OH
OH
HN
OBz
C17H35
HN
7
O
Final block glycosylation
Entry Concn of 6
Promoter
Time
(h)
Yield
(%)
(mM)
Linker
1
20
NIS (1.1 equiv), TfOH
(0.2 equiv)
2
Trace
O
O
OP
O
O
O
2
3
4
5.0
20
5.0
DMTST (3.0 equiv)
DMTST (3.0 equiv)
DMTSF (3.0 equiv)
2
2
6
92
88
50
HO
MPMO
O
LG
+
O
C13H27
C17H35
O
O
OP
HN
R
O
Intramolecular glycosidation
the 4,6-unprotected phenylthioglycoside of glucose 410 and the
ceramide derivative 3 were condensed in the presence of EDCꢀHCl
and DMAP in CH2Cl2 at room temperature to produce the C6-teth-
ered compound 5 exclusively in 93% yield. For the next intramolec-
ular glycosidation, the tethered compound 5 was then desilylated
by treatment with TBAF and AcOH in THF to afford 6 in 88% yield.
Intramolecular glycosidation13 of 6 was examined under vari-
ous conditions (Table 1). When using an NIS–TfOH system14 to pro-
mote the reaction, the olefin moiety at the C4–C5 position reacted
with iodonium cation, eventually affording the hydroxylated
byproduct after aqueous work-up along with other unknown
byproducts (entry 1). Next, a thiophilic promoter, namely, meth-
ylsulfonium cation, was examined. In entry 2, DMTST15 (3.0 equiv)
was used with 6. This reaction produced the glycosidated product
Linker
O
O
O
O
HO
MPMO
HO
LG
C13H27
C17H35
HN
OBz
P: Protecting group
LG: Leaving group
Scheme 1. Key concept of new synthetic strategy toward gangliosides.
mide as a critical step. The tethering of glucose and ceramide was
expected to increase the likelihood of the attack of C1 hydroxyl
group of ceramide to a glucosyl oxocarbenium ion, thus allowing
the C4 hydroxyl group of the glucose donor to remain unprotected.
Furthermore, the generated cyclic GlcCer acceptor is expected to
have a highly reactive hydroxyl group at C4 because the C6–O6
bond may not adopt a gauche/trans configuration due to ring
strain. In the design of the glucose moiety, a benzoyl group was
mounted at the C2 hydroxyl group to impart b-selectivity during
intramolecular glycosidation, and the C3 hydroxyl group was pro-
tected with an electron-donating p-methoxybenzyl group.
7
16 in 92% yield. Under highly concentrated conditions (6; 20 mM),
7 was also produced in high yield (88%) (entry 3). When the coun-
ter-anion was replaced with tetrafluoroborate, the reaction be-
came sluggish and the yield decreased to 50% (entry 4). The best
result was obtained in entry 2, which could also be reproduced
on gram scale. Finally, based on a free glucose, the cyclic GlcCer
acceptor 7 was synthesized in a total yield of 36% over 10 steps
(compound 4 was synthesized from glucose in 48% over seven
steps10). In contrast, the acyclic GlcCer acceptor 8,7b which was
previously reported in the synthesis of GQ1b, was obtained in
13% over 12 steps (Scheme 3).
With the cyclic GlcCer acceptor 7 in hand, glycosylation with
various oligosaccharide donors, including linear and branched do-
nors, was performed (Table 2). The sialyl galactosyl imidate 9,17
upon treatment with a catalytic amount of TMSOTf in CHCl3 at
0 °C, was successfully glycosidated with 7 to afford the GM3 gan-
glioside skeleton 14 in 85% yield (entry 1). For GM2 epitope and
GM1 epitope donors, 1018 and 11,19 which have a branch at C3
and C4 of galactose, GlcCer 7 served as an excellent coupling part-
ner, producing GM2 and GM1 ganglioside skeletons 15 and 1620 in
high yield, respectively (entries 2 and 3). A more complex donor,
For the tethering, the C1 hydroxyl group of ceramide 112 was
selectively protected as the silyl ether, and then succinylated at
the C3 position by reaction with succinic anhydride and DMAP in
pyridine to afford 3 in high yield (80%, two steps) (Scheme 2). Next,
O
OH
HO
O
O
b
O
RO
C13H27
C17H35
TBDMSO
HN
C13H27
C17H35
quant
HN
O
1 R = H
a
2 R = TBDMS
3
(80%)
OMPM
O
O
ClAcO
MPMO
OH
O
D-Glucose
O
CCl3
NH
O
29% (10 steps)
C13H27
HO
SPh
O
OBz
MP MO
O
SPh
OBz
4
O
OBz
HO
MPMO
RO
C13H27
C17H35
c (93%)
HN
HO
OBz
O
HN
C17H35
5 R = TBDMS
6 R = H
O
d
OMPM
HN
C17H35
C13H27
(88%)
O
O
HO
MPMO
O
Scheme 2. Reagents and conditions: (a) TBDMSCl, DMAP, Et3N/CH2Cl2, rt, 80%; (b)
succinic anhydride, DMAP/pyr, 40 °C, quant; (c) 4, EDCꢀHCl, DMAP/CH2Cl2, rt, 93%;
(d) TBAF, AcOH/THF, rt, 88%. TBDMSCl = tert-butyldimethylsilyl chloride, DMAP = 4-
dimethylaminopyridine, EDCꢀHCl = 1-ethyl-3-(3-dimethylaminopropyl)carbodiim-
ide hydrochloride, TBAF = tetrabutylammonium fluoride.
46% (2 steps)
OBz
OBz
8
Scheme 3. Overview of the synthesis of GlcCer acceptor 8 in the previous Letter.

1128
K. Fujikawa et al. / Tetrahedron Letters 51 (2010) 1126–1130
Table 2
Glycosylations of 7 with various oligosaccharide donors
O
O
O
O
O
O
O
O
O
O
O
TMSOTf (0.08 eq)
O
O
a
O
7
O
O
+
O
C13H27
C17H35
MPMO
CCl3
CHCl3
MS4Å(AW300)
(1.0 eq)
OBz
OBz
Temp (°C)
0
OBz
14~ 18
HN
HN
(1.0 eq)
9 ~ 13
Entry
Donor
Time (h)
Product
Yield (%)
BzO
O
OBz
O
AcO
AcHN
AcO
O
BzO
1
2
14
85
COOMe
O
CCl3
NH
OAc
AcO
9
3:1
)
(α:β =
AcO
OAc
O
O
AcO
AcO
OBz
O
NHAc
AcHN
AcO
2
0
2
15
70
O
O
BzO
COOMe
O
CCl3
NH
OAc
AcO
10
4:1
(α:β =
)
AcO
OAc
O
AcO
OAc
O
e
d
AcO
O
O
OAc
AcHN
AcO
OBz
O
NHAc
O
AcO
c
b
3
0
2
16
73
O
BzO
COOMe
CCl3
O
OAc
AcO
11 (α:β =4:1)NH
AcO OAc
O
AcO
O
OAc
O
AcO
OBz
O
AcO
NHAc
AcHN
AcO
O
O
O
O
OBz
AcHN
AcO
OBz
O
NHAc
AcO
COOMe
4
rt
2
17
60
OAc
O
O
AcO
BzO
COOMe
O
CCl3
NH
OAc
AcO
12 (α only)
OAc
OAc
O
COOMe
AcO
AcHN
O
AcO
AcO
AcO
O
NHAc
O
BzO
AcO
5
rt
1
18
49
O
OAc
AcO
OBz
OAc
O
O
O
COOMe
O
AcO
AcHN
AcO
OAc
O
OBz
O
O
O
AcO
BzO
NHAc
AcO OBz
O
CCl3
NH
13 (α only)
a
0.1 equiv of TMSOTf was used.
GalNAc-GD1a hexasaccharide epitope 12, was also successfully
combined with 7 in 60% yield (entry 4). To our delight, even hepta-
saccharyl donor 13, which has heavy branching at C3 and C6 of gal-
actose, reacted with GlcCer to afford octaosyl ceramide 18 in 49%
yield (entry 5).
On the other hand, the glycosylation of the acyclic GlcCer accep-
tor 19 with reactive donor 9 produced the corresponding GM3
skeleton 20 in 53% yield (Scheme 4). The distinct difference be-
tween the cyclic and the acyclic is in accordance with the afore-
said initial expectation in the design of GlcCer acceptor.

K. Fujikawa et al. / Tetrahedron Letters 51 (2010) 1126–1130
1129
17
a, b (88%, 2 steps)
OH OH
O
HO
O
OH OH
O
OH
O
NHAc
HO
AcHN
HO
O
O
O
O
OH
O
OH
OH
O
OH
O
NHAc
HO
COOH
HO
AcHN
HO
O
OH
O
C13H27
C17H35
O
HO
O
HN
OH
OH
COOH
HO OH
21
Scheme 5. Reagents and conditions: (a) TFA/CH2Cl2, 0 °C, quant; (b) NaOMe/MeOH–THF (1:1), then H2O, rt, 88%. TFA = trifluoroacetic acid.
O
3. Allende, M. L.; Proia, R. L. Curr. Opin. Struct. Biol. 2002, 12, 587–592.
4. Buskas, T.; Thompson, P.; Boons, G.-J. Chem. Commun. 2009, 5335–5349.
5. Kameyama, A.; Ishida, H.; Kiso, M.; Hasegawa, A. Carbohydr. Res. 1991, 209, C1–
C4.
6. Kameyama, A.; Ishida, H.; Kiso, M.; Hasegawa, A. J. Carbohydr. Chem. 1994, 13,
641–654.
O
O
O
HN
C17H35
C13H27
O
9
HO
+
O
MP MO
(1.0 eq)
OBz
7. (a) Ishida, H.-K.; Ishida, H.; Kiso, M.; Hasegawa, A. Tetrahedron: Asymmetry
1994, 5, 2493–2512; (b) Imamura, A.; Ando, H.; Ishida, H.; Kiso, M. J. Org. Chem.
2009, 74, 3009–3023.
OBz
19
(1.0 eq)
TMSOTf (0.08 eq)
AW300/ CHCl3,
2 h
8. (a) Hasegawa, A.; Nagahama, T.; Ohki, H.; Kiso, M. J. Carbohydr. Chem. 1992, 11,
699–714; (b) Ando, T.; Ishida, H.; Kiso, M. Carbohydr. Res. 2003, 338, 503–514.
9. (a) Ito, Y.; Numata, M.; Sugimoto, M.; Ogawa, T. J. Am. Chem. Soc. 1989, 111,
8508–8510; (b) Numata, M.; Sugimoto, M.; Koike, K.; Ogawa, T. Carbohydr. Res.
1990, 203, 205–217; (c) Matsuzaki, Y.; Numomura, S.; Ito, Y.; Sugimoto, M.;
Nakahara, Y.; Ogawa, T. Carbohydr. Res. 1993, 242, C1–C6; (d) Endo, A.; Iida, M.;
Fujita, S.; Numata, M.; Sugimoto, M.; Nunomura, S. Carbohydr. Res. 1995, 270,
C9–C13; (e) Morales-Serna, J. A.; Boutureira, O.; Díaz, Y.; Matheu, M. I.;
Castillón, S. Carbohydr. Res. 2007, 342, 1595–1612.
0
oC
53%
BzO OBz
OBz
AcO
OBz
MPMO
O
AcHN
AcO
O
O
O
C13H27
C17H35
O
O
O
HN
OBz
COOMe
10. Fujikawa, K.; Imamura, A.; Ishida, H.; Kiso, M. Carbohydr. Res. 2008, 343, 2729–
OAc
O
AcO
O
2734.
O
20
11. Recent review on intramolecular glycosylation: (a) Jung, K.-H.; Müller, M.;
Schmidt, R. R. Chem. Rev. 2000, 100, 4423–4442; (b) Cumpstey, I. Carbohydr.
Res. 2008, 343, 1553–1573.
Scheme 4. Glycosylation of acyclic GlcCer acceptor 19 with donor 9.
12. Chaudhary, S. K.; Hernandez, O. Tetrahedron Lett. 1979, 20, 99–102.
13. Original Letter on intramolecular glycosidation exploiting succinyl tethering:
Ziegler, T.; Lau, R. Tetrahedron Lett. 1995, 36, 1417–1420.
14. (a) Veeneman, G. H.; van Leeuwen, S. H.; van Boom, J. H. Tetrahedron Lett. 1990,
31, 1331–1334; (b) Konradsson, P.; Udodong, U. E.; Fraser-Reid, B. Tetrahedron
Lett. 1990, 31, 4313–4316.
The obtained protected gangliosides 14–18 were successfully
deprotected to afford the corresponding gangliosides in pure form.
For example, 17 was treated with TFA in CH2Cl2 at 0 °C to remove
the MPM group, followed by the deprotection of the acyl groups
and hydrolysis of the methyl ester, furnishing ganglioside Gal-
NAc-GD1a21 21 in 88% yields over two steps (Scheme 5).
In conclusion, we have developed a cyclic GlcCer acceptor 7
which is a versatile building block for intricate ganglioside synthe-
ses. The cyclic GlcCer acceptor 7 was synthesized with high effi-
ciency via regioselective tethering of glucose and ceramide, and
subsequent intramolecular glycosidation in high yield. The results
of couplings with complex oligosaccharide donors have success-
fully demonstrated the high utility of 7.
15. Fugedi, P.; Garegg, P. J. Carbohydr. Res. 1986, 149, C9–C12.
16. Spectroscopic data of compound 7:
[a
]
D
ꢁ29.2 (c 0.5, CHCl3); 1H NMR
(600 MHz, CDCl3) d 8.03–7.45 (m, 5H, Ph), 7.19–6.78 (2 d, 4H, Ar), 5.78 (m,
1H, H-5Cer), 5.70 (d, JNH,2 = 8.9 Hz, 1H, NH), 5.26 (m, 2H, H-3Cer, H-4Cer), 5.17 (t,
J1,2 = J2,3 = 7.6 Hz, 1H, H-2), 4.63 (2 d, 2H, PhCH2), 4.54 (d, 1H, H-1), 4.41 (near t,
J5,6 = 8.9 Hz, Jgem = 11.7 Hz, 1H, H-6), 4.26 (m, 2H, H-60, H-2Cer), 3.88 (dd,
Jgem = 9.6 Hz, J1,2 = 3.4 Hz, 1H, H-1Cer), 3.75 (s, 3H, OMe), 3.69–3.59 (m, 4H, H-4,
H-3, H-5, H-10Cer), 2.75–2.51 (m, 4H, OCOCH2CH2COO), 2.50 (d, J4,4-OH = 2.7 Hz,
1H, 4-OH), 2.04 (t, 2H, NHCOCH2), 1.95 (m, 2H, H-6Cer, H-60Cer), 1.48 (m, 2H,
NHCOCH2CH2), 1.26 (m, 50H, 25CH2), 0.88 (t, 6H, 2CH3); 13C NMR (150 MHz,
CDCl3) d 172.7, 171.9, 170.6, 165.2, 159.5, 138.3, 133.4, 129.9, 129.7, 129.6,
128.5, 124.8, 114.0, 100.0, 82.0, 73.9, 73.7, 73.4, 72.9, 70.9, 66.7, 64.1, 55.2,
50.0, 36.7, 32.3, 31.9, 29.71, 29.66, 29.62, 29.55, 29.5, 29.38, 29.36, 29.3, 29.2,
28.9, 25.6, 22.7, 14.1; HRMS (ESI) m/z found [M+Na]+ 1056.6752, C61H95NO12
calcd for [M+Na]+ 1056.6751.
Acknowledgements
17. Otsubo, N.; Ishida, H.; Kiso, M. Tetrahedron Lett. 2000, 41, 3879–3882.
18. Fuse, T.; Ando, H.; Imamura, A.; Sawada, N.; Ishida, H.; Kiso, M.; Ando, T.; Li, S.-
C.; Li, Y.-T. Glycoconjugate J. 2006, 23, 329–343.
This work was financially supported by MEXT of Japan (WPI
program and grant-in-aid for Scientific Research to M.K., No.
1701007). We thank Ms. Kiyoko Ito for technical assistance.
19. Yoshikawa, T.; Kato, Y.; Yuki, N.; Yabe, T.; Ishida, H.; Kiso, M. Glycoconjugate J.
2008, 25, 545–553.
20. Spectroscopic data of compound 16: [a]
D = +10.0 (c 0.9, CHCl3); 1H NMR
(600 MHz, CDCl3) d 8.17–7.38 (m, 15H, 3Ph), 7.16–6.68 (2 d, 4H, Ar), 5.94 (d,
JNH,2 = 6.8 Hz, 1H, NH-d), 5.70 (m, 1H, H-5Cer), 5.64 (m, 1H, H-8c), 5.60 (d,
JNH,2 = 9.6 Hz, 1H, NHCer), 5.42 (t, J2,3 = J1,2 = 9.7 Hz, 1H, H-2b), 5.33 (m, 2H, H-
4d, H-4e), 5.24 (dd, J6,7 = 2.8 Hz, J7,8 = 11.6 Hz, 1H, H-7c), 5.20 (m, 2H, H-3Cer, H-
Supplementary data
Supplementary data (1H and 13C NMR spectra of compounds 5–
7, 14–18 and 21) associated with this article can be found, in the
online version, at doi:10.1016/j.tetlet.2009.12.121.
4
Cer), 5.12 (m, 3H, H-2e, H-1d, H-2a), 5.01 (d, JNH,5 = 10.3 Hz, 1H, NH-c), 4.96 (m,
2H, H-3e, H-1b), 4.89 (dd, J2,3 = 9.6 Hz, J3,4 = 2.8 Hz, 1H, H-3d), 4.83 (m, 1H, H-
4c), 4.80–4.59 (2 d, 2H, PhCH2), 4.67 (dd, Jgem = 11.0 Hz, J5,6 = 6.2 Hz, 1H, H-6b),
4.60 (m, 1H, H-1e), 4.51 (dd, J2,3 = 9.6 Hz, J3,4 = 2.8 Hz, 1H, H-3b), 4.43 (d,
J1,2 = 6.8 Hz, 1H, H-1a), 4.33 (m, 1H, H-9c), 4.21(m, 3H, H-2Cer, H-6e, H-60e),
4.05 (m, 5H, H-5e, H-6a, H-60a, H-60b, H-90c), 3.80 (m, 13H, H-6d, H-60d, H-5d,
OMe, H-5b, H-3a, H-4a, H-5a, H-5c, H-4b, H-1Cer), 3.62 (s, 3H, OMe), 3.52 (m,
2H, H-6c, H-10Cer), 3.41 (m, 1H, H-2d), 2.73 (dd, Jgem = 12.4 Hz, J3eq,4 = 4.1 Hz,
1H, H-3ceq), 2.60–2.44 (m, 4H, OCOCH2CH2COO), 2.19–1.57 (s, 36H, 12Ac), 1.97
(m, 2H, NHCOCH2), 1.89 (m, 2H, H-6Cer, H-60Cer), 1.78 (m, 1H, H-3cax), 1.45 (m,
References and notes
1. (a) Angata, T.; Varki, A. Chem. Rev. 2002, 102, 439–470; (b) Varki, A. Nature
2007, 446, 1023–1029.
2. Varki, A. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 7390–7397.

1130
K. Fujikawa et al. / Tetrahedron Letters 51 (2010) 1126–1130
2H, NHCOCH2CH2), 1.25 (m, 50H, 25CH2), 0.88 (t, 6H, 2CH3); 13C NMR
60.8, 54.9, 52.8, 49.9, 49.3, 36.63, 36.56, 32.2, 31.9, 30.0, 29.7, 29.53, 29.45,
29.4, 29.34, 29.25, 28.8, 25.5, 23.9, 23.1, 22.7, 21.4, 20.82, 20.76, 20.70, 20.66,
20.5, 20.4, 20.3, 14.1; HRMS (ESI) m/z found [M+Na]+ 2517.1294, C127H175N3O47
calcd for [M+Na]+ 2517.1290.
(150 MHz, CDCl3) d 172.6, 171.8, 171.1, 170.7, 170.3, 170.1, 170.0, 169.2,
168.3, 165.6, 165.1, 165.0, 158.9, 137.9, 133.33, 133.26, 133.0, 130.3, 130.2,
129.9, 129.6, 129.5, 129.4, 129.3, 128.5, 128.42, 128.35, 124.7, 113.5, 101.1,
101.0, 99.5, 99.2, 97.9, 80.7, 78.5, 77.3, 74.3, 73.9, 73.8, 73.3, 73.2, 72.6, 72.2,
71.9, 71.0, 70.9, 70.5, 68.9, 68.8, 67.3, 66.7, 66.5, 66.3, 63.4, 63.0, 62.6, 62.2,
21. Casellato, R.; Brocca, P.; Li, S.-C.; Li, Y.-L. Eur. J. Biochem. 1995, 234, 786–
793.