Ganglioside GQ1b: Efficient total synthesis and the expansion to synthetic derivatives to elucidate its biological roles

Article abstract of DOI:10.1021/jo8027888

The convergent total synthesis of ganglioside GQ1b based on the "cassette approach" between the nonreducing end GQ1b-core heptasaccharide and glucosylceramide building blocks was accomplished in high overall yield. The use of a sialylα(2→8)sialylα(2→3) ga

Full text of DOI:10.1021/jo8027888

Ganglioside GQ1b: Efficient Total Synthesis and the Expansion to
Synthetic Derivatives To Elucidate Its Biological Roles†
Akihiro Imamura,*,‡,§,| Hiromune Ando,‡,§ Hideharu Ishida,‡ and Makoto Kiso*,‡,§
Department of Applied Bioorganic Chemistry, Faculty of Applied Biological Sciences, Gifu UniVersity,
1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan, and Institute for Integrated Cell-Material Sciences (iCeMS),
Kyoto UniVersity, 69 Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
aimamura@ualberta.ca; kiso@gifu-u.ac.jp
ReceiVed December 25, 2008
The convergent total synthesis of ganglioside GQ1b based on the “cassette approach” between the
nonreducing end GQ1b-core heptasaccharide and glucosylceramide building blocks was accomplished
in high overall yield. The use of a sialylR(2f8)sialylR(2f3)galactose sequence as the key building
block enhanced the efficiency of the glycan assembly and led to preparative-scale synthesis readily
applicable for large-scale preparation. In addition, a judicious choice of p-methoxybenzyl protecting groups
on glucosylceramide provided a solution to the previous synthetic problems, including a decrease in the
yield of the deprotection steps, and led to elevation of the total yield. Furthermore, unnatural-type GQ1b
derivatives were synthesized systematically in good yields by capitalizing on a similar approach in order
to elucidate their biological roles.
Introduction
they play various important roles in vital processes. Ganglioside
GQ1b, which is classified as one of the b-series gangliosides,
exists abundantly in the mammalian central nervous system and
participates in many physiological events, such as neurite
extension,3 toxin binding,4 modulation of protein phosphory-
lation,5 cell adhesion and growth,6,7 and apoptosis.8 Despite its
biological importance, advancement in the biological study of
b-series gangliosides, including GQ1b, has been restricted due
Gangliosides, sialylated glycosphingolipids, are the compo-
nents of the membranes in the cells of all living organisms and
are particularly abundant in the nervous system on the vertebrate
cell plasma membrane.2 For the past two decades, gangliosides
have attracted wide attention in various scientific fields, because
† Synthetic studies on sialoglycoconjugates, part 147. For part 146, see ref 1.
* To whom correspondence should be addressed. A.I.: phone, 81-58-293-
2918; fax, 81-58-293-2918. M.K.: phone, 81-58-293-2916; fax, 81-58-293-2918.
‡ Gifu University.
(2) Wiegandt, H. In Glycolipids; Wiegandt, H., Ed.; Elsevier: New York,
1985; pp 199-260. (b) Lloyd, K. O.; Furukawa, K. Glycoconjugate J. 1998,
15, 627–636. (c) Sonnino, S.; Mauri, L.; Chigorno, V.; Prinetti, A. Glycobiology
2006, 17, 1R–13R.
(3) Tsuji, S.; Arita, M.; Nagai, Y. J. Biochem. 1983, 94, 303–306.
(4) Ångstro¨m, J.; Teneberg, S.; Karlsson, K.-L. Proc. Natl. Acad. Sci. U.S.A.
1994, 91, 11859–11863.
§ Kyoto University.
| Current address: Department of Chemistry, E5-55 Gunning-Lemieux
Chemistry Centre. The University of Alberta, Edmonton, AB, T6G 2G2, Canada.
(1) Yamaguchi, M.; Ishida, H.; Kiso, M. Carbohydr. Res. 2008, 343, 1849–
1857.
10.1021/jo8027888 CCC: $40.75
Published on Web 03/18/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 3009–3023 3009

Imamura et al.
FIGURE 1. Structure of target compounds.
to a deficiency in the supply of pure gangliosides. In 1994, our
group first achieved the total synthesis of ganglioside GQ1b,
which led to the elucidation of the biological functions of GQ1b
at the molecular level.9 However, there were problems yet to
be solved with regard to the overall yields and stereoselectivity
of the coupling reactions, which prevented large quantity
synthesis. Recently, it has become essential to develop large-
scale synthesis of gangliosides, because of multifaceted research
needs, e.g., microarray, molecular imaging, and X-ray crystal-
lographic studies. Therefore, we envisioned renewal of the total
synthetic method for natural ganglioside GQ1b (1) (Figure 1).
Furthermore, we decided to develop access to versatile unnatural
GQ1b derivatives to elucidate their biological roles. The
following were designed as unnatural GQ1b derivatives (Figure
1): (i) SE [2-(trimethylsilyl)ethyl]-type deriVatiVe (2) demon-
strated that SE-type GT1b derivatives serve as good tools for
X-ray crystallographic analysis with lectins such as Siglec-7,10
botulinum neurotoxin,11 and tetanus toxin,12 because replace-
ment of ceramide with an SE group may render it more
amenable to crystallization (being more water-soluble, less
flexible, and less likely to form micelles) and (ii) Glc-ended
deriVatiVe (3) allowed accomplishment of the synthesis of GM1,
GM2, and GM3 bearing D-glucose at the reducing terminal and
succeeded in the assembly of the sugar microarray.13 The
D-glucose residue in this derivative provided a reactive aldehyde
functionality at the reducing end and served as a spacer between
the targeted sugar chain and the scaffold for immobilization
because of its appropriate hydrophilicity and flexibility.
Herein, we report the renewed efficient synthesis of natural
ganglioside GQ1b and its unnatural derivatives.
Results and Discussion
To achieve the efficient and systematic synthesis of the
targeted compounds bearing different reducing terminals,
sialylR(2f8)sialylR(2f3)galactose sequences were focused on
as the common trisaccharide building blocks. Using this
common sequence, a synthetic scheme for the targets was
devised, as shown in Figure 2. This included four important
glycosylation steps: (1) sialylation to produce the common
trisaccharide; (2) galactosaminidation; (3) coupling of the
trisaccharide donor and the tetrasaccharide acceptor, derived
from the common trisaccharide; and (4) final glycosylation of
the reducing terminal acceptors.
According to the above-mentioned scheme, disialylgalactose
unit 6 was selected as the key compound and was prepared by
glycosylation of the known galactose acceptor 514 with
sialylR(2f8)sialyl phenylthioglycoside donor 4.9 We were eager
to find out how stereo- and regioselectivity in sialylation
increases, and therefore a series of sialylations under various
conditions were conducted. The results are summarized in Table
1. First, the sialylation of 5 in the presence of dimethyl(meth-
ylthio)sulfonium triflate (DMTST)15 as a promoter in acetonitrile
at -35 °C hardly gave 6 (entry 1). In entry 2, by using
(5) Tsuji, S.; Nakajima, T.; Sasaki, Y.; Nagai, Y. J. Biochem. 1985, 97, 969–
972.
(6) (a) Kleinman, H. K.; Martin, G. R.; Fishman, P. H. Proc. Natl. Acad.
Sci. U.S.A. 1979, 76, 3367–3371. (b) Cheresh, D. A.; Pierschbacher, M. D.;
Herzig, M. A.; Mujoo, K. J. Cell Biol. 1986, 102, 688–696.
(7) (a) Nakano, J.; Raj, B. K.; Asagami, C.; Lloyd, K. O. J. InVest. Dermatol.
1996, 107, 543–548. (b) Birkle, S.; Ren, S.; Slominski, A.; Zeng, G.; Gao, L.;
Yu, R. K. J. Neurochem. 1999, 72, 954–961.
(8) De Maria, R.; Lenti, L.; Malisan, F.; d′Agostino, F.; Tomassini, B.;
Zeuner, A.; Rippo, M. R.; Testi, R. Science 1997, 277, 1652–1655.
(9) (a) Ishida, H.-K.; Ishida, H.; Kiso, M.; Hasegawa, A. Carbohydr. Res.
1994, 260, C1-C6. (b) Ishida, H.-K.; Ishida, H.; Kiso, M.; Hasegawa, A.;
Tetrahedron: Asymmetry 1994, 5, 2493-2512. (c) Nunomura, S.; Matsuzaki,
Y.; Ito, Y.; Ogawa, T. Pure Appl. Chem. 1994, 66, 2123–2126.
(10) (a) Attrill, H.; Imamura, A.; Sharma, R. S.; Kiso, M.; Crocker, P. R.;
van Aalten, D. M. F. J. Biol. Chem. 2006, 281, 32774–32783. (b) Attrill, H.;
Takazawa, H.; Witt, S.; Kelm, S.; Isecke, R.; Brossmer, R.; Ando, T.; Ishida,
H.; Kiso, M.; Crocker, P. R.; van Aalten, D. M. F. Biochem. J. 2006, 397, 271–
278.
(13) Imamura, A.; Yoshikawa, T.; Komori, T.; Ando, M.; Ando, H.; Wakao,
M.; Suda, Y.; Ishida, H.; Kiso, M. Glycoconjugate J. 2008, 25, 269–278.
(14) Komba, S.; Ishida, H.; Kiso, M.; Hasegawa, A. Glycoconjugate J. 1996,
13, 241–254.
(15) (a) Ravenscroft, M.; Roberts, R. M. G.; Tillett, J. G. J. Chem. Soc.,
Perkin Trans. 2 1982, 1569–1572. (b) Fugedi, P.; Garegg, P. J. Carbohydr. Res.
1986, 149, C9–C12.
(11) Stenmark, P.; Dupuy, J.; Imamura, A.; Kiso, M.; Stevens, R. C. PLoS
Pathog. 2008, 4, e1000129.
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K. A.; Fairweather, N. F.; Isaacs, N. W. J. Biol. Chem. 2001, 276, 32274–32281.
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Lett. 1990, 31, 1331–1334.
3010 J. Org. Chem. Vol. 74, No. 8, 2009

Ganglioside GQ1b
FIGURE 2. Outline of renewed synthetic approach for ganglioside GQ1b and its analogs.
TABLE 1. Preparation of the Key Building Block 6, Sialylr(2f8)sialylr(2f3)galactose Unit
% yield of productsa
(2f3) glycoside
entry
promoter
DMTSTb
NIS-TfOH
NIS-BF3 ·OEt2
NIS-TMSOTf
NIS-TfOH
solvent
T (°C)
R
ꢀ
(2f4) glycoside
2,3-ene of donor
1
2
3
4
5
MeCN
MeCN
MeCN
MeCN
EtCN
-35
-35
-35
-35
-50
trace
33
21
31
44
trace
17
19
15
14
trace
10
11
9
trace
22
23
20
16
8
a Isolated yield. b DMTST: dimethyl(methylthio)sulfonium triflate.
NIS-TfOH16 as a promoter system with the assistance of the
solvent effect of acetonitrile,17 the desired R-sialoside 6 was
obtained in 33% yield with a scarcely better R/ꢀ-ratio (2/1).
However, adverse side reactions also occurred and resulted in
a 2,3-ene derivative of the donor as a byproduct. In entry 3, the
use of BF3 ·OEt2 instead of TfOH led to a reduction in both the
yield of 6 and its stereoselectivity. On the other hand, the use
of NIS-TMSOTf (entry 4) as a promoter system gave results
similar to NIS-TfOH. In entry 5, when the reaction was
conducted in the presence of NIS-TfOH in propionitrile at -50
°C, the desired 6 was obtained in a rewarding 44% yield, and
stereoselectivity was improved with a slight reduction of the
byproduct. The R-configuration of the glycoside of 6 was
assigned according to empirical rules18 and was further con-
firmed by observation of a strong cross peak between Ha-3ax
and Ca-1 in the HMBC spectrum19 of 6, because the R-sialosides
has a larger heteronuclear coupling constant (3JC-1,H-3ax) than
ꢀ-sialoside (see the Supporting Information).
The difficulty of introducing a ꢀ-galactosaminyl glycoside
at the C-4 position of galactose has been revealed in the
literature20 in relation to the assembly of a ganglio-series
(18) (a) van der Vleugel, D. J. M.; van Heeswijk, W. A. R.; Vliegenthart,
J. F. G. Carbohydr. Res. 1982, 102, 121–130. (b) Paulsen, H.; Tietz, H.
Carbohydr. Res. 1984, 125, 47–64.
(19) Xia, J.; Alderfer, J. L.; Piskorz, C. F.; Matta, K. L. Chem.sEur. J. 2001,
7, 356–367.
(17) (a) Schmidt, R. R.; Ru¨cker, E. Tetrahedron Lett. 1980, 21, 1421–1424.
(b) Hashimoto, S.; Hayashi, M.; Noyori, R. Tetrahedron Lett. 1984, 25, 1379–
1382. (c) Murase, T.; Kameyama, A.; Kartha, K. P. R.; Ishida, H.; Kiso, M.;
Hasegawa, A. J. Carbohydr. Chem. 1989, 8, 265–283.
J. Org. Chem. Vol. 74, No. 8, 2009 3011

Imamura et al.
SCHEME 1. Preparation of Novel GalNAc Glycosyl Donors
TABLE 2. Galactosaminidations of 6 and Subsequent Conversion into Tetrasaccharide Acceptor 11
entry
donor
promoter
solvent
CH2Cl2
T (°C)
% yielda
1
2
3
4
5
8
8
9
9
9
NIS-TfOH
NIS-TfOH
SnCl2-AgClO4
HNTf2
0
-35
rt
rt
-20
58
50
52
trace
85
CH2Cl2
CH2Cl2
BTF-tBuCNb
CH2Cl2
Cp2ZrCl2-AgOTf
a Isolated yield. b BTF: benzotrifluoride.
ganglioside skeleton, and the choice of the neighboring group
of the anomeric center and the mode of protection for GalNAc
has been examined in several ways.21 In this study, two kinds
of GalNAc donors 8 and 9, which commonly carry a 2,2,2-
trichloroethoxycarbonyl (Troc) group at C-2, were designed,
as shown in Scheme 1. It is known that the Troc group should
ensure ꢀ-selective glycosylation as well as increased reactiv-
ity as a glycosyl donor compared with the N-phthaloyl
group.22 Additionally, the advantage of the Troc group lies
in the high degree of efficiency in installment and chemose-
lective deprotection.
Acetalization of the previously described phenylthio-galac-
tosaminide 723 with PhCH(OMe)2 and (()-10-camphorsulfonic
acid (CSA) and subsequent protection of the remaining C-3-
hydroxyl group by the Troc group afforded novel GalNAc
thioglycoside donor 8 in 90% yield over two steps. Thiogly-
coside 8 was then efficiently converted into fluoride 9 as another
GalNAc donor.24 In the design of GalNAc donors, the Troc
group was also exploited for the protection of the C-3 hydroxyl
group to facilitate access to the tetrasaccharide acceptor for the
next coupling reaction. The obtained GalNAc donors 8 and 9
were subjected to galactosaminidation with 6. The results are
summarized in Table 2.
In entries 1 and 2, the glycosidations of thioglycoside 8 with
6 were carried out in the presence of NIS-TfOH in CH2Cl2,
affording the tetrasaccharide 10 in moderate yield along with
several byproducts. Although the byproducts were inseparable,
the mass spectrum of the mixture of byproducts indicated the
presence of a molecule with the same molecular weight of 10,
probably R-glycoside. This result is in accordance with the
report25 that the galacto-type donor bearing the benzylidene
group at the C-4,6 positions gave R-glycoside, which is unusual
even in the presence of the neighboring participating acyl group
at C-2. Next, in entries 3-5, the glycosidation of fluoride donor
9 in the presence of various promoters was attempted. When
(20) (a) Wessel, H. P.; Iversen, T.; Bundle, D. R. Carbohydr. Res. 1984,
130, 5–21. (b) Sugimoto, M.; Horisaki, T.; Ogawa, T. Glycoconjugate J. 1985,
2, 11–15. (c) Paulsen, H.; Paal, M. Carbohydr. Res. 1985, 137, 39–62. (d) Stauch,
T.; Greilich, U.; Schmidt, R. R. Liebigs Ann. 1995, 2101–2111.
(21) (a) Banoub, J.; Boullanger, P.; Lafont, D. Chem. ReV. 1992, 92, 1167–
1195. (b) Matsuzaki, Y.; Nunomura, S.; Ito, Y.; Sugimoto, M.; Nakahara, Y.;
Ogawa, T. Carbohydr. Res. 1993, 242, C1–C6. (c) Greilich, U.; Brescello, R.;
Jung, K.-H.; Schmidt, R. R. Liebigs Ann. 1996, 663–672. (d) Castro-Palmino,
J. C.; Ritter, G.; Fortunato, S. R.; Reinhardt, S.; Old, L. J.; Schmidt, R. R. Angew.
Chem., Int. Ed. 1997, 36, 1998–2001. (e) Castro-Palomino, J. C.; Schmidt, R. R.
Tetrahedron Lett. 1995, 36, 6871–6874. (f) Debenham, J. S.; Madsen, R.; Robert,
C.; Fraser-Reid, B. J. Am. Chem. Soc. 1995, 177, 3302–3303. (g) Jiao, H.;
Hindsgaul, O. Angew. Chem., Int. Ed. 1999, 38, 346–348. (h) Bhattacharya, S. K.;
Danishefsky, S. J. J. Org. Chem. 2000, 65, 144–151. (i) Liao, W.; Piskorz, C. F.;
Locke, R. D.; Matta, K. L. Bioorg. Med. Chem. Lett. 2000, 10, 793–795.
(22) (a) Dullenkopf, W.; Castro-Palomino, J. C.; Manzoni, L.; Schmidt, R. R.
Carbohydr. Res. 1996, 296, 135–147. (b) Ellervik, U.; Magnusson, G. Carbohydr.
Res. 1996, 280, 251–260.
26
SnCl2-AgClO4 was used (entry 3), the yield of 10 was not
improved, and the stereoselectivity did not change appreciably.
27
The use of HNTf2 in the mixture solvent (BTF/tBuCN) hardly
gave 10 (entry 4). On the other hand, when the reaction was
conducted in the presence of Cp2ZrCl2-AgOTf28 at -20 °C
(entry 5), both yield and stereoselectivity were dramatically
improved to afford 10 in 85% yield. Furthermore, it was found
(25) (a) Yule, J. E.; Wong, T. C.; Ganghi, S. S.; Qiu, D.; Riopel, M. A.;
Koganty, R. R. Tetrahedron Lett. 1995, 36, 6839–6842. (b) Be´lot, F.; Jacquinet,
J.-C. Carbohydr. Res. 2000, 325, 93–106. (c) Chen, L.; Kong, F. Tetrahedron
Lett. 2003, 44, 3691–3695.
(23) Imamura, A.; Ando, H.; Ishida, H.; Kiso, M. Org. Lett. 2005, 7, 4415–
4418.
(24) Nicolaou, K. C.; Dolle, R. E.; Papahatjis, D. P.; Randall, J. L. J. Am.
Chem. Soc. 1984, 106, 4189–4192.
(26) Mukaiyama, T.; Murai, Y.; Shoda, S. Chem. Lett. 1981, 431–432.
(27) (a) Mukaiyama, T.; Maeshima, H.; Jona, H. Chem. Lett. 2001, 426–
427. (b) Jona, H.; Mandai, H.; Chavasiri, W.; Takeuchi, K.; Mukaiyama, T.
Bull. Chem. Soc. Jpn. 2002, 75, 291–309.
3012 J. Org. Chem. Vol. 74, No. 8, 2009

Ganglioside GQ1b
SCHEME 2. Conversion of 6 into Donor Form 15
SCHEME 3. Glycosylation of 11 with 15 and Conversion into GQ1b Epitope Donor 20
that these conditions were applicable in a large-scale synthesis.
As expected, the obtained tetrasaccharide 10 could be efficiently
converted into tetrasaccharide acceptor 11 through the removal
of the Troc groups by treatment with preactivated zinc, followed
by the selective acetylation of the liberated amine of the GalNAc
residue at C-2.
Scheme 2 shows the facile conversion of the key common
unit 6 into donor form 15. Thus, hydrogenolysis of the benzyl
groups afforded the triol 12 in excellent yield, and subsequent
benzoylation of the exposed three hydroxyl groups successfully
proceeded to give 13 in 85% yield. In order to introduce a
leaving group at the reducing end of 13, the SE group was
removed by exposure to trifluoroacetic acid.29 The obtained
hemiacetal 14 was then converted into R-trichloroacetimidate
15 by treatment with CCl3CN and DBU.30
surprisingly afforded the desired GQ1b-core heptasaccharide 16
in excellent yield (93%). The reaction was also successful in
large scale (∼10 g). Undoubtedly, the branched tetrasaccharide
acceptor 11 performed excellent couplings with other glycosyl
donors. As shown in Scheme 4, the glycosylation of 11 with
the known sialylR(2f3)galactose donor 2131 and galactose
donor 2232 resulted in the delivery of other glycan structures
of b-series gangliosides, 23 (GT1b-core hexasaccharide) and
24 (GD1b-core saccharide) in excellent 95% and 90% yields,
respectively. These results demonstrated that 11 was the
expedient common unit for the synthesis of the entire b-series
gangliosides.
Referring back to Scheme 3, the cleavage of benzyl groups
and the benzylidene group of 16 was executed by hydrogenolysis
on Pd(OH)2, and the following benzoylation of the resulting
hydroxyl groups gave 18. In this benzoylation, the combination
of Bz2O and DMAP in pyridine could not completely protect
Next, as shown in Scheme 3, the coupling reaction of 15
and 11 was conducted. The reaction was performed in the
presence of TMSOTf in CH2Cl2 at 0 °C. This block coupling
(30) (a) Grundler, G.; Schmidt, R. R. Liebigs Ann. Chem. 1984, 1826–1847.
(b) Schmidt, R. R. Angew. Chem., Int. Ed. 1986, 25, 212–235. (c) Schmidt,
R. R.; Michel, J. Angew. Chem., Int. Ed. 1980, 19, 731–732.
(31) Hasegawa, A. Suzuki, N. Ishida, H. Kiso, M. J. Carbohydr. Chem. 1996,
15, 623–637. Physical data of compound 21 was described in the Supporting
Information.
(28) (a) Matsumoto, T.; Maeta, H.; Suzuki, K.; Tsuchihashi, G. Tetrahedron
Lett. 1988, 29, 3567–3570. (b) Matsumoto, T.; Maeta, H.; Suzuki, K.;
Tsuchihashi, G. Tetrahedron Lett. 1988, 29, 3571–3574. (c) Nicolaou, K. C.;
Caulfield, T. J.; Kataoka, H.; Stylianides, N. A. J. Am. Chem. Soc. 1990, 112,
3693–3695.
(29) Jansson, K.; Ahlfors, S.; Frejd, T.; Kihlberg, J.; Magnusson, G.; Dahme´n,
J.; Noori, G.; Stenvall, K. J. Org. Chem. 1988, 53, 5629–5647.
(32) Nikolaev, A. V.; Watt, G. M.; Ferguson, M. A. J.; Brimacombe, J. S.
J. Chem. Soc., Perkin Trans. 1 1997, 969–979.
J. Org. Chem. Vol. 74, No. 8, 2009 3013

Imamura et al.
SCHEME 4. Potential as an Acceptor of 11 for the Systematical Synthesis of B-Series Gangliosides
the hydroxyl groups. Therefore, to complete the reaction, BzCl
and AgOTf were added, which generated more reactive BzOTf
in situ, whereas the addition of BzCl and DMAP could not
complete the reaction. The use of BzOTf from the beginning
of the reaction gave a crude mixture of O- and N-benzoylated
products. The reason underlying this phenomenon is yet unclear.
Liberation of the anomeric hydroxyl group of 18 was achieved
by treatment with TFA, and the resulting hemiacetal 19 was
then converted into the R-trichloroacetimidate 20, which was
ready for the final glycosylation.
Hashimoto et al. reported the useful convergent synthesis of
ganglioside GM3 using a glucosylceramide (GlcCer) building
block equipped with benzyl groups at the C-3 and C-6 positions
of the Glc residue.33 However, the use of benzyl groups impaired
the efficiency of the deprotection steps, since conventional
hydrogenolysis of benzyl groups cannot be utilized due to the
presence of the olefin functionality at the ceramide moiety. As
a result, it has caused great loss of the samples at the final stage.
Therefore, in this study, we envisioned the use of the p-
methoxybenzyl (PMB) group as a surrogate of the benzyl group,
since it can be removed by nonreductive conditions without
affecting olefin functionality.
afforded the 6-O-PMB derivative 29 (89%), along with a small
amount (8%) of the 4-O-PMB derivative 30. Monochloroacety-
lation of 29 proceeded smoothly to provide 31 in 95% yield.
Selective exposure of the anomeric hydroxyl group of 31 was
executed by treatment of polymethylhydrosiloxane (PMHS),
Pd(PPh3)4, and ZnCl2 in THF,37 which afforded the hemiacetal
32 in 85% yield. The obtained hemiacetal 32 was converted
into the corresponding trichloroacetimidate 33 in 93% (R/ꢀ )
40/53) yield upon reaction with CCl3CN and DBU. The
R-imidate 33r was then subjected to glycosidation with the
known ceramide acceptor 3438 in the presence of TMSOTf in
CH2Cl2 to afford 35 in 48% yield. The selective deprotection
of the monochloroacetyl group was accomplished by treatment
of DABCO in the mixed solvent of EtOH/1,2-dichloroethane39
to furnish the novel GlcCer acceptor 36 in 96% yield.
The final couplings of GQ1b-core heptasaccharide donor 20
(1.0 equiv) with glucosyl acceptors 36, 37, 38, and 39 (1.5 equiv
each) were conducted in the presence of TMSOTf (0.1 equiv)
in CH2Cl2 at 0 °C, and the results are summarized in Table 3.
In entry 1, the glycosylation of the novel GlcCer acceptor 36
with 20 afforded the desired fully protected ganglioside GQ1b
40 in an excellent 91% yield. On the other hand, a Hashimoto-
type GlcCer acceptor 37 bearing the corresponding benzyl
groups at the C-3 and C-6 positions afforded 41 in 73% yield
(entry 2). These results indicated that the PMB groups at the
C-3 and C-6 positions of the Glc residue enhanced the reactivity
of the 4-hydroxyl group owing to its electron-donating property
and elevated the coupling yield. Next, the previously described
glucose derivative 3840 was used as a coupling partner of 20
for the preparation of the SE-type GQ1b derivative (entry 3).
As a result, the desired compound 42 was obtained in 63% yield.
Starting from the known glucose derivative 25,34 the GlcCer
acceptor with PMB groups at the C-3 and C-6 positions (36)
was prepared via eight steps (Scheme 5). Derivative 25 was
subjected to selective p-methoxybenzylation by way of stan-
nylidenation35 with DBTO in toluene, followed by treatment
of PMBCl with TBAB to afford the 3-PMB and 2-PMB
derivatives in 61% and 35% yields, respectively. Benzoylation
of 26 was achieved under standard conditions to give 28 in
almost a quantitative yield. Reductive opening of the anisylidene
ring of 28 by treatment with NaBH3CN and TFA in DMF36
(37) Chandrasekhar, S.; Reddy, Ch. R.; Rao, R. J. Tetrahedron 2001, 57,
3435–3438.
(33) Sakamoto, H.; Nakamura, S.; Tsuda, T.; Hashimoto, S. Tetrahedron
Lett. 2000, 41, 7691–7695.
(34) Aspinall, G. O.; Gammon, D. W.; Sood, R. K.; Chatterjee, D.; Rivoire,
B.; Brennan, P. J. Carbohydr. Res. 1992, 237, 57–77.
(35) Qin, H.; Grindley, B. J. Carbohydr. Chem. 1996, 15, 95–108.
(36) Johansson, R.; Samuelsson, B. J. Chem. Soc., Perkin Trans. 1 1984,
2371–2374.
(38) (a) Kiso, M.; Nakamura, A.; Tomita, Y.; Hasegawa, A. Carbohydr. Res.
1986, 158, 101–111. (b) Kiso, M.; Nakamura, A.; Nakamura, J.; Tomita, Y.;
Hasegawa, A. J. Carbohydr. Chem. 1986, 5, 335–340.
(39) Lefeber, D. J.; Kamerling, J. P.; Vliegenthart, J. F. G. Org. Lett. 2000,
2, 701–703.
(40) 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.
3014 J. Org. Chem. Vol. 74, No. 8, 2009

Ganglioside GQ1b
SCHEME 5. Preparation of a Novel Glucosyl Ceramide Acceptor 36
In entry 4, glycosylation of the previously described gentiobiose
acceptor 3913 with 20 provided the nonasaccharide 43 in 80%
yield. These results strongly suggested that our synthetic strategy
is applicable to the assembly of both natural gangliosides and
unnatural ganglioside derivatives.
positions of the GlcCer led to not only the elevation of coupling
yields but also to facilitate global deprotection with almost
quantitative yields. Furthermore, our approach can efficiently
reach various unnatural ganglioside derivatives with azide or
alkyne groups for 1,3-dipolar cycloaddition. We are currently
undertaking the syntheses of various gangliosides using this
approach, and the extension of synthesized ganglioside deriva-
tives to the chemical biology field is in progress.
Scheme 6 incorporated global deprotection steps toward target
compounds. Selective removal of the PMB groups of 40 was
performed in the presence of TFA in CH2Cl2 at 0 °C, and the
reaction was completed within 1 h. After a facile workup and
purification by silica gel column chromatography, the target
compound 44 was obtained in almost a quantitative yield (97%).
The outcome demonstrated that the use of the PMB group was
effective for the synthesis of natural gangliosides. Importantly,
this strategy can be applied to the syntheses of compounds with
hydrogenolysis-sensitive functionalities, such as allyls, alkynes,
azides, and so on. Furthermore, the sustainability of azide and
alkyne groups enables their application to 1,3-dipolar cycload-
ditions. Finally, the conventional deacylation41 and subsequent
saponification gave natural ganglioside GQ1b 1 in 97% yield.
It is noteworthy that the synthesis of the complex ganglioside
GQ1b was first accomplished in the scale of ca. 80 mg per batch.
Global deprotections of 42 and 43 were also executed by
conventional methods to provide the targeted unnatural GQ1b
derivatives 2 and 3 in good yields, respectively.
Experimental Section
Ganglioside GQ1b (1). To a mixture of 44 (122 mg, 0.0316 mmol)
in MeOH (6.2 mL) was added catalytic amounts of sodium methoxide
(28% solution in MeOH). After stirring for 24 h at room temperature
as the reaction was monitored by TLC (1-BuOH/MeOH/5% CaCl2
(aq) ) 2:1:1), the mixure was heated at 50 °C, and stirring was
continued for 2 days at 50 °C. Then, H2O (0.3 mL) was added to the
mixture. After stirring for 5 h at room temperature as the reaction was
monitored by TLC (1-BuOH/MeOH/5% CaCl2 (aq) ) 2:1:1), the
reaction was neutralized with IR-120 (H+) resin and filtered through
cotton, and the resin was washed with mixed solvent (CHCl3/MeOH/
H2O ) 5:5:1). The combined filtrate and washings were concentrated.
The resulting residue was purified by gel filtration column chroma-
tography on Sephadex LH-20 using CHCl3/MeOH/H2O (5:5:1) as the
eluent to give 1 (77 mg, 97%): [R]D ) -6.3° (c 0.3, CHCl3/MeOH/
H2O ) 5:5:1); 1H NMR (600 MHz, CDCl3/CD3OD/D2O ) 5:5:1) δ
5.70 (m, 1 H, J4,5 ) 15.1 Hz, J5,6 ) 8.2 Hz, J5,6′ ) 6.8 Hz, H-5Cer),
5.43 (dd, 1 H, J4,5 ) 15.1 Hz, J3,4 ) 7.5 Hz, H-4Cer), 4.88 (d, 1 H, J1,2
Conclusion
) 8.2 Hz, anomer H), 4.61 (d, 1 H, anomer H), 4.46 (d, 1 H, J1,2
)
In conclusion, we have accomplished the highly efficient and
practical synthesis of complex ganglioside GQ1b and its
unnatural derivatives by convergent synthetic routes, based on
the key coupling reactions of a GQ1b-core heptasaccharide and
derivatized-Glc building blocks. In particular, a judicious choice
of a PMB group as a protecting group at the C-3 and C-6
7.5 Hz, anomer H), 4.34 (d, 1 H, J1,2 ) 7.5 Hz, anomer H), 3.02,
2.80, 2.74, and 2.63 (4 br dd, 4 H, 4 H-3eq), 2.17 (t, 1 H, NHCOCH2),
2.06, 2.03, 2.03, and 2.02 (4 s, 17 H, 5 NAc, H-6Cer, and 6′Cer), 1.84
(br t, 1 H, H-3ax), 1.69 (m, 3 H, 3 H-3ax), 1.57 (m, 1 H, NHCOCH2),
1.36 (m, 1 H, H-7Cer), 1.27 (m, 51 H, H-7′Cer, 25 CH2), 0.89 (t, 6 H,
2 Me); 13C NMR (150 MHz, CDCl3/CD3OD/D2O ) 5:5:1) δ 174.8,
174.0, 173.8, 173.7, 173.4, 173.3, 172.8, 172.6, 172.4, 172.3, 133.6,
128.8, 103.7, 102.7, 102.2, 101.9, 100.7, 100.1, 100.1, 99.0, 80.5, 78.5,
(41) Zemple´n, G. Ber. Dtsch. Chem. Ges. 1927, 60, 1555–1564.
J. Org. Chem. Vol. 74, No. 8, 2009 3015

Imamura et al.
TABLE 3. Final Glycosylations
a Isolated yield.
74.3, 73.9, 73.8, 73.8, 73.5, 73.4, 73.3, 73.2, 73.0, 72.8, 72.5, 72.4,
70.9, 70.8, 69.1, 69.0, 68.9, 68.9, 68.3, 68.1, 68.0, 68.0, 67.9, 67.3,
67.3, 67.0, 66.6, 66.2, 66.1, 65.5, 65.5, 64.9, 62.6, 62.5, 61.2, 61.1,
61.0, 60.9, 60.7, 60.6, 60.5, 59.7, 59.6, 59.3, 59.3, 52.7, 52.4, 52.1,
51.9, 51.7, 50.9, 40.3, 37.9, 35.5, 31.5, 31.0, 31.0, 28.8, 28.8, 28.7,
28.7, 28.6, 28.6, 28.4, 28.4, 25.2, 22.2, 21.7, 21.4, 21.3, 21.2, 21.0,
12.7; HRMS (ESI) m/z found [M - 2H+]2- 1208.5783, C106H182N6O55
calcd for [M - 2H+]2- 1208.5736.
2-(Trimethylsilyl)ethyl (5-Acetamido-3,5-dideoxy-D-glycero-
r-D-galacto-2-nonulopyranosylonic acid)-(2f8)-(5-acetamido-
3,5-dideoxy-D-glycero-r-D-galacto-2-nonulopyranosylonic acid)-
(2f3)-ꢀ-D-galactopyranosyl-(1f3)-2-acetamido-2-deoxy-ꢀ-D-
galactopyranosyl-(1f4)-[(5-acetamido-3,5-dideoxy-D-glycero-r-
D-galacto-2-nonulopyranosylonic acid)-(2f8)-(5-acetamido-3,5-
dideoxy-D-glycero-r-D-galacto-2-nonulopyranosylonic acid)-
(2f3)]-ꢀ-D-galactopyranosyl-(1f4)-ꢀ-D-glucopyranoside (2). To
a mixture of 45 (40 mg, 0.0121 mmol) in MeOH (1.0 mL) was
added catalytic amounts of sodium methoxide (28% solution in
MeOH). After stirring for 17 h at room temperature as the reaction
was monitored by TLC (1-BuOH/MeOH/5% CaCl2 (aq) ) 2:1:1),
the mixure was heated at 50 °C, and the stirring was continued for
17 h at 50 °C. Then, 0.2 M KOH (0.5 mL) was added to the
mixture. After stirring for 30 h at 75 °C as the reaction was
monitored by TLC (1-BuOH/MeOH/5% CaCl2 (aq) ) 2:1:1), the
reaction was neutralized with IR-120 (H+) resin and filtered through
cotton, and the resin was washed with MeOH and H2O. The
combined filtrate and washings were concentrated. The resulting
residue was purified by gel filtration column chromatography on
Sephadex LH-20 using H2O as the eluent to give 2 (20 mg, 87%):
1
[R]D ) -5.0° (c 0.7, H2O); H NMR (500 MHz, D2O/(CD3)2CO
) 10:1) δ 4.73 (d, 1 H, H-1h), 4.59 (d, 1 H, J1,2 ) 7.4 Hz, H-1e),
4.49 (d, 1 H, J1,2 ) 8.6 Hz, H-1c), 4.47 (d, 1 H, J1,2 ) 8.0 Hz,
H-1d), 3.41 (t, 1 H, J1,2 ) J2,3 ) 8.6 Hz, H-2c), 3.25 (near t, 1 H,
J1,2 ) 8.0 Hz, J2,3 ) 9.1 Hz, H-2d), 2.77-2.63 (m, 4 H, H-3eq-a,
3eq-b, 3eq-f, and 3eq-g), 2.05, 2.04, and 2.01 (3 s, 15 H, 5 NAc),
1.76-1.69 (m, 4 H, H-3ax-a, 3ax-b, 3ax-f, and 3ax-g), 1.07-0.91
(m, 2 H, OCH2CH2SiMe3), 0.00 (s, 9 H, OCH2CH2SiMe3); 13C
NMR (125 MHz, D2O/(CD3)2CO ) 10:1) δ 175.2, 175.1, 175.0,
173.9, 173.6, 173.6, 173.5, 104.5, 103.1, 102.8, 101.7, 100.8, 100.6,
100.5, 100.5, 80.2, 78.8, 78.6, 75.6, 75.5, 75.1, 74.9, 74.7, 74.6,
74.5, 74.3, 74.0, 73.1, 72.9, 72.0, 69.8, 69.8, 69.7, 69.5, 68.8, 68.7,
68.5, 68.3, 68.3, 67.9, 67.6, 62.9, 61.9, 61.8, 61.3, 61.2, 60.9, 60.3,
52.6, 52.5, 52.1, 51.4, 40.9, 40.8, 39.9, 39.8, 22.9, 22.6, 22.6, 22.3,
17.8, -2.1; HRMS (ESI) m/z found [M s 4H+]4- 491.9194,
C75H125N5O53Si calcd for [M s 4H+]4- 491.9192.
(5-Acetamido-3,5-dideoxy-D-glycero-r-D-galacto-2-nonulopy-
ranosylonic acid)-(2f8)-(5-acetamido-3,5-dideoxy-D-glycero-r-
D-galacto-2-nonulopyranosylonic acid)-(2f3)-ꢀ-D-galactopyra-
nosyl-(1f3)-2-acetamido-2-deoxy-ꢀ-D-galactopyranosyl-(1f4)-
[(5-acetamido-3,5-dideoxy-D-glycero-r-D-galacto-2-non-
ulopyranosylonic acid)-(2f8)-(5-acetamido-3,5-dideoxy-D-gly-
cero-r-D-galacto-2-nonulopyranosylonic acid)-(2f3)]-ꢀ-D-galacto-
3016 J. Org. Chem. Vol. 74, No. 8, 2009

Ganglioside GQ1b
SCHEME 6. Global Deprotections
pyranosyl-(1f4)-ꢀ-D-glucopyranosyl-(1f6)-D-glucopyranose (3).
To a mixture of 43 (46 mg, 0.0118 mmol) in MeOH (0.8 mL) was
added catalytic amounts of sodium methoxide (28% solution in
MeOH). After stirring for 12 h at room temperature as the reaction
was monitored by TLC (1-BuOH/MeOH/5% CaCl2 (aq) ) 2:1:1),
the mixure was heated at 50 °C, and the stirring was continued for
24 h at 50 °C. Then 0.2 M KOH (0.2 mL) was added to the mixture.
After stirring for 3 h at room temperature as the reaction was
monitored by TLC (1-BuOH/MeOH/5% CaCl2 (aq) ) 2:1:1), the
reaction was neutralized with IR-120 (H+) resin and filtered through
cotton, and the resin was washed with H2O. The combined filtrate
and washings were concentrated. The resulting residue was purified
by gel filtration column chromatography on Sephadex LH-20 using
H2O as the eluent. Then, to a solution of the obtained white solid
46 in EtOH/H2O (1.0 mL/1.0 mL) was added palladium hydroxide
[20 wt % Pd (dry basis) on carbon, wet] (90 mg) at room
temperature. After stirring for 14 h at room temperature under a
H2 atmosphere as the reaction was monitored by TLC (1-BuOH/
MeOH/5% CaCl2 (aq) ) 1:1:1), the mixture was filtered through a
membrane filter and washed with H2O. The combined filtrate and
washings were concentrated. The resulting residue was purified by
gel filtration column chromatography on Sephadex LH-20 using
H2O as the eluent to give 3 (20 mg, 83%): [R]D ) -3.7° (c 0.4,
and 3eq-g), 2.04, 2.03, 2.02, and 2.00 (4 s, 15 H, 5 NAc), 1.78-1.69
(m, 4 H, H-3ax-a, 3ax-b, 3ax-f, and 3ax-g); 13C NMR (150 MHz,
D2O/(CD3)2CO ) 10:1) δ 165.9, 164.8-163.9, 95.3, 93.8, 93.6,
93.5, 92.0-90.9, 87.0, 83.1, 71.0, 69.2, 69.1, 66.7, 66.4, 65.9, 65.8,
65.8, 65.6, 65.3, 65.2, 65.1, 65.1, 64.8, 63.7, 62.7, 62.4, 61.4, 60.6,
60.5, 60.4, 60.2, 59.8, 59.8, 59.6, 59.4, 59.3, 59.2, 59.0, 58.6, 58.6,
53.6, 52.5, 52.4, 52.0, 52.0, 51.6, 51.0, 43.3, 43.2, 42.8, 42.1, 31.6,
31.5, 30.7, 30.2, 13.6, 13.4, 13.3, 13.1; HRMS (ESI) m/z found
[M - 4H+]4- 507.4145, C76H123N5O58 calcd for [M - 4H+]4-
507.4143.
2-(Trimethylsilyl)ethyl [Methyl 5-acetamido-8-O-(5-aceta-
mido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-r-D-galacto-
2-nonulopyranosylono-1′,9-lactone)-4,7-di-O-acetyl-3,5-dideoxy-
D-glycero-r-D-galacto-2-nonulopyranosylonate]-(2f3)-2,6-di-O-
benzyl-ꢀ-D-galactopyranoside (6). To a mixture of 4 (200 mg,
210 µmol) and 5 (196 mg, 420 µmol) in propionitrile (4.0 mL)
were added 3 Å molecular sieves (400 mg) at room temperature.
After stirring for 1 h, NIS (96 mg, 420 µmol) was added to the
mixture. After cooling to -50 °C, TfOH (11 µL, 130 µmol) was
added to the mixture. After stirring for 96 h at -50 °C as the
reaction was monitored by TLC (EtOAc/MeOH ) 10:1), reagents
(NIS, 2 × 96 mg, 192 mg in total; TfOH, 2 × 11 µL, 22 µL in
total) were added to the mixture after 120 and 144 h. The mixture
was stirred for a total of 168 h at the same temperature. Then,
the reaction was quenched by triethylamine and filtered through a
Celite pad, and the pad was washed with CHCl3. The combined
filtrate and washings were evaporated. The residue was extracted
with CHCl3 and washed with saturated Na2CO3 (aq), saturated
Na2S2O3 (aq), and brine, dried over Na2SO4, and concentrated. The
residue was purified by flash column chromatography twice (first
with CHCl3/MeOH ) 50:1 and second with EtOAc) to give 6 (120
1
H2O); H NMR (600 MHz, D2O) δ 5.20 (d, 1 H, J1,2 ) 3.4 Hz,
H-1 of Glc unit), 4.71 (m, anomer H), 4.63 (d, 1 H, J1,2 ) 8.2 Hz,
H-1 of Glc unit), 4.58 (m, anomer H), 4.52 (d, 1 H, J1,2 ) 8.2 Hz,
anomer H), 4.50 (d, 1 H, J1,2 ) 7.5 Hz, anomer H), 4.47 (d, 1 H,
J1,2 ) 8.2 Hz, anomer H), 3.51 (dd, 1 H, J1,2 ) 3.4 Hz, J2,3 ) 10.3
Hz, H-2 of Glc unit), 3.44 (t, 1 H, J2,3 ) J3,4 ) 8.9 Hz, H-3 of Glc
unit), 3.40-3.30 (m, 3 H, 3 H-2), 3.22 (near t, 1 H, J1,2 ) 8.2 Hz,
J2,3 ) 8.9 Hz, H-2), 2.76-2.62 (m, 4 H, H-3eq-a, 3eq-b, 3eq-f,
J. Org. Chem. Vol. 74, No. 8, 2009 3017

Imamura et al.
mg, 44%) and its ꢀ-isomer 6ꢀ (39 mg, 14%). 6r: [R]D ) -28.1°
d, 2 H, Jgem ) 11.2 Hz, PhCH2), 4.96 (d, 1 H, H-4d), 4.92 (dd, 1
H, H-7a), 4.77 (d, 1 H, J1,2 ) 8.3 Hz, H-1d), 4.60 and 4.52 (2 d,
2 H, Jgem ) 11.7 Hz, PhCH2), 4.44 (d, 1 H, J1,2 ) 7.5 Hz, H-1c),
4.43 (dd, 1 H, Jgem ) 12.4 Hz, H-9a), 4.26 (dd, 1 H, H-9′b), 4.19
(q, 1 H, J4,5 ) J5,6 ) J5,NH )10.4 Hz, H-5b), 4.17 (m, 2 H, H-2d
and 4c), 4.15-3.98 (m, 14 H, H-6a, 5a, 6d, 6′d, 5d, 3c, 9b, 6′c, 8a,
and OCH2CH2SiMe3), 3.89 (s, 3 H, COOMe), 3.82 (dd, 1 H, Jgem
) 12.4 Hz, H-9′a), 3.74 (dd, 1 H, J5,6 ) 10.4 Hz, J6,7 ) 2.1 Hz,
H-6b), 3.70 (s, 3 H, COOMe), 3.66 (dd, 1 H, H-6c), 3.62-3.54
1
(c 3.7, CHCl3); H NMR (500 MHz, CDCl3) δ 7.35-7.24 (m, 10
H, 2 Ph), 5.69 (d, 1 H, NH-a), 5.67 (d, 1 H, NH-b), 5.38 (dt, 1 H,
H-4b), 5.35 (dd, 1 H, H-7b), 5.15 (dt, 1 H, H-8b), 5.09 (dd, 1 H,
H-7a), 5.07 (dt, 1 H, H-4a), 4.90 and 4.62 (2 d, 2 H, Jgem ) 11.2
Hz, PhCH2), 4.56 (2 d, 2 H, Jgem ) 11.6 Hz, PhCH2), 4.40 (d, 1 H,
J1,2 ) 8.0 Hz, H-1c), 4.37 (dd, 1 H, H-9′a), 4.29-4.19 (m, 3 H,
H-9a, 9′b, and 8a), 4.18 (q, 1 H, H-5b), 4.07-3.95 (m, 6 H, H-9b,
5a, 3c, 6a, 6b, and OCH2CH2SiMe3), 3.87 (br s, 1 H, H-4c), 3.82
(s, 3 H, CO2Me), 3.81 (dd, 1 H, H-6′c), 3.73 (dd, 1 H, H-6c), 3.61
(m, 2 H, H-5c and OCH2CH2SiMe3), 3.54 (t, 1 H, J1,2 ) 8.0 Hz,
J2,3 ) 9.1 Hz, H-2c), 2.80 (s, 1 H, OH), 2.46 (dt, 2 H, H-3eq-a and
H-3eq-b), 2.14-1.88 (8 s and 2 t, 26 H, H-3ax-a, H-3ax-b, and 8
Ac), 1.03 (t, 2 H, OCH2CH2SiMe3), 0.02 (s, 9 H, OCH2CH2SiMe3);
13C NMR (100 MHz, CDCl3) δ 170.8, 170.7, 170.6, 170.5, 170.2,
169.8, 169.7, 168.1, 165.4, 138.6, 138.1, 128.4, 128.1, 128.0, 127.7,
127.6, 127.5, 103.3, 99.4, 96.1, 75.8, 74.9, 73.6, 73.0, 72.8, 72.1,
70.7, 69.4, 69.2, 69.1, 68.9, 67.8, 67.4, 67.1, 67.1, 66.6, 61.8, 53.1,
49.3, 49.0, 38.3, 35.8, 23.1, 20.9, 20.8, 20.7, 20.6, 18.5; HRMS
(ESI) m/z found [M + Na]+ 1313.4779, C60H82N2O27Si calcd for
[M + Na]+ 1313.4771. 6ꢀ: [R]D ) -31.9° (c 1.0, CHCl3); 1H NMR
(500 MHz, CDCl3) δ 7.50-7.27 (m, 10 H, 2 Ph), 5.46 (dt, 1 H,
J3eq,4 ) 5.4 Hz, J4,5 ) 10.2 Hz, H-4b), 5.38 (d, 1 H, NH-b), 5.35
(dd, 1 H, H-7b), 5.17-5.09 (m, 3 H, H-4a, 7a, and 8b), 5.06 and
4.62 (2 d, 2 H, Jgem ) 10.9 Hz, PhCH2), 4.58-4.52 (m, 4 H, H-9′a,
PhCH2, and H-9a), 4.45 (d, 1 H, J1,2 ) 7.5 Hz, H-1c), 4.34-4.28
(m, 3 H, H-6a, 8a, and 9b), 4.17 (q, 1 H, J4,5 ) 10.2 Hz, H-5b),
4.05-3.99 (m, 3 H, H-5a, 9b, and OCH2CH2SiMe3), 3.83 (br s, 1
H, H-4c), 3.81-3.75 (m, 3 H, H-6b, 3c, and 6′c), 3.73 (s, 3 H,
(m, 3 H, OCH2CH2SiMe3, H-3d, and 5c), 3.51 (near t, 1 H, J1,2
)
7.5 Hz, H-2c), 3.02 (s, 1 H, OH), 2.32 (m, 3 H, H-3eq-b, 3eq-a,
and 3ax-a,), 2.12-1.89 (8 s, 24 H, 8 Ac), 1.81 (near t, 1 H, H-3ax-
b), 1.04 (m, 2 H, OCH2CH2SiMe3), 0.02 (s, 9 H, OCH2CH2SiMe3);
HRMS (ESI) m/z found [M + Na]+ 1604.5873, C75H99N3O32Si calcd
for [M + Na]+ 1604.5878.
[Methyl 5-Acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-
3,5-dideoxy-D-glycero-r-D-galacto-2-nonulopyranosylono-1′,9-
lactone)-4,7-di-O-acetyl-3,5-dideoxy-D-glycero-r-D-galacto-2-nonulo-
pyranosylonate]-(2f3)-2,4,6-tri-O-benzoyl-r-D-galactopyrano-
syl Trichloroacetimidate (15). To a solution of 13 (2.50 g, 1.75
mmol) in CH2Cl2 (12 mL) was added trifluoroacetic acid (4.0 mL)
at 0 °C. After stirring for 5 h at room temperature as the reaction
was monitored by TLC (CHCl3/MeOH ) 10:1), the reaction mixture
was coevaporated with toluene. The residue was purified by flash
column chromatography using CHCl3/MeOH (30:1) as the eluent
to give the hemiacetal 14 (2.29 g, 98%): HRMS (ESI) m/z found
[M + Na]+ 1345.3912, C62H70N2O30 calcd for [M + Na]+
1345.3911.
To a solution of 14 (827 mg, 624 µmol) in CH2Cl2 (6.2 mL)
were added trichloroacetonitrile (1.25 mL, 12.5 mmol) and DBU
(112 µL, 750 µmol) at 0 °C. After stirring for 2 h at room
temperature as the reaction was monitored by TLC (CHCl3/MeOH
) 10:1), the reaction mixture was concentrated. The resulting
residue was purified by flash column chromatography using CHCl3/
CO2Me), 3.71 (dd, 1 H, J5,6 ) 9.6 Hz, H-6c), 3.61 (m, 2 H, J5,6
)
9.6 Hz, H-5c, and OCH2CH2SiMe3), 3.64 (t, 1 H, J1,2 ) 7.5 Hz,
H-2c), 3.62-3.58 (m, 2 H, H-5c and OCH2CH2SiMe3), 3.30 (s, 1
H, OH), 2.56 (dd, 1 H, Jgem ) 13.7 Hz, J3eq,4 ) 4.3 Hz, H-3eq-a),
2.46 (dd, 1 H, Jgem ) 13.5 Hz, J3eq,4 ) 5.4 Hz, H-3eq-b), 2.12,
2.08, 2.04, 2.03, 2.02, and 2.00 (6 s, 18 H, 6 Ac), 2.02 (m, 1 H,
Jgem ) 13.7 Hz, H-3ax-a), 1.91 (t, 1 H, Jgem ) 13.5 Hz, H-3ax-b),
1.89 and 1.73 (2 s, 6 H, 2 NAc), 1.02 (t, 2 H, OCH2CH2SiMe3),
0.01 (s, 9 H, OCH2CH2SiMe3); 13C NMR (100 MHz, CDCl3) δ
171.0, 170.9, 170.6, 170.5, 170.3, 169.9, 169.8, 169.6, 168.2, 164.7,
138.9, 137.8, 128.5, 128.4, 128.3, 128.1, 128.1, 127.8, 127.7, 103.3,
99.3, 96.6, 77.9, 77.7, 74.9, 73.6, 72.7, 72.3, 72.2, 70.8, 69.8, 69.0,
68.7, 68.6, 68.2, 67.6, 67.5, 66.6, 61.6, 53.2, 49.0, 48.4, 37.9, 34.7,
30.3, 23.2, 23.1, 21.0, 20.9, 20.8, 20.7, 20.6, 18.5; HRMS (ESI)
m/z found [M + Na]+ 1313.4773, C60H82N2O27Si calcd for [M +
Na]+ 1313.4771.
MeOH (30:1) as the eluent to give 15 (862 mg, 94%): [R]D
)
1
+21.4° (c 1.0, CHCl3); H NMR (500 MHz, CDCl3) δ 8.59 (s, 1
H, CdNH), 8.10-7.40 (m, 15 H, 3 Ph), 6.83 (d, 1 H, J1,2 ) 3.6
Hz, H-1c), 5.94 (d, 1 H, J3,4 ) 3.6 Hz, J4,5 ) 1.2 Hz, H-4c), 5.68
(dd, 1 H, J1,2 ) 3.6 Hz, J2,3 ) 10.4 Hz, H-2c), 5.56 (dt, 1 H, J3eq,4
) 5.3 Hz, J3ax,4 ) 11.4 Hz, J4,5 ) 10.4 Hz, H-4b), 5.44 (d, 1 H,
NH-a), 5.35 (dd, 1 H, J6,7 ) 2.1 Hz, H-7b), 5.27 (d, 1 H, J5,NH
10.4 Hz, NH-b), 5.19 (m, 2 H, H-4a and 8b), 4.98 (dd, 1 H, J6,7
1.7 Hz, J7,8 ) 9.2 Hz, H-7a), 4.93 (dd, 1 H, J2,3 ) 10.4 Hz, J3,4
)
)
)
3.6 Hz, H-3c), 4.74 (near dt, 1 H, J4,5 ) 1.2 Hz, H-5c), 4.65 (dt, 1
H, J7,8 ) 9.2 Hz, J8,9′ ) 2.6 Hz, H-8a), 4.48-4.40 (m, 3 H, H-6′c,
9a, and 6c), 4.28 (dd, 1 H, Jgem ) 12.6 Hz, H-9′b), 4.17 (q, 1 H,
J4,5 ) J5,NH ) 10.4 Hz, H-5b), 4.15 (q, 1 H, H-5a), 4.04 (dd, 1 H,
J8,9′ ) 2.6 Hz, H-9′a), 4.02 (dd, 1 H, Jgem ) 12.6 Hz, H-9b), 3.96
(dd, 1 H, J6,7 ) 1.7 Hz, H-6a), 3.91 (dd, 1 H, J6,7 ) 2.1 Hz, H-6b),
3.36 (s, 3 H, COOMe), 2.56 (dd, 1 H, Jgem ) 13.1 Hz, J3eq,4 ) 5.3
Hz, H-3eq-b), 2.24 (dd, 1 H, H-3eq-a), 2.12-1.89 (8 s and t, 25
H, 8 Ac and H-3ax-a), 1.70 (t, 1 H, Jgem ) 13.1 Hz, J3ax,4 ) 11.4
Hz, H-3ax-b); 13C NMR (100 MHz, CDCl3) δ 170.6, 170.5, 170.4,
170.4, 170.0, 169.8, 169.8, 167.4, 166.0, 165.6, 165.2, 164.4, 160.2,
133.5, 133.3, 133.2, 129.9, 129.7, 129.5, 129.3, 129.3, 128.9, 128.5,
128.4, 98.9, 97.0, 93.9, 90.8, 77.1, 72.5, 71.9, 70.6, 69.8, 69.5, 69.5,
69.2, 68.8, 68.4, 68.3, 67.9, 67.7, 66.7, 62.9, 62.0, 52.5. 49.1, 38.2,
36.1, 23.1, 23.0, 20.7, 20.7, 20.7, 20.7, 20.6, 20.4; HRMS (ESI)
m/z found [M + Na]+ 1488.3004, C64H70Cl3N3O30 calcd for [M +
Na]+ 1488.3007.
2-(Trimethylsilyl)ethyl [Methyl 5-acetamido-8-O-(5-aceta-
mido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-r-D-galacto-
2-nonulopyranosylono-1′,9-lactone)-4,7-di-O-acetyl-3,5-dideoxy-
D-glycero-r-D-galacto-2-nonulopyranosylonate]-(2f3)-2,4,6-tri-
O-benzoyl-ꢀ-D-galactopyranosyl-(1f3)-2-acetamido-4,6-O-
benzylidene-2-deoxy-ꢀ-D-galactopyranosyl-(1f4)-{[methyl 5-
acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-
dideoxy-D-glycero-r-D-galacto-2-nonulopyranosylono-1′,9-lactone)-
4,7-di-O-acetyl-3,5-dideoxy-D-glycero-r-D-galacto-2-non-
2-(Trimethylsilyl)ethyl 2-Acetamido-4,6-O-benzylidene-2-
deoxy-ꢀ-D-galactopyranosyl-(1f4)-{[methyl 5-acetamido-8-O-
(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-r-D-
galacto-2-nonulopyranosylono-1′,9-lactone)-4,7-di-O-acetyl-3,5-
dideoxy-D-glycero-r-D-galacto-2-nonulopyranosylonate]-(2f3)}-
2,6-di-O-benzyl-ꢀ-D-galactopyranoside (11). To a solution of 10
(6.30 g, 3.33 mmol) in (CH2Cl)2 (30 mL) were added activated Zn
powder (25.2 g) and acetic acid (60 mL) at room temperature. After
stirring for 1 h at 40 °C as the reaction was monitored by TLC
(CHCl3/MeOH ) 10:1), the mixture was filtered through a Celite
pad and washed with CHCl3. The combined filtrate and washings
were diluted with CHCl3 and washed with saturated NaHCO3 (aq),
H2O, and brine. After drying over Na2SO4 and being concentrated,
the resulting residue was dissolved in CH2Cl2 (50 mL). Acetic
anhydride (471 µL, 5.00 mmol) was then added to the mixture at
room temperature. After stirring for 30 min as the reaction was
monitored by TLC (CHCl3/MeOH ) 10:1), the reaction mixture
was concentrated. The residue was purified by flash column
chromatography using CHCl3/MeOH (28:1 to 20:1) as the eluent
to give 11 (5.04 g, 96%): [R]D ) -23.6° (c 0.5, CHCl3); 1H NMR
(500 MHz, CDCl3) δ 7.53-7.23 (m, 15 H, 3 Ph), 6.86 (d, 1 H,
NH-d), 5.59 (s, 1 H, PhCH<), 5.56 (d, 1 H, NH-b), 5.46 (near d,
1 H, NH-a), 5.40 (dt, 1 H, J4,5 ) 10.4 Hz, H-4b), 5.33 (dd, 1 H,
J6,7 ) 2.1 Hz, H-7b), 5.12 (m, 2 H, H-8b and 4a), 4.98 and 4.51 (2
3018 J. Org. Chem. Vol. 74, No. 8, 2009

Ganglioside GQ1b
ulopyranosylonate]-(2f3)}-2,6-di-O-benzyl-ꢀ-D-galactopyranoside
(16). To a mixture of 15 (2.71 g, 1.84 mmol) and 11 (1.93 g, 1.22
mmol) in CH2Cl2 (30 mL) was added 4 Å molecular sieves (AW-
300) (4.6 g) at room temperature. After stirring for 1 h and then
cooling to 0 °C, TMSOTf (6.7 µL, 36.8 µmol) was added to the
mixture. After stirring for 22 h at 0 °C as the reaction was monitored
by TLC (CHCl3/MeOH/EtOAc ) 15:1:1), the reaction was
quenched by saturated NaHCO3 (aq) and filtered through a Celite
pad, and the pad was washed with CHCl3. The combined filtrate
and washings were washed with brine, dried over Na2SO4, and
concentrated. The resulting residue was purified by flash column
chromatography using CHCl3/MeOH/EtOAc (20:1:1) to CHCl3/
MeOH (9:1) as the eluent to give 16 (3.29 g, 93%): [R]D ) -11.5°
(20:1 to 13:1) as the eluent to give 20 (199 mg, 95%): [R]D )
+4.8° (c 0.9, CHCl3); 1H NMR (500 MHz, CDCl3) δ 8.46 (s, 1 H,
CdNH), 8.12-7.25 (m, 35 H, 7 Ph), 6.55 (d, 1 H, J1,2 ) 3.4 Hz,
H-1c), 5.95 (br d, 1 H, H-4d), 5.89 (br d, 2 H, 2 NH), 5.70 (d, 1
H, H-4e), 5.63 (dd, 1 H, J1,2 ) 3.4 Hz, J2,3 ) 10.4 Hz, H-2c), 5.58
(d, 1 H, NH-b), 5.55 (dt, 1 H, H-4g), 5.46 (2 d, 2 H, 2 NH),
5.36-5.31 (m, 4 H, H-4b, 2e, 7g, and 7b), 5.29 (d, 1 H, J1,2 ) 8.5
Hz, H-1d), 5.24 (m, 1 H, H-8b), 5.16 (m, 1 H, H-8g), 5.10 (near q,
1 H, H-4f), 5.04 (br d, 1 H, H-1e), 5.20 (m, 2 H, H-4a and 7a),
4.93 (br dd, 1 H, H-3d), 4.86 (dd, 1 H, H-7f), 4.80 (dd, 1 H, J2,3
)
10.4 Hz, H-3c), 4.63-4.58 (m, 3 H, H-8f, 6′e, and 6′d), 4.45-4.33
(m, 5 H, H-5d, 6′c, 3e, 6c, and 6d), 4.30-4.16 (m, 10 H, H-8a, 9g,
9b, 9f, 4c, 6b, 5b, 9′a, 9a, and 5e), 4.11 (q, 1 H, H-5g), 4.06-3.98
(m, 6 H, H-5f, 9b, 9g, 6b, 5c, and 5a), 3.91 (2 dd, 2 H, H-6a and
6g), 3.86 (dd, 1 H, H-6f), 3.82 (s, 3 H, COOMe-a), 3.75 (m, 2 H,
H-2d and 9′f), 3.24 (s, 3 H, COOMe-f), 2.57-2.49 (m, 3 H, H-3eq-
a, 3eq-b, and 3eq-g), 2.10-1.81 (m, 53 H, 17 Ac, H-3eq-f, and
3ax-f), 1.63 (t, 1 H, H-3ax-g); 13C NMR (150 MHz, CDCl3) δ 174.5,
171.2, 170.6, 170.6, 170.4, 170.2, 170.2, 169.8, 169.7, 169.6, 167.7,
167.1, 166.5, 166.0, 165.9, 165.5, 165.3, 164.8, 164.2, 160.0, 133.4,
133.2, 133.1, 133.0, 132.8, 132.8, 130.0, 129.9, 129.8, 129.7, 129.6,
129.5, 129.4, 129.4, 129.3, 129.0, 128.4, 128.3, 128.2, 101.3, 99.8,
99.0, 98.9, 96.8, 95.4, 95.1, 94.1, 90.8, 76.2, 75.0, 73.3, 72.5, 71.9,
71.5, 71.3, 71.1, 71.0, 70.6, 70.1, 69.8, 69.6, 69.3, 69.2, 69.1, 68.8,
68.6, 68.1, 67.5, 67.1, 66.8, 66.7, 66.4, 64.2, 62.3, 62.1, 62.1, 61.9,
54.3, 53.0, 52.3, 49.0, 48.9, 48.7, 38.8, 38.2, 36.9, 36.1, 35.4, 29.5,
22.9, 22.8, 22.8, 22.6, 22.5, 20.7, 20.6, 20.6, 20.5, 20.4, 20.3, 20.2,
1
(c 1.0, CHCl3); H NMR (500 MHz, CDCl3) δ 8.09-7.18 (m, 30
H, 6 Ph), 5.74 (d, 1 H, H-4e), 5.54 (dt, 1 H, J3eq,4 ) 5.2 Hz, J4,5
)
10.5 Hz, H-4g), 5.48 (t, 1 H J1,2 ) 7.7 Hz, H-2e), 5.43 (m, 3 H,
H-4b, NH-f, and PhCH), 5.34 (m, 6 H, H-7b, 7g, and 4 NH), 5.17
(m, 3 H, H-4f, 8b, and 8g), 5.14 (d, 1 H, J1,2 ) 8.0 Hz, H-1d), 5.03
(dd, 1 H, H-7a), 4.97 (br d, 1 H, J1,2 ) 7.7 Hz, H-1e), 4.95 (dd, 1
H, J7,8 ) 9.6 Hz, H-7f), 4.88 (m, 2 H, H-4a and 3d), 4.80 and 4.52
(2 d, 2 H, Jgem ) 11.4 Hz, PhCH2), 4.65 (dt, 1 H, J7,8 ) 9.6 Hz,
H-8f), 4.57 (dd, 1 H, H-6e), 4.52 and 4.46 (2 d, 2 H, Jgem ) 11.6
Hz, PhCH2), 4.42 (m, 3 H, H-9′a, 6′e, and 3e), 4.38-4.19 (m, 8 H,
H-8a, 9′f, 1c, 4d, 9′g, 9′b, 5b, and 5e), 4.11 (2 q, 2 H, H-5g, and
5f), 4.08-3.80 (m, 18 H, OCH2CH2SiMe3, H-5a, 9a, 9b, 9g, 6a,
6′d, 4c, 9f, 3c, 6g, 6f, 6b, 6′c, 5d, and COOMe-a), 3.71 (d, 1 H,
H-6d), 3.55 (m, 2 H, H-6c and OCH2CH2SiMe3), 3.44 (t, 1 H,
H-5c), 3.34 (near q, 1 H, J1,2 ) 8.0 Hz, H-2d), 3.33 (near t, 1 H,
H-2c), 3.17 (s, 3 H, COOMe-f), 2.54 (dt, 2 H, H-3eq-a and 3eq-b),
2.44 (dd, 1 H, J3eq,4 ) 5.2 Hz, Jgem ) 13.5 Hz, H-3eq-g), 2.13-1.88
(m, 55 H, 17 Ac, H-3ax-a, 3ax-b, 3ax-f, and 3eq-f), 1.59 (t, 1 H,
Jgem ) 13.5 Hz, H-3ax-g), 1.01 (near t, 2 H, OCH2CH2SiMe3), 0.00
(s, 9 H, OCH2CH2SiMe3); 13C NMR (100 MHz, CDCl3) δ 170.8,
170.8, 170.7, 170.6, 170.5, 170.5, 170.5, 170.4, 170.4, 170.3, 170.3,
169.9, 169.8, 169.8, 169.8, 169.7, 169.6, 167.7, 167.3, 166.0, 164.7,
164.4, 164.2, 138.7, 138.5, 138.4, 133.4, 133.2, 133.0, 130.2, 129.9,
129.6, 129.5, 128.7, 128.6, 128.4, 128.4, 128.1, 128.0, 128.0, 127.9,
127.6, 127.5, 127.3, 126.4, 126.2, 103.4, 102.3, 100.7, 99.4, 99.1,
98.1, 97.1, 96.7, 77.8, 77.2, 75.9, 75.5, 74.6, 73.3, 72.9, 72.6, 72.5,
72.4, 72.1, 71.8, 71.5, 71.0, 70.6, 70.1, 69.6, 69.5, 69.3, 68.9, 68.7,
68.6, 68.5, 67.8, 67.7, 67.4, 66.7, 66.6, 66.0, 62.7, 62.0, 61.8, 54.3,
52.3, 49.1, 49.0, 48.9, 38.2, 35.9, 35.7, 30.0, 29.6, 23.1, 22.8, 20.9,
20.7, 20.7, 20.6, 20.6, 20.6, 20.5, 20.5, 18.5, 14.1, -1.5; HRMS
(ESI) m/z found [M + 2Na]2+ 1465.9833, C137H167N5O61Si calcd
for [M + 2Na]2+ 1465.9838.
13.9; HRMS (ESI) m/z found [M
141H155Cl3N6O65 calcd for [M + 2Na]2+ 1561.3934.
2-O-Benzoyl-4-O-chloroacetyl-3,6-di-O-p-methoxylbenzyl-D-
+
2Na]2+ 1561.3934,
C
glucopyranosyl Trichloroacetimidate (33). To a solution of 31
(500 mg, 0.779 mmol) in degassed THF (7.8 mL) were added
polymethylhydrosiloxane (PMHS) (140 µL, 2.33 mmol), tetraki-
s(triphenylphosphine)palladium (179 mg, 0.155 mmol), and ZnCl2
(106 mg, 0.779 mmol) at room temperature. After stirring for 32 h
at room temperature, the completion of the reaction was confirmed
by TLC (EtOAc/PhMe ) 1:4). Then, H2O was added to the mixture
and filtered through a Celite pad, and the pad was washed with
EtOAc. The combined filtrate and washings were washed with
saturated NaHCO3 (aq), and brine. After drying over Na2SO4 and
being concentrated, the resulting residue was purified by flash
column chromatography using EtOAc/PhMe (1:5) as the eluent to
1
give the hemiacetal 32 (400 mg, 85%, R/ꢀ ) 7/1): H NMR (600
MHz, CDCl3) δ 8.05-7.42 (m, 5 H, Ph), 7.21-6.75 (4 d, 8 H,
Ar), 5.55 (br t, 1 H, J1,2 ) J1,OH ) 3.4 Hz, H-1R), 5.19 (t, 1 H, J3,4
) 8.9 Hz, H-4ꢀ), 5.15 (t, 1 H, J1,2 ) J2,3 ) 8.9 Hz, H-2ꢀ), 5.09 (t,
1 H, J3,4 ) J4,5 ) 9.6 Hz, H-4R), 5.08 (dd, 1 H, J1,2 ) 3.4 Hz, J2,3
) 9.6 Hz, H-2R), 4.73 (t, 1 H, J1,2 ) J1,OH ) 8.9 Hz, H-1ꢀ), 4.67
and 4.52 (2 d, 2 H, Jgem ) 11.6 Hz, ArCH2O), 4.44 and 4.39 (2 d,
2 H, Jgem ) 11.7 Hz, ArCH2O), 4.18 (m, 2 H, J2,3 ) J3,4 ) 9.6 Hz,
H-3R and 5R), 3.92 (d, 1 H, J1,OH ) 8.9 Hz, OH-ꢀ), 3.87 (t, 1 H,
J2,3 ) J3,4 ) 8.9 Hz, H-3ꢀ), 3.78 and 3.74 (2 s, 6 H, 2 MeO), 3.69
[Methyl 5-Acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-
3,5-dideoxy-D-glycero-r-D-galacto-2-nonulopyranosylono-1′,9-
lactone)-4,7-di-O-acetyl-3,5-dideoxy-D-glycero-r-D-galacto-2-
nonulopyranosylonate]-(2f3)-2,4,6-tri-O-benzoyl-ꢀ-D-
galactopyranosyl-(1f3)-2-acetamido-4,6-di-O-benzoyl-2-deoxy-
ꢀ-D-galactopyranosyl-(1f4)-{[methyl 5-acetamido-8-O-(5-acet-
amido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-r-D-galacto-
2-nonulopyranosylono-1′,9-lactone)-4,7-di-O-acetyl-3,5-dideoxy-
D-glycero-r-D-galacto-2-nonulopyranosylonate]-(2f3)}-2,6-di-O-
benzoyl-r-D-galactopyranosyl Trichloroacetimidate (20). To a
solution of 18 (795 mg, 261 µmol) in CH2Cl2 (3.9 mL) was added
trifluoroacetic acid (1.3 mL) at 0 °C. After stirring for 3 h at room
temperature as the reaction was monitored by TLC (PhMe/MeOH
) 5:1), the reaction mixture was coevaporated with toluene. The
resulting residue was purified by flash column chromatography
using CHCl3/MeOH (17.5:1 f 15:1 f 10:1) as the eluent to give
19 (765 mg, 99%): HRMS (ESI) m/z found [M + 2Na]+ 1489.9383,
and 3.61 (2 d, 2 H, Jgem ) 14.4 Hz, ClCH2), 3.58 (d, 1 H, J1,OH
)
3.4 Hz, OH-R), 3.47 (dd, 1 H, Jgem ) 10.3 Hz, J5,6 ) 5.5 Hz, H-6R),
3.43 (dd, 1 H, Jgem ) 10.3 Hz, J5,6′ ) 3.4 Hz, H-6′R); HRMS (ESI)
m/z found [M + Na]+ 623.1658, C31H33ClO10 calcd for [M + Na]+
623.1659.
To a solution of 32 (352 mg, 0.585 mmol) in CH2Cl2 (5.8 mL)
were added trichloroacetonitrile (1.2 mL, 11.7 mmol) and K2CO3
(243 mg, 1.76 mmol) at room temperature. After stirring for 3 h at
room temperature as the reaction was monitored by TLC (EtOAc/
hexane ) 1:2), the reaction mixture was filtered through cotton,
washed with CH2Cl2, and then evaporated. The resulting residue
was purified by flash column chromatography using EtOAc/hexane
(1:5 to 1:4) as the eluent to give 33: [R-isomer, 176 mg (40%) and
ꢀ-isomer, 230 mg (53%)]. 33r: [R]D ) +77.1° (c 0.7, CHCl3); 1H
NMR (500 MHz, CDCl3) δ 8.54 (s, 1 H, CdNH), 7.98-7.41 (m,
5 H, Ph), 7.23-6.75 (4 d, 8 H, Ar), 6.63 (d, 1 H, J1,2 ) 3.5 Hz,
H-1), 5.38 (dd, 1 H, J1,2 ) 3.5 Hz, J2,3 ) 9.5 Hz, H-2), 5.35 (t, 1
C
139H155N5O65 calcd for [M + 2Na]+ 1489.9380.
To a solution of 19 (200 mg, 68.1 µmol) in CH2Cl2 (0.68 mL)
were added trichloroacetonitrile (136 µL, 1.36 mmol) and DBU
(12 µL, 81.7 µmol) at 0 °C. After stirring for 2 h at room
temperature as the reaction was monitored by TLC (PhMe/MeOH
) 5:1), the reaction mixture was evaporated. The resulting residue
was purified by flash column chromatography using CHCl3/MeOH
J. Org. Chem. Vol. 74, No. 8, 2009 3019

Imamura et al.
H, J3,4 ) J4,5 ) 10.0 Hz, H-4), 4.65 and 4.54 (2 d, 2 H, Jgem
)
column chromatography using EtOAc/PhMe (1:5) as the eluent to
1
11.5 Hz, ArCH2O), 4.46 and 4.37 (2 d, 2 H, Jgem ) 11.5 Hz,
ArCH2O), 4.23 (near t, 1 H, J2,3 ) 9.5 Hz, J3,4 ) 10.0 Hz, H-3),
4.11 (m, 1 H, J4,5 ) 10.0 Hz, J5,6 ) J5,6′ ) 4.0 Hz, H-5), 3.80 and
3.75 (2 s, 6 H, 2 MeO), 3.71 and 3.66 (2 d, 2 H, Jgem ) 15.0 Hz,
ClCH2), 3.57 (dd, 1 H, Jgem ) 11.0 Hz, J5,6 ) 4.0 Hz, H-6), 3.52
(dd, 1 H, Jgem ) 11.0 Hz, J5,6′ ) 4.0 Hz, H-6′); 13C NMR (125
MHz, CDCl3) δ 165.8, 165.1, 160.3, 159.3, 133.4, 129.7, 129.7,
129.7, 129.4, 129.0, 128.4, 113.7, 93.5, 75.8, 74.3, 73.2, 72.3, 71.7,
71.1, 68.2, 55.2, 55.2, 40.5; HRMS (ESI) m/z found [M + Na]+
766.0750, C33H33Cl4NO10 calcd for [M + Na]+ 766.0756. 33ꢀ: [R]D
give 36 (85 mg, 96%): [R]D ) +5.4° (c 1.7, CHCl3); H NMR
(400 MHz, CDCl3) δ 8.01-7.37 (m, 10 H, 2 Ph), 7.18-6.66 (4 d,
8 H, Ar), 5.81 (m, 1 H, J4,5 ) 15.1 Hz, J5,6 ) 7.8 Hz, J5,6′ ) 6.8
Hz, H-5i), 5.70 (d, 1 H, J2,NH ) 9.1 Hz, NH), 5.48 (t, 1 H, J2,3
)
J3,4 ) 7.3 Hz, H-3i), 5.42 (dd, 1 H, J3,4 ) 7.3 Hz, J4,5 ) 15.1 Hz,
H-4i), 5.16 (near t, 1 H, J1,2 ) 7.8 Hz, J2,3 ) 9.2 Hz, H-2h), 4.64
(t, 2 H, Jgem ) 11.4 Hz, 2 ArCH2O), 4.45 (d, 1 H, J1,2 ) 7.8 Hz,
H-1h), 4.40 and 4.33 (2 d, 2 H, Jgem ) 11.4 Hz, 2 ArCH2O), 4.38
(m, 1 H, H-2i), 4.08 (dd, 1 H, Jgem ) 9.6 Hz, J1,2 ) 2.3 Hz, H-1i),
3.78 and 3.74 (2 s, 6 H, 2 MeO), 3.74 (dt, 1 H, J3,4 ) J4,5 ) 9.2
Hz, J4,OH ) 1.8 Hz, H-4h), 3.63 (t, 1 H, J2,3 ) J3,4 ) 9.2 Hz, H-3h),
3.57 (m, 3 H, H-6h, 6′h, and H-1′i), 3.45 (m, 1 H, J4,5 ) 9.2 Hz,
H-5h), 2.93 (d, 1 H, J4,OH ) 1.8 Hz, OH), 1.97 (near dd, 2 H, Jgem
) 13.2 Hz, J5,6 ) 7.8 Hz, J5,6′ ) 6.8 Hz, H-6i and 6′i), 1.72 (t, 1
H, NHCOCH2), 1.37 (m, 1 H, NHCOCH2), 1.26 (m, 52 H, 26 CH2),
0.87 (t, 6 H, 2 Me); 13C NMR (100 MHz, CDCl3) δ 172.5, 165.2,
165.0, 159.2, 159.1, 137.1, 133.2, 132.7, 130.3, 130.0, 129.6, 129.5,
129.3, 128.4, 128.2, 124.7, 113.7, 113.6, 100.8, 81.1, 74.3, 73.9,
73.8, 73.5, 73.3, 72.6, 70.1, 67.0, 55.1, 55.0, 50.3, 36.3, 32.2, 31.8,
29.6, 29.6, 29.4, 29.4, 29.3, 29.2, 29.1, 28.8, 25.4, 22.6, 14.0; HRMS
(ESI) m/z found [M + Na]+ 1198.7533, C72H105NO12 calcd for [M
+ Na]+ 1198.7534.
1
) +43.5° (c 1.0, CHCl3); H NMR (400 MHz, CDCl3) δ 8.63 (s,
1 H, CdNH), 7.98-7.40 (m, 5 H, Ph), 7.24-6.69 (4 d, 8 H, Ar),
5.96 (d, 1 H, J1,2 ) 7.8 Hz, H-1), 5.58 (near t, 1 H, J1,2 ) 7.8 Hz,
J2,3 ) 8.6 Hz, H-2), 5.33 (t, 1 H, J3,4 ) J4,5 ) 9.1 Hz, H-4), 4.58
and 4.50 (2 d, 2 H, Jgem ) 11.4 Hz, ArCH2O), 4.45 and 4.40 (2 d,
2 H, Jgem ) 11.2 Hz, ArCH2O), 3.93 (near t, 1 H, J2,3 ) 8.6 Hz,
J3,4 ) 9.1 Hz, H-3), 3.85 (m, 1 H, J4,5 ) 9.1 Hz, H-5), 3.79 and
3.71 (2 s, 6 H, 2 MeO), 3.74-3.59 (m, 4 H, ClCH2, H-6, and 6′);
13C NMR (100 MHz, CDCl3) δ 165.9, 164.5, 161.2, 159.3, 159.2,
133.3, 129.7, 129.6, 129.5, 129.4, 129.3, 128.4, 113.7, 113.6, 95.8,
90.2, 78.5, 73.7, 73.4, 73.2, 72.2, 71.8, 68.8, 55.2, 55.1, 40.5; HRMS
(ESI) m/z found [M + Na]+ 766.0750, C33H33Cl4NO10 calcd for
[M + Na]+ 766.0756.
[Methyl 5-acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-
3,5-dideoxy-D-glycero-r-D-galacto-2-nonulopyranosylono-1′,9-
lactone)-4,7-di-O-acetyl-3,5-dideoxy-D-glycero-r-D-galacto-2-
nonulopyranosylonate]-(2f3)-2,4,6-tri-O-benzoyl-ꢀ-D-
galactopyranosyl-(1f3)-2-acetamido-4,6-di-O-benzoyl-2-deoxy-
ꢀ-D-galactopyranosyl-(1f4)-{[methyl 5-acetamido-8-O-(5-acet-
amido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-r-D-galacto-
2-nonulopyranosylono-1′,9-lactone)-4,7-di-O-acetyl-3,5-dideoxy-
D-glycero-r-D-galacto-2-nonulopyranosylonate]-(2f3)}-2,6-di-O-
benzoyl-ꢀ-D-galactopyranosyl-(1f4)-2-O-benzoyl-3,6-di-O-p-
methoxybenzyl-ꢀ-D-glucopyranosyl-(1f1)-(2S,3R,4E)-3-O-benzoyl-
2-octadecanamido-4-octadecene-1,3-diol (40). To a mixture of 20
(146 mg, 0.0474 mmol) and 36 (85 mg, 0.0722 mmol) in CH2Cl2
(1.2 mL) was added 4 Å molecular sieves (AW-300) (200 mg) at
room temperature. After stirring for 2 h and then cooling to 0 °C,
TMSOTf (1.0 µL, 5.52 µmol) was added to the mixture. After
stirring for 1 h at 0 °C as the reaction was monitored by TLC
(PhMe/MeOH ) 4:1), the reaction was quenched by saturated
NaHCO3 (aq) and filtered through a Celite pad, and the pad was
washed with CHCl3. The combined filtrate and washings were
washed with brine, dried over Na2SO4, and concentrated. The
resulting residue was purified by flash column chromatography
using PhMe/MeOH (8:1 to 7:1) as the eluent to give 40 (177 mg,
91%): [R]D ) +3.2° (c 0.5, CHCl3); 1H NMR (600 MHz, CDCl3)
δ 8.08-7.28 (m, 45 H, 9 Ph), 7.07-6.56 (4 d, 8 H, Ar), 5.97 (near
2-O-Benzoyl-4-O-chloroacetyl-3,6-di-O-p-methoxybenzyl-ꢀ-D-
glucopyranosyl-(1f1)-(2S,3R,4E)-3-O-benzoyl-2-octadecanamido-
4-octadecene-1,3-diol (35). To a mixture of 33r (176 mg, 0.236
mmol) and 34 (105 mg, 0.157 mmol) in CH2Cl2 (3.9 mL) was added
4 Å molecular sieves (AW-300) (300 mg) at room temperature.
After stirring for 2 h, TMSOTf (2.1 µL, 11.8 µmol) was added to
the mixture. After stirring for 3 h at room temperature as the reaction
was monitored by TLC (EtOAc/PhMe ) 1:5), the reaction was
quenched by saturated NaHCO3 (aq) and filtered through a Celite
pad, and the pad was washed with CHCl3. The combined filtrate
and washings were washed with brine, dried over Na2SO4, and
concentrated. The resulting residue was purified by flash column
chromatography using EtOAc/PhMe (1:10) as the eluent to give
1
35 (95 mg, 48%): [R]D ) +10.7° (c 1.6, CHCl3); H NMR (400
MHz, CDCl3) δ 8.03-7.39 (m, 10 H, 2 Ph), 7.16-6.68 (4 d, 8 H,
Ar), 5.83 (m, 1 H, J4,5 ) 15.1 Hz, J5,6 ) 7.3 Hz, J5,6′ ) 6.8 Hz,
H-5i), 5.71 (d, 1 H, J2,NH ) 9.1 Hz, NH), 5.51 (t, 1 H, J2,3 ) J3,4
) 6.8 Hz, H-3i), 5.44 (dd, 1 H, J3,4 ) 6.8 Hz, J4,5 ) 15.1 Hz,
H-4i), 5.25 (near t, 1 H, J1,2 ) 8.2 Hz, J2,3 ) 9.6 Hz, H-2h), 5.15
(t, 1 H, J3,4 ) J4,5 ) 9.6 Hz, H-4h), 4.53 and 4.46 (2 d, 2 H, Jgem
) 11.4 Hz, ArCH2O), 4.50 (d, 1 H, J1,2 ) 8.2 Hz, H-1h), 4.40 (m,
1 H, J1,2 ) 2.7 Hz, J2,3 ) 6.8 Hz, H-2i), 4.28 and 4.22 (2 d, 2 H,
Jgem ) 11.0 Hz, ArCH2O), 4.10 (dd, 1 H, Jgem ) 9.6 Hz, J1,2 ) 2.7
Hz, H-1i), 3.82 (t, 1 H, J2,3 ) J3,4 ) 9.6 Hz, H-3h), 3.78 and 3.70
(2 s, 6 H, 2 MeO), 3.65 (m, 2 H, ClCH2), 3.58 (m, 2 H, H-5h and
H-1′i), 3.45 (dd, 1 H, Jgem ) 10.0 Hz, J5,6 ) 5.0 Hz, H-6h), 3.38
(dd, 1 H, Jgem ) 10.0 Hz, J5,6′ ) 4.6 Hz, H-6′h), 1.98 (br dd, 2 H,
Jgem ) 14.1 Hz, J5,6 ) 7.3 Hz, J5,6′ ) 6.8 Hz, H-6i and 6′i), 1.74
and 1.37 (2 m, 2 H, NHCOCH2), 1.26 (m, 52 H, 26 CH2), 0.87 (t,
6 H, 2 Me); 13C NMR (100 MHz, CDCl3) δ 172.5, 165.9, 165.0,
164.9, 159.2, 159.1, 137.2, 133.3, 132.8, 130.2, 129.6, 129.5, 129.5,
129.3, 128.4, 128.2, 124.7, 113.7, 113.6, 100.6, 78.8, 74.3, 73.6,
73.5, 73.2, 72.9, 72.6, 69.3, 67.1, 55.1, 55.0, 50.3, 40.5, 36.3, 32.2,
31.8, 29.6, 29.4, 29.4, 29.3, 29.2, 29.1, 28.8, 25.4, 22.6, 14.0; HRMS
(ESI) m/z found [M + Na]+ 1274.7255, C74H106ClNO13 calcd for
[M + Na]+ 1274.7250.
s, 1 H, H-4d), 5.76 (m, 1 H, J4,5 ) 14.4 Hz, J5,6 ) 7.5 Hz, J5,6′
)
6.9 Hz, H-5i), 5.69 (d, 1 H, J3,4 ) 4.1 Hz, H-4e), 5.66 (d, 1 H,
J2,NH ) 8.9 Hz, NH-i), 5.55 (dt, 2 H, J3eq,4 ) 4.0 Hz, J4,5 ) 10.9
Hz, H-4g and NH-d), 5.49 (br d, 1 H, NH-b), 5.45 (t, 1 H, H-3i),
5.39 (dd, 2 H, H-4i and NH-f), 5.35-5.26 (m, 5 H, H-7g, 7b, 4b,
2c, and 2e), 5.22 (d, 1 H, J1,2 ) 8.9 Hz, H-1d), 5.15 (m, 4 H, H-8b,
8g, 2h, and NH-a), 5.08 (m, 1 H, H-4f), 4.98 (br dd, 1 H, H-7a),
4.95 (m, 1 H, H-4a), 4.84 (br dd, 1 H, H-7f), 4.82 (d, 1 H, J1,2
)
9.6 Hz, H-1c), 4.80 (m, 2 H, H-3d and ArCH2O), 4.63 (m, 3 H,
H-6c, 8f, and ArCH2O), 4.55 (d, 1 H, Jgem ) 10.9 Hz, ArCH2O),
4.40 (br d, 2 H, J1,2 ) 7.5 Hz, H-1e and 3e), 4.34 (d, 1 H, J1,2
)
8.2 Hz, H-1h), 4.32 (m, 1 H, H-2i), 4.28-3.96 (m, 24 H, H-9′b,
9′g, 9′f, 9′a, 4c, 5b, 3c, 6′c, 5g, 6b, 8a, 9a, 9b, 9g, 5a, 4h, 5e, 6e,
6′e, 5d, 6′d, 6d, 1i, and ArCH2O), 3.89 (dd, 1 H, H-6g), 3.84 (dd,
2 H, H-6a and 6f), 3.80 (t, 1 H, J2,3 ) J3,4 ) 8.9 Hz, H-3h), 3.77
(s, 3 H, COOMe-a), 3.71 (s, 3 H, MeO), 3.70 (m, 2 H, H-2d and
9f), 3.62 (near t, 1 H, H-5c), 3.43 (m, 6 H, H-6′h, 6h, 1′i, and
MeO), 3.33 (m, 1 H, H-5h), 3.23 (s, 3 H, COOMe-f), 2.57 (dd, 1
H, Jgem ) 13.0 Hz, J3eq,4 ) 4.1 Hz, H-3eq-b), 2.50 (dd, 1 H, Jgem
) 12.2 Hz, J3eq,4 ) 4.0 Hz, H-3eq-g), 2.33 (br dd, 1 H, H-3eq-a),
2.10-1.76 (m, 57 H, 17 Ac, H-3eq-f, 3ax-f, 3ax-a, 3ax-b, 6i, and
2-O-Benzoyl-3,6-di-O-p-methoxybenzyl-ꢀ-D-glucopyranosyl-
(1f1)-(2S,3R,4E)-3-O-benzoyl-2-octadecanamido-4-octadecene-
1,3-diol (36). To a solution of 35 (95 mg, 0.0758 mmol) in EtOH/
(CH2Cl)2 (3.6 mL/1.2 mL) was added DABCO (127 mg, 1.13
mmol) at room temperature. After stirring for 5 h at 55 °C as the
reaction was monitored by TLC (EtOAc/PhMe ) 1:3), the mixture
was diluted with EtOAc. The organic layer was washed with 2 M
HCl, saturated NaHCO3 (aq), and brine. After drying over Na2SO4
and being concentrated, the resulting residue was purified by flash
3020 J. Org. Chem. Vol. 74, No. 8, 2009

Ganglioside GQ1b
6′i), 1.67 (t, 1 H, NHCOCH2), 1.63 (t, 1 H, Jgem ) J3ax,4 ) 12.2
Hz, H-3ax-g), 1.34 (m, 1 H, NHCOCH2), 1.26 (m, 52 H, 26 CH2),
0.87 (2 t, 6 H, 2 Me); 13C NMR (100 MHz, CDCl3) δ 172.4, 170.8,
170.6, 170.5, 170.4, 170.4, 170.3, 170.3, 170.1, 170.1, 169.7, 169.6,
169.5, 167.3, 167.1, 166.3, 165.9, 165.8, 165.6, 165.4, 165.2, 165.0,
164.9, 164.7, 164.1, 164.0, 158.9, 158.7, 136.9, 133.1, 133.0, 132.9,
132.6, 130.1, 130.1, 130.0, 129.8, 129.6, 129.5, 129.4, 129.4, 129.3,
128.9, 128.8, 128.4, 128.3, 128.1, 124.6, 113.4, 113.3, 101.3, 100.8,
100.3, 99.6, 99.4, 98.9, 96.8, 95.7, 80.1, 77.2, 76.4, 75.1, 74.3, 73.9,
73.8, 73.4, 73.1, 72.8, 72.5, 72.1, 71.8, 71.5, 71.3, 71.2, 71.1, 70.8,
70.7, 70.3, 69.8, 69.4, 69.3, 69.2, 68.7, 68.5, 68.2, 67.8, 67.1, 66.8,
66.6, 63.3, 62.0, 61.7, 55.0, 54.6, 53.0, 52.2, 50.2, 48.9, 48.7, 38.8,
38.2, 36.9, 36.2, 35.4, 32.5, 32.1, 31.7, 29.8, 29.5, 29.4, 29.3, 29.2,
29.1, 29.0, 28.8, 25.3, 22.9, 22.8, 22.6, 22.5, 20.6, 20.6, 20.5, 20.4,
20.2, 20.1, 14.0; HRMS (ESI) m/z found [M + 2Na]2+ 2068.8101,
75.6, 74.8, 74.2, 74.0, 73.6, 73.3, 73.1, 72.5, 72.1, 72.0, 71.6, 71.4,
71.0, 70.9, 70.4, 70.1, 69.9, 69.5, 69.4, 69.4, 69.0, 68.7, 68.6, 68.5,
67.9, 67.7, 67.2, 67.0, 66.7, 63.7, 62.1, 62.0, 61.8, 54.0, 53.2, 52.4,
51.2, 49.1, 48.9, 48.8, 38.8, 38.3, 36.4, 35.4, 32.2, 31.9, 29.7, 29.6,
29.5, 29.3, 29.2, 29.2, 25.4, 23.1, 23.1, 23.0, 22.6, 20.8, 20.7, 20.6,
20.3, 14.1; HRMS (ESI) m/z found [M + 2Na]2+ 2031.8146,
C
209H256N6O73 calcd for [M + 2Na]2+ 2031.8149.
2-(Trimethylsilyl)ethyl [Methyl 5-acetamido-8-O-(5-aceta-
mido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-r-D-galacto-
2-nonulopyranosylono-1′,9-lactone)-4,7-di-O-acetyl-3,5-dideoxy-
D-glycero-r-D-galacto-2-nonulopyranosylonate]-(2f3)-2,4,6-tri-
O-benzoyl-ꢀ-D-galactopyranosyl-(1f3)-2-acetamido-4,6-di-O-
benzoyl-2-deoxy-ꢀ-D-galactopyranosyl-(1f4)-{[methyl 5-
acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-
D-glycero-r-D-galacto-2-nonulopyranosylono-1′,9-lactone)-4,7-
di-O-acetyl-3,5-dideoxy-D-glycero-r-D-galacto-2-nonulopyra-
nosylonate]-(2f3)}-2,6-di-O-benzoyl-ꢀ-D-galactopyranosyl-(1f4)-
2-O-benzoyl-3,6-di-O-benzyl-ꢀ-D-glucopyranoside (42). To a mixture
of 20 (189 mg, 0.0613 mmol) and 38 (52 mg, 0.0919 mmol) in CH2Cl2
(1.5 mL) was added 4 Å molecular sieves (AW-300) (250 mg) at room
temperature. After stirring for 2 h and then cooling to 0 °C, TMSOTf
(1.1 µL, 6.13 µmol) was added to the mixture. After stirring for 2 h
at 0 °C as the reaction was monitored by TLC (PhMe/MeOH ) 4:1),
the reaction was quenched by saturated NaHCO3 (aq) and filtered
through a Celite pad, and the pad was washed with CHCl3. The
combined filtrate and washings were washed with brine, dried over
Na2SO4, and concentrated. The residue was purified by flash column
chromatography using PhMe/MeOH (6:1) as the eluent to give 42 (135
mg, 63%): [R]D ) -0.6° (c 1.5, CHCl3); 1H NMR (500 MHz, CDCl3)
δ 8.13-6.89 (m, 50 H, 10 Ph), 5.95 (br s, 1 H, H-4d), 5.85 (br d, 1
H, NH-d), 5.70 (d, 1 H, J3,4 ) 3.4 Hz, H-4e), 5.63 (d, 1 H, J5,NH ) 9.0
Hz, NH-b), 5.54 (dt, 1 H, J3eq,4 ) 5.3 Hz, J3ax,4 ) 12.2 Hz, J4,5 ) 10.2
C
211H258N6O76 calcd for [M + 2Na]2+ 2068.8146.
[Methyl 5-acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-
3,5-dideoxy-D-glycero-r-D-galacto-2-nonulopyranosylono-1′,9-
lactone)-4,7-di-O-acetyl-3,5-dideoxy-D-glycero-r-D-galacto-2-
nonulopyranosylonate]-(2f3)-2,4,6-tri-O-benzoyl-ꢀ-D-
galactopyranosyl-(1f3)-2-acetamido-4,6-di-O-benzoyl-2-deoxy-
ꢀ-D-galactopyranosyl-(1f4)-{[methyl 5-acetamido-8-O-(5-acet-
amido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-r-D-galacto-
2-nonulopyranosylono-1′,9-lactone)-4,7-di-O-acetyl-3,5-dideoxy-
D-glycero-r-D-galacto-2-nonulopyranosylonate]-(2f3)}-2,6-di-O-
benzoyl-ꢀ-D-galactopyranosyl-(1f4)-2-O-benzoyl-3,6-di-O-benzyl-
ꢀ-D-glucopyranosyl-(1f1)-(2S,3R,4E)-3-O-benzyl-2-
octadecanamido-4-octadecene-1,3-diol (41). To a mixture of 20
(148 mg, 0.0480 mmol) and 37 (79 mg, 0.0720 mmol) in CH2Cl2
(1.0 mL) was added 4 Å molecular sieves (AW-300) (180 mg) at
room temperature. After stirring for 2 h and then cooling to 0 °C,
TMSOTf (1.0 µL, 5.52 µmol) was added to the mixture. After
stirring for 2 h at 0 °C as the reaction was monitored by TLC
(PhMe/MeOH ) 4:1), additional TMSOTf (1.0 µL, 5.52 µmol) was
added to the mixture. After the stirring was continued for 24 h, the
reaction was quenched by saturated NaHCO3 (aq) and filtered
through a Celite pad, and the pad was washed with CHCl3. The
combined filtrate and washings were washed with brine, dried over
Na2SO4 and concentrated. The resulting residue was purified by
flash column chromatography (PhMe/MeOH ) 9:1 to 8:1) to give
Hz, H-4g), 5.45 (d, 1 H, J5,NH ) 8.7 Hz, NH-g), 5.43 (d, 1 H, J5,NH
)
8.5 Hz, NH-a), 5.34 (m, 1 H, H-4b), 5.32 (dd, 3 H, J6,7 ) 2.1 Hz, J7,8
) 9.0 Hz, J1,2 ) 7.8 Hz, H-7b, 7g, and 2e), 5.27 (d, 1 H, NH-f), 5.24
(t, 1 H, J1,2 ) 7.8 Hz, J2,3 ) 9.5 Hz, H-2c), 5.21 (d, 1 H, J1,2 ) 8.5
Hz, H-1d), 5.17 (m, 3 H, J1,2 ) 7.8 Hz, J7,8 ) 9.0 Hz, H-2h, 8b, and
8g), 5.08 (m, 1 H, H-4f), 5.01 (dd, 1 H, J6,7 ) 1.7 Hz, J7,8 ) 11.2 Hz,
H-7a), 4.96 (br dt, 1 H, H-4a), 4.86 and 4.62 (2 d, 2 H, Jgem ) 10.9
Hz, PhCH2), 4.84 (dd, 1 H, J6,7 ) 2.9 Hz, J7,8 ) 9.2 Hz, H-7f), 4.75
(br dd, 1 H, H-3d), 4.67 (d, 1 H, J1,2 ) 7.8 Hz, H-1c), 4.63 (m, 1 H,
J7,8 ) 9.2 Hz, H-8f), 4.55 (br d, 1 H, H-6c), 4.50 and 4.28 (2 d, 2 H,
Jgem ) 12.2 Hz, PhCH2), 4.42 (d, 3 H, J1,2 ) 7.8 Hz, H-1e, 3e, and
1h), 4.33-4.19 (m, 10 H, H-9′b, 9′g, 9′a, 9′f, 8a, 6e, 6′e, 6′d, 6d, and
5b), 4.11 (q, 1 H, J4,5 ) 10.2 Hz, J5,6 ) 10.4 Hz, J5,NH ) 8.7 Hz,
H-5g), 4.06-3.97 (m, 12 H, H-5f, 6b, 5a, 3c, 9a, 9b, 4c, 4h, 6′c, 9b,
5e, and 5d), 3.92 (dd, 1 H, J5,6 ) 10.4 Hz, J6,7 ) 2.1 Hz, H-6g), 3.87
(m, 1 H, OCH2CH2SiMe3), 3.85-3.72 (m, 8 H, H-6a, 6f, 3h, 9f, 2d,
and COOMe-a), 3.56 (m, 2 H, Jgem ) 10.7 Hz, H-6′h and 5c), 3.50
(dd, 1 H, Jgem ) 10.7 Hz, H-6h), 3.41 (m, 1 H, OCH2CH2SiMe3),
3.35 (m, 1 H, H-5h), 3.22 (s, 3 H, COOMe-f), 2.58 (br dd, 1 H, H-3eq-
b), 2.50 (dd, 1 H, J3eq,4 ) 5.3 Hz, Jgem ) 12.2 Hz, H-3eq-g), 2.27 (br
dd, 1 H, H-3eq-a), 2.11-1.80 (m, 55 H, 17 Ac, H-3ax-b, 3ax-a, 3eq-
f, and 3ax-f), 1.63 (t, 1 H, J3ax,4 ) Jgem ) 12.2 Hz, H-3ax-g), 0.81 (m,
2 H, OCH2CH2SiMe3), -0.12 (s, 9 H, OCH2CH2SiMe3); 13C NMR
(100 MHz, CDCl3) δ 170.9, 170.6, 170.5, 170.5, 170.5, 170.4, 170.3,
170.2, 170.2, 169.8, 169.7, 169.7, 169.6, 167.4, 167.2, 166.1, 165.9,
165.9, 165.7, 165.4, 164.9, 164.6, 164.1, 138.2, 138.2, 133.2, 133.1,
133.1, 132.9, 132.8, 132.7, 130.2, 130.1, 129.9, 129.9, 129.7, 129.6,
129.6, 129.5, 129.5, 129.4, 128.9, 128.5, 128.4, 128.4, 128.3, 128.2,
128.2, 127.9, 127.8, 127.7, 127.4, 127.1, 101.2, 100.4, 100.1, 99.8,
99.5, 99.0, 97.1, 96.0, 80.8, 77.2, 76.4, 76.2, 74.7, 74.0, 73.8, 73.2,
73.1, 72.5, 72.1, 72.0, 71.6, 71.3, 70.9, 70.4, 69.8, 69.5, 69.3, 69.2,
69.0, 68.7, 68.5, 68.4, 68.0, 67.2, 67.1, 67.0, 66.9, 66.7, 63.5, 62.1,
62.0, 61.8, 54.3, 53.1, 52.3, 49.1, 48.9, 38.7, 38.2, 35.5, 35.4, 29.6,
23.0, 23.0, 22.9, 22.7, 20.7, 20.7, 20.6, 20.6, 20.6, 20.5, 20.3, 20.2,
17.8, -1.5; HRMS (ESI) m/z found [M + 2Na]2+ 1763.0599,
1
41 (140 mg, 73%): [R]D ) -2.5° (c 1.0, CHCl3); H NMR (600
MHz, CDCl3) δ 8.01-6.89 (m, 55 H, 11 Ph), 5.97 (near s, 1 H,
H-4d), 5.69 (d, 1 H, J3,4 ) 2.7 Hz, H-4e), 5.54 (m, 4 H, H-4g, 5i,
and 2 NH), 5.36 (m, 5 H, H-4b, 7b, and 3 NH), 5.32 (dd, 1 H, J6,7
) 2.0 Hz, J7,8 ) 8.2 Hz, H-7g), 5.19 (m, 7 H, H-8b, 2e, 2c, 1d, 2h,
8g, and 4i), 5.08 (m, 1 H, H-4f), 5.01 (near d, 1 H, J7,8 ) 8.9 Hz,
H-7a), 4.98 (m, 1 H, H-4a), 4.89 (d, 1 H, Jgem ) 10.9 Hz, PhCH2),
4.83 (near dd, 1 H, J7,8 ) 9.6 Hz, H-7f), 4.62 (m, 5 H, H-3d, 8f,
6c, 6′c, and PhCH2), 4.60 (d, 1 H, J1,2 ) 7.5 Hz, H-1c), 4.49 and
4.28 (2 d, 2 H, Jgem ) 11.6 Hz, PhCH2), 4.49 and 4.17 (2 d, 2 H,
Jgem ) 11.6 Hz, PhCH2), 4.44 (m, 2 H, H-1e and 3e), 4.35 (d, 1 H,
J1,2 ) 7.5 Hz, H-1h), 4.31-4.20 (m, 8 H, H-9′g, 9′b, 9′f, 9f, 5b,
9′a, 1′i, and 8a), 4.13-3.97 (m, 10 H, H-6b, 5a, 5g, 4h, 4c, 3c, 5f,
2i, 9b, and 9g), 3.89 (dd, 1 H, J5,6 ) 10.3 Hz, J6,7 ) 2.0 Hz, H-6g),
3.84 (m, 2 H, H-6a and 6f), 3.78 (m, 5 H, H-3h, 2d, and COOMe-
a), 3.71 (m, 2 H, H-3i and 9a), 3.61 (br t, 1 H, H-5c), 3.53 (br dd,
1 H, Jgem ) 10.9 Hz, H-6′h), 3.46 (br d, 1 H, Jgem ) 10.9 Hz,
H-6h), 3.35 (br dd, 1 H, H-1i), 3.26 (m, 1 H, H-5h), 3.23 (s, 3 H,
COOMe-f), 2.57 (br dd, 1 H, H-3eq-b), 2.48 (dd, 1 H, H-3eq-g),
2.22 (m, 1 H, H-3eq-a), 2.11-1.82 (13 s and m, 57 H, 17 Ac,
H-3eq-f, 3ax-f, 3ax-a, 3ax-b, 6i, and 6′i), 1.61 (m, 3 H, H-3ax-g,
NHCOCH2), 1.26 (m, 52 H, 26 CH2), 0.87 (t, 6 H, 2 Me); 13C
NMR (125 MHz, CDCl3) δ 172.3, 170.8, 170.7, 170.6, 170.6, 170.5,
170.4, 170.4, 170.2, 169.8, 169.8, 169.7, 167.5, 167.3, 166.2, 166.0,
165.8, 165.4, 165.2, 164.6, 164.2, 164.1, 138.5, 138.2, 138.0, 137.0,
133.4, 133.3, 133.1, 133.1, 133.0, 132.8, 130.3, 130.0, 129.9, 129.8,
129.8, 129.7, 129.6, 129.6, 129.5, 129.5, 129.3, 128.6, 128.5, 128.5,
128.4, 128.3, 128.1, 128.0, 128.0, 127.9, 127.6, 127.5, 127.4, 127.3,
127.2, 101.3, 100.2, 100.2, 99.9, 99.6, 99.0, 97.1, 96.1, 80.3, 79.0,
C
171H193N5O71Si calcd for [M + 2Na]2+ 1763.0599.
J. Org. Chem. Vol. 74, No. 8, 2009 3021

Imamura et al.
Benzyl [Methyl 5-acetamido-8-O-(5-acetamido-4,7,8,9-tetra-
O-acetyl-3,5-dideoxy-D-glycero-r-D-galacto-2-nonulopyranosy-
lono-1′,9-lactone)-4,7-di-O-acetyl-3,5-dideoxy-D-glycero-r-D-ga-
lacto-2-nonulopyranosylonate]-(2f3)-2,4,6-tri-O-benzoyl-ꢀ-D-
galactopyranosyl-(1f3)-2-acetamido-4,6-di-O-benzoyl-2-deoxy-
ꢀ-D-galactopyranosyl-(1f4)-{[methyl 5-acetamido-8-O-(5-acet-
amido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-r-D-galacto-
2-nonulopyranosylono-1′,9-lactone)-4,7-di-O-acetyl-3,5-dideoxy-
D-glycero-r-D-galacto-2-nonulopyranosylonate]-(2f3)}-2,6-di-O-
benzoyl-ꢀ-D-galactopyranosyl-(1f4)-2,3,6-tri-O-benzyl-ꢀ-D-
glucopyranosyl-(1f6)-2,3,4-tri-O-benzyl-ꢀ-D-glucopyranoside (43).
To a mixture of 20 (140 mg, 0.0454 mmol) and 39 (66 mg, 0.0681
mmol) in CH2Cl2 (1.1 mL) was added 4 Å molecular sieves (AW-
300) (210 mg) at room temperature. After stirring for 2 h and then
cooling to 0 °C, TMSOTf (1.0 µL, 5.53 µmol) was added to the
mixture. After stirring for 5 h at 0 °C as the reaction was monitored
by TLC (PhMe/MeOH ) 4:1), the reaction was quenched by saturated
NaHCO3 (aq) and filtered through a Celite pad, and the pad was
washed with CHCl3. The combined filtrate and washings were washed
with brine, dried over Na2SO4, and concentrated. The resulting residue
was purified by flash column chromatography using PhMe/MeOH (8:
1) as the eluent to give 43 (140 mg, 80%): [R]D ) -5.0 (c 2.0, CHCl3);
1H NMR (600 MHz, CDCl3) δ 8.13-6.94 (m, 70 H, 14 Ph), 5.97 (br
s, 1 H, H-4d), 5.78 (br d, 1 H, NH-d), 5.70 (d, 1 H, J3,4 ) 3.4 Hz,
H-4e), 5.55 (dt, 1 H, J3eq,4 ) 4.8 Hz, J3ax,4 ) 13.0 Hz, J4,5 ) 10.3 Hz,
H-4g), 5.52 (d, 1 H, J5,NH ) 9.6 Hz, NH-b), 5.39-5.31 (m, 6 H, H-4b,
7b, 7g, and 3 NH), 5.28 (m, 1 H, H-2e), 5.24 (d, 1 H, J1,2 ) 8.9 Hz,
H-1d), 5.20 (near t, 1 H, J1,2 ) 7.5 Hz, J2,3 ) 8.2 Hz, H-2c), 5.16 (m,
2 H, H-8b and 8g), 5.08 (m, 1 H, H-4f), 5.01 (dd, 1 H, J6,7 ) 1.7 Hz,
J7,8 ) 10.3 Hz, H-7a), 4.95 (dt, 1 H, J3eq,4 ) 4.1 Hz, H-4a), 4.92-4.20
(14 d, 14 H, PhCH2), 4.84 (dd, 1 H, H-7f), 4.67 (d, 1 H, J1,2 ) 7.5
Hz, H-1c), 4.63 (dt, 1 H, H-8f), 4.41 (d, 3 H, J1,2 ) 7.5 Hz, H-1e, 3e,
and H-1h), 4.36 (d, 1 H, J1,2 ) 7.5 Hz, H-1h), 4.28-4.18 (m, 7 H,
H-9′b, 9′g, 9f, 9a, 8a, 6b, and 5b), 4.13-3.98 (m, 8 H, H-5g, 5a, 3c,
4c, 5f, 9′a, 9b, and 9g), 3.91-3.35 (m, 11 H, Glc unit), 3.89 (br dd,
1 H, H-6g), 3.85 (br dd, 1 H, H-6f), 3.83 (br dd, 1 H, J6,7 ) 1.7 Hz,
H-6a), 3.78 (s, 3 H, COOMe-a), 3.70 (br d, 1 H, H-9′f), 3.60 (m, 1 H,
H-2d), 3.24 (s, 3 H, COOMe-f), 3.15 (m, 1 H, H-5h), 2.57 (dd, 1 H,
Jgem ) 13.0 Hz, J3eq,4 ) 4.8 Hz, H-3eq-b), 2.50 (dd, 1 H, Jgem ) 13.0
Hz, J3eq,4 ) 4.8 Hz, H-3eq-g), 2.29 (br dd, 1 H, H-3eq-a), 2.11-1.78
(m, 55 H, 17 Ac, H-3ax-b, 3ax-a, 3ax-f, and 3eq-f), 1.63 (t, 1 H, Jgem
) J3ax,4 ) 13.0 Hz, H-3ax-g); 13C NMR (125 MHz, CDCl3) δ 171.0,
170.7, 170.6, 170.6, 170.5, 170.5, 170.4, 170.3, 170.2, 169.8, 169.8,
169.7, 167.4, 167.3, 166.1, 166.0, 165.7, 165.7, 165.4, 164.7, 164.2,
138.8, 138.5, 138.5, 138.3, 138.2, 138.0, 137.5, 133.3, 133.2, 133.1,
133.0, 132.8, 132.8, 130.3, 129.9, 129.9, 129.7, 129.7, 129.6, 129.6,
129.5, 129.4, 129.3, 128.5, 128.3, 128.3, 128.2, 128.2, 128.2, 128.0,
128.0, 127.8, 127.7, 127.7, 127.6, 127.5, 127.4, 127.3, 103. 7, 102.6,
101.4, 100.0, 99.5, 99.0, 97.1, 96.0, 84.6, 82.8, 82.2, 81.5, 78.2, 76.2,
76.0, 75.6, 75.1, 75.0, 74.8, 74.8, 74.7, 74.3, 74.0, 73.3, 73.1, 72.5,
72.2, 72.0, 71.6, 71.4, 71.1, 70.8, 70.4, 69.9, 69.8, 69.5, 69.4, 69.4,
69.2, 69.0, 68.8, 68.6, 68.4, 68.4, 68.1, 67.3, 67.0, 66.7, 66.7, 63.4,
62.1, 62.0, 61.9, 54.6, 53.2, 52.4, 49.1, 48.9, 48.9, 38.7, 38.3, 35.7,
35.4, 29.6, 23.1, 23.0, 22.8, 20.8, 20.7, 20.7, 20.7, 20.6, 20.6, 20.3,
20.3; HRMS (ESI) m/z found [M + 2Na]2+ 1967.1553, C200H217N5O75
calcd for [M + 2Na]2+ 1967.1557.
at 0 °C. After stirring for 1 h at 0 °C as the reaction was monitored
by TLC (PhMe/MeOH ) 4:1), the reaction mixture was diluted
with CHCl3. The organic layer was washed with ice-cooled saturated
Na2CO3 (aq) (twice) and brine. After drying over Na2SO4 and being
concentrated, the resulting residue was purified by flash column
chromatography using CHCl3/MeOH (25:1 to 10:1) to give 44 (131
mg, 97%): [R]D ) +4.7 (c 0.5, CHCl3); 1H NMR (600 Hz, CDCl3)
δ 8.08-7.28 (m, 45 H, 9 Ph), 5.94 (br s, 1 H, H-4d), 5.86 (m, 1 H,
J4,5 ) 15.1 Hz, J5,6 ) 7.5 Hz, J5,6′ ) 6.9 Hz, H-5i), 5.74 (d, 1 H,
J2,NH ) 9.6 Hz, NH-i), 5.70 (d, 1 H, J3,4 ) 3.4 Hz, H-4e), 5.57 (m,
1 H, H-4g), 5.54 (t, 1 H, J2,3 ) J3,4 ) 8.2 Hz, H-3i), 5.42 (dd, 1 H,
J3,4 ) 8.2 Hz, J4,5 ) 15.1 Hz, H-4i), 5.38 (d, 1 H, J5,NH ) 10.9 Hz,
NH-f), 5.34 (m, 3 H, H-7b, 7g, and 2c), 5.28 (m, 1 H, H-2e), 5.20
(m, 2 H, H-8b and 8g), 5.16 (d, 1 H, J1,2 ) 8.2 Hz, H-1d), 5.10 (m,
2 H, H-4f and 2h), 5.00 (br dd, 1 H, H-7a), 4.92 (m, 1 H, H-4a),
4.86 (d, 2 H, H-7f and 3d), 4.77 (d, 1 H, J1,2 ) 7.5 Hz, H-1c), 4.72
(m, 1 H, H-6′c), 4.65 (br dt, 1 H, H-8f), 4.61 (m, 1 H, H-6′e),
4.45-4.39 (m, 7 H, H-1e, 3e, 1h, 4c, 5d, 5e, and 2i), 4.28-4.21
(m, 9 H, H-3c, 8a, 9′b, 9′g, 9′a, 9f, 5c, 6c, and 6e), 4.12 (q, 2 H,
J4,5 ) 10.3 Hz, H-5g and 5b), 4.07-3.94 (m, 6 H, H-5f, 9b, 9g,
9a, 6d, and 6′d), 3.92-3.83 (m, 7 H, H-3h, 6g, 6b, 6f, 6a, 5a, and
1i), 3.77 (t, 1 H, J4,5 ) 9.6 Hz, H-4h), 3.76 (m, 4 H, COOMe-a
and H-9′f), 3.64 (m, 1 H, H-2d), 3.50 (dd, 1 H, Jgem ) 9.6 Hz, J1′,2
) 3.4 Hz, H-1′i), 3.24 (s, 3 H, COOMe-f), 3.16 (t, 1 H, Jgem
)
10.9 Hz, H-6h), 3.05 (d, 1 H, J4,5 ) 9.6 Hz, H-5h), 2.91 (br dd, 1
H, Jgem ) 10.9 Hz, H-6′h), 2.66 (dd, 1 H, 6h-OH), 2.59 (br dd, 1
H, H-3eq-b), 2.50 (dd, 1 H, J3eq,4 ) 5.4 Hz, Jgem ) 12.3 Hz, H-3eq-
g), 2.41 (br dd, 1 H, H-3eq-a), 2.11-1.81 (m, 58 H, 17 Ac, H-3eq-
f, 3ax-f, 3ax-a, 3ax-b, 6i, 6′i, and NHCOCH2), 1.63 (t, 1 H, Jgem
)
J3ax,4 ) 12.3 Hz, H-3ax-g), 1.43 (m, 1 H, NHCOCH2), 1.26 (m, 52
H, 26 CH2), 0.88 (t, 6 H, 2 Me); 13C NMR (125 MHz, CDCl3) δ
172.5, 171.1, 170.6, 170.5, 170.3, 170.1, 169.7, 169.6, 167.4, 167.2,
166.1, 166.0, 165.9, 165.7, 165.5, 165.4, 165.3, 164.7, 164.3, 164.1,
138.3, 133.2, 133.1, 133.0, 132.9, 132.7, 130.0, 129.9, 129.8, 129.7,
129.6, 129.5, 129.4, 129.4, 129.2, 129.1, 128.4, 128.3, 128.2, 124.6,
101.5, 101.3, 99.6, 99.4, 99.2, 98.9, 96.8, 95.8, 80.4, 75.8, 73.8,
73.6, 73.0, 72.7, 72.5, 72.3, 71.9, 71.5, 71.3, 71.7, 71.0, 70.5, 69.8,
69.7, 69.3, 69.3, 68.9, 68.7, 68.5, 68.2, 67.1, 66.9, 66.6, 66.6, 66.1,
64.0, 63.9, 62.3, 62.3, 62.2, 62.1, 62.0, 61.9, 61.9, 59.4, 54.7, 54.6,
54.6, 54.5, 54.5, 53.1, 52.2, 50.2, 49.1, 49.1, 48.9, 48.8, 48.7, 38.6,
38.2, 36.5, 35.4, 32.1, 31.7, 29.5, 29.5, 29.4, 29.4, 29.3, 29.2, 29.1,
28.7, 25.4, 22.9, 22.9, 22.7, 22.5, 20.7, 20.6, 20.6, 20.5, 20.5, 20.3,
20.2, 14.0; HRMS (ESI) m/z found [M + 2Na]2+ 1948.7547,
C
195H242N6O74 calcd for [M + 2Na]2+ 1948.7571.
2-(Trimethylsilyl)ethyl [Methyl 5-acetamido-8-O-(5-acetamido-
4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-r-D-galacto-2-nonu-
lopyranosylono-1′,9-lactone)-4,7-di-O-acetyl-3,5-dideoxy-D-glycero-
r-D-galacto-2-nonulopyranosylonate]-(2f3)-2,4,6-tri-O-benzoyl-ꢀ-
D-galactopyranosyl-(1f3)-2-acetamido-4,6-di-O-benzoyl-2-deoxy-
ꢀ-D-galactopyranosyl-(1f4)-{[methyl 5-acetamido-8-O-(5-acetamido-
4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-r-D-galacto-2-
nonulopyranosylono-1′,9-lactone)-4,7-di-O-acetyl-3,5-dideoxy-D-
glycero-r-D-galacto-2-nonulopyranosylonate]-(2f3)}-2,6-di-O-
benzoyl-ꢀ-D-galactopyranosyl-(1f4)-2-O-benzoyl-ꢀ-D-
glucopyranoside (45). To a solution of 42 (75 mg, 0.0215 mmol)
in EtOH (2.1 mL) was added palladium hydroxide [20 wt % Pd
(dry basis) on carbon, wet] (75 mg) at room temperature. After
stirring for 33 h at 40 °C under a H2 atmosphere as the reaction
was monitored by TLC (PhMe/MeOH ) 4:1), the mixture was
filtered through a Celite pad and washed with CHCl3. The combined
filtrate and washings were concentrated. The resulting residue was
purified by flash column chromatography using CHCl3/MeOH (20:1
to 15:1) as the eluent to give 45 (63 mg, 90%): [R]D ) -2.3° (c
1.2, CHCl3); 1H NMR (500 MHz, CDCl3) δ 8.10-7.26 (m, 40 H,
8 Ph), 5.93 (br s, 1 H, H-4d), 5.74 (br d, 1 H, NH-b), 5.70 (d, 1 H,
J3,4 ) 3.6 Hz, H-4e), 5.55 (dt, 1 H, J4,5 ) 10.4 Hz, J3eq,4 ) 5.1 Hz,
J3ax,4 ) 12.2 Hz, H-4g), 5.45 (d, 1 H, J5,NH ) 10.0 Hz, NH-b),
5.34 (m, 7 H, H-4b, 2c, 2e, 7g, 7b, NH-g, and NH-f), 5.18 (d, 1 H,
J1,2 ) 8.0 Hz, H-1d), 5.17 (m, 2 H, H-8b and 8g), 5.11 (t, 1 H, J1,2
[Methyl 5-acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-
3,5-dideoxy-D-glycero-r-D-galacto-2-nonulopyranosylono-1′,9-
lactone)-4,7-di-O-acetyl-3,5-dideoxy-D-glycero-r-D-galacto-2-
nonulopyranosylonate]-(2f3)-2,4,6-tri-O-benzoyl-ꢀ-D-
galactopyranosyl-(1f3)-2-acetamido-4,6-di-O-benzoyl-2-deoxy-
ꢀ-D-galactopyranosyl-(1f4)-{[methyl 5-acetamido-8-O-(5-acet-
amido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-r-D-galacto-
2-nonulopyranosylono-1′,9-lactone)-4,7-di-O-acetyl-3,5-dideoxy-
D-glycero-r-D-galacto-2-nonulopyranosylonate]-(2f3)}-2,6-di-O-
benzoyl-ꢀ-D-galactopyranosyl-(1f4)-2-O-benzoyl-ꢀ-D-
glucopyranosyl-(1f1)-(2S,3R,4E)-3-O-benzoyl-2-octadecanamido-
4-octadecene-1,3-diol (44). To a solution of 40 (144 mg, 0.0351
mmol) in CH2Cl2 (4.0 mL) was added trifluoroacetic acid (2.0 mL)
3022 J. Org. Chem. Vol. 74, No. 8, 2009

Ganglioside GQ1b
) 8.0 Hz, H-2h), 5.10 (m, 2 H, H-4f and NH-a), 5.01 (dd, 1 H, J6,7
) 1.7 Hz, J7,8 ) 8.5 Hz, H-7a), 4.92 (m, 2 H, H-3d and 4a), 4.87
129.6, 129.6, 129.2, 128.6, 128.5, 128.4, 128.4, 128.2, 101.6, 100.5,
99.4, 99.2, 99.0, 97.1, 96.2, 81.2, 77.2, 75.8, 74.0, 73.8, 73.4, 73.2,
73.0, 72.8, 72.5, 72.1, 71.7, 71.4, 71.2, 70.6, 70.1, 69.9, 69.6, 69.4,
68.9, 68.8, 68.6, 68.5, 67.4, 67.3, 66.7, 64.0, 62.1, 62.0, 61.8, 60.6,
54.8, 53.2, 52.4, 49.3, 49.1, 49.1, 48.9, 38.6, 38.5, 38.3, 36.1, 35.6,
29.6, 23.1, 23.1, 23.0, 22.9, 20.8, 20.7, 20.7, 20.7, 20.6, 20.4, 20.3,
17.9, -1.1; HRMS (ESI) m/z found [M + 2Na]2+ 1673.0130,
(dd, 1 H, J6,7 ) 1.7 Hz, J7,8 ) 9.5 Hz, H-7f), 4.77 (d, 1 H, J1,2
)
8.0 Hz, H-1c), 4.71 (br dd, 1 H, H-6c), 4.63 (dt, 1 H, J7,8 ) 9.5
Hz, H-8f), 4.59 (m, 1 H, H-6e), 4.50 (d, 1 H, J1,2 ) 8.0 Hz, H-1h),
4.42 (m, 4 H, H-1e, 3e, 4c, and 6d), 4.29-4.19 (m, 11 H, H-5b,
8a, 3c, 6′e, 6b, 5e, 6′c, 9b, 9g, 9′f, and 9a), 4.12 (q, 1 H, J4,5
)
C
157H181N5O71Si calcd for [M + 2Na]2+ 1673.0130.
10.4 Hz, J5,6 ) 10.2 Hz, H-5g), 4.06-3.98 (m, 5 H, H-5f, 9′a, 9′b,
9′g, and 6′d), 3.94-3.85 (m, 7 H, H-3h, 6g, 6f, 5a, 5c, 5d, and
OCH2CH2SiMe3), 3.81 (dd, 1 H, J6,7 ) 1.7 Hz, H-6a), 3.75 (m, 4
H, H-9f and COOMe-a), 3.69 (t, 1 H, J3,4 ) J4,5 ) 8.7 Hz, H-4h),
3.63 (br q, 1 H, J1,2 ) 8.0 Hz, H-2d), 3.46 (m, 2 H, H-6h and
OCH2CH2SiMe3), 3.43 (m, 1 H, H-6′h), 3.30 (m, 1 H, H-5h), 3.24
(s, 3 H, COOMe-f), 2.57 (br dd, 1 H, H-3eq-b), 2.51 (dd, 1 H, Jgem
) 12.2 Hz, J3eq,4 ) 5.1 Hz, H-3eq-g), 2.45 (m, 1 H, H-3eq-a),
2.11-1.70 (m, 55 H, 17 Ac, H-3ax-b, 3ax-a, 3eq-f, and 3ax-f),
1.64 (t, 1 H, Jgem ) J3ax,4 ) 12.2 Hz, H-3ax-g), 0.82 (m, 2 H,
Acknowledgment. This work was financially supported by
the Ministry of Education, Culture, Sports, Science, and
Technology (MEXT) of Japan (Grant-in-Aid for Scientific
Research to M.K., No. 17101007).
Supporting Information Available: Experimental data for
compounds 8-10, 12, 13, 17-19, 23, 24, and 26-31, and
copies of 1H and 13C NMR spectra for all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OCH2CH2SiMe3), 0.00 and -0.12 (2 s, 9 H, OCH2CH2SiMe3); 13
C
NMR (100 MHz, CDCl3) δ 171.3, 170.7, 170.7, 170.6, 170.5, 170.4,
170.4, 170.4, 170.3, 169.9, 169.8, 169.8, 169.8, 169.7, 167.6, 167.3,
166.2, 166.1, 166.0, 165.6, 165.4, 165.1, 164.6, 164.5, 164.2, 133.5,
133.3, 133.3, 133.1, 133.0, 132.8, 130.3, 130.2, 129.9, 128.8, 129.7,
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