Synthesis of XylβCer, Galβ1-4XylβCer, NeuAcα2-3Galβ1-4XylβCer and the Corresponding Lactone and Lactam Trisaccharides

Article abstract of DOI:10.1021/jo970298k

2-(Trimethylsilyl)ethyl 2-O-benzoyl- and 2,3-di-O-acetyl-β-D-xylopyranosides (12 and 14) were synthesized in high yields and subjected to glycosylation with various glycosyl donors. Galactosylation of 12 gave the xylose analogue of TMSEt lactoside (3), which was transformed into the glycosyl acceptor 19. Sialylation then gave the xylose analogue of G_M3 trisaccharide (5). The TMSEt glycosides 10, 25, and 32 were transformed into the corresponding trichloroacetimidates, which were used for glycosylation of an azidosphingosine derivative. The resulting sphingosyl glycosides were transformed into the title ceramides. Treatment of NeuAcα2-3Galβ1-4XylβCer (5) with acetic acid gave the corresponding 1″→2′-lactone 7. Glycosylation of 12 or 14 with a G_M4-lactam donor (40) gave the xylose analogue of G_M3-lactam (42). There was a 3-fold increase in the formation of GAG chains in the presence of 0.5 μM XylβCer (2) in the medium.

Full text of DOI:10.1021/jo970298k

J . Org. Chem. 1997, 62, 7961-7971
7961
Syn th esis of XylâCer , Ga lâ1-4XylâCer , Neu Acr2-3Ga lâ1-4XylâCer
a n d th e Cor r esp on d in g La cton e a n d La cta m Tr isa cch a r id es
Michael Wilstermann and Go¨ran Magnusson*
Organic Chemistry 2, Center for Chemistry and Chemical Engineering, Lund University, P.O. Box 124,
S-221 00 Lund, Sweden
Received February 18, 1997X
2-(Trimethylsilyl)ethyl 2-O-benzoyl- and 2,3-di-O-acetyl-â-D-xylopyranosides (12 and 14) were
synthesized in high yields and subjected to glycosylation with various glycosyl donors. Galac-
tosylation of 12 gave the xylose analogue of TMSEt lactoside (3), which was transformed into the
glycosyl acceptor 19. Sialylation then gave the xylose analogue of GM3 trisaccharide (5). The TMSEt
glycosides 10, 25, and 32 were transformed into the corresponding trichloroacetimidates, which
were used for glycosylation of an azidosphingosine derivative. The resulting sphingosyl glycosides
were transformed into the title ceramides. Treatment of NeuAcR2-3Galâ1-4XylâCer (5) with
acetic acid gave the corresponding 1′′f2′-lactone 7. Glycosylation of 12 or 14 with a GM4-lactam
donor (40) gave the xylose analogue of GM3-lactam (42). There was a 3-fold increase in the formation
of GAG chains in the presence of 0.5 µM XylâCer (2) in the medium.
In tr od u ction
Gangliosides are known to lactonize upon treatment
with acid in vitro.6 The question of lactonization in vivo
has been debated for decades, and experimental evidence
has come from investigations such as reductive radiola-
beling with tritium6b and immunostaining of cells with
antibodies raised against ganglioside lactones.7 However,
the hydrolytic lability of the lactones has made it difficult
to draw any safe conclusions about their presence in vivo,
especially since the antibodies cross-reacted with the
nonlactonized form of the ganglioside. Ganglioside lac-
tones are in practice poor immunogens because of the
easy hydrolysis of the lactone ring. We have synthesized
ganglioside lactams, which are quite stable against
hydrolysis and have conformations very similar to those
of the ganglioside lactones.8 Antibodies, raised against
Glycosaminoglycan (GAG) chains are anchored to
specific core proteins via a xylosyl-serine glycosidic
linkage.1 Xylosides carrying hydrophobic aglycons can
function as competitive inhibitors of proteoglycan bio-
synthesis by serving as primers for free (not protein-
bound) GAG-chain assembly. While certain monoxylo-
sides are taken up by cells,2 disaccharides carrying the
hydrophobic naphthyl aglycon on the xylose moiety were
not taken up unless the saccharide moiety was partially
methylated or acetylated.3 The xyloside naroparcil was
recently shown to have an in vivo effect on GAG biosyn-
thesis in rabbits.4
In addition to the inhibitory effect of xylosides on
protein-bound GAG-chain assembly, treatment of hu-
man melanoma cells or Chinese hamster ovary cells
with 4-methylumbelliferyl-â-D-xylopyranoside (Xylâ4MU)
caused the expected free GAG-chain synthesis to trans-
gress to a substantial degree into the glycolipid biosyn-
thetic pathway, resulting in the formation of the novel
trisaccharide NeuAcR2-3Galâ1-4Xylâ4MU,5 a xylose
analogue of the ganglioside GM3 trisaccharide. However,
further sialylation into the GD3 analogue NeuAcR2-
8NeuAcR2-3Galâ1-4Xylâ4MU was not observed. It
thus seems as if the sialyl-2,3-transferase involved in GM3
synthesis does not discriminate between its substrates
Galâ1-4GlcâCer and Galâ1-4XylâMU, whereas the
sialyl-2,8-transferase of GD3 synthesis cannot use Neu-
AcR2-3Galâ1-4Xylâ4MU as a substrate. It is not clear
if the Xyl or the MU moiety is responsible for this lack
of recognition by the sialyl-2,8-transferase.
the GM3-lactam, were found to cross-react with GM3
lactone in vitro, but not with the open form GM3
-
-
ganglioside.9 Mouse melanoma cells that are known to
carry large amounts of surface-bound GM3-ganglioside,
were stained by the anti-GM3-lactam antibodies, which
strongly indicates that GM3-lactone is present on the cell
surface.10
Xylose and ceramide are intrinsic components of pro-
teoglycans and glycosphingolipids, respectively. The
XylâCer-containing hybrids presented here might well
be taken up by cells in a more efficient way than other
glycosides and would therefore be of use for investigations
of the specificity of the glycosyl transferases involved in
glycoprotein and glycolipid biosynthesis. We now report
(6) (a) Wiegandt, H. Physiol. Biol. Chem. Exp. Pharmacol. 1966, 57,
190-222. (b) Gross, S. K.; Williams, M. A.; McCluer, R. H. J .
Neurochem. 1980, 34, 1351-1361. (c) Riboni, L.; Sonnino, S.; Acquotti,
D.; Malesci, A.; Ghidoni, R.; Egge, H.; Mingrino, S.; Tettamanti, G. J .
Biol. Chem. 1986, 261, 8514-8519. (d) Bassi, R.; Riboni, L.; Sonnino,
S.; Tettamanti, G. Carbohydr. Res. 1989, 193, 141-146. (e) Maggio,
B.; Ariga, T.; Yu, R. K. Biochemistry 1990, 29, 8729-8734.
(7) (a) Nores, G. A.; Dohi, T.; Taniguchi, M.; Hakomori, S. J .
Immunol. 1987, 139, 3171-3176. (b) Bouchon, B.; Levery, S. B.;
Clausen, H.; Hakomori, S. Glycoconj. J . 1992, 9, 27-38.
(8) (a) Ray, A. K.; Nilsson, U.; Magnusson, G. J . Am. Chem. Soc.
1992, 114, 2256-2257. (b) Wilstermann, M.; Kononov, L. O.; Nilsson,
U.; Ray, A. K.; Magnusson, G. J . Am. Chem. Soc. 1995, 117, 4742-
4754.
(9) Ding, K.; Rose´n, A.; Ray, A. K.; Magnusson, G. Glycoconj. J . 1993,
9, 303-306.
(10) Magnusson, G.; Ding, K.; Nilsson, U.; Ray, A. K.; Rose´n, A.;
Sjo¨gren, H.-A. In Complex Carbohydrates in Drug Research; Alfred
Benzon Symposium 36, Bock, K., Clausen, H., Eds.; Munksgaard:
Copenhagen, 1994; pp 89-100.
X Abstract published in Advance ACS Abstracts, October 15, 1997.
(1) (a) Muir, H.; Hardingham, T. E. In Biochemistry of Carbohy-
drates, Whelan, W. J ., Ed., M. T. P. Internat. Rev. Sci. Biochem., Ser.
1, Butterworths: London, 1975; Vol. 5. (b) Schwartz, N. B. Trends
Glycosci. Glycotechnol. 1995, 7, 429-445.
(2) (a) Okayama, M.; Kimata, K.; Suzuki, S. J . Biochem. (Tokyo)
1973, 74, 1069-1073. (b) Sobue, M.; Habuchi, H.; Ito, K.; Yonekura,
H.; Oguri, K.; Sakurai, K.; Kamohara, S.; Ueno, Y.; Noyori, R.; Suzuki,
S. Biochem. J . 1987, 241, 591-601.
(3) Sarkar, A. K.; Fritz, T. A.; Taylor, W. H.; Esko, J . D. Proc. Natl.
Acad. Sci. U.S.A. 1995, 92, 3323-3327.
(4) Masson, P. J .; Coup, D.; Millet, J .; Brown, N. L. J . Biol. Chem.
1995, 270, 2662-2668.
(5) (a) Freeze, H. H.; Sampath, D.; Varki, A. J . Biol. Chem. 1993,
268, 1618-1627. (b) Freeze, H. H.; Etchison, J . R. Trends Glycosci.
Glycotechnol. 1996, 8, 65-77.
S0022-3263(97)00298-3 CCC: $14.00 © 1997 American Chemical Society

7962 J . Org. Chem., Vol. 62, No. 23, 1997
Wilstermann and Magnusson
F igu r e 1. Synthetic xylosides.
Sch em e 1a
the chemical synthesis of the novel TMSEt xylosides 1,
3, and 5, and the glycolipids XylâCer (2), Galâ1-
4XylâCer (4), and NeuAcR2-3Galâ1-4XylâCer (6) (Fig-
ure 1), with potential for further investigations of GAG
and glycolipid biosynthesis. XylâCer (2) was found to
initiate the biosynthesis of GAG chains in cell culture,
as discussed below. Furthermore, the GM3-lactone and
-lactam analogues 7 and 8 were synthesized (Figure 1)
for intended use in investigations of the possible in vivo
sialylation of ganglioside lactones (e.g. GM3-lactone f GD3
-
lactone), a question that has not been addressed in the
literature.
Resu lts a n d Discu ssion
I. Syn th esis of Glycosyl Accep tor Xylosid es. Gly-
cosylation of 2-(trimethylsilyl)ethanol with acetobro-
moxylose11 (9, Scheme 1) gave 10 (90%), and the acetyl
groups were removed to give the TMSEt xyloside 1 (98%).
Attempted isopropylidenation, as well as regioselective
acylation and allylation via stannylene complexes as
described for the corresponding methyl xyloside,12 were
unsuccessful. Instead, silylation of 1 with tert-butylchlo-
rodiphenylsilane provided the 4-O-silylated compound 11
(49%) together with the corresponding 2-O- (27%) and
3-O- (trace) silylated isomers. The diol 11 was O-
benzoylated by benzoyl chloride (1.3 equiv) at the 2-posi-
tion in a completely regioselective reaction. The same
result was obtained with 3 equiv of benzoyl chloride,
a
(a) HgO, HgBr2, TMSEtOH, CH2Cl2, MS 4 Å; (b) MeONa,
MeOH; (c) TBDPSCl, Et3N, DMAP, CHCl3; (d) PhCOCl, pyridine,
then Bu4NF‚3H2O, HOAc, THF; (e) Ac2O, pyridine; (f) Bu4NF‚3H2O,
HOAc, THF.
showing that HO-3 of 2-O-benzoylated 11 is highly
unreactive. Removal of the silyl protecting group with
Bu4NF/acetic acid in THF provided the diol 12 (81%
overall yield from 11). In contrast to the benzoylation
of 11, acetylation with an excess of acetic anhydride
furnished the diacetate 13 (99%), and desilylation of 13
as above gave 14 (94%). Attempted desilylation of 13
(11) Weygand, F. Methods in Carbohydrate Chemistry; Academic
Press: New York and London, 1962; Vol. 1, pp 182-185.
(12) Helm, R. F.; Ralph, J . J . Org. Chem. 1991, 56, 7015-7021.

Synthesis of Xylosyl Ceramides
J . Org. Chem., Vol. 62, No. 23, 1997 7963
Sch em e 2a
Sch em e 3a
a
(a) CF3COOH, CH2Cl2; (b) Cl3CCN, DBU, CH2Cl2, 0 °C; (c)
BF3‚Et2O, CH2Cl2, MS 300AW, -33 °C; (d) H2S, pyridine, H2O,
then C17H35COOH, EDC‚HCl, CH2Cl2; (e) MeONa, MeOH, CH2Cl2
3-5. Acetylation of the TMSEt disaccharide 3 gave 25
(95%) (Scheme 4). Sialylation of 19 with the sialyl
xanthate donor 3015 (Scheme 5) gave the trisaccharide
31 (56%), and O-acetylation of 31 permitted isolation of
the per-O-acetate 32 (99%).
Treatment of 10, 25, and 32 with trifluoroacetic acid16
(TFA) furnished the hemiacetals 20 (97%), 26 (100%), and
33 (100%), respectively (Schemes 3-5), and subsequent
treatment of the hemiacetals with trichloroacetonitrile17
provided the trichloroacetimidates 2118 (84%), 27 (92%),
and 34 (81%) as R,â mixtures. Glycosylation of the
azidosphingosine derivative 2219 with imidates 21, 27,
and 34 gave the glycosides 23 (59%), 28 (70%), and 35
(66%), respectively. An excess of boron trifluoride ether-
ate (10 equiv) was used in all these glycosylations in order
to avoid contamination of the product by the correspond-
ing ortho esters. The azidosphingosine glycosides were
reduced with hydrogen sulfide, and the resulting amines
were acylated with octadecanoic acid in the presence of
1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide, to give
the protected glycosyl ceramides 24 (89%), 29 (80%), and
36 (88%). Removal of the acetyl groups in 24 and 29 by
treatment with methanolic sodium methoxide provided
XylâCer (2, 89%, Scheme 3) and Galâ1-4XylâCer (4,
95%, Scheme 4). Treatment of 36 with methanolic
sodium methoxide, followed by aqueous sodium hydrox-
ide, gave NeuAcR2-3Galâ1-4XylâCer (6, 53%; Scheme
5).
a
(a) NIS, TfOH, MeCN, CH2Cl2, MS 300AW, -45 °C; (b)
MeONa, MeOH; (c) Me2C(OMe)2, MePhSO3H; (d) Ac2O, pyridine;
(e) AcOH, H2O, 50 °C.
with Bu4NF in THF resulted in partial acetyl migration
from position 3 to position 4. Compounds 12 and 14 were
used as glycosyl acceptors in the ensuing reactions, as
shown below.
II. Syn th esis of Ga lâ1-4XylâOTMSEt. The diol
acceptor 12 was glycosylated with the thiogalactoside
15,13 under activation with N-iodosuccinimide (NIS) and
trifluoromethanesulfonic acid (TfOH),14 to provide the
disaccharide derivative 16 (86%, Scheme 2), contami-
nated with approximately 10% of the corresponding â-1,3
regioisomer. De-O-benzoylation with methanolic sodium
methoxide gave a mixture of two disaccharides; chro-
matographic purification permitted the isolation of pure
3 (84%). Treatment of 3 with 2,2-dimethoxypropane and
p-toluenesulfonic acid gave the 3,4-O-isopropylidene
derivative 17 (80%), and subsequent O-acetylation af-
forded 18 (99%). De-O-isopropylidenation of 18 with
aqueous acetic acid at 50 °C gave the glycosyl acceptor
19. When the reaction was performed at 90 °C, the 6′-
O-acetyl group migrated partially to the 4′-position.
III. Syn th esis of XylâCer , Ga lâ1-4XylâCer , a n d
Neu Acr2-3Ga lâ1-4XylâCer . Transformation of the
TMSEt glycosides 10, 25, and 32 into the corresponding
glycosyl ceramides was performed as depicted in Schemes
IV. Syn th esis of Neu Acr2-3Ga lâ1-4XylâTMSEt-
la cton e a n d -la cta m . Ganglioside lactones, in equilib-
rium with the parent gangliosides, have been found to
(15) Marra, A. Sinay¨, P. Carbohydr. Res. 1990, 195, 303-308.
(16) J ansson, K.; Ahlfors, S.; Frejd, T.; Kihlberg, J .; Magnusson, G.;
Dahme´n, J .; Noori, G.; Stenvall, K. J . Org. Chem. 1988, 53, 5629-
5647.
(17) Schmidt, R. R.; Zimmermann, P.; Michel, J . Angew. Chem., Int.
Ed. Engl. 1980, 19, 731-732.
(13) Ferrier, R. J .; Furneaux, R. H. J . Chem. Soc., Perkin Trans. 1
1977, 1993-1996.
(14) (a) Konradsson, P.; Mootoo, D. R.; McDewitt, R. E.; Fraser-Reid,
B. J . Chem. Soc., Chem. Commun. 1990, 270-272. (b) Veeneman, G.
H.; van Leeuwen, S. H.; van Boom, J . H. Tetrahedron Lett. 1990, 31,
1331-1334.
(18) Mori, M.; Ito, Y.; Ogawa, T. Carbohydr. Res. 1990, 195, 199-
224.
(19) (a) Schmidt, R. R.; Zimmermann, P.; Angew. Chem., Int. Ed.
Engl. 1986, 25, 725-726. (b) Ito, Y.; Kiso, M.; Hasegawa, A. J .
Carbohydr. Chem. 1989, 8, 285-294.

7964 J . Org. Chem., Vol. 62, No. 23, 1997
Wilstermann and Magnusson
Sch em e 4a
a
(a) Ac2O, pyridine; (b) CF3COOH, CH2Cl2; (c) Cl3CCN, DBU, CH2Cl2, 0 °C; (d) BF3‚Et2O, CH2Cl2, MS 300AW, -33 °C; (e) H2S, pyridine,
H2O, then C17H35COOH, EDC‚HCl, CH2Cl2; (f) MeONa, MeOH, CH2Cl2.
Sch em e 5a
a
(a) MeSBr, TfOAg, MeCN, CH2Cl2, MS 3 Å, -72 °C; (b) Ac2O, pyridine; (c) CF3COOH, CH2Cl2; (d) Cl3CCN, DBU, CH2Cl2, 0 °C; (e)
BF3‚Et2O, CH2Cl2, MS 300AW, -33 °C; (f) H2S, pyridine, H2O, then C17H35COOH, EDC‚HCl, CH2Cl2; (g) MeONa, NaOH (aq), MeOH,
CH2Cl2.
be present on the surface of inter alia tumor cells, as
discussed in the Introduction. The corresponding lac-
tams have conformations very similar to those of the
lactones and are much more stable against hydrolysis.8
Therefore, ganglioside lactams can be used as well-
defined antigens for the production of antibodies that
recognize ganglioside lactones.9,10
Compound 31 was treated with methanolic sodium
methoxide followed by aqueous sodium hydroxide, to
furnish the xylose analogue (5, 93%) of the GM3 TMSEt
trisaccharide (Scheme 6).8 Treatment of 5 with acetic
acid caused formation of the 1′′f2′ lactone 7 as the main
product (Scheme 6), together with unreacted 5 (7/5 ∼3:
1) and a small amount (∼5%) of the corresponding 1′′f4′
lactone.
The GM4-lactam disaccharide 378b was acetylated to
give 38 (91%). Removal of the TMSEt protecting group
with trifluoroacetic acid16 provided the hemiacetal 39
(100%), and treatment of the latter with oxalyl bromide
gave the glycosyl bromide 40 (61%). Compound 40 was
transformed into the xanthate 41 by treatment with
potassium ethylxanthate (Scheme 7).
The substituent in the 2-position of glycosyl donors 40
and 41 is unable (for steric reasons) to participate in

Synthesis of Xylosyl Ceramides
J . Org. Chem., Vol. 62, No. 23, 1997 7965
Sch em e 6a
Exp er im en ta l Section
Melting points are uncorrected. 1H NMR spectra were
recorded at 300, 400, and 500 MHz. Assignment of 1H signals
was based on COSY and HETCOR 2D-techniques. Reactions
were performed at room temperature unless stated otherwise.
Concentrations were made by rotary evaporation with bath
temperature at or below 40 °C. TLC was performed on
Kiselgel 60 F254 plates (Merck) and column chromatography
on SiO2 (Matrex LC-gel: 60A, 35-70 MY, Grace).
2-(Tr im eth ylsilyl)eth yl â-D-Xylop yr a n osid e (1). Meth-
anolic sodium methoxide (2 M, 10 mL) was added to a solution
of compound 10 (13.9 g, 37.0 mmol) in dry MeOH (200 mL),
and the mixture was stirred for 2 h and then neutralized with
Amberlite IR 120 (H+) resin, filtered, and concentrated. The
residue was chromatographed (SiO2, CH2Cl2/EtOH 8:1) to give
1 (9.1 g, 98%); [R]25 -33 (c 1.0, MeOH); 1H NMR data (D2O):
D
δ 4.28 (d, 1 H, J ) 7.9 Hz, H-1), 3.89-3.75 (m, 2 H), 3.61 (m,
1 H, OCH2), 3.47 (m, 1 H, OCH2), 3.28 (t, 1 H, J ) 9.2 Hz,
H-3), 3.20-3.12 (m, 2 H), 0.89 (m, 2 H, CH2Si), -0.11 (s, 9 H,
SiMe3); HRMS calcd for C10H23O5Si (M + H): 251.1315;
found: 251.1309.
(2S,3R,4E)-3-Hyd r oxy-2-octa d eca n a m id oocta d ec-4-en -
yl â-D-Xylop yr a n osid e (2). Methanolic sodium methoxide
(1.1 M, 0.010 mL) was added to a solution of compound 24
(10.5 mg, 0.011 mmol) in dry MeOH (0.5 mL) and dry CH2Cl2
(0.5 mL) under Ar. The mixture was stirred for 3 h and then
neutralized with acetic acid and concentrated. The residue
a
(a) MeONa, MeOH, then H2O, NaOH, MeOH; (b) AcOH.
stabilizing a positive charge at the anomeric carbon.
Therefore, it was anticipated that 40 and 41 might give
R/â mixtures on glycosylation. However, this was not the
case with silver silicate-promoted20 glycosylation of xy-
loside 14 with the bromide donor 40, and the desired
trisaccharide 42 was obtained, albeit in low yield (24%).
In an attempt to raise the yield, the less hindered diol
acceptor 12 was used, but this led to a mixture of the
desired 43 and it’s O-3 regioisomer 44 (45%; 1:2). In
another attempt, glycosylation of 14 with the xanthate
donor 41 also failed. De-O-acetylation of 42 gave the
xylose analogue (8, 95%) of the GM3-lactam8 TMSEt
trisaccharide.
The preponderant formation of the O-3 regioisomer 44
in the glycosylation of 12 with 40, as discussed above, is
in sharp contrast to the glycosylation of 12 with the
galactose donor 15, where the O-4:O-3 ratio of regioiso-
mers was 10:1 (Scheme 2). However, glycosylation of 12
with the donor 3,4,6-tri-O-acetyl-2-azido-2-deoxy-R-D-
galactopyranosyl bromide21 proceeded with the same O-4:
O-3 ratio (1:2) as in the glycosylation with the donor 40;
both donors carry a nonparticipating group in the 2-posi-
tion.
VII. In d u ction of GAG Ch a in Biosyn th esis. In a
preliminary investigation, it was found that the xylosyl-
ceramide 2 induced the biosynthesis of GAG chains.22 The
test was performed by incubating skin fibroblasts with
35S-sulfate-containing medium in the presence of various
concentrations of 2 in fetal calf serum, sonicated to
improve uptake by the fibroblasts. Radiosulfated xylo-
side-primed and secreted GAGs were recovered from the
medium, using methods described in detail elsewhere.23
There was a 3-fold increase in the formation of GAG
chains at a 0.5 µM concentration of 2 in the medium. A
full account of the induction of GAG chains by the xylose-
containing ceramides 2 and 4 will be reported in due
course.
was chromatographed (SiO2, CH2Cl2/MeOH 15:1) to give 2 (7.1
1
mg, 89%); [R]22 -16 (c 1.0, CHCl3); H NMR data (CDCl3 +
D
2% CD3OD): δ (assignment of aglycon protons are shown in
italic) 5.71 (m, 1 H, H-5), 5.44 (dd, 1 H, J ) 15.4, 6.4 Hz, H-4),
4.23 (d, 1 H, J ) 6.9 Hz, H-1), 4.15-4.00 (m, 3 H), 3.96 (dd, 1
H, J ) 11.6, 4.9 Hz, H-5), 3.64-3.55 (m, 2 H), 3.44 (t, 1 H, J
) 8.2 Hz, H-3), 3.28 (dd, 1 H, J ) 8.2, 7.0 Hz, H-2), 3.25 (dd,
1 H, J ) 11.7, 9.3 Hz, H-5), 2.18 (t, 2 H, J ) 7.2 Hz, H-2′),
1.71-1.15 (m, 54 H, CH2), 0.86 (t, 6 H, J ) 6.9 Hz, CH3); 13C
NMR data (CDCl3 + 2% CD3OD): δ 174.7, 134.7, 128.9, 104.0,
75.8, 73.6, 72.9, 69.8, 69.3, 65.4, 53.3, 32.7, 32.3, 30.1-29.5,
26.2, 23.1, 14.5; HRMS calcd for C41H79O7NNa (M + Na):
720.5754; found 720.5756.
2-(Tr im eth ylsilyl)eth yl 4-O-(â-D-Ga la ctop yr a n osyl)-â-
D-xylop yr a n osid e (3). Compound 16 (200 mg, 0.217 mmol)
was deacylated as described in the preparation of 1, to give 3,
contaminated with approximately 10% of the corresponding
3-O regioisomer. Column chromatography (SiO2, CH2Cl2/
MeOH 5:1) gave pure 3 (75 mg, 84%); [R]24D -32 (c 1.0, MeOH);
1H NMR data (D2O): δ 4.33 (d, 1 H, J ) 7.8 Hz, H-1′), 4.30 (d,
1 H, J ) 7.8 Hz, H-1), 3.94 (dd, 1 H, J ) 11.7, 5.3 Hz), 3.84
(m, 1 H), 3.78 (d, 1 H, J ) 3.4 Hz), 3.75-3.54 (m, 5 H), 3.51
(dd, 1 H, J ) 10.0, 3.4 Hz, H-3′), 3.44 (t, 1 H, J ) 11.1 Hz,
H-3), 3.37 (dd, 1 H, J ) 10.0, 7.7 Hz, H-2′), 3.25 (t, 1 H, J )
11.5 Hz, H-5), 3.12 (dd, 1 H, J ) 9.2, 7.9 Hz, H-2), 0.88 (m, 2
H, CH2Si), -0.11 (s, 9 H, SiMe3); 13C NMR data (D2O): δ 103.0,
102.6, 73.7, 73.5, 71.5, 69.5, 69.2, 67.4, 63.8, 61.9, 18.4, -1.7;
HRMS calcd for C16H33O10Si (M + H): 413.1843; found:
413.1844. 2-(Trimethylsilyl)ethyl 3-O-(â-D-galactopyranosyl)-
1
â-D-xylopyranoside: [R]24 -30 (c 1.0, MeOH); H NMR data
D
(D2O): δ 4.55 (d, 1 H, J ) 7.7 Hz, H-1), 4.36 (d, 1 H, J ) 7.9
Hz, H-1′), 3.92-3.86 (m, 2 H), 3.82 (brd, 1 H, J ) 3.2 Hz, H-4′),
3.73-3.56 (m, 7 H), 3.50 (dd, 1 H, J ) 9.9, 7.7 Hz, H-2′), 3.34
(t, 1 H, J ) 8.4 Hz, H-3), 3.24 (t, 1 H, J ) 10.7 Hz, H-5), 0.92
(m, 2 H, CH2Si), -0.07 (s, 9 H, SiMe3).
(2S,3R,4E)-3-Hyd r oxy-2-octa d eca n a m id oocta d ec-4-en -
yl 4-O-(â-D-galactopyr an osyl)-â-D-xylopyr an oside (4). Meth-
anolic sodium methoxide (1.1 M, 0.008 mL) was added to a
solution of compound 29 (10.4 mg, 0.0086 mmol) in dry MeOH
(0.2 mL) and dry CH2Cl2 (0.8 mL) under Ar. The mixture was
stirred overnight and then neutralized with acetic acid and
concentrated. The residue was chromatographed (SiO2, CH2-
Cl2/MeOH 5:1) to give 4 (7.0 mg, 95%); [R]22D -3 (c 0.4, CHCl3/
MeOH 4:1); 1H NMR data (CDCl3/CD3OD 4:1): δ (assignment
of aglycon protons are shown in italic) 5.66 (m, 1 H, H-5), 5.40
(m, 1 H, H-4), 4.25 (d, 1 H, J ) 7.6 Hz, H-1′), 4.17 (d, 1 H, J
) 7.4 Hz, H-1), 4.09-4.02 (m, 2 H, H-2,3), 3.99-3.94 (m, 2 H,
(20) van Boeckel, C. A. A.; Beetz, T. Rec. Trav. Chim. Pays-Bas 1987,
106, 596-598.
(21) (a) Sabesan, S.; Lemieux, R. U. Can. J . Chem. 1984, 62, 644-
654. (b) Broddefalk, J .; Nilsson, U.; Kihlberg, J . J . Carbohydr. Chem.
1994, 13, 129-132.
(22) Fransson, L.-Å., personal communication.
(23) (a) Fransson, L.-Å.; Havsmark, B.; Sakuari, K.; Suzuki, S.
Glycoconj. J . 1992, 9, 45-55. (b) Fransson, L.-Å.; Karlsson, P.;
Schmidtchen, A. Biochim. Biophys. Acta 1992, 1137, 287-297.

7966 J . Org. Chem., Vol. 62, No. 23, 1997
Wilstermann and Magnusson
Sch em e 7a
a
(a) Ac2O, pyridine; (b) CF3COOH, CH2Cl2; (c) (COBr)2, DMF, CH2Cl2, 0 °C; (d) KSCSOEt, EtOH; (e) Ag-silicate, CH2Cl2, MS 4 Å; (f)
MeONa, MeOH.
H-1, H-5), 3.81 (d, 1 H, J ) 2.2 Hz, H-4′), 3.79 (dd, 1 H, J )
11.8, 7.2 Hz, H-6′), 3.68 (dd, 1 H, J ) 11.8, 4.2 Hz, H-6′), 3.64
(m, 1 H, H-4), 3.53 (dd, 1 H, J ) 10.3, 3.2 Hz, H-1), 3.51-3.48
(m, 3 H), 3.44 (dd, 1 H, J ) 9.7, 3.2 Hz, H-3′), 3.29-3.23 (m,
2 H), 2.13 (t, 2 H, J ) 7.6 Hz, H-2′), 1.97 (dd, 2 H, J ) 14.1,
7.0 Hz, H-6), 1.53 (m, 2 H, H-3′), 1.47-1.07 (m, 50 H, CH2),
0.83 (t, 6 H, J ) 7.0 Hz, CH3); 13C NMR data (CDCl3/CD3OD
4:1): δ 174.5, 134.1, 128.9, 103.5, 102.6, 75.3, 74.1, 73.2, 72.7,
72.3, 70.7, 68.9, 68.8, 63.3, 61.5, 53.0, 37.3, 32.2, 31.7, 29.5-
29.0, 25.7, 22.5, 13.8; HRMS calcd for C47H89O12NNa (M +
Na): 882.6282; found 882.6265.
0.0028 mL) was added to a solution of compound 36 (5.1 mg,
0.0031 mmol) in dry MeOH (1 mL) and dry CH2Cl2 (0.1 mL)
under Ar. The mixture was stirred for 4.5 h and then aqueous
sodium hydroxide (0.1 M, 0.062 mL) was added, and the
mixture was stirred for 1 h. Aqueous acetic acid (0.4 M, 0.1
mL) was added, and the mixture was immediately chromato-
graphed (SiO2, CH2Cl2/MeOH/H2O + 0.1% AcOH 65:35:1 f
65:35:5) to give 6 (1.9 mg, 53%); [R]22 -20 (c 0.15, CHCl3/
D
MeOH 1:1); 1H NMR data (CDCl3/CD3OD 1:1): δ (assignments
of aglycon protons are shown in italic) 5.66 (dt, 1 H, J ) 14.9,
6.8 Hz, H-5), 5.42 (dd, 1 H, J ) 15.3, 7.3 Hz, H-4), 4.34 (d, 1
H, J ) 7.7 Hz, H-1′), 4.20 (d, 1 H, J ) 7.3 Hz, H-1), 4.11 (dd,
1 H, J ) 10.3, 4.6 Hz), 4.07-3.46 (m, 21 H), 2.79 (brd, 1 H, J
) 10.1 Hz, H-3′′eq), 2.15 (t, 2 H, J ) 7.6 Hz, H-2′), 1.72 (t, 1
H, J ) 10.4 Hz, H-3′′ax), 1.60-1.20 (m, 54 H, CH2), 0.85 (t, 6
H, J ) 6.8 Hz, CH3); 13C NMR data (CDCl3/CD3OD 1:1): δ
175.1, 174.1, 165.4, 134.6, 130.9, 104.0, 102.9, 99.3, 76.5, 75.8,
74.6, 73.9, 73.3, 72.3, 71.7, 69.4, 69.3, 69.1, 68.1, 67.9, 63.7,
63.6, 61.9, 53.5, 53.0, 37.0, 32.8, 32.3, 30.0-29.5, 26.3, 23.9,
2-(Tr im et h ylsilyl)et h yl 4-O-[3-O-(5-Acet a m id o-3,5-d i-
deoxy-D-glycer o-r-D-galacto-2-n on u lopyr an osylon ic acid)-
â-D-ga la ctop yr a n osyl]-â-D-xylop yr a n osid e (5). Methanolic
sodium methoxide (2 M, 0.013 mL) was added to a solution of
compound 31 (26 mg, 0.025 mmol) in dry MeOH (1 mL) under
Ar. The mixture was stirred at room temperature for 1 h 45
min and then neutralized with Duolite C-26 (H+) resin and
concentrated. The residue was dissolved in water (1 mL), and
MeOH (1 mL) and aqueous sodium hydroxide (1 M, 0.078 mL)
were added. The mixture was stirred for 3.5 h and then
neutralized with Duolite C-26 (H+) resin and concentrated. The
residue was chromathographed (SiO2, CH2Cl2/MeOH/H2O +
22.3, 14.1; HRMS calcd for
1173.7237; found: 1173.7224.
C58H106O20N2Na (M + Na):
2-(Tr im et h ylsilyl)et h yl 4-O-[3-O-(5-Acet a m id o-3,5-d i-
deoxy-D-glycer o-r-D-galacto-2-n on u lopyr an osyloyl-1′′f2′-
la cton e)-â-D-ga la ctop yr a n osyl]-â-D-xylop yr a n osid e (7). A
mixture of compound 5 (4.10 mg, 0.0058 mmol) and AcOH (1
mL) was stirred overnight and then concentrated. The residue
was chromatographed (SiO2, CH2Cl2/MeOH/H2O + 0.1% AcOH
65:35:4) to give a mixture (2.57 mg, 64%) of 7 and residual 5
(3:1), and a small amount (∼5%) of the corresponding 1′′f4′-
lactone. Compound 7: 1H NMR data (selected, D2O): δ 4.73
(d, 1 H, J ) 7.8 Hz, H-1′), 4.30 (d, 1 H, J ) 7.9 Hz, H-1), 4.17
(dt, 1 H, J ) 10.7, 5.4 Hz, H-4′′), 4.07 (dd, 1 H, J ) 10.6, 2,9
Hz, H-3′), 4.01 (brd, 1 H, J ) 3.0 Hz, H-4′), 3.99 (dd, 1 H, J )
11.8, 5.3 Hz, H-5), 3.79 (t, 1 H, J ) 10.3 Hz, H-5′′), 3.46 (t, 1
H, J ) 9.2 Hz, H-3), 3.28 (dd, 1 H, J ) 11.7, 10.5 Hz, H-5),
3.15 (dd, 1 H, J ) 9.3, 7.9 Hz, H-2), 2.50 (dd, 1 H, J ) 13.4,
5.3 Hz, H-3′′eq), 1.91 (s, 3 H, NHAc), 1.63 (dd, 1 H, J ) 13.4,
11.2 Hz, H-3′′ax), 0.96-0.78 (m, 2 H, CH2Si), -0.12 (s, 9 H,
SiMe3); HRMS calcd for C27H47O17NSiNa (M + Na): 708.2511;
found: 708.2504.
0.1% AcOH 5:5:1) to give 5 (15.5 mg, 93%); [R]22 -23 (c 1.0,
D
MeOH); 1H NMR data (D2O): δ 4.61 (d, 1 H, J ) 7.9 Hz, H-1′),
4.49 (d, 1 H, J ) 7.9 Hz, H-1), 4.16 (m, 2 H), 4.06-4.00 (m, 2
H), 3.96-3.88 (m, 4 H), 3.82-3.77 (m, 7 H), 3.65 (t, 1 H, J )
7.7 Hz, H-3), 3.64 (m, 1 H), 3.61 (dd, 1 H, J ) 9.8, 7.9 Hz,
H-2′), 3.44 (dd, 1 H, J ) 11.7, 10.5 Hz, H-5), 3.33 (dd, 1 H, J
) 9.3, 7.9 Hz, H-2), 2.80 (dd, 2 H, J ) 12.5, 4.6 Hz, H-3′′eq),
2.10 (s, 3 H, NHAc), 1.88 (t, 1 H, J ) 12.2 Hz, H-3′′ax), 1.07
(m, 2 H, CH2Si), 0.15 (s, 9 H, SiMe3); 13C NMR data (D2O): δ
175.8, 174.4, 102.9, 102.2, 100.5, 77.1, 76.4, 75.9, 75.0, 73.7,
72.4, 69.9, 69.3, 69.1, 68.9, 68.3, 63.7, 63.4, 61.9, 52.5, 40.3,
22.9, 18.4, -1.7; HRMS calcd for C27H49O18NSiNa (M + Na):
726.2617; found: 726.2643.
(2S,3R,4E)-3-Hyd r oxy-2-octa d eca n a m id oocta d ec-4-en -
yl 4-O-[3-O-(5-acetam ido-3,5-dideoxy-D-glycer o-r-D-galacto-
2-n on u lop yr a n osylon ic a cid )-â-D-ga la ctop yr a n osyl]-â-D-
xylop yr a n osid e (6). Methanolic sodium methoxide (1.1 M,

Synthesis of Xylosyl Ceramides
J . Org. Chem., Vol. 62, No. 23, 1997 7967
2-(Tr im eth ylsilyl)eth yl 4-O-[2-Am in o-2-d eoxy-3-O-(5-
acetam ido-3,5-dideoxy-D-glycer o-r-D-galacto-2-n on u lopy-
r a n osyloyl-1′′f2′-la ct a m )-â-D-ga la ct op yr a n osyl]-â-D-xy-
lop yr a n osid e (8). Compound 42 (3.14 mg, 0.0031 mmol) was
deacetylated as described in the preparation of 1 (neutraliza-
tion was made with Duolite C-26 (H+) resin). Column chro-
matography (SiO2, CH2Cl2/MeOH/H2O 65:35:5) gave 8 (2.0 mg,
69.9, 67.1, 64.0, 18.1, -1.5; HRMS calcd for C17H26O6SiNa (M
+ Na): 377.1396; found: 377.1389.
2-(Tr im eth ylsilyl)eth yl 2,3-d i-O-Acetyl-4-O-(ter t-bu tyl-
d ip h en ylsilyl)-â-D-xylop yr a n osid e (13). Compound 11 (400
mg, 0.818 mmol) was acetylated overnight with acetic anhy-
dride (10 mL), pyridine (10 mL), and DMAP (catalytic amount).
The mixture was concentrated and coconcentrated with tolu-
ene, and the residue was chromatographed (SiO2, heptane/
EtOAc 6:1) to give 13 (473 mg, 99%): [R]22D -22 (c 0.9, CHCl3);
1H NMR data (CHCl3): δ 7.65-7.34 (m, 10 H, Ar), 5.17 (t, 1
H, J ) 9.2 Hz, H-3), 4.68 (dd, 1 H, J ) 9.5, 7.8 Hz, H-2), 4.40
(d, 1 H, J ) 7.8 Hz, H-1), 3.85 (m, 2 H), 3.67 (dd, 1 H, J )
11.5, 5.4 Hz, H-5), 3.48 (dt, 1 H, J ) 9.8, 6.8 Hz, OCH2), 3.25
(t, 1 H, J ) 11.0 Hz, H-5), 2.01, 1.82 (s, 3 H each, OAc), 1.02
(s, 9 H, (CH3)3C), 0.89 (m, 2 H, CH2Si), -0.03 (s, 9 H, SiMe3);
HRMS calcd for C30H44O7Si2Na (M + Na): 595.2523; found:
595.2523.
95%); [R]22 -30 (c 0.16, MeOH); 1H NMR data (D2O): δ 4.58
D
(d, 1 H, J ) 8.1 Hz, H-1′), 4.31 (d, 1 H, J ) 7.8 Hz, H-1), 4.21
(dt, 1 H, J ) 11.0, 5.5 Hz, H-4′′), 3.99 (dd, 1 H, J ) 11.6, 5.4
Hz, H-5), 3.92 (brd, 1 H, J ) 2.5 Hz, H-4′), 3.81-3.56 (m, 13
H), 3.50 (dd, 1 H, J ) 11.8, 5.4 Hz, H-9′′), 3.47 (t, 1 H, J ) 9.2
Hz, H-3), 3.39 (dd, 1 H, J ) 9.5, 1.1 Hz, H-7′′), 3.31 (dd, 1 H,
J ) 11.6, 10.5 Hz, H-5), 3.16 (dd, 1 H, J ) 9.3, 7.9 Hz, H-2),
2.45 (dd 1 H, J ) 13.4, 5.5 Hz, H-3′′eq), 1.91 (s, 3 H, NHAc),
1.56 (dd, 1 H, J ) 13.4, 11.2 Hz, H-3′′ax), 0.88 (m, 2 H, CH2-
Si), -0.12 (s, 9 H, SiMe3); 13C NMR data (D2O): δ 175.9, 169.5,
102.9, 99.4, 98.8, 77.3, 76.9, 76.5, 74.7, 73.7, 73.1, 70.9, 69.3,
68.7, 68.6, 66.3, 64.2, 63.6, 61.8, 52.6, 51.0, 40.1, 22.9, 18.4,
-1.7; HRMS calcd for C27H48O16N2SiNa (M + Na): 707.2670;
found: 707.2672.
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-a cetyl-â-D-xylop yr a -
n osid e (14). To a solution of 13 (1.23 g, 2.15 mmol) and HOAc
(0.49 mL, 8.61 mmol) in THF (90 mL) was added tetrabutyl-
ammonium fluoride trihydrate (2.03 g, 6.46 mmol). After 12
h, the mixture was diluted with CH2Cl2 and successively
washed with saturated aqueous NaHCO3 and water, dried
(Na2SO4), and concentrated. The residue was chromato-
graphed (SiO2, heptane/EtOAc 3:2) to give 14 (679 mg, 94%):
2-(Tr im eth ylsilyl)eth yl 2,3,4-Tr i-O-a cetyl-â-D-xylop y-
r a n osid e (10). To a mixture of compound 911 (14.0 g, 41.4
mmol), HgO (8.95 g, 41.4 mmol), HgBr2 (80 mg, 0.22 mmol),
molecular sieves (6 g, 3 Å), and dry CH2Cl2 (150 mL) under
Ar and protected from light was added 2-(trimethylsilyl)-
ethanol (8.88 mL, 70 mmol). After 1 h, the mixture was
diluted with CH2Cl2, filtered (Celite), and concentrated. The
residue was chromatographed (SiO2, heptane/EtOAc 3:1) to
[R]22 -58 (c 1.0, CHCl3); 1H NMR data (CHCl3): δ 4.90 (m, 2
D
H), 4.46 (m, 1 H), 4.07 (dd, 1 H, J ) 11.7, 4.8 Hz), 3.93 (dt, 1
H, J ) 9.9, 6.1 Hz), 3.80 (m, 1 H), 3.54 (dt, 1 H, J ) 9.7, 6.7
Hz), 3.36 (dd, 1 H, J ) 11.8, 8.8 Hz), 2.55 (d, 1 H, J ) 6.0 Hz),
2.10, 2.06 (s, 3 H each), 0.93 (m, 2 H), 0.01 (s, 9 H); 13C NMR
data (CDCl3): δ 171.6, 169.5, 100.2, 75.5, 70.7, 68.6, 67.1, 64.8,
20.9, 20.8, 18.0, -1.4; HRMS calcd for C14H26O7SiNa (M +
Na): 357.1346; found: 357.1362.
give 10 (14.0 g, 90%); [R]23 -62 (c 1.0, CHCl3); 1H NMR data
D
(CDCl3): δ 5.15 (t 1 H, J ) 8.7 Hz, H-3), 4.92 (m, 2 H, H-2,4),
4.48 (d, 1 H, J ) 6.8 Hz, H-1), 4.10 (dd, 1 H, J ) 11.8, 5.1 Hz,
H-5), 3.92 (dt, 1 H, J ) 9.6, 6.3 Hz, OCH2), 3.53 (dt, 1 H, J )
9.7, 6.8 Hz, OCH2), 3.34 (dd, 1 H, J ) 11.7, 9.0 Hz, H-5), 2.04,
2.04, 2.03 (s, 3 H each, OAc), 0.92 (m, 2 H, CH2Si), 0.00 (s, 9
H, SiMe3); 13C NMR data (CDCl3): δ 170.2, 169.9, 169.4, 100.2,
71.7, 71.0, 70.0, 69.0, 67.1, 62.0, 20.7 17.9, -1.4; HRMS calcd
for C16H28O8SiNa (M + Na): 399.1451; found: 399.1440.
2-(Tr im eth ylsilyl)eth yl 2-O-Ben zoyl-4-O-(2,3,4,6-tetr a -
O-ben zoyl-â-D-galactopyr an osyl)-â-D-xylopyr an oside (16).
A mixture of the thiogalactoside 1513 (116 mg, 0.169 mmol),
compound 12 (40 mg, 0.113 mmol), molecular sieves (130 mg,
AW 300), dry MeCN (1.7 mL), and dry CH2Cl2 (0.66 mL) was
stirred for 1 h under Ar and then cooled to -45 °C. A solution
of N-iodosuccinimide (41 mg, 0.181 mmol) and trifluoromethane-
sulfonic acid (0.003 mL, 0.03 mmol) in dry MeCN (0.3 mL)
was added dropwise to the cooled mixture. After 45 min,
triethylamine (0.25 mL) was added, and the mixture was
filtered (Celite), diluted with CH2Cl2, washed with saturated
aqueous NaHCO3, dried (Na2SO4), filtered, and concentrated.
The residue was chromatographed (SiO2, toluene/EtOAc 10:
1) to give 16 (91 mg, 86%), contaminated with approximately
10% of the corresponding 3-O regioisomer. Compound 16: 1H
NMR data (CDCl3): δ 8.13-7.19 (m, 25 H, Ar), 5.97 (d, 1 H, J
) 3.4 Hz, H-4′), 5.82 (dd, 1 H, J ) 10.5, 7.9 Hz, H-2′), 5.60
(dd, 1 H, J ) 10.5, 3.4 Hz, H-3′), 5.15 (dd, 1 H, J ) 9.1, 7.6
Hz, H-2), 4.96 (d, 1 H, J ) 8.1 Hz, H-1′), 4.62 (m, 1 H), 4.50
(d, 1 H, J ) 7.5 Hz, H-1), 4.39 (m, 2 H), 4.13 (d, 1 H, J ) 2.2
Hz), 3.99-3.73 (m, 4 H), 3.49 (dt, 1 H, J ) 9.8, 6.4 Hz, OCH2),
3.33 (m, 1 H, H-5), 0.83 (m, 2 H, CH2Si), -0.10 (s, 9 H, SiMe3);
HRMS calcd for C51H52O15SiNa (M + Na): 955.2973; found:
955.2961. An analytical sample was acetylated in order to
simplify determination of the regioselectivity. 1H NMR gave
H-3 at 5.39 ppm (t, 1 H, J ) 8.3 Hz) and a new singlet at 1.93
ppm (3 H, OAc).
2-(Tr im eth ylsilyl)eth yl 4-O-(ter t-Bu tyld ip h en ylsilyl)-
â-D-xylopyr an oside (11). tert-Butylchlorodiphenylsilane (3.32
mL, 12.8 mmol) was added to a mixture of 1 (1.60 g, 6.39
mmol), DMAP (860 mg, 7.03 mmol), triethylamine (1.78 mL,
12.8 mmol), and dry CHCl3 (100 mL). After 48 h, MeOH (5
mL) was added and the mixture was concentrated. The
residue was chromatographed (SiO2, heptane/EtOAc 5:1) to
give 11 (1.53 g, 49%), the 2-silylated analogue (839 mg, 27%),
and trace amounts of the 3-silylated analogue. Compound
11: [R]22 -68 (c 1.0, CHCl3); 1H NMR data (CDCl3): δ 7.71-
D
7.36 (m, 10 H, Ar), 4.66 (brd, 1 H, J ) 3.4 Hz, H-1), 3.88-3.70
(m, 4 H), 3.60-3.45 (m, 3 H), 3.28 (dd, 1 H, J ) 12.3, 4.6 Hz,
H-5), 3.19 (d, 1 H, J ) 7.3 Hz), 1.10 (s, 9 H, CMe3), 0.94 (m, 2
H, CH2Si), 0.00 (s, 9 H, SiMe3); HRMS calcd for C26H40O5Si2-
Na (M + Na): 511.2312; found: 511.2321. 2-(Trimethylsilyl)-
ethyl 2-O-{tert-butyldiphenylsilyl)-â-D-xylopyranoside: [R]24
D
1
-11 (c 1.0, CHCl3); H NMR data (CDCl3): δ 7.73-7.38 (m,
10 H, Ar), 4.42 (brd, 1 H, J ) 2.9 Hz, H-1), 4.05 (dd, 1 H, J )
10.7, 1.6 Hz, H-5), 3.87 (m, 1 H, H-3), 3.74-3.57 (m, 5 H), 3.23
(m, 1 H, OCH2), 3.16 (d, 1 H, J ) 8.7 Hz), 1.11 (s, 9 H, CMe3),
0.67 (m, 2 H, CH2Si), -0.05 (s, 9 H, SiMe3).
2-(Tr im et h ylsilyl)et h yl 2-O-Ben zoyl-â-D-xylop yr a n o-
sid e (12). To a solution of compound 11 (1.51 g, 3.09 mmol)
in dry pyridine (70 mL) at 0 °C was added benzoyl chloride
(0.470 mL, 4.02 mmol). After 3.5 h, MeOH (5 mL) was added,
and the mixture was diluted with CH2Cl2 and successively
washed with saturated aqueous NaHCO3 and water, dried
(Na2SO4), and concentrated. The residue was desilylated as
described in the preparation of 14. The crude product was
chromatographed (SiO2, heptane/EtOAc 1:1) to give 12 (890
mg, 81%): [R]22D -40 (c 1.0, CHCl3); 1H NMR data (CHCl3): δ
8.05-7.43 (m, 15 H, Ar), 4.97 (dd, 1 H, J ) 6.9, 5.2 Hz, H-2),
4.74 (d, 1 H, J ) 5.1 Hz, H-1), 4.14 (dd, 1 H, J ) 11.9, 3.3 Hz,
H-5), 3.93 (m, 1 H, OCH2), 3.80 (m, 2 H, H-3,4), 3.58 (dt, 1 H,
J ) 10.2, 6.5 Hz, OCH2), 3.48 (dd, 1 H, J ) 11.9, 6.9 Hz, H-5),
0.95 (m, 2 H, CH2Si), -0.02 (s, 9 H, SiMe3); 13C NMR data
(CDCl3): δ 166.2, 133.4, 129.9, 129.6, 128.4, 99.9, 73.8, 73.4,
2-(Tr im eth ylsilyl)eth yl 4-O-(3,4-O-Isop r op ylid en e-â-D-
ga la ctop yr a n osyl)-â-D-xylop yr a n osid e (17). To a mixture
of 3 (25 mg, 0.061 mmol) and 2,2-dimethoxypropane (1 mL)
was added p-toluenesulfonic acid (catalytic amount), and the
mixture was stirred overnight and then neutralized with
triethylamine. The mixture was concentrated, and the residue
was dissolved in MeOH (3 mL) and water (0.3 mL) and stirred
for 6 h at 80 °C. The mixture was concentrated, and the
residue was chromatographed (SiO2, CH2Cl2/EtOH 15:1 + 0.1%
1
Et3N) to give 17 (22 mg, 80%): [R]26 -13 (c 1.0, MeOH); H
D
NMR data (CD3OD): δ 4.32 (d, 1 H, J ) 8.2 Hz, H-1′), 4.23 (d,
1 H, J ) 7.6 Hz, H-1), 4.18 (dd, 1 H, J ) 5.5, 2.1 Hz, H-4′),
4.05-3.97 (m, 2 H, H-5, H-3′), 3.95-3.88 (m, 2 H, H-5′, OCH2),
3.80 (dd, 1 H, J ) 11.6, 7.8 Hz, H-6′), 3.73 (dd, 1 H, J ) 11.6,
4.2 Hz, H-6′), 3.68 (m, 1 H, H-4), 3.62 (m, 1 H, OCH2), 3.45
(m, 2 H, H-3, H-2′), 3.28 (dd, 1 H, J ) 11.6, 10.2 Hz, H-5),

7968 J . Org. Chem., Vol. 62, No. 23, 1997
Wilstermann and Magnusson
3.19 (dd, 1 H, J ) 9.1, 7.6 Hz), 1.47, 1.32 (s, 3 H each, CCH3),
0.99 (m, 2 H, CH2Si), 0.03 (s, 9 H, SiMe3); HRMS calcd for
C19H37O10Si (M + H): 453.2156; found: 453.2182.
then it was concentrated and coconcentrated with toluene. The
residue was dissolved in dry CH2Cl2 (1 mL), and octadecanoic
acid (24 mg, 0.084 mmol) and 1-ethyl-3-[3-(dimethylamino)-
propyl]carbodiimide hydrochloride (16 mg, 0.084 mmol) were
added. After 3 h, the mixture was chromatographed (SiO2,
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-a cetyl-4-O-(2,6-d i-O-
a cet yl-3,4-O-isop r op ylid en e-â-D-ga la ct op yr a n osyl)-â-D-
xylop yr a n osid e (18). Compound 17 (200 mg, 0.442 mmol)
was acetylated as described in the preparation of 13. The
crude product was chromatographed (SiO2, heptane/EtOAc 1:1
heptane/EtOAc 3:2) to give 24 (17.5 mg, 89%): [R]23 -13 (c
D
0.6, CHCl3); 1H NMR data (CDCl3): δ (assignment of aglycon
protons are shown in italic) 8.05-7.42 (m, 5 H, Ar), 5.88 (dt,
1 H, J ) 14.6, 6.8 Hz, H-5), 5.79 (d, 1 H, J ) 7.3 Hz, NH),
5.57-5.45 (m, 2 H, H-3,4), 5.14 (t, 1 H, J ) 8.1 Hz, H-3), 4.89
(dd, 1 H, J ) 8.4, 6.1 Hz, H-2), 4.88 (m, 1 H, H-4), 4.51 (m, 1
H, H-2), 4.48 (d, 1 H, J ) 6.3 Hz, H-1), 4.03 (dd, 1 H, J ) 10.0,
3.6 Hz, H-1), 3.98 (dd, 1 H, J ) 12.0, 4.7 Hz, H-5), 3.60 (dd, 1
H, J ) 10.1, 4.1 Hz, H-1), 3.30 (dd, 1 H, J ) 12.0, 7.9 Hz,
H-5), 2.36 (t, 2 H, J ) 7.6 Hz, H-2′), 2.08, 2.06, 2.05 (s, 3 H
each, OAc), 1.70-1.15 (m, 54 H, CH2), 0.89 (t, 6 H, J ) 6.5
Hz, CH3); 13C NMR data (CDCl3): δ 173.1, 170.4, 170.2, 170.0,
165.7, 138.1, 133.5, 130.7, 130.1, 128.8, 125.2, 100.8, 74.6, 71.2,
71.0, 69.1, 67.6, 62.1, 51.0, 37.3, 33.9, 32.7, 32.4, 30.1-29.3,
+ 0.1% Et3N) to give 18 (272 mg, 99%): [R]22 -13 (c 1.0,
D
CHCl3); 1H NMR data (CDCl3): δ 5.10 (t, 1 H, J ) 8.5 Hz,
H-3), 4.83 (m, 2 H, H-2,2′), 4.43 (d, 1 H, J ) 7.0 Hz, H-1), 4.41
(d, 1 H, J ) 7.4 Hz, H-1′), 4.35-4.10 (m, 4 H), 4.01-3.85 (m,
3 H), 3.81 (dd, 1 H, J ) 8.4, 3.7 Hz), 3.52 (dt, 1 H, J ) 9.6, 7.1
Hz, OCH2), 3.31 (dd, 1 H, J ) 11.7, 9.1 Hz, H-5), 2.10, 2.06,
2.04, 2.03 (s, 3 H, each OAc), 1.53, 1.31 (s, 3 H each, C(CH3)3),
0.90 (m, 2 H, CH2Si), 0.00 (s, 9 H, SiMe3); HRMS calcd for
C27H45O14Si (M + H): 643.2398; found: 643.2401.
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-a cetyl-4-O-(2,6-d i-O-
acetyl-â-D-galactopyr an osyl)-â-D-xylopyr an oside (19). Com-
pound 18 (150 mg, 0.242 mmol) was dissolved in aqueous acetic
acid (5 mL, 80%), and the mixture was kept at 50 °C for 8 h
and then concentrated and co-concentrated with toluene. The
residue was chromatographed (SiO2, CH2Cl2/EtOH 20:1) to
26.2, 25.2, 23.1, 21.18, 21.16, 14.6; HRMS calcd for C54H89O11
-
NNa (M + Na): 950.6333; found 950.6335.
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-acetyl-4-O-(2,3,4,6-tetr a-
O-a cetyl-â-D-ga la ctop yr a n osyl)-â-D-xylop yr a n osid e (25).
Compound 3 (15 mg, 0.036 mmol) was acetylated with acetic
anhydride (5 mL) and pyridine (5 mL) overnight. The mixture
was concentrated and coconcentrated with toluene, and the
give 19 (120 mg, 85%): [R]23 -34 (c 1.0, CHCl3); 1H NMR
D
data (CDCl3): δ 5.11 (t, 1 H, J ) 8.6 Hz, H-3), 4.85 (m, 2 H,
H-2,2′), 4.43 (d, 1 H, J ) 7.0 Hz, H-1), 4.39 (d, 1 H, J ) 7.9
Hz, H-1′), 4.36 (dd, 1 H, J ) 11.5, 6.0 Hz, H-6′), 4.22 (dd, 1 H,
J ) 11.4, 6.7 Hz, H-6′), 3.98 (dd, 1 H, J ) 11.8, 5.0 Hz, H-5),
3.91 (m, 1 H, OCH2), 3.86 (d, 1 H, J ) 3.4 Hz, H-4′), 3.80 (m,
1 H, H-4), 3.66 (t, 1 H, J ) 6.7 Hz, H-5′), 3.61 (dd, 1 H, J )
9.7, 3.5 Hz, H-3′), 3.53 (dt, 1 H, J ) 9.8, 6.7 Hz, OCH2), 3.32
(dd, 1 H, J ) 11.9, 9.5 Hz, H-5), 2.11, 2.10, 2.039, 2.036 (s, 3
H each, OAc), 0.91 (m, 2 H, CH2Si), 0.00 (s, 9 H, SiMe3); 13C
NMR data (CDCl3): δ 171.7, 171.5, 170.9, 170.1, 101.3, 100.8,
76.3, 73.8, 73.0, 72.7, 71.5, 68.9, 67.7, 63.4, 63.1, 21.4, 21.3,
21.2, 18.4, -1.0; HRMS calcd for C24H40O14NSiNa (M + Na):
603.2085; found: 603.2079.
residue was chromathographed (SiO2
, heptane/EtOAc 1:1) to
give 25 (23 mg, 95%); [R]21 -34 (c 1.0, CHCl3); 1H NMR data
D
(CDCl3): δ 5.36 (d, 1 H, J ) 2.6 Hz, H-4′), 5.15-5.07 (m, 2 H,
H-2′,3), 4.98 (dd, 1 H, J ) 10.4, 3.4 Hz, H-3′), 4.83 (dd, 1 H, J
) 8.6, 7.0 Hz, H-2), 4.51 (d, 1 H, J ) 7.9 Hz, H-1′), 4.45 (d, 1
H, J ) 7.0 Hz, H-1), 4.11 (d, 2 H, J ) 6.6 Hz, H-6′), 3.97 (dd,
1 H, J ) 11.9, 5.1 Hz, H-5), 3.94-3.88 (m, 2 H), 3.82 (dt, 1 H,
J ) 5.3, 4.7 Hz, H-4), 3.54 (dt, 1 H, J ) 9.9, 6.5 Hz, OCH2),
3.33 (dd, 1 H, J ) 11.8, 9.3 Hz, H-5), 2.16, 2.07, 2.05, 1.98 (s,
3 H each, OAc), 0.91 (m, 2 H, CH2
Si), -0.01 (s, 9 H, SiMe3);
13C NMR data (CDCl3): δ 170.4, 170.2, 170.1, 170.0, 169.7,
169.0, 101.2, 100.3, 75.9, 72.2, 71.1, 70.9, 69.0, 67.2, 66.8, 62.7,
2,3,4-Tr i-O-a cetyl-r,â-D-xylop yr a n ose (20). Compound
10 (56 mg, 0.149 mmol) was treated with trifluoroacetic acid,16
as described in the preparation of 33, to give 20 (41 mg, 97%).
The crude product was used, without further purification, in
the preparation of 21.
2,3,4-Tr i-O-a cetyl-râ-D-xylop yr a n osyl Tr ich lor oa cet-
im id a te (21). Compound 20 (35 mg, 0.127 mmol) was treated
as described in the preparation of 34. The crude product was
chromatographed (SiO2, heptane/EtOAc 2:1) to give 21 (46 mg,
84%). Analytical data were in full accordance with those
previously published.18
61.2, 20.8, 20.7, 20.6, 18.0, -1.4; HRMS calcd for C28H44O16
SiNa (M + Na): 687.2296; found 687.2297.
-
2,3-Di-O-a cetyl-4-O-(2,3,4,6-tetr a -O-a cetyl-â-D-ga la cto-
p yr a n osyl)-râ-D-xylop yr a n ose (26). Compound 25 (53 mg,
0.080 mmol) was treated as described in the preparation of
33 to give 26 (45 mg, 100%). The crude product was used
without further purification in the preparation of 27.
2,3-Di-O-a cetyl-4-O-(2,3,4,6-tetr a -O-a cetyl-â-D-ga la cto-
pyr an osyl)-râ-D-xylopyr an osyl Tr ich lor oacetim idate (27).
Compound 26 (45 mg, 0.080 mmol) was treated as described
in the preparation of 34. The crude product was chromato-
graphed (SiO2, heptane/EtOAc 1:1) to give 27 (52 mg, 92%) as
an anomeric mixture (R/â 3:1). Selected 1H NMR data
(CDCl3): δ 8.68 (s, 1 H), 8.64 (s, 1 H), 6.41 (d, 1 H, J ) 3.7
Hz), 6.00 (d, 1 H, J ) 3.8 Hz), 5.48 (t, 1 H, J ) 9.6 Hz), 5.36
(d, 1 H, J ) 3.2 Hz), 4.57 (d, 1 H, J ) 8.0 Hz), 4.51 (d, 1 H, J
) 7.8 Hz); HRMS calcd for C25H32O16NCl3Na (M + Na):
730.0684; found 730.0689.
(2S,3R,4E)-2-Azid o-3-(ben zoyloxy)octa d ec-4-en yl 2,3,4-
Tr i-O-a cetyl-â-D-xylop yr a n osid e (23). A mixture of com-
pound 21 (21 mg, 0.050 mmol), azidosphingosine 2219 (42 mg,
0.099 mmol), and molecular sieves (100 mg, 300 AW) in dry
CH2Cl2 (1 mL) was stirred for 1 h under Ar and then cooled to
-33 °C. Boron trifluoride etherate (0.062 mL, 0.495 mmol)
and, after 90 min, Et3N (0.2 mL) were added, and the mixture
was filtered (Celite) and concentrated. The residue was
chromatographed (SiO2, heptane/EtOAc 4:1) to give 23 (20 mg,
(2S,3R,4E)-2-Azid o-3-(ben zoyloxy)octa d ec-4-en yl 2,3-
Di-O-a cetyl-4-O-(2,3,4,6-tetr a -O-a cetyl-â-D-ga la ctop yr a n -
osyl)-â-D-xylop yr a n osid e (28). Compound 27 (22 mg, 0.031
mmol) and 2219 (33 mg, 0.078 mmol) were treated as described
in the preparation of 23. Column chromatography (SiO2,
59%): [R]22 -57 (c 0.9, CHCl3); 1H NMR data (CDCl3): δ
D
(assignment of aglycon protons are shown in italic) 8.06-7.45
(m, 5 H, Ar), 5.92 (dt, 1 H, J ) 14.4, 6.9 Hz,H-5), 5.62-5.53
(m, 2 H, H-3,4), 5.50 (t, 1 H, J ) 7.9 Hz, H-3), 4.94 (dd, 1 H,
J ) 7.9, 6.1 Hz, H-2), 4.92 (m, 1 H, H-4), 4.56 (d, 1 H, J ) 6.1
Hz, H-1), 4.12 (dd, 1 H, J ) 12.0, 4.7 Hz, H-5), 3.95-3.83 (m,
2 H, H-1,2), 3.59 (dd, 1 H, J ) 10.0, 4.9 Hz, H-1), 3.40 (dd, 1
H, J ) 12.1, 7.8 Hz, H-5), 2.11, 2.08, 2.07 (s, 3 H each, OAc),
1.48-1.15 (m, 24 H, CH2), 0.89 (t, 3 H, J ) 6.9 Hz, CH3); 13C
NMR data (CDCl3): δ 170.5, 170.2, 169.8, 165.6, 139.5, 133.7,
130.3, 130.2, 128.9, 123.2, 100.4, 75.0, 71.1, 70.5, 68.9, 68.3,
64.0, 62.0, 32.8, 32.3, 30.1-29.1, 23.1, 21.2, 21.1, 14.6; HRMS
calcd for C36H53O10N3Na (M + Na): 710.3629; found 720.3625.
(2S,3R,4E)-3-(Ben zoyloxy)-2-octa d eca n a m id oocta d ec-
4-en yl 2,3,4-Tr i-O-a cetyl-â-D-xylop yr a n osid e (24). Hydro-
gen sulfide was bubbled through a mixture of compound 23
(14.5 mg, 0.021 mmol) and aqueous pyridine (5 mL, Pyr/H2O
∼6:1) for 1 h at 0 °C. The mixture was kept under H2S at 22
°C for 48 h. N2 was bubbled through the mixture for 1 h, and
heptane/EtOAc 3:2) gave 28 (21 mg, 70%); [R]22 -41 (c 1.0,
D
CHCl3); δ (assignment of aglycon protons are shown in italic)
8.07-7.44 (m, 5 H, Ar), 5.93 (dt, 1 H, J ) 14.6, 6.7 Hz, H-5),
5.62-5.51 (m, 2 H, H-3,4), 5.37 (d, 1 H, J ) 2.6 Hz, H-4′), 5.17-
5.10 (m, 2 H, H-3, H-2′), 5.00 (dd, 1 H, J ) 10.4, 3.4 Hz, H-3′),
4.86 (dd, 1 H, J ) 7.4, 5.8 Hz, H-2), 4.54 (d, 1 H, J ) 5.8 Hz,
H-1), 4.52 (d, 1 H, J ) 7.9 Hz, H-1′), 4.12 (d, 2 H, J ) 6.7 Hz,
H-6′), 3.98 (dd, 1 H, J ) 12.0, 4.4 Hz, H-5), 3.93-3.77 (m, 4
H), 3.59 (dd, 1 H, J ) 10.0, 4.7 Hz, H-1), 3.37 (dd, 1 H, J )
12.1, 7.8 Hz, H-5), 2.16, 2.11, 2.08, 2.07, 2.03, 1.99 (s, 3 H each,
OAc), 1.45-1.12 (m, 24 H, CH2), 0.89 (t, 3 H, J ) 6.8 Hz, CH3);
13C NMR data (CDCl3): δ 170.9, 170.6, 170.5, 170.3, 170.1,
169.4, 165.6, 139.4, 133.7, 130.3, 130.2, 128.9, 123.3, 101.6,
100.4, 75.6, 74.9, 71.34, 71.28, 71.2, 70.5, 69.4, 68.4, 67.3, 64.0,
62.2, 61.6, 32.8, 32.3, 30.1-29.1, 23.1, 21.22, 21.20, 21.11,

Synthesis of Xylosyl Ceramides
J . Org. Chem., Vol. 62, No. 23, 1997 7969
21.08, 20.99, 14.5; HRMS calcd for C48H69O18N3Na (M + Na):
998.4474; found 998.4481.
9.0 Hz, H-3), 5.08 (d, 1 H, J ) 10.2 Hz, NH′′), 4.92 (dd, 1 H, J
) 10.1, 8.0 Hz, H-2′), 4.85 (m, 3 H), 4.63 (d, 1 H, J ) 7.9 Hz,
H-1′), 4.48 (dd, 1 H, J ) 10.2, 3.4 Hz, H-3′), 4.42 (d, 1 H, J )
7.5 Hz, H-1), 4.38 (dd, 1 H, J ) 12.0, 2.4 Hz, H-9′′), 4.15-3.77
(m, 11 H), 3.63 (dd, 1 H, J ) 10.7, 2.7 Hz, H-6′′), 3.52 (dt, 1 H,
J ) 9.8, 6.6 Hz, OCH2), 3.30 (dd, 1 H, J ) 11.6, 10.0 Hz, H-5),
2.57 (dd, 1 H, J ) 12.6, 4.5 Hz, H-3′′eq), 2.23, 2.18, 2.09, 2.08,
2.06, 2.05, 2.03, 2.00, 1.85 (s, 3 H each, OAc, NHAc), 1.82 (t,
1 H, J ) 12.5 Hz, H-3′′ax), 0.89 (m, 2 H, CH2Si), -0.01 (s, 9H,
SiMe3); HRMS calcd for C46H69O27NSiNa (M + Na): 1118.3724;
found: 1118.3748.
2,3-Di-O-a cetyl-4-O-[2,4,6-tr i-O-a cetyl-3-O-(m eth yl 5-a c-
eta m id o-4,7,8,9-tetr a -O-a cetyl-3,5-d id eoxy-D-glycer o-r-D-
ga la ct o-2-n on u lop yr a n osyla t e)-â-D-ga la ct op yr a n osyl]-
râ-D-xylop yr a n ose (33). Compound 32 (52 mg, 0.047 mmol)
was dissolved in CH2Cl2 (0.27 mL), trifluoroacetic acid (0.54
mL) was added, and the mixture was stirred for 1 h.16
n-Propyl acetate (1.6 mL) and toluene (3.2 mL) were added,
and the mixture was concentrated to give 33 (47 mg, 100%).
The crude product was used without further purification in
the preparation of 34.
(2S,3R,4E)-3-(Ben zoyloxy)-2-octa d eca n a m id oocta d ec-
4-en yl 2,3-d i-O-a cetyl-4-O-(2,3,4,6-tetr a -O-a cetyl-â-D-ga -
la ctop yr a n osyl)-â-D-xylop yr a n osid e (29). Compound 28
(16.4 mg, 0.0174 mmol) was treated as described in the
preparation of 24. Column chromatography (SiO2, heptane/
EtOAc 1:1) gave 29 (17 mg, 80%); [R]22 -14 (c 1.0, CHCl3);
D
1H NMR data (CDCl3): δ (assignment of aglycon protons are
shown in italic) 8.04-7.43 (m, 5 H, Ar), 5.88 (dt, 1 H, J ) 14.4,
6.8 Hz, H-5), 5.75 (d, 1 H, J ) 9.4 Hz, NH), 5.54-5.43 (m, 2
H, H-3,4), 5.36 (d, 1 H, J ) 2.6 Hz, H-4′), 5.15-5.07 (m, 2 H,
H-3, H-2′), 4.98 (dd, 1 H, J ) 10.4, 3.5 Hz, H-3′), 4.83 (dd, 1
H, J ) 7.7, 5.9 Hz, H-2), 4.51 (m, 1 H, H-2), 4.48 (d, 1 H, J )
7.9 Hz, H-1′), 4.45 (d, 1 H, J ) 5.9 Hz, H-1), 4.11 (d, 2 H, J )
6.6 Hz, H-6′), 4.01 (dd, 1 H, J ) 9.8, 3.0 Hz, H-1), 3.90 (t, 1 H,
J ) 6.8 Hz, H-5′), 3.82-3.72 (m, 2 H, H-4,5), 3.55 (dd, 1 H, J
) 10.0, 3.9 Hz, H-1), 3.22 (m, 1 H, H-5), 2.15, 2.10, 2.07, 2.06,
1.98, 1.97 (s, 3 H each, OAc), 1.70-1.15 (m, 54 H, CH2), 0.89
(t, 6 H, J ) 6.8 Hz, CH3); 13C NMR data (CDCl3): δ 173.1,
170.9, 170.6, 170.5, 170.3, 170.2, 169.4, 165.7, 136.4, 133.5,
130.7, 130.0, 128.9, 125.3, 101.5, 100.5, 75.6, 74.5, 71.30, 71.26,
71.20, 70.9, 69.3, 67.7, 67.3, 62.1, 61.6, 50.9, 37.3, 32.7, 32.4,
30.1-29.3, 26.2, 23.1, 21.2, 21.1, 21.0, 14.6; HRMS calcd for
C66H105O19NNa (M + Na): 1238.7179; found 1238.7191.
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-a cetyl-4-O-[2,6-d i-O-
a cetyl-3-O-(m eth yl 5-a ceta m id o-4,7,8,9-tetr a -O-a cetyl-3,5-
d id eoxy-D-glycer o-r-D-ga la cto-2-n on u lop yr a n osyla te)-â-
D-ga la ctop yr a n osyl]-â-D-xylop yr a n osid e (31). A mixture
of compound 3015 (205 mg, 0.344 mmol), compound 19 (100
mg, 0.172 mmol), molecular sieves (100 mg, 3 Å), dry MeCN
(1.3 mL), and dry CH2Cl2 (1.33 mL) was stirred under Ar for
2.5 h. The mixture was protected from light, silver trifluo-
romethanesulfonate (91 mg, 0.353 mmol) in dry MeCN (0.7
mL) was added, and the mixture was cooled to -72 °C.
Methylsulfenyl bromide (0.086 mL, 4 M, 0.344 mmol, dissolved
in ClCH2CH2Cl) was added in four portions over 15 min. After
4 h, diisopropylamine (0.15 mL) was added, and the stirring
was continued for 1 h at -72 °C. The mixture was diluted
with CH2Cl2, filtered (Celite), successively washed with satu-
rated aqueous NaHCO3 and water, dried (Na2SO4), filtered,
and concentrated. The residue was chromatographed (SiO2,
toluene/EtOH 15:1 f 5/1) to give 31 (102 mg, 56%): [R]22D -26
2,3-Di-O-a cetyl-4-O-[2,4,6-tr i-O-a cetyl-3-O-(m eth yl 5-a c-
eta m id o-4,7,8,9-tetr a -O-a cetyl-3,5-d id eoxy-D-glycer o-r-D-
ga la ct o-2-n on u lop yr a n osyla t e)-â-D-ga la ct op yr a n osyl]-
râ-D-xylop yr a n osyl Tr ich lor oa cet im id a t e (34). DBU
(0.0031 mL, 0.021 mmol) was added to a solution of compound
33 (26 mg, 0.026 mmol) and Cl3CCN (0.085 mL, 0.84 mmol)
in dry CH2Cl2 (0.5 mL) at 0 °C under Ar. After 75 min, the
mixture was concentrated, and the residue was chromato-
graphed (SiO2, CH2Cl2/EtOH 20:1) to give 34 (24 mg, 81%) as
an anomeric mixture (R/â 3:1); [R]20 +12 (c 1.1, CHCl3);
D
Selected 1H NMR data (CDCl3): δ 8.69, 8.63 (s), 6.44 (d, J )
3.7 Hz), 5.99 (d, J ) 4.7 Hz). HRMS calcd for C43H57O27N2-
Cl3Na (M + Na): 1161.2112; found: 1161.2085.
(2S,3R,4E)-2-Azid o-3-(ben zoyloxy)octa d ec-4-en yl 2,3-
Di-O-a cet yl-4-O-[2,4,6-t r i-O-a cet yl-3-O-(m et h yl 5-a cet -
a m id o-4,7,8,9-t et r a -O-a cet yl-3,5-d id eoxy-D-glycer o-r-D-
ga la cto-2-n on u lop yr a n osyla te)-â-D-ga la ctop yr a n osyl]-â-
D-xylop yr a n osid e (35). Boron trifluoride etherate (0.021 mL,
0.167 mmol) was added to a mixture of compound 34 (19 mg,
0.0167 mmol), azidosphingosine 2219 (17.9 mg, 0.0417 mmol),
and molecular sieves (40 mg, 300 AW) in dry CH2Cl2 (0.5 mL)
at -33 °C under Ar. After 90 min, Et3N (0.06 mL) was added,
and the mixture was immediately chromatographed (SiO2,
1
(c 1.0, CHCl3); H NMR data (CDCl3): δ 5.58 (ddd, 1 H, J )
CH2Cl2/EtOH 30:1) to give 35 (15.4 mg, 66%); [R]23 -26 (c
9.4, 7.2, 2.5 Hz, H-8′′), 5.31 (dd, 1 H, J ) 9.1, 2.6 Hz, H-7′′),
5.12 (d, 1 H, J ) 10.1 Hz, NH′′), 5.08 (t, 1 H, J ) 8.9 Hz, H-3),
4.95 (dd, 1 H, J ) 9.9, 8.0 Hz, H-2′), 4.82 (dd, 1 H, J ) 9.1, 7.4
Hz, H-2), 4.77 (m, 1 H, H-4′′), 4.56 (d, 1 H, J ) 8.0 Hz, H-1′),
4.41 (d, 1 H, J ) 7.3 Hz, H-1), 4.37 (m, 1 H), 4.24 (m, 3 H),
4.04 (m, 2 H), 3.94-3.80 (m, 4 H), 3.79 (s, 3 H, OMe), 3.63 (t,
1 H, J ) 6.0 Hz), 3.52 (dt, 1 H, J ) 9.8, 6.4 Hz, OCH2), 3.38
(brd, 1 H, J ) 2.6 Hz, H-4′), 3.28 (dd, 1 H, J ) 11.8, 9.9 Hz,
H-5), 2.63 (dd, 1 H, J ) 12.7, 4.5 Hz, H-3′′eq), 2.19, 2.13, 2.09,
2.07, 2.04, 2.02, 2.013, 2.012, 1.85 (s, 3 H each, OAc, NHAc),
1.82 (t, 1 H, J ) 12.5 Hz, H-3′′ax), 0.90 (m, 2 H, CH2Si), -0.01
(s, 9 H, SiMe3); 13C NMR data (CDCl3): δ 170.9, 170.64, 170.60,
170.4, 170.3, 169.8, 169.7, 169.5, 168.4 (J C1′′-H3′′ax ) 6.6 Hz24),
101.1, 100.5, 97.0, 76.1, 73.7, 72.8, 72.4, 71.9, 71.5, 69.3, 68.8,
67.8, 67.5, 67.4, 67.2, 63.3, 63.1, 63.0, 57.0, 53.1, 49.1, 37.7,
23.1, 21.3, 20.86, 20.79, 20.77, 20.73, 18.0, -1.4; HRMS calcd
for C44H67O26NSiNa (M + Na): 1076.3618; found: 1076.3635.
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-a cetyl-4-O-[2,4,6-tr i-O-
a cetyl-3-O-(m eth yl 5-a ceta m id o-4,7,8,9-tetr a -O-a cetyl-3,5-
d id eoxy-D-glycer o-r-D-ga la cto-2-n on u lop yr a n osyla te)-â-
D-ga la ctop yr a n osyl]-â-D-xylop yr a n osid e (32). Compound
31 (60 mg, 0.057 mmol) was acetylated as described in the
preparation of 25. Column chromatography (SiO2, CH2Cl2/
D
1.0, CHCl3); 1H NMR data (CDCl3): δ (assignments of aglycon
protons are shown in italic) 8.05-7.41 (m, 5 H, Ar), 5.91 (dt,
1 H, J ) 14.2, 6.8 Hz, H-5), 5.63 (ddd, 1 H, J ) 9.4, 7.5, 2.7
Hz, H-8′′), 5.65-5.50 (m, 2 H, H-3,4), 5.30 (dd, 1 H, J ) 9.3,
2.8 Hz, H-7′′), 5.12 (t, 1 H, J ) 8.3 Hz, H-3), 5.03 (d, 1 H, J )
10.2 Hz), 4.93 (dd, 1 H, J ) 10.2, 7.9 Hz, H-2′), 4.88-4.82 (m,
3 H), 4.62 (d, 1 H, J ) 8.0 Hz, H-1′), 4.50 (dd, 1 H, J ) 10.2,
3.4 Hz, H-3′), 4.47 (d, 1 H, J ) 6.7 Hz, H-1), 4.05 (m, 4 H),
3.90-3.79 (m, 5 H), 3.84 (s, 3 H, OMe), 3.62 (dd, 1 H, J )
10.8, 2.8 Hz, H-6′′), 3.57 (dd, 1 H, J ) 10.0, 5.0 Hz, H-1), 3.35
(dd, 1 H, J ) 11.9, 8.0 Hz, H-5), 2.57 (dd, 1 H, J ) 12.5, 4.7
Hz, H-3′′eq), 2.22, 2.17, 2.09, 2.08, 2.07, 2.05, 2.02, 2.00, 1.84
(s, 3 H each, OAc, NHAc), 1.70 (t, 1 H, J ) 12.4 Hz, H-3′′ax),
1.39-1.24 (m, 22 H, CH2), 0.87 (t, 1 H, J ) 7.0 Hz, CH3); 13C
NMR data (CDCl3): δ 170.9, 170.7, 170.6, 170.4, 170.3, 170.2,
169.9, 169.8, 169.7, 169.4, 167.9, 165.1, 139.0, 133.2, 129.9,
129.7, 128.4, 122.8, 101.4, 100.5, 96.8, 75.9, 74.6, 72.1, 72.0,
71.3, 70.8, 70.7, 69.7, 69.3, 68.1, 67.6, 67.3, 63.6, 63.0, 62.8,
61.9, 53.1, 49.0, 37.4, 32.4, 31.9, 29.7, 29.66, 29.64, 29.63, 29.62,
29.56, 29.4, 29.3, 29.1, 28.7, 23.1, 22.7, 21.5, 20.9, 20.8, 20.74,
20.69, 20.6, 14.1; HRMS calcd for C66H94O29N4Na (M + Na):
1429.5901; found: 1429.5896.
(2S,3R,4E)-3-(Ben zoyloxy)-2-octa d eca n a m id oocta d ec-
4-en yl 2,3-Di-O-a cetyl-4-O-[2,4,6-tr i-O-a cetyl-3-O-(m eth yl
5-a ceta m id o-4,7,8,9-tetr a -O-a cetyl-3,5-d id eoxy-D-glycer o-
r-D-galacto-2-n on u lopyr an osylate)-â-D-galactopyr an osyl]-
â-D-xylop yr a n osid e (36). Hydrogen sulfide was bubbled
through a mixture of compound 35 (7.92 mg, 0.00563 mmol)
and aqueous pyridine (5 mL, 83%) for 1 h at 0 °C. The mixture
was kept under H2S at 22 °C for 48 h. N2 was bubbled through
the mixture for 1 h, and then it was concentrated and
EtOH 20:1) gave 32 (62 mg, 99%): [R]22 -23 (c 1.0, CHCl3);
D
1H NMR data (CDCl3): δ 5.63 (ddd, 1 H, J ) 9.5, 7.3, 2.4 Hz,
H-8′′), 5.30 (dd, 1 H, J ) 9.4, 2.8 Hz, H-7′′), 5.09 (t, 1 H, J )
(24) (a) Hori, H.; Nakajima, T.; Nishida, Y.; Ohrui, H.; Meguro, H.
Tetrahedron Lett. 1988, 29, 6317-6320. (b) Prytulla, S.; Lauterwein,
J .; Klessinger, M.; Thiem, J . Carbohydr. Res. 1991, 215, 345-349. (c)
Erce´govic, T.; Magnusson, G. J . Chem. Soc., Chem. Commun. 1994,
831-832.

7970 J . Org. Chem., Vol. 62, No. 23, 1997
Wilstermann and Magnusson
coconcentrated with toluene. The residue was dissolved in dry
CH2Cl2 (0.5 mL), and octadecanoic acid (6.4 mg, 0.0225 mmol)
and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydro-
chloride (4.3 mg, 0.0225 mmol) were added. After 2.5 h, the
mixture was chromatographed (SiO2, CH2Cl2/EtOH 30:1) to
give 36 (8.2 mg, 88%); [R]23D -14 (c 0.8, CHCl3); 1H NMR data
(CDCl3): δ (assignments of aglycon protons are shown in italic)
8.07-7.42 (m, 5 H, Ar), 5.87 (dt, 1 H, J ) 14.5, 6.9 Hz, H-5),
5.74 (d, 1 H, J ) 9.3 Hz, NH′′), 5.62 (ddd, 1 H, J ) 9.5, 7.0, 2.6
Hz, H-8′′), 5.48 (m, 2 H), 5.32 (dd, 1 H, J ) 9.4, 2.8 Hz, H-7′′),
5.13 (t, 1 H, J ) 8.3 Hz, H-3), 5.03 (d, 1 H, J ) 10.3 Hz, NH′),
4.95-4.81 (m, 4 H), 4.62 (d, 1 H, J ) 7.9 Hz, H-1′), 4.50 (m, 2
H), 4.43 (d, 1 H, J ) 6.6 Hz, H-1), 4.39 (dd, 1 H, J ) 12.2, 2.5
Hz, H-9′′), 4.03 (m, 5 H), 3.94-3.79 (m, 6 H), 3.64 (dd, 1 H, J
) 10.8, 2.8 Hz, H-6′′), 3.56 (dd, 1 H, J ) 9.9, 4.2 Hz, H-1),
3.27 (dd, 1 H, J ) 12.1, 8.9 Hz, H-5), 2.58 (dd, 1 H, J ) 12.6,
4.6 Hz, H-3′′eq), 2.21, 2.19, 2.11, 2.09, 2.08, 2.07, 2.05, 2.02,
2.00, 1.86 (s, 3 H each, OAc, NHAc), 1.71 (t, 1 H, J ) 12.5 Hz,
H-3′′ax), 1.30-1.20 (m, 54 H, CH2), 0.89 (m, 6 H, CH3); 13C
NMR data (CDCl3): δ 173.0, 171.3, 171.1, 171.0, 170.8, 170.75,
170.70, 170.3, 170.2, 169.9, 168.3, 165.7, 138.2, 133.4, 130.7,
130.0, 128.8, 125.2, 101.7, 101.1, 97.2, 76.2, 74.7, 72.4, 72.2,
71.3, 71.2, 70.0, 69.7, 68.0, 67.8, 67.6, 63.4, 63.0, 62.3, 53.6,
50.9, 49.4, 37.3, 32.8, 32.4, 30.1-29.7, 30.0, 29.4, 26.2, 23.6,
23.1, 21.9, 21.29, 21.25, 21.19, 21.18, 21.16, 21.1, 14.6; HRMS
4,6-Di-O-a cet yl-2-a m in o-2-d eoxy-3-O-(5-a cet a m id o-4,-
7,8,9-tetr a -O-a cetyl-3,5-d id eoxy-D-glycer o-r-D-ga la cto-2-
n on u lop yr a n osyloyl-1′f2-la ct a m )-â-D-ga la ct op yr a n o-
syl Eth yl Xa n th a te (41). Potassium ethylxanthate (7.5 mg,
0.047 mmol) was added to a solution of compound 40 (24 mg,
0.031 mmol) in EtOH (1 mL). The mixture was stirred for 16
h while protected from light and then diluted with CH2Cl2,
washed with water, dried (Na2SO4), filtered, and concentrated.
The residue was chromatographed (SiO2, CH2Cl2/EtOH 20:1)
to give 41 (20 mg, 78%); [R]25D -7 (c 1.1, CHCl3); 1H NMR data
(CDCl3): δ 7.21 (s, 1 H, NH), 6.30 (d, 1 H, J ) 10.0 Hz, NH′),
5.49 (brd, 1 H, J ) 1.8 Hz, H-4), 5.44 (d, 1 H, J ) 10.4 Hz,
H-1), 5.37 (dd, 1 H, J ) 3.8, 2.2 Hz, H-7′), 5.23 (dt, 1 H, J )
11.0, 5.4 Hz, H-4′), 5.11 (m, 1 H, H-8′), 4.68 (m, 2 H, OCH2),
4.44 (dd, 1 H, J ) 12.2, 1.7 Hz, H-9′), 4.25-4.00 (m, 7 H), 3.93
(dd, 1 H, J ) 10.5, 2.1 Hz, H-6′), 2.52 (dd, 1 H, J ) 13.1, 5.4
Hz, H-3′eq), 2.25, 2.12, 2.09, 2.07, 2.04, 1.96, 1.89, (s, 3 H each,
OAc, NHAc), 1.45 (t, 3 H, J ) 7.1 Hz, CH3); 13C NMR data
(CDCl3): δ 209.5, 170.8, 170.4, 170.1, 169.9, 166.6, 98.4, 85.6,
78.0, 75.9, 73.2, 71.9, 71.1, 70.7, 68.3, 65.4, 63.3, 61.7, 48.4,
48.3, 37.0, 29.7, 23.2, 21.04, 21.01, 20.9, 20.7, 20.5, 13.8; HRMS
calcd for C32H44O18N2S2Na (M + Na): 831.1928; found:
831.1945.
2-(Tr im et h ylsilyl)et h yl 2,3-Di-O-a cet yl-4-O-[4,6-d i-O-
a cetyl-2-a m in o-2-d eoxy-3-O-(5-a ceta m id o-4,7,8,9-tetr a -O-
acetyl-3,5-dideoxy-D-glycer o-r-D-galacto-2-n on u lopyr an o-
syloyl-1′′f2′-la ct a m )-â-D -ga la ct op yr a n osyl]-â-D -xylo-
p yr a n osid e (42). A solution of compound 40 (40 mg, 0.052
mmol), compound 14 (14.5 mg, 0.043 mmol), and molecular
sieves (30 mg, 4 Å) in dry CH2Cl2 (0.5 mL) was stirred under
Ar for 1 h. Silver silicate20 (73 mg) was added, and the mixture
was protected from light and stirred for 3 days and then
filtered (Celite) and concentrated. The residue was chromato-
calcd for
1669.8579.
C84H130O30N2Na (M + Na): 1669.8606; found:
2-(Tr im eth ylsilyl)eth yl 4,6-Di-O-acetyl-2-am in o-2-deoxy-
3-O-(5-acetam ido-4,7,8,9-tetr a-O-acetyl-3,5-dideoxy-D-glyc-
er o-r-D-ga la cto-2-n on u lop yr a n osyloyl-1′f2-la cta m )-â-D-
ga la ctop yr a n osid e (38). Compound 378b (34 mg, 0.062
mmol) was acetylated as described in the preparation of 13.
The crude product was chromathographed (SiO2, CH2Cl2/
graphed (SiO2, CH2Cl2/EtOH 20:1) to give 42 (10.7 mg, 24%);
EtOAc 1:4) to give 38 (45 mg, 91%); [R]27 -47 (c 1.0, CHCl3);
D
1
[R]23 -60 (c 0.6, CHCl3); H NMR data (CDCl3): δ 6.57 (s, 1
1H NMR data (CDCl3): δ 7.39 (s, 1 H, NH), 6.37 (d, 1 H, J )
10.3 Hz, NH′), 5.51 (dd, 1 H, J ) 3.4, 2.3 Hz, H-7′), 5.40 (dd,
1 H, J ) 2.8, 1.6 Hz, H-4), 5.21 (dt, 1 H, J ) 10.8, 5.4 Hz,
H-4′), 5.05 (ddd, 1 H, J ) 5.1, 3.2, 1.7 Hz, H-8′), 4.55 (dd, 1 H,
J ) 12.3, 1.6 Hz, H-9′), 4.37 (d, 1 H, J ) 7.7 Hz, H-1), 4.31
(dd, 1 H, J ) 12.3, 4.8 Hz, H-9′), 4.27-4.20 (m, 2 H, H-6, H-5′),
4.12 (dd, 1 H, J ) 11.3, 6.5 Hz, H-6), 4.03 (dd, 1 H, J ) 10.4,
2.2 Hz, H-6′), 4.00-3.91 (m, 2 H, H-5, OCH2), 3.89 (dd, 1 H, J
) 11.1, 3.1 Hz, H-3), 3.81 (dd, 1 H, J ) 11.0, 7.5 Hz, H-2),
3.62 (m, 1 H, OCH2), 2.50 (dd, 1 H, J ) 13.1, 5.5 Hz, H-3′eq),
2.26, 2.13, 2.09, 2.05, 1.94, 1.89, (s, 3 H each, OAc, NHAc),
1.88 (dd, 1 H, J ) 13.0, 11.3 Hz, H-3′ax), 0.98 (m, 2 H, CH2-
Si), 0.02 (s, 9 H, SiMe3); HRMS calcd for C34H52O18N2SiNa (M
+ Na): 827.2882; found: 827.2889.
D
H, NH′), 5.55 (d, 1 H, J ) 10.6 Hz, NH′′), 5.46 (dt, 1 H, J )
10.8, 5.1 Hz, H-4′′), 5.39 (brs, 1 H, H-4′), 5.28 (dd, 1 H, J )
6.0, 2.1 Hz, H-7′′), 5.13 (m, 2 H), 4.85 (dd, 1 H, J ) 7.9, 6.3
Hz, H-2), 4.51 (d, 1 H, J ) 6.3 Hz, H-1), 4.45 (brd, 1 H, J )
7.4 Hz, H-1′), 4.31 (dd, 1 H, J ) 12.3, 2.6 Hz, H-9′′), 4.20-
4.05 (m, 5 H), 4.00 (dt, 1 H, J ) 7.8, 4.5 Hz, H-4), 3.95-3.80
(m, 5 H), 3.54 (dt, 1 H, J ) 9.8, 6.4 Hz, OCH2), 3.49 (dd, 1 H,
J ) 12.2, 8.1 Hz, H-5), 2.44 (dd, 1 H, J ) 13.2, 5.6 Hz, H-3′′eq),
2.22, 2.10, 2.09, 2.07, 2.063, 2.062, 2.059, 1.99, 1.87, (s, 3 H
each, OAc, NHAc), 1.81 (dd, 1 H, J ) 13.1, 11.5 Hz, H-3′′ax),
0.91 (m, 2 H, CH2Si), 0.01 (s, 9 H, SiMe3); 13C NMR data
(CDCl3): δ 170.9, 170.7, 170.51, 170.47, 170.40, 170.2, 170.1,
170.0, 169.9, 169.5, 100.0, 99.0, 98.0, 75.4, 73.6, 72.9, 72.0, 71.6,
70.9, 70.6, 70.2, 67.9, 67.2, 65.1, 62.6, 61.6, 61.4, 57.0, 50.3,
50.2, 49.14, 49.06, 37.4, 29.7, 23.2, 20.93, 20.86, 20.81, 20.79,
4,6-Di-O-a cet yl-2-a m in o-2-d eoxy-3-O-(5-a cet a m id o-4,-
7,8,9-tetr a -O-a cetyl-3,5-d id eoxy-D-glycer o-r-D-ga la cto-2-
n on u lop yr a n osyloyl-1′f2-la ct a m )-râ-D-ga la ct op yr a n -
ose (39). Compound 38 (367 mg, 0.456 mmol) was treated as
described in the preparation of 33 to give 39 (327 mg, 100%).
The crude product was used without further purification in
the preparation of compound 40.
20.74, 20.72, 20.66, 20.5, 17.9, -1.4; HRMS calcd for C43H64
O24N2SiNa (M + Na): 1043.3516; found: 1043.3512.
-
2-(Tr im eth ylsilyl)eth yl 2-O-Ben zoyl-4-O-[4,6-di-O-acetyl-
2-a m in o-2-d eoxy-3-O-(5-a ceta m id o-4,7,8,9-tetr a -O-a cetyl-
3,5-d id eoxy-D-glycer o-r-D-ga la cto-2-n on u lop yr a n osyloyl-
1 ′′f2 ′-l a c t a m ) -â-D -g a l a c t o p y r a n o s y l ] -â-D -x y l o -
p yr a n osid e (43) a n d 2-(Tr im eth ylsilyl)eth yl 2-O-Ben zoyl-
3-O-[4,6-d i-O-a cet yl-2-a m in o-2-d eoxy-3-O-(5-a cet a m id o-
4,7,8,9-tetr a -O-a cetyl-3,5-d id eoxy-D-glycer o-r-D-ga la cto-
2-nonulopyranosyloyl-1′′f2′-lactam)-â-D-galactopyranosyl]-
â-D-xylop yr a n osid e (44). Compound 40 (40 mg, 0.052 mmol)
and compound 12 (15.4 mg, 0.0434 mmol) were treated as
described in the preparation of 42. The crude product was
chromatographed (SiO2, toluene/EtOH 10:1) to give almost
pure 43 (6.9 mg, 15%) and pure 44 (13.6 mg, 30%). Compound
43: 1H NMR data (CDCl3): δ 8.06-7.40 (m, 5 H, Ar), 5.91 (d,
1 H, J ) 10.4 Hz, NH′′), 5.40 (m, 2 H), 5.31 (dd, 1 H, J ) 6.4,
1.9 Hz, H-7′′), 5.21 (dt, 1 H, J ) 6.7, 2.4 Hz, H-8′′), 5.12 (dd, 1
H, J ) 9.5, 7.8 Hz, H-2), 4.60 (d, 1 H, J ) 7.3 Hz, H-1′), 4.55
(d, 1 H, J ) 7.8 Hz, H-1), 4.38 (dd, 1 H, J ) 12.4, 2.5 Hz, H-9′′),
4.30-3.80 (m, 13 H), 3.56 (dt, 1 H, J ) 10.1, 6.0 Hz, OCH2),
3.43 (dd, 1 H, J ) 11.6, 10.0 Hz, H-5), 2.48 (dd, 1 H, J ) 13.2,
5.5 Hz, H-3′′eq), 2.25, 2.14, 2.13, 2.09, 2.04, 1.91, 1.89, (s, 3 H
each, OAc, NHAc), 1.81 (dd, 1 H, J ) 13.3, 11.4 Hz, H-3′′ax),
0.90 (m, 2 H, CH2Si), -0.04 (s, 9 H, SiMe3); HRMS calcd for
C46H64O23N2SiNa (M + Na): 1063.3567; found: 1063.3607.
4,6-Di-O-a cet yl-2-a m in o-2-d eoxy-3-O-(5-a cet a m id o-4,-
7,8,9-tetr a -O-a cetyl-3,5-d id eoxy-D-glycer o-r-D-ga la cto-2-
n on u lop yr a n osyloyl-1′f2-la ct a m )-r-D-ga la ct op yr a n o-
syl Br om id e (40). Oxalyl bromide (0.031 mL, 0.328 mmol)
was dissolved in dry CH2Cl2 (1.7 mL), and the mixture was
added to a cooled (0 °C) solution of compound 39 (77 mg, 0.109
mmol) in dry CH2Cl2 (2.5 mL) and dry DMF (0.024 mL, 0.306
mmol) under Ar. The mixture was stirred at 0 °C for 1 h and
for 12 h at 22 °C and then diluted with CH2Cl2, washed with
saturated aqueous NaHCO3 and water, dried (Na2SO4), fil-
tered, and concentrated. The residue was chromatographed
(SiO2, CH2Cl2/EtOH 20:1) to give 40 (51 mg, 61%), contami-
nated with a trace of DMF; [R]27D +74 (c 1.2, CHCl3); 1H NMR
data (CDCl3): δ 6.88 (s, 1 H, NH), 6.64 (d, 1 H, J ) 2.7 Hz,
H-1), 6.08 (d, 1 H, J ) 10.2 Hz, NH′), 5.49 (brs, 1 H, H-4),
5.35-5.18 (m, 3 H), 4.44-4.05 (m, 8 H), 3.80 (dd, 1 H, J )
10.5, 1.8 Hz, H-6′), 2.48 (dd, 1 H, J ) 13.1, 5.6 Hz, H-3′eq),
2.26, 2.13, 2.11, 2.07, 2.02, 2.00, 1.89, (s, 3 H each, OAc, NHAc),
1.76 (dd, 1 H, J ) 12.9, 11.4 Hz, H-3′ax); HRMS calcd for
C29H39O17N2BrNa (M + Na): 789.1330; found: 789.1305.

Synthesis of Xylosyl Ceramides
J . Org. Chem., Vol. 62, No. 23, 1997 7971
Compound 44: [R]25 +2 (c 1.0, CHCl3); 1H NMR data
Si), -0.15 (s, 9 H, SiMe3); 13C NMR data (CDCl3): δ 171.1,
170.64, 170.57, 170.54, 170.0, 169.8, 169.6, 167.1, 165.7, 134.1,
130.0, 129.0, 128.8, 100.5, 97.9, 84.7, 75.1, 73.7, 71.9, 71.8, 70.3,
68.8, 68.3, 67.5, 67.0, 65.2, 64.9, 61.8, 61.5, 56.9, 50.3, 49.2,
37.4, 29.7, 23.3, 21.0, 20.9, 20.77, 20.75, 20.6, 20.5, 18.1, -1.4;
HRMS calcd for C46H64O23N2SiNa (M + Na): 1063.3567;
found: 1063.3544.
D
(CDCl3): δ 8.08-7.45 (m, 5 H, Ar), 6.61 (brs, 1 H, NH′), 5.54
(dt, 1 H, J ) 10.9, 5.3 Hz, H-4′′), 5.34 (m, 2 H), 5.28 (dd, 1 H,
J ) 2.7, 1.4 Hz, H-4′), 5.08 (m, 2 H), 4.58 (d, 1 H, J ) 7.5 Hz,
H-1), 4.32 (dd, 1 H, J ) 12.5, 3.0 Hz, H-9′′), 4.20-4.10 (m, 5
H), 4.01 (dd, 1 H, J ) 12.5, 4.8 Hz, H-9′′), 3.97 (m, 1 H, OCH2),
3.92 (ddd, 1 H, J ) 10.0, 8.2, 5.5 Hz, H-4), 3.86 (m, 1 H, H-5′),
3.81 (dd, 1 H, J ) 10.5, 2.0 Hz, H-6′′), 3.77 (dd, 1 H, J ) 11.0,
7.7 Hz, H-2′), 3.73 (t, 1 H, J ) 8.4 Hz, H-3), 3.62 (dd, 1 H, J )
11.1, 3.0 Hz, H-3′), 3.59 (m, 1 H, OCH2), 3.34 (dd, 1 H, J )
11.8, 10.0 Hz, H-5), 2.32 (dd, 1 H, J ) 13.2, 5.5 Hz, H-3′′eq),
2.23, 2.22, 2.09, 2.05, 2.04, 1.99, 1.88, (s, 3 H each, OAc, NHAc),
1.75 (dd, 1 H, J ) 13.0, 11.5 Hz, H-3′′ax), 0.89 (m, 2 H, CH2-
Ack n ow led gm en t. This work was supported by the
Swedish Research Council for Engineering Sciences and
the Swedish Natural Science Research Council.
J O970298K