Synthesis of lactam and acetamido analogues of sialyl Lewis x tetrasaccharide and Lewis x trisaccharide

Article abstract of DOI:10.1021/jo981204p

Virtually complete regioselective galactosylation of the diol acceptor p-methoxyphenyl 6-O-benzyl-2-deoxy-2-tetrachlorophthalimido-β-D- glucopyranoside (15) with the donors ethyl 3,4-di-O-acetyl-6-O-benzyl-2- deoxy-2-[[(2,2,2-trichloroethoxy)carbonyl]amino]-1-thio-β-D- galactropyranoside (14), 4-methylphenyl 2,3-di-O-acetyl-4-azido-6-O-benzyl- 4-deoxy-1-thio-β-D-galactopyranoside (30), and 4-methylphenyl 2-O-acetyl-4- azido-6-O-benzyl-4-deoxy-3-O-(methoxyethanoyl)-1-thio-β-D-galactopyranoside (44) gave the lactose-diamine derivatives 16, 33, and 45, respectively. Fucosylation of the NHAc derivatives of 16 and 33 (17 and 34) with the donor 18 gave, after deprotection and N-acetylation, the 2-NHAc-Le(x) and 4-NHAc- Le(x) trisaccharides 3 and 5, respectively. Removal of the Troc group from the tetrasaccharide intermediate 23, followed by N-acetylation (→ 24), gave the NHAc-SLe(x) tetrasaccharide 2. Regioselective sialylation of the partially protected trisaccharide diols 21 and 37 with the sialyl donors 22 and 38 gave, after deprotection and lactamization, the SLe(x)-1'''→2'- lactam 1 and the SLe(x)-1'''→4'-lactam 4, respectively. The stannylidene acetal of the trisaccharide diol 21 was regioselectively 3-O-alkylated with tert-butyl bromoacetate; reductive removal of the Troc protecting group and addition of methanolic MeONa caused formation of a lactam ring. Compound 40 was thus obtained over four steps in an overall yield of 52%. Deprotection of 40 furnished the Le(x)-3,2-lactam 6 in 74% yield. Fucosylation of the lactose-diamine derivative 46 with donor 18 gave the N₃-Le(x) trisaccharide derivative 47. The azido function of 47 was reduced with H₂S, which caused spontaneous closure of a lactam ring. Removal of the protecting groups then gave the Le(x)-3,4-lactam 7. The total yields of 1, 2, 3, 4, 5, and 7 from the monosaccharide starting materials 14, 15, 18, 22, 30, 38, and 44 were 10%, 10%, 22%, 14%, 62%, and 28%, respectively.

Full text of DOI:10.1021/jo981204p

J . Org. Chem. 1998, 63, 9323-9338
9323
Syn th esis of La cta m a n d Aceta m id o An a logu es of Sia lyl Lew is x
Tetr a sa cch a r id e a n d Lew is x Tr isa cch a r id e
Ulf Ellervik, Hans Grundberg, and Go¨ran Magnusson*
Organic Chemistry 2, Center for Chemistry and Chemical Engineering, Lund University,
P.O. Box 124, SE-221 00 Lund, Sweden
Received J une 22, 1998
Virtually complete regioselective galactosylation of the diol acceptor p-methoxyphenyl 6-O-benzyl-
2-deoxy-2-tetrachlorophthalimido-â-D-glucopyranoside (15) with the donors ethyl 3,4-di-O-acetyl-
6-O-benzyl-2-deoxy-2-[[(2,2,2-trichloroethoxy)carbonyl]amino]-1-thio-â-D-galactopyranoside (14), 4-
methylphenyl 2,3-di-O-acetyl-4-azido-6-O-benzyl-4-deoxy-1-thio-â-D-galactopyranoside (30), and
4-methylphenyl 2-O-acetyl-4-azido-6-O-benzyl-4-deoxy-3-O-(methoxyethanoyl)-1-thio-â-D-galacto-
pyranoside (44) gave the lactose-diamine derivatives 16, 33, and 45, respectively. Fucosylation of
the NHAc derivatives of 16 and 33 (17 and 34) with the donor 18 gave, after deprotection and
N-acetylation, the 2-NHAc-Lex and 4-NHAc-Lex trisaccharides 3 and 5, respectively. Removal of
the Troc group from the tetrasaccharide intermediate 23, followed by N-acetylation (f 24), gave
the NHAc-SLex tetrasaccharide 2. Regioselective sialylation of the partially protected trisaccharide
diols 21 and 37 with the sialyl donors 22 and 38 gave, after deprotection and lactamization, the
SLex-1′′′f2′-lactam 1 and the SLex-1′′′f4′-lactam 4, respectively. The stannylidene acetal of the
trisaccharide diol 21 was regioselectively 3-O-alkylated with tert-butyl bromoacetate; reductive
removal of the Troc protecting group and addition of methanolic MeONa caused formation of a
lactam ring. Compound 40 was thus obtained over four steps in an overall yield of 52%.
Deprotection of 40 furnished the Lex-3,2-lactam 6 in 74% yield. Fucosylation of the lactose-diamine
derivative 46 with donor 18 gave the N3-Lex trisaccharide derivative 47. The azido function of 47
was reduced with H2S, which caused spontaneous closure of a lactam ring. Removal of the protecting
groups then gave the Lex-3,4-lactam 7. The total yields of 1, 2, 3, 4, 5, and 7 from the
monosaccharide starting materials 14, 15, 18, 22, 30, 38, and 44 were 10%, 10%, 22%, 14%, 62%,
and 28%, respectively.
In tr od u ction
about their presence in vivo, especially since some of the
anti-ganglioside-lactone antibodies cross-reacted with the
The Sialyl Lewis x ganglioside (SLex) has been identi-
fied as an important compound for intercellular molec-
ular recognition. References to the biological background,
as well as the different syntheses of SLex glycosides, were
summarized in the preceding paper in this issue.1 Fol-
lowing the initial investigations of the biological effects
of SLex, the focus has now turned toward the synthesis
and biological potential of SLex analogues, where an
anionic (e.g., carboxylate) center is retained.2
Gangliosides are known to lactonize upon treatment
with acid in vitro, thus removing the anionic charge
present in the parent ganglioside.3 The question of
lactonization in vivo has been debated for decades, and
experimental evidence has come from investigations such
as reductive radiolabeling with tritium3b and immun-
ostaining of cells with antibodies raised against ganglio-
side lactones.4 However, the hydrolytic lability of the
lactones has made it difficult to draw any safe conclusions
nonlactonized form of the ganglioside.4
In an alternative approach, we have synthesized gan-
glioside lactams, which are quite stable against hydroly-
sis and have conformations very similar to those of the
ganglioside lactones.5 A cyclic ether analogue of GM3
-
1′′f2′-lactone has also been reported.6 Antibodies raised
against the GM3-1′′f2′-lactam were found to cross-react
with GM3-lactone in vitro, but not with the open form of
GM3-ganglioside.7 Mouse melanoma cells that are known
to carry large amounts of surface-bound GM3-ganglioside
were stained by the anti-GM3-1′′f2′-lactam antibodies,
which strongly indicates that GM3-lactone is present on
the cell surface.8
The question of SLex-lactones as naturally occurring
entities has not been subject to experimental investiga-
tion, except for a molecular mechanics calculation (MM3)
(4) (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. (c) Kawashima,
I.; Kotani, M.; Ozawa, H.; Suzuki, M.; Tai, T. Int. J . Cancer 1994, 58,
263-268.
(5) (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. (c) Wilstermann, M.; Magnusson, G. J . Org. Chem. 1997, 62,
7961-7971.
(6) Tietze, L. F.; Keim, H. Angew. Chem., Int. Ed. Engl. 1997, 36,
1615-1617.
(7) Ding, K.; Rose´n, A.; Ray, A. K.; Magnusson, G. Glycoconj. J . 1993,
9, 303-306.
(1) Ellervik, U.; Magnusson, G. J . Org. Chem. 1998, 63, 9314.
(2) (a) Bertozzi, C. R. Chem. Biol. 1995, 2, 703-708. (b) Wong, C.-
H.; Mori-Varas, F.; Hung, S.-C.; Marron, T. G.; Lin, C.-C.; Gong, K.
W.; Weitz-Schmidt, G. J . Am. Chem. Soc. 1997, 119, 8152-8158. (c)
Kolb, C. H.; Ernst, B. Chem. Eur. J . 1997, 3, 1571-1578.
(3) (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.
10.1021/jo981204p CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/24/1998

9324 J . Org. Chem., Vol. 63, No. 25, 1998
Ellervik et al.
F igu r e 1. Structures of lactam and acetamido analogues of SLex tetrasaccharide and Lex trisaccharide.
of their conformations.9 A few reports have appeared
where SLex-lactones were found to be intermediates
formed during synthesis.10 Similar to the situation with
GM3-lactones, SLex-lactones are potentially strong tumor
antigens in vivo. Consequently, we have developed
synthetic routes to the SLex-lactams. We now disclose
the details of our syntheses of SLex-1′′′f2′-lactam (1) and
SLex-1′′′-4′-lactam (4), as well as the acetamido analogues
of SLex tetrasaccharide (2) and Lewis x trisaccharide (3
and 5), depicted in Figure 1.
We realized the possibility that the lactam ring per se
was mainly responsible for the immunogenicity action,
and it was therefore deemed to be of interest to prepare
ganglioside lactam analogues, where the sialic acid ring
system had been removed. We report therefore the
synthesis of the Lex-3,2- and -3,4-lactam trisaccharides
6 and 7 (Figure 1), which are simplified analogues of the
SLex-lactams. We plan to use these compounds as
potential inhibitors of recognition between SLex-lactam
and the corresponding antibodies obtainable by im-
munization of mice with SLex-lactam neoglycoproteins,
essentially as described for the GM3-lactam system.5,7,8
The fully O-acetylated derivatives of 6 and 7 were
important for securing the structure of the SLex-1′′′f4′-
lactam (4). In addition, the synthetic targets 6 and 7
provided incentive to further investigate the versatility
of NTroc-protection11 en route to lactams (21 f 40) and
to develop and test a complex galactosyl donor (44) for
regioselective glycosylation (f 45).
Resu lts a n d Discu ssion
I. Syn th esis of Sia lyl Lew is x-1′′′f2′-la cta m a n d
th e Cor r esp on d in g Aceta m id o An a logu es of Sia lyl
Lew is x Tetr a sa cch a r id e a n d Lew is x Tr isa cch a -
r id e. The overall synthetic strategy was based on
considerations of the various functionalities in the final
products and on the need to develop generally useful
intermediates that would lead to both the lactam (1) and
the acetamido (2, 3) analogues. Since both the glu-
cosamine and galactosamine moieties are present as
â-glycosides in 1-3, the nitrogens had to carry partici-
pating protecting groups that permitted selective ma-
nipulations following the glycosylation steps. This was
realized by using the tetrachlorophthalimido12 (NTCP)
and [(2,2,2-trichloroethoxy)carbonyl]amino11,13 (NTroc)
protecting groups. We also used regioselective glycosy-
lations of diol acceptors for the introduction of the
galactosamine and sialic acid units, in correspondence
with earlier successful similar reactions (see below).
(8) Magnusson, G.; Ding, K.; Nilsson, U.; Ray, A. K.; Rose´n, A.;
Sjo¨gren, H.-A. In Complex Carbohydrates in Drug Research; Bock, K.,
Clausen, H., Eds.; Alfred Benzon Symposium 36; Munksgaard: Copen-
hagen, 1994; pp 89-100.
(9) Ellervik, U.; Magnusson, G. Bioorg. Med. Chem. 1994, 2, 1261-
1266.
(10) (a) Nicolaou, K. C.; Hummel, C. W.; Bockovich, N. J .; Wong,
C.-H. J . Chem. Soc., Chem. Commun. 1991, 870-872. (b) Nicolaou, K.
C.; Hummel, C. W.; Iwabuchi, Y. J . Am. Chem. Soc. 1992, 114, 3126-
3128. (c) Danishefsky, S. J .; Gervay, J .; Peterson, J . M.; McDonald, F.
E.; Koseki, K.; Oriyama, T.; Griffith, D. A. J . Am. Chem. Soc. 1992,
114, 8329-8331. (d) Danishefsky, S. J .; Gervay, J .; Peterson, J . M.;
McDonald, F. E.; Koseki, K.; Griffith, D. A.; K.; Oriyama, T.; Marsden,
S. P. J . Am. Chem. Soc. 1995, 117, 1940-1953. (e) Sprengard, U.;
Kretzschmar, G.; Bartnik, E.; Hu¨ls, C.; Kunz, H. Angew. Chem., Int.
Ed. Engl. 1995, 34, 990-993. (f) Kretzschmar, G.; Stahl, W. Tetrahe-
dron 1998, 54, 6341-6358.
Syn th esis of th e Ga la ctosa m in e Don or 14. We
have developed a route to 14 starting with glucosamine
instead of galactosamine. The known route to 8 from
glucosamine is straightforward and includes high-yield-
(11) Ellervik, U.; Magnusson, G. Carbohydr. Res. 1996, 280, 251-
260.
(12) (a) Debenham, J . S.; Madsen, R.; Roberts, C.; Fraser-Reid, B.
J . Am. Chem. Soc. 1995, 117, 3302-3303. (b) Debenham, J . S.; Fraser-
Reid, B. J . Org. Chem. 1996, 61, 432-433. (c) Castro-Palomino, J . C.;
Schmidt, R. R. Tetrahedron Lett. 1995, 36, 5343-5346.
(13) Windholz, T. B.; J ohnston, D. B. R. Tetrahedron Lett. 1967, 27,
2555-2557.

Analogs of Sialyl Lewis x Tetrasaccharide
J . Org. Chem., Vol. 63, No. 25, 1998 9325
Sch em e 1a
Sch em e 2a
a
Key: (a) HCl-MeOH, ∼22 °C, 16 h; (b) C6H5CH(OMe)2, TsOH,
MeCN, 4 h; (c) Ac2O, pyridine, DMAP, ∼22 °C, 1 h; (d) NaBH3CN,
THF, then HCl-OEt2 (pH 2-3), 0 °C, 2 h; (e) (CF3SO2)2O, pyridine,
CH2Cl2, -20 °C, 2 h; (f) CsOAc, DMF, ∼22 °C, 2.5 h.
ing steps and a crystalline intermediate,11 whereas the
corresponding reactions starting with galactosamine were
much less efficient and gave syrups that were difficult
to purify. The reactions leading from 8 to 14 (Scheme 1)
are highly efficient and the only (formal) drawback is the
glucosamine f galactosamine inversion step (12 f 14),
which, however, proceeds in high yield.
De-O-acetylation of the known11 NTroc-protected thio-
glycoside 8 was accomplished by treatment with HCl-
saturated methanol overnight to give 9 (100%). Treat-
ment of 9 with R,R-dimethoxytoluene under acidic con-
ditions furnished 10 (95%), and the ensuing O-acetylation
gave 11 (96%). Reductive opening of the 4,6-O-ben-
zylidene ring14 in 11 yielded 12 (93%), and trifluoro-
methanesulfonylation of HO-4 gave crude 13, which was
treated with cesium acetate in freshly distilled DMF to
furnish the NTroc-protected galactosamine donor 14
(80%). Treatment of 13 with sodium acetate instead of
cesium acetate also provided 14, albeit in low yield and
purity.
a
Key: (a) AgOTf, MeCN, -70 °C, Ar, 5 min, then MeSBr,
ClCH2CH2Cl, -78 °C, 2 h; (b) H2NCH2CH2NH2, EtOH, 60 °C, 16
h, then Ac2O, MeOH, H2O, ∼22 °C, 1.5 h; (c) Br2, CH2Cl2,
cyclohexene, then MS 4 Å, Bu4NBr, CH2Cl2, DMF, ∼22 °C, 48 h,
then pyridine, 3 h; (d) Zn, AcOH, ∼22 °C, 1.5 h, then Ac2O,
pyridine; (e) H2, Pd-C, AcOH, then MeONa, MeOH.
Regioselective Glycosyla tion of Diol Accep tor 15
a n d Syn th esis of Lex Tr isa cch a r id e An a logu e 3.
Regioselective methylsulfenyl bromide15 (MSB)- and sil-
ver trifluoromethanesulfonate (AgOTf)-mediated glyco-
sylation of the known1 acceptor 15 with the donor 14
yielded the disaccharide derivative 16 (62%) as depicted
purpose to guide the regioselective glycosylation with 14)
was replaced by the smaller NHAc group in order to ease
the ensuing fucosylation. Thus, treatment of 16 with 1.2
equiv of 1,2-diaminoethane12 in ethanol at 60 °C over-
night, followed by selective N-acetylation with aqueous
acetic anhydride furnished the NTroc-protected disac-
charide 17 (80%). The efficient regioselective deblocking
of the NTCP group in the presence of an NTroc group is
a potentially useful reaction for the synthesis of other
saccharides containing multiple amino sugar units.
Fucosylation of HO-3 in 17 was performed by first
treating the thiofucoside 1816 with bromine (Br2, distilled
from P2O5) to generate the corresponding fucosyl bro-
mide17 and then add the mixture to 17 in the presence
of Bu4NBr18 (kept under vacuum at 80 °C overnight), thus
furnishing 19 (66%).
1
in Scheme 2. The structure of 16 was confirmed by H
NMR analysis of the 3-O-acetylated derivative. The
isomeric â-1,3-glycoside could not be detected in the
reaction mixture. Such high regioselectivity was also
observed in previous glycosylations of 15 and its NPhth
analogue.1,11 Several attempts to improve the synthesis
of 16 were unsuccessful; in all cases, the yield was
approximately 60%.
As in the SLex synthesis described in the previous
paper,1 the large NTCP group (which had served its
(14) Garegg, P. J .; Hultberg, H.; Wallin, S. Carbohydr. Res. 1982,
(16) Lo¨nn, H. Carbohydr. Res. 1985, 139, 105-113.
(17) Nilsson, S.; Lo¨nn, H.; Norberg, T. Glycoconj. J . 1989, 6, 21-
34.
(18) Lemieux, R. U.; Hendriks, K. B.; Stick, R. V.; J ames, K. J . Am.
Chem. Soc. 1975, 97, 4056.-4062.
108, 97-101.
(15) (a) Dasgupta, F.; Garegg, P. J . Carbohydr. Res. 1988, 177, C13-
C17. (b) Dasgupta, F.; Garegg, P. J . Carbohydr. Res. 1990, 202, 225-
238.

9326 J . Org. Chem., Vol. 63, No. 25, 1998
Ellervik et al.
Regioselective R-sialylation of 21 with the donor 2220
under promotion of AgOTf and MSB,15 followed by
O-acetylation, furnished 23 in 58% yield; dry AgOTf and
freshly distilled acetonitrile were essential for a good
result. The primary sialylation product was difficult to
purify, but the O-acetylated derivative 23 was easily
obtained in pure form by chromatography. The R-sialyl
linkage was deduced from the coupling constant between
the carbonyl carbon and the axial proton in the 3′′′-
position21 (J C-1′′′:H-3′′′ax ) 6.1 Hz).
Sch em e 3a
The NTroc group of 23 was transformed into an
acetamido group by reduction with activated zinc, fol-
lowed by N-acetylation, to give 24 (70%). Hydrogenolytic
de-O-benzylation of 24, followed by de-O-acetylation gave
the SLex tetrasaccharide analogue 2 (79%).
The final transformations of 23 to obtain the lactam 1
required four different reactions (removal of the Troc
group, de-O-acetylation, lactamization, and de-O-benz-
ylation). The product lactamized under the conditions
used for de-O-acetylation. The yield and purity of 1 was
highly dependent on the reaction sequence and the
quality of the reagents, as revealed by several prelimi-
nary experiments.
It was eventually found that removal of the Troc group
by zinc reduction, followed by de-O-acetylation with
concomitant lactamization and a final hydrogenolytic de-
O-benzylation with Pd(OH)2-C as catalyst, furnished the
SLex-1′′′f2′-lactam 1 in an overall yield of 54%.
It is essential to use newly activated zinc (see the
Experimental Section) in the removal of the Troc group
in order to reduce the reaction time (from 15 h with
unactivated Zn to 2.5 h) and thereby obtain a pure
product; nonactivated zinc gives several byproducts. In
addition, the acetic acid solvent should not be dried, since
this seriously decreased the reaction rate. The de-O-
acetylation/lactamization step should be performed in
regular methanol, since methanol dried over molecular
sieves gave mainly undesired products. The de-O-ben-
zylation step was best performed in ethanol with Pd-
(OH)2-C as catalyst; Pd-C in AcOH caused substantial
cleavage of the Fuc-R glycosidic bond.
II. Syn th esis of Sia lyl Lew is x-1′′′f4′-la cta m a n d
th e Cor r esp on d in g Aceta m id o An a logu e of Lew is
x Tr isa cch a r id e. The synthetic strategy was to develop
generally useful intermediates leading to both the lactam
4 and the acetamido analogue 5. Furthermore, the
previous1 successful regioselective glycosylation of the
acceptor 15 was planned to be a key step also in the
present synthesis.
a
Key: (a) guanidinium nitrate, MeONa, MeOH, CH2Cl2, ∼22
°C, 15 min; (b) MS 3 Å, CH2Cl2, MeCN, Ar, -60 °C, 5 min, then
AgOTf, MeCN, MeSBr, ClCH2CH2Cl, -60 °C, 3 h, then Ac2O,
pyridine; (c) Zn, AcOH, ∼22 °C, 2.5 h, then MeONa, MeOH, ∼22
°C, 14 h, then H2, Pd(OH)2-C, EtOH, ∼22 °C, 5 h; (d) Zn, AcOH,
∼22 °C, 15 h, then Ac2O, pyridine, 4.5 h; (e) H2, Pd-C, AcOH,
∼22 °C, 3 h, then MeONa, MeOH, ∼22 °C, 1 h, then aqueous
NaOH, ∼22 °C, 1.5 h.
Removal of the NTroc protecting group in 19 was
performed by treatment with zinc in regular (not dried)
acetic acid.13 Activation of the zinc dust prior to use was
important for obtaining a good yield. Thus, the zinc was
washed with 2 M aqueous HCl, followed by washing with
water, ethanol, and ether and drying under vacuum. The
resulting crude amine was N-acetylated with acetic
anhydride in pyridine to give 20 (83%).
Compound 20 was de-O-benzylated by hydrogenolysis
in freshly distilled acetic acid, and the crude product was
de-O-acetylated in methanolic MeONa to furnish 3 (82%)
as a bis-acetamido analogue of the Lex trisaccharide.
Syn th esis of SLex-1′′′f2′-la cta m 1 a n d SLex Tet-
r a sa cch a r id e An a logu e 2. A critical step in the
synthesis was the removal of the O-acetyl groups of 19
while leaving the NTroc group intact. We have recently
reported that dilute guanidine-guanidinium nitrate
solution is an effective reagent for such selective de-O-
acetylations.19 In the present case, 19 was transformed
within 15 min into 21 (Scheme 3) in 98% isolated yield.
Compound 21 crystallized from a mixture of EtOAc and
heptane, thus ensuring the purity of this important
intermediate, which was used for the preparation of
compounds 1, 2, and 6.
Syn th esis of th e Ga la ctosa m in e Don or s 30 a n d 32.
Treatment of the known22 thioglucoside 25 with R,R-
dimethoxytoluene and p-toluenesulfonic acid (Scheme 4)
gave the 4,6-O-benzylidene derivative 26 (96%), and
O-acetylation of 26 gave the di-O-acetate 27 (97%).
Reductive opening14 of the benzylidene ring of 27 with
NaBH3CN then furnished the partially protected thio-
glucoside 28 (92%).
Trifluoromethanesulfonylation of HO-4 in 28 provided
the crude triflate 29, which was treated, without further
(20) Marra, A.; Sinay¨, P. Carbohydr. Res. 1990, 195, 303-308.
(21) (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.
(19) Ellervik, U.; Magnusson, G. Tetrahedron Lett. 1997, 38, 1627-
1628.
(22) Montgomery, E. M.; Richtmyer, N. K.; Hudson, C. S. J . Org.
Chem. 1946, 11, 301-306.

Analogs of Sialyl Lewis x Tetrasaccharide
J . Org. Chem., Vol. 63, No. 25, 1998 9327
Sch em e 4a
Sch em e 5a
a
Key: (a) C6H5CH(OMe)2, TsOH, MeCN, 17 h; (b) Ac2O,
pyridine, ∼22 °C, 18 h; (c) NaBH3CN, THF, MS 3 Å, HCl-OEt2
(pH 2), 0 °C, 40 min; (d) (F3CSO2)2O, pyridine, CH2Cl2, -78 f
∼20 °C, 3 h; (e) NaN3, DMF, ∼22 °C, 17 h; (f) H2S, pyridine, H2O,
0 f ∼22 °C, 42 h; (g) Cl3CCH2OCOCl, pyridine, ∼22 °C, 1 h.
purification, with NaN3 in DMF to furnish the 4-azido-
4-deoxygalactoside 30 in 95% overall yield. The donor
30 was used for the glycosylation of 15 (see below).
Reduction of the azido group of 30 with H2S gave the
crude amine 31, which was transformed into the NTroc
derivative 32 in 85% overall yield. Compound 32 is a
potential glycosyl donor, although in the present case,
attempted glycosylation of the acceptor 15 failed. More
specifically, compound 32 was not fully stable under the
same glycosylation conditions that were used successfully
with donor 30.
a
Key: (a) AgOTf, CH2Cl2, MeCN, -78 °C, Ar, 5 min, then
MeSBr, ClCH2CH2Cl, -78 °C, 2 h; (b) H2NCH2CH2NH2, EtOH,
60 °C, 4 h, then Ac2O, MeOH, H2O, ∼22 °C, 1 h; (c) Br2, CH2Cl2,
cyclohexene, then MS 4 Å, Bu4NBr, CH2Cl2, DMF, ∼22 °C, 3 d,
then pyridine, 3 h; (d) H2S, pyridine, H2O, ∼22 °C, 48 h; (e) H2,
Pd-C, AcOH, ∼22 °C, 4 h, then MeONa, MeOH.
fucosyl bromide17 and addition of the mixture to 34 in
the presence of Bu4NBr18 (kept under vacuum at 80 °C
overnight) furnished the trisaccharide 35 in a very
pleasing 93% yield.
Regioselective Glycosyla tion of Diol Accep tor 15
a n d Syn th esis of Lex Tr isa cch a r id e An a logu e 5.
Regioselective methylsulfenyl bromide15 (MSB)- and sil-
ver trifluoromethanesulfonate (AgOTf)-mediated glyco-
sylation (Scheme 5) of the known1 acceptor 15 with the
donor 30 furnished the disaccharide 33 (78%); no isomeric
glycosides could be isolated from the reaction mixture.
Such high regioselectivity was also observed in previous
glycosylations of 15.1,11 The structure of 33 was con-
Reduction of the azido group in 35 with H2S gave a
crude amine, which was N-acetylated with acetic anhy-
dride in pyridine to furnish 36 (99%). Compound 36 was
de-O-benzylated by hydrogenolysis in freshly distilled
acetic acid, and the crude product was de-O-acetylated
in methanolic MeONa to furnish 5 (94%), a bis-acetamido
analogue of the Lex trisaccharide.
1
firmed by H NMR analysis of the corresponding 3-O-
acetylated derivative.
As in the SLex and SLex-1′′′f2′-lactam syntheses
described previously, the large NTCP group in 33 (which
had served its purpose to guide the regioselective glyco-
sylation with 30) was replaced by the smaller NHAc
group in order to ease the ensuing fucosylation. Thus,
treatment of 33 with 1,2-diaminoethane12 in ethanol at
60 °C, followed by selective N-acetylation with aqueous
acetic anhydride, furnished the acetamido compound 34
(92%).
Syn th esis of th e SLex-1′′′f4′-la cta m 4. Compound
35 was treated with methanolic MeONa (Scheme 6) to
give the diol acceptor 37 (96%). Attempted sialylation
of 37 with the xanthate sialyl donor used in the syntheses
of SLex and SLex-1′′′f2′-lactam was unsuccessful; the
desired tetrasaccharide could not be detected in the
reaction mixture, and 82% of the acceptor 37 was
recovered unchanged.
We have developed the donor 38 for demanding sialy-
lations where normal donors are ineffective, as exempli-
fied by our syntheses of a bis-sialic acid disaccharide and
Fucosylation of HO-3 in 34 is a highly efficient process.
Thus, treatment of the thiofucoside 1816 with bromine
(Br2, distilled from P2O5) to generate the corresponding

9328 J . Org. Chem., Vol. 63, No. 25, 1998
Ellervik et al.
Sch em e 6a
Sch em e 7a
a
Key: (a) Bu2SnO, MS 4 Å, toluene, 80 °C, 8 h, then Bu4NBr,
BrCH2COOC(CH3)3, 80 °C, 4 h, then Zn, AcOH, ∼22 °C, 4 h, then
MeONa, MeOH, ∼22 °C, 1 h; (b) H2, Pd(OH)2-C, EtOH, ∼22 °C,
19 h.
Sch em e 8a
a
Key: (a) MeONa, MeOH, ∼22 °C, 30 min; (b) CH2Cl2, MS 3
Å, MeCN, Ar, -45 °C, 5 min, then AgOTf, MeSBr, ClCH2CH2Cl,
-45 °C, 2.5 h; (c) RaNi, EtOH, ∼22 °C, 1 H, then MeONa, MeOH,
∼22 °C, 1.5 H, then H2, Pd(OH)2-C, ∼22 °C, 14 h.
its lactone and lactam analogues.23 It was found that
these sialylations with 38 proceeded with very high regio-
and stereoselectivities, which is difficult to obtain with
most other sialyl donors. This trend was followed in the
present investigation, where 38 effectively sialylated the
acceptor 37 to give the tetrasaccharide 39 (73%), free of
isomeric compounds. The 2′-O-acetylated derivative of
39 confirmed the regioselectivity in the sialylation step.
A structural variant of 38 was recently reported.24
The deprotection-lactamization of compound 39 was
much more troublesome than anticipated. Even so, the
final product 4 could be obtained in 30% overall yield
from 39 in conjunction with substantial amounts (32%)
of a byproduct. Compound 39 was treated with Raney
nickel (RaNi) in EtOH in order to remove the phenylthio
group and reduce the azido group. A crude product was
obtained by trituration with MeOH-toluene. Residual
aluminum salts (emanating from the RaNi) were re-
moved by filtration on SiO2. Aluminum salts are detri-
mental to catalytic hydrogenolysis with Pd catalysts.25
Treatment with MeONa-MeOH caused de-O-acetylation
and lactamization, and the resulting crude product was
hydrogenated (H2, Pd(OH)2-C) to give pure 4 in 30%
yield after chromatographic purification, together with
32% of the unidentified byproduct.
a
Key: (a) Bu2SnO, MeOH, reflux, 75 min, then Bu4NBr,
BrCH2COOC(CH3)3, MS 3 Å, reflux, 3 h, then MeONa, MeOH,
∼22 °C, 1 h; (b) Ac2O, pyridine, DMAP, ∼22 °C, 40 min; (c)
NaBH3CN, THF, MS 4 Å, then HCl-OEt2 (pH 2), 0 °C, 1.5 h; (d)
(F3CSO2)2O, pyridine, CH2Cl2, ∼22 °C, 3 h, then NaN3, DMF, ∼22
°C, 15 h.
seemed to be intact, but NMR data differed from those
of acetylated 4. We cannot at present provide a structure
for the unknown byproduct.
The byproduct was acetylated to furnish a product with
the following NMR characteristics: (1) the signals for the
“Lex” trisaccharide moiety were essentially identical with
those of acetylated 4; (2) only 11 O-and N-acetyl groups
were present, as compared to 12 groups in fully acety-
lated 4; (3) the carbon chain of the sialic acid residue
III. Syn th esis of Tw o La cta m An a logu es of th e
Lew is x Tr isa cch a r id e. The synthetic strategy for the
preparation of 6 was based on the use of trisaccharide
derivative 21 (Scheme 3) as starting material for regio-
selective alkylation, followed by closure of the lactam ring
(Scheme 7). The synthesis of the isomeric lactam 7 was
conducted by assembly of the monosaccharide moieties
15, 44, and 18 (Scheme 9).
(23) (a) Erce´govic, T.; Magnusson, G. J . Org. Chem. 1995, 60, 3378-
3384. (b) Erce´govic, T.; Magnusson, G. J . Org. Chem. 1996, 61, 179-
184.
(24) Martichonok, V.; Whitesides, G. M. J . Am. Chem. Soc. 1996,
118, 8187-8191.
(25) Freifelder, M. Practical Catalytic Hydrogenation; Wiley-Inter-
science: New York, 1971; p 24.
Syn th esis of th e Lex 3,2-La cta m Tr isa cch a r id e 6.
The NTroc-protected trisaccharide 21 was transformed
in one sequence into the lactam 40, without purification
of the intermediates (Scheme 7). Thus, compound 21 was

Analogs of Sialyl Lewis x Tetrasaccharide
J . Org. Chem., Vol. 63, No. 25, 1998 9329
Sch em e 9a
reaction conditions used, unless protected by steric
hindrance, as presumed in the trisaccharide 21.
Syn th esis of th e 4-Azid o-4-d eoxyga la ctose Don or
44. Thioglucoside 26 (Scheme 4) was regioselectively
alkylated with tert-butyl bromoacetate via the corre-
sponding 2,3-stannylene acetal. The crude alkylated
intermediate was treated with methanolic MeONa to give
the methyl ester 41 (Scheme 8) in an overall yield over
three steps of 72% (average yield per step: 90%). As in
the reaction of 21 above, ethyl bromoacetate gave mainly
the corresponding di-O-alkylated product. Obviously,
introduction of the tert-butyl (but not ethyl) ester group
at O-3 blocks HO-2 against further alkylation.
Conventional O-acetylation of 41 gave 42 (98%), and
reductive NaBH3CN-HCl-Et2O-mediated opening14 of
the 4,6-O-benzylidene ring of 42 yielded 43 (80%). Treat-
ment of 43 with trifluoromethanesulfonic anhydride in
pyridine and removal of the reagents and solvent gave
the corresponding 4-O-triflate, which was dried under
vacuum. The crude triflate was then treated with NaN3
in freshly distilled DMF, thus providing the glycosyl
donor 44 (75%). The ester and azido functionalities of
44 were left intact until the trisaccharide stage (47), in
order not to jeopardize the two ensuing glycosylation
steps: the donor properties of lactamized intermediates
would probably be hampered due to unwanted strain and/
or steric hindrance in the pyranosidic ring.
Regioselective Glycosyla tion of Diol Accep tor 15
a n d Syn th esis of th e Lex 3,4-La cta m Tr isa cch a r id e
7. Regioselective 4-O-glycosylation of the 3,4-diol 151
with donor 44 (Scheme 9) by activation with methyl-
sulfenyl bromide15 (MSB) and silver triflate (AgOTf) gave
the disaccharide 45 (67%). It is important to use freshly
distilled solvents in the glycosylation reaction in order
to obtain a high yield of 45. The regioselectivity was
virtually complete, which is in accordance with glycosy-
lations of 15 en route to the SLex and SLex-lactam
tetrasaccharides.
a
Key: (a) AgOTf, MeCN, CH2Cl2, -78 °C, Ar, 5 min, then
MeSBr, ClCH2CH2Cl, -78 °C, 1.5 h; (b) H2NCH2CH2NH2, EtOH,
60 °C, 15 h, then Ac2O, MeOH, H2O, ∼22 °C, 1 h; (c) Br2, CH2Cl2,
cyclohexene, then MS 4 Å, Bu4NBr, CH2Cl2, DMF, ∼22 °C, 3 d,
then pyridine, 3 h; (d) H2S, pyridine, Et3N, MeOH, 0 °C, 16 h; (e)
H2, Pd-C, AcOH, ∼22 °C, 1.5 h, then MeONa, MeOH, ∼22 °C, 3
h.
As in the previous syntheses, the large NTCP group
(which had served its purpose to guide the regioselective
glycosylation of 15) was replaced by the NHAc group.
Thus, treatment of 45 with 1.2 equiv of 1,2-diamino-
ethane12 in ethanol at 60 °C overnight, followed by
selective N-acetylation with aqueous acetic anhydride
(Ac2O), furnished the disaccharide 46 (70%). To obtain
46 in high yield and free from contaminants, it was
necessary to use freshly distilled 1,2-diaminoethane in
only a small excess (to minimize reaction with the ester
function) for removal of the TCP group.
treated with Bu2SnO to provide the corresponding 3,4-
stannylene acetal. Bu4NBr-mediated regioselective O-
alkylation of the 3-position of the galactosamine moiety,
using tert-butyl bromoacetate as alkylating agent, gave
an intermediate where the NTroc group was then re-
duced with activated zinc dust in acetic acid to give the
corresponding primary amine. (Attempted alkylation
with ethyl bromoacetate, instead of tert-butyl bromo-
acetate, gave mainly the 3,4-di-O-alkylated product).
Final treatment of the crude amine with methanolic
MeONa closed the lactam ring. Compound 40 was thus
obtained over four steps in an overall yield of 52%, which
is equivalent to an average yield of 85% per step.
Removal of the benzyl protecting groups of 40 by Pd-
(OH)2-C-catalyzed hydrogenolysis in EtOH then fur-
nished the Lex-3,2-lactam 6 in 74% yield.
Fucosylation of HO-3 in 46 was performed by first
treating the thiofucoside 1816 with bromine (Br2, distilled
from P2O5) to generate the corresponding fucosyl bro-
mide17 and then add the mixture to 46 in the presence
of Bu4NBr18 (kept under vacuum at 80 °C overnight) to
furnish 47 in 82% yield. As before, a high yield in this
and similar glycosylations requires that solvents and
volatile reagents are distilled prior to use.
Compound 48 was formed by H2S reduction of the azido
function in 47, followed by spontaneous closure of the
lactam ring.5 This reaction sequence is very efficient, and
48 was obtained in 98% yield after chromatography.
Hydrogenolytic cleavage of the benzyl protecting groups
of 48, using Pd-C as catalyst and freshly distilled acetic
acid as solvent, followed by de-O-acetylation with metha-
nolic MeONa gave the Lex-3,4-lactam 7 in 73% yield. An
An attempt to perform the same sequence of reactions
with ethylthio 6-O-benzyl-2-deoxy-2-(2,2,2-trichloro-
ethoxy)carbonylamino-â-D-galactopyranoside (prepared
by de-O-acetylation of compound 14) to create the cor-
responding monosaccharide lactam was unsuccessful,
indicating that the NTroc group is sensitive toward the

9330 J . Org. Chem., Vol. 63, No. 25, 1998
Ellervik et al.
added, the mixture was concentrated, and the residue was
attempt to prepare 48 by tert-butyl bromoacetate-
alkylation of compound 37 (Scheme 6) was totally unsuc-
cessful.
chromatographed (SiO2, 60:35:5 CH2Cl2-MeOH-H2O plus
0.1% AcOH) to give 2 (44 mg, 79%): [R]20 -62.3 (c 1.0 H2O);
D
1H NMR (D2O) δ 6.80-6.91 (m, 4 H, OPMP), 5.00 (d, 1 H, J )
4.0 Hz, H-1′′), 4.87 (d, 1 H, J ) 8.4 Hz, H-1), 4.60-4.75 (m,
H-5′′, HDO), 4.45 (d, 1 H, J ) 8.6 Hz, H-1′), 3.66 (s, 3 H, OMe),
2.56 (dd, 1 H, J ) 12.7, 4.7 Hz, H-3′′′eq), 1.88, 1.89, 1.95 (s, 3
H each, NHAc), 1.46 (t, 1 H, J ) 12.1 Hz, H-3′′′ax), 1.11 (d, 1
H, J ) 6.6 Hz, H-6′′); 13C NMR (D2O) δ 181.7, 175.5, 1.75.3,
174.9, 174.7, 155.2, 151.5, 118.6, 115.4, 100.8, 100.6, 99.5, 98.8,
75.9, 75.0, 74.7, 73.3, 73.04, 72.96, 72.3, 71.9, 69.5, 68.7, 68.4,
68.0, 67.3, 66.8, 62.9, 61.9, 60.1, 56.11, 56.05, 52.2, 51.3, 40.3,
23.6, 22.6, 22.5, 22.4, 15.8; HRMS calcd for C40H61O24N3Na (M
+ Na) 990.3543, found 990.3541.
Exp er im en ta l Section
The general methods were essentially as described in the
preceding paper in this issue.1 In addition zinc dust was
washed with aqueous HCl (2 M, three times), H2O (twice),
EtOH (twice), and Et2O (once) before use; 1,2-diaminoethane
was distilled before use; a clear stock solution of guanidinium
nitrate reagent was prepared by dissolving guanidinium
nitrate (622 mg, 5 mmol) in 9:1 MeOH-CH2Cl2 (50 mL) and
adding methanolic 1 M MeONa (1 mL); the stock solution was
kept at room temperature for several weeks without any
observed decrease in activity.19 Compounds 8,11 15,1 18,16 22,20
25,22 and 3823 were synthesized as described in the literature.
4-Meth oxyp h en yl (5-Aceta m id o-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 cta m )-(1f3)-
(2-d eoxy-2-a m in o-3-O-â-D-ga la ct op yr a n osyl)-(1f4)-[r-L-
fu cop yr a n osyl]-(1f3)-(2-a cet a m id o-2-d eoxy-â-D-glu co-
p yr a n osid e) (1). Compound 23 (120 mg, 0.07 mmol) was
dissolved in AcOH (10 mL), and freshly activated zinc dust
(750 mg) was added. The mixture was stirred for 2.5 h and
filtered through a short column (SiO2, 2:1 CH2Cl2-acetone).
The crude compound was dissolved in methanolic 0.04 M
NaOMe (14 mL), and the solution was stirred for 14 h,
neutralized with Amberlite IR 120 H+, and concentrated. The
residue was filtered through a short column (SiO2, 5:1 CH2-
Cl2-MeOH), and the solvent was removed. The residue was
dissolved in EtOH (4 mL), and Pd(OH)2-C (20%, 200 mg) was
added. The mixture was hydrogenated (H2, 1 atm) for 5 h,
filtered through Celite, and concentrated. The residue was
4-Meth oxyp h en yl (2-Aceta m id o-2-d eoxy-â-D-ga la cto-
pyr an osyl)-(1f4)-[r-L-fu copyr an osyl]-(1f3)-(2-acetam ido-
2-d eoxy-â-D-glu cop yr a n osid e) (3). Compound 20 (120 mg,
0.1 mmol) was dissolved in AcOH (3 mL, distilled from Ac2O),
and Pd-C (10%, 120 mg) was added. The mixture was
hydrogenated (H2, 1 atm) for 5 h, filtered through Celite, and
concentrated. The residue was dissolved in methanolic 0.05
M NaOMe (5 mL), and the mixture was stirred for 1 h and
then neutralized with Amberlite IR 120 H+. The mixture was
concentrated and chromatographed (SiO2, 65:30:5 CH2Cl2-
MeOH-H2O) to give 3 (55 mg, 82%): [R]23 -64.9 (c 1.0,
D
MeOH); 1H NMR (CD3OD) δ 6.80-6.97 (m, 4 H, OPMP), 5.08
(d, 1 H, J ) 3.9 Hz, H-1′′), 4.93 (d, 1 H, J ) 8.2 Hz, H-1), 4.75
(q, 1 H, J ) 7.0 Hz, H-5′′), 4.50 (d, 1 H, J ) 8.4 Hz, H-1′), 4.17
(t, 1 H, J ) 8.5 Hz, H-2), 3.70-4.00 (m, 10 H, H-3,4,6′′,2′,4′,6′,-
3′′,4′′), 3.73 (s, 3 H, OMe), 3.67 (dd, 1 H, J ) 10.2, 3.9 Hz,
H-2′′), 3.59 (dd, 1 H, J ) 10.2, 3.2 Hz, H-3′), 3.52 (dt, J ) 7.5,
3.9 Hz, H-5), 3.45 (bt, 1 H, J ) 6.6 Hz, H-5′), 1.99, 1.96 (s, 3 H
each, NHAc), 1.27 (d, 3 H, J ) 6.7 Hz, H-6′′); 13C NMR (CD3-
OD) δ 173.0, 172.8, 155.8, 152.0, 118.1, 114.5, 101.1, 100.5,
99.0, 76.8, 75.7, 74.9, 73.5, 72.8, 71.9, 70.3, 69.0, 68.3, 67.0,
61.8, 60.7, 55.7, 55.0, 53.2, 22.1, 22.0, 15.7; HRMS calcd for
chromatographed (SiO2, 65:30:5 CH2Cl2-MeOH-H2O) to give
1
1 (33 mg, 54%): [R]20 -53.4 (c 1.0, MeOH); H NMR (CD3-
D
C
29H44O16N2Na (M + Na) 699.2589, found 699.2584.
4-Meth oxyp h en yl (5-Aceta m id o-3,5-d id eoxy-D-glycer o-
OD) δ 6.80-6.95 (m, 4 H, OPMP), 5.06 (d, 1 H, J ) 3.9 Hz,
H-1′′), 5.01 (d, 1 H, J ) 8.3 Hz, H-1), 4.70 (q, 1 H, J ) 6.4 Hz,
H-5′′), 4.64 (d, 1 H, J ) 7.3 Hz, H-1′), 4.36 (m, 1 H, H-4′′′),
3.73 (s, 3 H, OMe), 2.51 (d, 1 H, J ) 13.4, 5.5 Hz, H-3′′′eq),
1.97, 2.00 (s, 3 H each, NHAc), 1.64 (dd, 1 H, J ) 13.3, 10.8
Hz, H-3′′′ax), 1.20 (d, 3 H, J ) 6.6 Hz); 13C NMR (CD3OD) δ
172.7, 171.5, 167.7, 154.3, 150.5, 116.7, 113.0, 98.9, 98.6, 97.9,
96.8, 75.9, 75.0, 74.2, 74.0, 73.7, 71.7, 71.1, 68.7, 68.5, 67.5,
67.1, 66.4, 65.4, 64.3, 62.1, 59.89, 59.85, 55.2, 53.5, 51.5, 49.5,
39.5, 20.6, 20.1, 14.5; HRMS calcd for C38H57O22N3Na (M +
Na) 930.3331, found 930.3332.
r-D-ga la cto-2-n on u lop yr a n osyloyl-1′′′f4′-la cta m )-(1f3)-
(4-a m in o -4-d e o x y -â-D -g a la c t o p y r a n o s y l)-(1f4)-[r-L -
fucopyranosyl)-(1f3)-(2-acetamido-2-deoxy-â-D-glucopyranoside)
(4). To compound 39 (100 mg, 0.059 mmol) was added a slurry
of Raney-nickel (approximately 1 g, washed twice with EtOH)
in EtOH (6 mL). The mixture was stirred for 1 h, the desired
compound was isolated from the Raney-nickel by trituration
six times with 1:1 MeOH-toluene (10 mL portions), and the
combined solutions were filtered (Celite). The solvent was
removed, and the residue was filtered through a short column
(SiO2, 5:1 CH2Cl2-EtOH). The solvent was removed, and the
residue was dissolved in methanolic 0.03 M MeONa (10 mL).
The mixture was stirred for 1.5 h, neutralized with Amberlite
IR 120 H+ resin, and concentrated. The residue was filtered
through a short column (SiO2, 5:1 CH2Cl2-EtOH). The solvent
was removed, the residue was dissolved in EtOH (5 mL), and
Pd(OH)2-C (20%, 300 mg) was added. The mixture was
hydrogenated (H2, 1 atm) for 14 h and then filtered and
concentrated. The residue was again dissolved in EtOH (5
mL), and a fresh portion of Pd(OH)2-C (20%, 300 mg) was
added. The mixture was hydrogenated (H2, 1 atm) for 24 h,
filtered, and concentrated. The residue was chromatographed
(SiO2, 65:30:5 CH2Cl2-MeOH-H2O) to give 4 (16 mg, 30%)
together with an unidentified byproduct (17 mg, 32%). Com-
A sample of 1 was conventionally acetylated (Ac2O-pyri-
dine-DMAP): 1H NMR (CDCl3) δ 7.34 (d, 1 H, J ) 11.3, NH),
6.80-7.05 (m, 4 H, OPMP), 5.64 (d, 1 H, J ) 9.8 Hz, NH′′′),
5.51 (d, 1 H, J ) 3.6 Hz, H-1′′), 5.46 (dt, 1 H, J ) 11.2, 6.2 Hz,
H-4′′′), 5.41 (bs, 1 H, H-4′), 5.37 (dd, 1 H, J ) 9.9, 1.8 Hz, H-7′′′),
5.29-5.35 (m, 3 H, H-1,3′′,4′′), 5.22 (dd, 1 H, J ) 10.6, 3.8 Hz,
H-2′′), 5.12 (dt, 1 H, J ) 9.9, 3.9 Hz, H-8′′′), 4.54-4.60 (m, 2
H, H-1′,6′), 4.49 (bd, 1 H, J ) 9.2 Hz, H-2), 4.35 (bs, 1 H, H-3),
4.15-4.25 (m, 5 H, H-6,6′,5′′,5′′′,9′′′), 4.03 (dd, 1 H, J ) 8.9,
4.0 Hz, H-9′′′), 3.97 (t, 1 H, J ) 8.0 Hz, H-6), 3.91 (bs, 1 H,
H-4), 3.43-3.85 (m, 5 H, H-5,2′,3′,5′,6′′′), 3.73 (s, 3 H, OMe),
2.42 (dd, 1 H, J ) 13.1, 5.4 Hz, H-3eq′′′), 2.19, 2.18, 2.16, 2.12,
2.09, 2.05, 2.04, 2.03, 2.02, 2.00, 1.97, 1.90 (s, 3 H each, OAc,
NHAc), 1.86 (t, 1 H, J ) 13.1 Hz, H-3ax′′′), 1.18 (d, 3 H, J )
6.5 Hz, H-6′′).
pound 4: [R]20 -33.2 (c 0.8, MeOH); 1H NMR (CD3OD) δ
D
4-Meth oxyp h en yl (5-Aceta m id o-3,5-d id eoxy-D-glycer o-
r-D-ga la cto-2-n on u lop yr a n osylon ic a cid )-(1f3)-(2-a cet-
a m i d o -2-d e o x y -â-D -g a la c t o p y r a n o s y l)-(1 f4)-[r-L -
fucopyranosyl]-(1f3)-(2-acetamido-2-deoxy-â-D-glucopyrano-
sid e) (2). Compound 24 (94 mg, 0.06 mmol) was dissolved in
AcOH (4 mL), and Pd-C (10%, 100 mg) was added. The
mixture was hydrogenated (H2, 1 atm) for 3 h, filtered through
Celite, and concentrated. The residue was chromatographed
(SiO2, 5:1 CH2Cl2-MeOH). The product was dissolved in
methanolic 0.03 M NaOMe (5 mL), the mixture was stirred
for 1 h, 1 M aqueous NaOH (0.3 mL) was added, and the
stirring was continued for 1.5 h. AcOH (0.19 mL) was
6.80-6.97 (m, 4 H, OPMP), 5.07 (d, 1 H, J ) 4.1 Hz, H-1′′),
4.97 (d, 1 H, J ) 8.4 Hz, H-1), 4.69 (q, 1 H, J ) 6.8 Hz, H-5′′),
4.57 (d, 1 H, J ) 7.9 Hz, H-1′), 4.46 (dd, 1 H, J ) 4.9, 1.5 Hz,
H-4′), 4.40 (dt, 1 H, J ) 10.9, 5.5 Hz, H-4′′′), 3.74 (s, 3 H, OMe),
2.45 (dd, 1 H, J ) 12.8, 5.4 Hz, H-3eq′′′), 2.02, 1.98 (s, 3 H each,
NHAc), 1.68 (dd, 1 H, J ) 12.8, 10.9 Hz, H-3ax′′′), 1.14 (d, 3 H,
J ) 6.6 Hz, H-6′′); 13C NMR (CD3OD) δ 174.6, 173.6, 168.7,
155.8, 152.1, 118.2, 114.5, 102.5, 100.6, 99.4, 97.6, 76.3, 75.4,
74.1, 73.2, 72.6, 71.9, 71.3, 70.9, 70.4, 68.9, 68.7, 68.1, 66.7,
64.3, 61.2, 60.0, 56.6, 55.0, 53.2, 50.1, 40.6, 22.1, 21.5, 15.7;
HRMS calcd for C38H57O22N3Na (M + Na) 930.3331, found
930.3314.

Analogs of Sialyl Lewis x Tetrasaccharide
J . Org. Chem., Vol. 63, No. 25, 1998 9331
A sample of 4 was conventionally acetylated (Ac2O-pyri-
dine): 1H NMR (CHCl3) δ 6.77-6.92 (m, 4 H, OPMP), 5.68
(dt, 1 H, J ) 11.0, 5.4 Hz, H-4′′′), 5.58 (d, 1 H, J ) 3.2 Hz,
H-1′′), 5.57 (d, 1 H, J ) 3.1 Hz, H-4′′), 5.50 (d, 1 H, J ) 8.4
Hz, NH), 5.28-5.36 (m, 2 H, H-8′′′, NH′′′), 5.22 (dd, 1 H, J )
10.0, 1.8 Hz, H-7′′′), 5.19 (dd, 1 H, J ) 10.8, 2.8 Hz, H-3′′),
5.04 (dd, 1 H, J ) 10.9, 3.7 Hz, H-2′′), 4.95 (d, 1 H, J ) 7.3 Hz,
H-1), 4.87 (dd, 1 H, J ) 9.0, 8.5 Hz, H-2′), 4.55-4.66 (m, 3 H,
H-6,6′,5′′), 4.46 (dd, 1 H, J ) 12.3, 4.0, H-6′), 4.37 (d, 1 H, J )
8.2 Hz, H-1′), 4.23 (dd, 1 H, J ) 12.3, 3.0 Hz, H-9′′′), 4.19 (d,
1 H, J ) 3.9 Hz, H-4′), 4.05-4.15 (m, 4 H, H-2,6,3′,5′′′), 3.98
(dd, 1 H, J ) 12.2, 5.8 Hz, H-9′′′), 3.66-3.88 (m, 5 H,
H-3,4,5,5′,6′′′), 3.77 (s, 3 H, OMe), 2.33 (dd, 1 H, J ) 13.6, 5.7
Hz, H-3eq′′′), 2.23, 2.17, 2.16, 2.15, 2.14, 2.13, 2.11, 2.04, 2.03,
2.00, 1.99, 1.87 (s, 3 H each, OAc, NHAc), 1.71 (dd, 1 H, J )
12.6, 11.9 Hz, H-3ax′′′), 1.13 (d, 3 H, J ) 6.6 Hz, H-6′′); 13C
NMR (CHCl3) δ 172.4, 171.8, 171.4, 171.1, 170.93, 170.87,
170.81, 170.75, 170.6, 169.8, 166.3, 156.0, 151.6, 118.6, 115.0,
100.44, 100.42, 97.2, 95.1, 74.7, 74.2, 73.3, 72.5, 71.8, 71.6, 71.5,
70.9, 70.6, 69.9, 68.1, 68.0, 67.2, 65.4, 62.8, 62.5, 62.1, 56.6,
56.1, 49.8, 49.7, 38.3, 23.9, 23.7, 21.5, 21.41, 21.35, 21.24, 21.20,
21.1, 16.3.
4-Meth oxyp h en yl (4-Aceta m id o-4-d eoxy-â-D-ga la cto-
pyr an osyl)-(1f4)-[r-L-fu copyr an osyl]-(1f3)-(2-acetam ido-
2-d eoxy-â-D-glu cop yr a n osid e) (5). Compound 36 (145 mg,
0.12 mmol) was dissolved in AcOH (5 mL, distilled from Ac2O),
and Pd-C (10%, 150 mg) was added. The mixture was
hydrogenated (H2, 1 atm) for 4 h, filtered through Celite, and
concentrated. The residue was dissolved in methanolic 0.05
M MeONa (6 mL), and the mixture was stirred for 40 min and
then neutralized with Amberlite IR 120 H+. The mixture was
concentrated and chromatographed (SiO2, 65:30:5 CH2Cl2-
MeOH-H2O) to give 5 (76 mg, 94%): [R]20D -53 (c 1.0, MeOH);
1H NMR (D2O) δ 6.77-6.93 (m, 4 H, OPMP), 5.11 (d, 1 H, J )
3.8 Hz, H-1′′), 4.92 (d, 1 H, J ) 8.2 Hz, H-1), 4.41 (d, 1 H, J )
8.0 Hz, H-1′), 4.38-4.45 (m, 1 H, H-5′′), 4.17 (broad d, 1 H, J
) 4.2 Hz, H-4′), 3.45-4.05 (m, 13 H, H-2,3,4,5,6,3′,5′,6′,2′′,3′′,4′′),
3.65 (s, 3 H, OMe), 3.29 (dd, 1 H, J ) 10.1, 8.0 Hz, H-3′), 1.95,
1.87 (s, 3 H each, NHAc), 1.10 (d, 3 H, J ) 6.6 Hz, H-6′′); 13C
NMR data (CDCl3) δ 175.5, 174.8, 155.2, 151.4, 118.6, 115.4,
102.7, 100.8, 98.0, 75.9, 75.0, 74.9, 72.5, 71.7, 71.3, 69.5, 68.3,
61.3, 60.2, 56.1, 55.8, 51.3, 22.6, 22.4, 15.9; HRMS calcd for
δ 171.6, 171.13, 171.06, 171.0, 170.7, 170.3, 169.4, 155.9, 151.6,
118.6, 115.0, 100.3, 99.7, 95.6, 74.7, 73.9, 73.4, 72.8, 71.5, 68.5,
68.3, 65.6, 64.7, 61.4, 56.1, 53.4, 23.8, 21.8, 21.4, 21.25, 21.19,
21.17 21.1, 21.0, 16.6.
4-Meth oxyp h en yl (4-Am in o-4-d eoxy-4,3-N,O-(2-oxoeth -
yliden e)-â-D-galactopyr an osyl)-(1f4)-[r-L-fu copyr an osyl]-
(1f3)-(2-acetam ido-2-deoxy-â-D-glu copyr an oside) (7). Com-
pound 48 (100 mg, 0.085 mmol) was dissolved in AcOH (3.0
mL, distilled from Ac2O), and Pd-C (10%, 100 mg) was added.
The mixture was hydrogenolyzed (H2, 1 atm) for 1.5 h, filtered
through Celite, and concentrated. The residue was dissolved
in MeONa-MeOH (5 mL, 0.05 M), and the mixture was stirred
for 3 h, neutralized with Amberlite IR 120 H+, and concen-
trated. The residue was chromatographed (SiO2, 65:30:5 CH2-
Cl2-MeOH-H2O) to give 7 (44 mg, 73%): [R]20 -54 (c 1.0,
D
MeOH); 1H NMR (CD3OD) δ 6.80-6.98 (m, 4 H, OPMP), 5.06
(d, 1 H, J ) 3.9 Hz, H-1′′), 4.97 (d, 1 H, J ) 8.4 Hz, H-1), 4.73
(q, 1 H, J ) 6.6 Hz, H-5′′), 4.60 (d, 1 H, J ) 7.6 Hz, H-1′),
4.22, 4.13 (ABq, 1 H each, J ) 17.6 Hz, CH2), 3.70-4.05 (m,
12 H, H-3,4,6,2′,3′,4′,6′,2′′,3′′,4′′), 3.74 (s, 3 H, OMe), 3.68 (dd,
1 H, J ) 10.5, 4.1 Hz, H-2), 3.60 (bt, 1 H, J ) 5.4 Hz, H-5′),
3.53 (b dt, 1 H, J ) 8.5, 2.4 Hz, H-5), 1.98 (s, 3 H, NHAc), 1.10
(d, 3 H, J ) 6.6 Hz, H-6′′); 13C NMR (CD3OD) δ 174.1, 171.4,
157.0, 153.3, 119.4, 115.7, 104.4, 101.8, 100.6, 77.5, 76.3, 75.3,
74.9, 73.7, 71.5, 70.0, 67.8, 66.4, 63.0, 62.8, 61.1, 57.8, 56.2,
53.7, 23.2, 16.6; HRMS calcd for C29H42O16N2Na (M + Na)
697.2432, found 697.2421.
A sample of 7 was conventionally acetylated (Ac2O-pyri-
dine): 1H NMR (CDCl3) δ 7.06, (s, 1 H, NH′), 6.77-6.93 (m, 4
H, OPMP), 5.53-5.57 (m, 3 H, NH, H-1′′,4′′), 5.21 (dd, 1 H, J
) 9.4, 8.0 Hz, H-2′), 5.15 (dd, 1 H, J ) 10.9, 3.0 Hz, H-3′′),
5.04 (dd, 1 H, J ) 11.2, 3.5 Hz, H-2′′), 5.03 (d, 1 H, J ) 7.2 Hz,
H-1), 4.65 (dd, 1 H, J ) 12.0, 7.1 Hz, H-6′), 4.55-4.60 (m, 2 H,
H-6,5′′), 4.49 (d, 1 H, J ) 7.7 Hz, H-1′), 4.35, 4.20 (ABq, 1 H
each, J ) 17.7 Hz, OCH2CO), 4.34 (dd, 1 H, J ) 11.9, 7.4 H,
H-6′), 3.95-4.19 (m, 5 H, H-2,3,6,3′,4′), 3.90 (t, 1 H, J ) 9.0
Hz, H-4), 3.70-3.81 (m, 2 H, H-5,5′), 3.77 (s, 3 H, OMe), 2.16,
2.15, 2.14, 2.12, 2.11, 2.06, 2.00 (s, 1 H each, OAc, NHAc), 1.15
(d, 3 H, J ) 6.6 Hz, H-6′′); 13C NMR (CDCl3) δ 172.0, 171.8,
171.0, 170.8, 170.5, 170.0, 168.5, 155.9, 151.7, 118.6, 115.0,
101.0, 100.2, 95.3, 74.3, 73.3, 72.8, 72.4, 71.5, 70.9, 69.5, 68.3,
66.5, 65.5, 63.0, 62.6, 60.9, 56.1, 51.1, 23.9, 21.6, 21.5, 21.25,
21.19, 21.1, 16.2.
C
29H44O16N2Na (M + Na) 699.2589, found 699.2587.
4-Meth oxyp h en yl (2-Am in o-2-d eoxy-2,3-N,O-(2-oxoeth -
Eth yl 2-Deoxy-2-[[(2,2,2-tr ich lor oeth oxy)car bon yl]am i-
n o]-1-th io-â-D-glu cop yr a n osid e (9). Compound 811 (12.65
g, 24.1 mmol) was dissolved in MeOH (300 mL), and the
mixture was saturated with HCl at 0 °C and then stirred for
16 h at room temperature. The solvent was removed, and the
yliden e)-â-D-galactopyr an osyl)-(1f4)-[r-L-fu copyr an osyl]-
(1f3)-(2-acetam ido-2-deoxy-â-D-glu copyr an oside) (6). Com-
pound 40 (76 mg, 0.068 mmol) was dissolved in EtOH (4.0 mL),
and Pd(OH)2-C (20%, 150 mg, moist) was added. The mixture
was hydrogenolyzed (H2, 1 atm) for 19 h, filtered through
Celite, and concentrated. The residue was chromatographed
resulting syrup was chromatographed (SiO2, 9:1 CH2Cl2-
1
MeOH) to give 9 (9.80 g, 100%): [R]20 -7.5 (c 0.8, D2O); H
D
(SiO2, 30:10:1 CH2Cl2-MeOH-H2O) to give 6 (33 mg, 74%):
NMR (CD3OD) δ 4.89, 4.75 (ABq, 1 H each, J ) 12.1 Hz, Cl3-
CCH2), 4.55 (m, virtual coupling similar to entry 19 in ref 26,
H-1), 3.91, 3.70 (dABq, 1 H each, J ) 12.1, 5.5, 2.2 Hz, H-6),
3.30-3.50 (m, 4 H, H-2,3,4,5), 2.81, 2.76 (ddABq, 1 H each, J
) 12.5, 7.5, 5.0 Hz, SCH2CH3), 1.28 (t, 3 H, J ) 7.4 Hz,
SCH2CH3); 13C NMR (CD3OD): δ 155.9, 96.2, 84.7, 81.1, 76.3,
74.6, 71.0, 62.0, 57.3, 23.9, 14.2; HRMS calcd for C11H18O6-
NCl3SNa (M + Na) 419.9818, found 419.9839.
1
[R]20 -51 (c 0.9, MeOH); H NMR (CD3OD) δ 6.80-6.98 (m,
D
4 H, OPMP), 5.06 (d, 1 H, J ) 4.1 Hz, H-1′′), 5.00 (d, 1 H, J )
7.7 Hz, H-1), 4.78 (q, 1 H, J ) 6.7 Hz, H-5′′), 4.63 (d, 1 H, J )
7.3 Hz, H-1′), 4.28, 4.22 (ABq, 1 H each, J ) 16.8 Hz, CH2),
3.55-4.05 (m, 15 H, H-2,3,4,5,6,2′,3′,4′,5′,6′,2′′,3′′, 4′′), 3.74 (s,
3 H, OMe), 1.98 (s, 3 H, NHAc), 1.18 (d, 3 H, J ) 6.6 Hz, H-6′′);
13C NMR (CD3OD) δ 173.0, 170.9, 155.9, 152.1, 118.2, 114.5,
100.6, 100.3, 99.5, 76.9, 76.5, 75.9, 75.3, 73.7, 72.7, 70.2, 69.0,
67.8, 66.7, 65.9, 61.5, 60.5, 56.7, 55.0, 52.3, 27.3, 22.0, 15.6;
HRMS calcd for C29H42O16N2Na (M + Na) 697.2432, found
697.2445.
Eth yl 4,6-O-Ben zylid en e-2-d eoxy-2-[[(2,2,2-tr ich lor o-
eth oxy)ca r bon yl]a m in o]-1-th io-â-D-glu cop yr a n osid e (10).
Compound 9 (9.74 g, 24 mmol) was dissolved in MeCN (110
mL), R,R-dimethoxytoluene (6.5 mL) and p-toluenesulfonic acid
(50 mg) were added and the mixture was stirred for 4 h. Et3N
(5 mL) was added and the mixture was co-concentrated with
toluene. The residue was chromatographed (SiO2, 1:1 hep-
A sample of 6 was conventionally acetylated (Ac2O-pyri-
dine): 1H NMR (CDCl3) δ 6.79-6.95 (m, 4 H, OPMP), 5.94 (d,
1 H, J ) 8.7 Hz, NH), 5.52 (d, 1 H, J ) 4.1 Hz, H-1′′), 5.50 (d,
1 H, J ) 2.1 Hz, H-4′), 5.36 (d, 1 H, J ) 2.9 Hz, H-4′′), 5.25
(dd, 1 H, J ) 10.9, 3.2 Hz, H-3′′), 5.14 (d, 1 H, J ) 7.6 Hz,
H-1), 5.07 (dd, 1 H, J ) 10.9, 3.8 Hz, H-2′′), 4.75 (q, 1 H, J )
6.3 Hz, H-5′′), 4.48 (bd, 1 H, J ) 12.0 Hz, H-6), 4.44 (dd, 1 H,
J ) 11.7, 6.8 Hz, H-6′), 4.40 (d, 1 H, J ) 8.0 Hz, H-1′), 4.32,
4.19 (ABq, 1 H each, J ) 17.1 Hz, OCH2CO), 4.20-4.31 (m, 3
H, H-3,6,6′), 3.85-4.02 (m, 4 H, H-2,4,5,5′), 3.77 (s, 3 H, OMe),
3.56 (dd, 1 H, J ) 9.5, 2.4 Hz, H-3′), 3.48 (dd, 1 H, J ) 9.8, 8.0
Hz, H-2′), 2.18, 2.16, 2.14, 2.11, 2.10, 2.00, 1.99 (s, 3 H each,
OAc, NHAc), 1.14 (d, 3 H, J ) 6.5, Hz, H-6′′); 13C NMR (CDCl3)
tane-EtOAc) to give 10 (11.1 g, 95%): [R]20 -38.5 (c 0.9,
D
1
CHCl3); H NMR (CDCl3) δ 7.35-7.50 (m, 5 H, ArH), 5.57 (s,
1 H, ArCH), 5.22 (bd, 1 H, J ) 8.7 Hz, NH), 4.81, 4.73 (ABq,
1 H each, J ) 12.2 Hz, Cl3CCH2), 4.68 (d, 1 H, J ) 8.7 Hz,
H-1), 4.35 (dd, 1 H, J ) 10.5, 4.9 Hz, H-5), 3.96 (bt, 1 H, J )
9.0 Hz, H-3), 3.78 (t, 1 H, J ) 10.2 Hz, H-6), 3.50-3.65 (m, 3
(26) Dahme´n, J .; Frejd, T.; Gro¨nberg, G.; Magnusson, G.; Noori, G.
Carbohydr. Res. 1984, 125, 161-164.

9332 J . Org. Chem., Vol. 63, No. 25, 1998
Ellervik et al.
H, H-2,4,6), 3.05 (bs, 1 H, OH), 2.76, 2.72 (ddABq, 1 H each,
J ) 12.4, 7.7, 5.0 Hz, SCH2CH3), 1.30 (t, 3 H, J ) 7.6 Hz,
SCH2CH3); 13C NMR (CDCl3): δ 155.0, 137.4, 129.9, 128.9,
126.8, 102.3, 95.8, 84.9, 81.7, 75.1, 72.8, 70.8, 69.0, 57.7, 24.8,
15.3; HRMS calcd for C18H22O6NCl3SNa (M + Na) 508.0131,
found 508.0133.
1 H each, J ) 12.4, 7.4, 5.0 Hz, SCH2CH3), 2.08, 2.00 (s, 3 H
each, OAc), 1.20-1.30 (m, 3 H, SCH2CH3); 13C NMR (CDCl3)
δ 170.89, 170.59, 154.59, 137.92, 128.90, 128.89, 128.38,
128.32, 95.90, 85.43, 77.65, 76.39, 74.91, 74.00, 71.78, 68.05,
67.76, 52.12, 25.01, 21.16, 21.09, 15.27; HRMS calcd for
C
22H28O8NCl3SNa (M + Na) 594.0499, found 594.0492.
4-Meth oxyp h en yl [3,4-Di-O-a cetyl-6-O-ben zyl-2-d eoxy-
Eth yl 3-O-Acetyl-4,6 -O-ben zylid en e-2-d eoxy-2-[[(2,2,2-
tr ich lor oeth oxy)ca r bon yl]a m in o]-1-th io-â-D-glu cop yr a -
n osid e (11). Compound 10 (10.24 g, 21 mmol) was dissolved
in pyridine (100 mL) at 0 °C, and Ac2O (80 mL) and N,N-
(dimethylamino)pyridine (20 mg) was added. The mixture was
stirred at 0 °C for 45 min and at room temperature for another
45 min. The mixture was co-concentrated with toluene, and
the residue was chromatographed (SiO2, 1:1 heptane-EtOAc)
to give 11 (10.61 g, 96%): [R]20D -59.5 (c 1.1, CHCl3); 1H NMR
(CDCl3) δ 7.30-7.50 (m, 5 H, ArH), 5.52 (s, 1 H, ArCH), 5.46
(d, 1 H, J ) 9.8 Hz, NH), 5.32 (t, 1 H, J ) 9.8 Hz, H-3), 4.84,
4,68 (ABq, 1 H each, J ) 12.1 Hz, Cl3CCH2), 4.55 (d, 1 H, J )
10.4 Hz, H-1), 4.36 (dd, 1 H, J ) 10.5, 4.9 Hz, H-5), 3.87 (q, 1
H, J ) 10.2 Hz, H-2), 3.77 (t, 1 H, J ) 10.2 Hz, H-6), 3.72 (t,
1 H, J ) 9.5 Hz, H-6), 3.56 (dt, 1 H, J ) 9.8, 4.9 Hz, H-4),
2.72, 2.67 (ABq, 1 H each, J ) 7.5 Hz, SCH2CH3), 2.08 (s, 3 H,
OAc), 1.26 (t, 3 H, J ) 7.4 Hz, SCH2CH3). 13C NMR (CDCl3)
δ 171.5, 164.9, 137.3, 129.6, 128.7, 126.5, 101.7, 95.9, 86.0, 79.1,
75.0, 73.0, 71.0, 68.9, 55.9, 24.8, 21.3, 15.2; HRMS calcd for
2-[[(2,2,2-t r ich lor oet h oxy)ca r b on yl]a m in o]-â-D-ga la ct o-
p y r a n o s y l]-(1f4)-(6-O -b e n zy l-2-d e o x y -2-(t e t r a c h lo -
r op h th a lim id o)-â-D-glu cop yr a n osid e) (16). To a solution
of 14 (310 mg, 0.54 mmol) and 151 (250 mg, 0.39 mmol) in
CH2Cl2 (3.5 mL) at -78 °C under Ar was added a solution of
AgOTf (300 mg, 1.16 mmol) in MeCN (1.75 mL). After 5 min,
a 4 M solution of methylsulfenyl bromide15 in 1,2-dichloro-
ethane (0.245 mL) was added during 10 min, and the mixture
was stirred for 2 h at -78 °C. Isopropylamine (0.5 mL) was
added, and the mixture was stirred at -78 °C for 1.5 h and
then filtered through a short column (SiO2, 1:1 heptane-
EtOAc). The solvent was removed, and the residue was
chromatographed (SiO2, 3:1 f 2:1 heptane-EtOAc) to give 16
1
(278 mg, 62%): [R]20 -9.4 (c 0.9 CHCl3); H NMR (CDCl3) δ
D
7.20-7.50 (m, 10 H, Ar), 6.70-6.90 (m, 4 H, OPMP), 5.67 (m,
1 H, virtual coupling similar to entry 23 in ref 26, H-1), 5.32
(d, 1 H, J ) 3.0 Hz, H-4′), 4.87, 4.32 (ABq, 1 H each, J ) 12.1
Hz, OBn), 4.76, 4.67 (ABq, 1 H each, J ) 12.0 Hz, Cl3CCH2),
4.57-4.71 (m, 1 H, H-3), 4.51, 4.36 (ABq, 1 H each, J ) 11.7
Hz, OBn), 4.43-4.49 (m, 2 H, H-2, NH), 4.27 (s, 1 H, OH),
4.12 (d, 1 H, J ) 8.4 Hz, H-1′), 3.65-3.95, m, 7 H, H-3,4,5,6,2′,-
5′), 3.75 (s, 3 H, OMe), 3.54, 3.44 (dABq, 1 H each, J ) 9.5,
7.1, 5.6 Hz, H-6′), 2.05, 1.98 (s, 3 H each, OAc); 13C NMR
(CDCl3) δ 170.4, 155.9, 154.6, 150.9, 140.6, 138.6, 137.5, 129.6,
129.3, 129.1, 128.9, 128.31, 128.27, 119.0, 114.9, 102.2, 97.5,
95.9, 81.7, 75.1, 74.4, 74.1, 73.7, 72.8, 70.5, 69.6, 68.1, 67.4,
67.0, 57.0, 56.0, 52.5, 20.99, 20.97. HRMS calcd for C48H45O16N2-
Cl7Na (M + Na) 1173.0486, found 1173.0484.
C
20H24O7NCl3SNa (M + Na) 550.0237, found 550.0215.
Eth yl 3-O-Acetyl-6-O-ben zyl-2-d eoxy-2-[[(2,2,2-tr ich lo-
r oet h oxy)ca r b on yl]a m in o]-1-t h io-â-D-glu cop yr a n osid e
(12). Compound 11 (10.45 g, 19.8 mmol) was dissolved in dry
THF (150 mL), and the mixture was cooled to 0 °C. NaBH3-
CN (7.5 g) and 3A molecular sieves (10 g) were added. An
ice-cold, saturated solution of HCl in Et2O was added until
the pH (checked with a moist pH paper) reached 2-3. The
mixture was stirred for 2 h, diluted with CH2Cl2, and filtered
through Celite. The solution was washed with saturated
aqueous NaHCO3 and brine, dried (Na2SO4), concentrated, and
chromatographed (SiO2, 3:1 f 1:1 heptane-EtOAc) to give 12
A sample of 16 was conventionally O-acetylated (Ac2O-
pyridine), which gave a signal at δ 5.64 (t, 1 H, J ) 9.3 Hz,
H-3).
(9.80 g, 93%): [R]20 -33.6 (c 1.1, CHCl3); 1H NMR (CDCl3) δ
D
7.30-7.40 (m, 5 H, ArH), 5.52 (d, 1 H, J ) 9.8 Hz, NH), 5.07
(t, 1 H, J ) 9.9 Hz, H-3), 4.80, 4.69 (ABq, 1 H each, J ) 12.2
Hz, Cl3CCH2), 4.62, 4.57 (ABq, 1 H each, J ) 11.7 Hz, OBn),
4.56, (d, 1 H, J ) 10.3 Hz, H-1), 3.55-3.90 (m, 5 H, H-2,4,5,6),
3.30 (bs, 1 H, OH), 2.76, 2.71 bddABq, 1 H each, J ) 12.3, 7.3,
5.0 Hz, SCH2CH3), 2.10 (s, 3 H, OAc), 1.26 (t, 3 H, J ) 7.4 Hz,
SCH2CH3); 13C NMR (CDCl3) δ 172.1, 154.7, 137.8, 129.0,
128.5, 128.2, 95.9, 85.1, 78.2, 76.4, 74.9, 74.3, 71.2, 71.0, 55.3,
24.7, 21.3, 15.3; HRMS calcd for C20H26O7NCl3SNa (M + Na)
552.0393, found 552.0367.
Eth yl 3-O-Acetyl-6-O-ben zyl-2-d eoxy-2-[[(2,2,2-tr ich lo-
r oeth oxy)car bon yl]am in o]-4-O-(tr iflu or om eth an su lfon yl)-
1-th io-â-D-glu cop yr a n osid e (13). Compound 12 (1.00 g, 1.9
mmol) was dissolved in CH2Cl2 (7 mL), the mixture was cooled
to -50 °C, and pyridine (0.62 mL) was added. Trifluo-
romethansulfonic anhydride (0.62 mL, 3.8 mmol) was added
during 10 min. The temperature was gradually raised to -20
°C during 2 h. The mixture was diluted with CH2Cl2, washed
with 1 M aqueous HCl and saturated aqueous NaHCO3, dried,
and concentrated. The residue was dried under vacuum and
used in the next step without further purification.
Eth yl 3,4-Di-O-a cetyl-6-O-ben zyl-2-d eoxy-2-[[(2,2,2-tr i-
ch lor oet h oxy)ca r b on yl]a m in o]-1-t h io-â-D-ga la ct op yr a -
n osid e (14). Crude 13 was dissolved in DMF (35 mL), CsOAc
(3.6 g, 18.8 mmol) was added, and the mixture was stirred for
2.5 h at room temperature, diluted with Et2O, and washed with
H2O. The aqueous phase was extracted with four portions of
Et2O. The organic phase was dried (Na2SO4) and concen-
trated, and the residue was chromathographed (SiO2, 3:1
heptane-EtOAc) to give 14 (864 mg, 80% overall yield from
12): [R]20D -36.8 (c 1.0, CHCl3); 1H NMR (CDCl3) δ 7.20-7.35
(m, 5 H, ArH), 5.49 (d, 1 H, J ) 2.9 Hz, H-4), 5.11 (dd, 1 H, J
) 10.8, 2.9 Hz, H-3), 5.03 (d, 1 H, J ) 9.6 Hz, NH), 4.81, 4.70
(ABq, 1 H each, J ) 11.2 Hz, Cl3CCH2), 4.63 (d, 1 H, J ) 10.3,
H-1), 4.55, 4.42 (ABq, 1 H each, J ) 12.1 Hz, OBn), 3.98 (q, 1
H, J ) 10.3 Hz, H-2), 3.87 (dt, 1 H, J ) 6.8, 6.0 Hz, H-5), 3.58,
3.48 (dABq, 1 H each, J ) 9.5, 6.9, 5.9, H-6), 2.79, 2.73 (ddABq,
4-Meth oxyp h en yl (3,4-Di-O-a cetyl-6-O-ben zyl-2-d eoxy-
2-[[(2,2,2-t r ich lor oet h oxy)ca r bon yl]a m in o]-â-D-ga la ct o-
p yr a n osyl)-(1f4)-(2-a cet a m id o-6-O-b en zyl-2-d eoxy-â-D-
glu cop yr a n osid e) (17). Compound 16 (408 mg, 0.35 mmol)
was dissolved in dry EtOH (10 mL), and diaminoethane12
(0.029 mL, 0.42 mmol) was added. The mixture was kept at
60 °C for 16 h and then co-concentrated with toluene. The
residue was dissolved in MeOH-H2O-Ac2O (5.0, 1.0, 1.5 mL)
and stirred for 1.5 h, co-concentrated with toluene, and
chromatographed (SiO2, 5:1 CH2Cl2-acetone) to give 17 (263
mg, 80%): [R]20D -30.4 (c 1.1 CHCl3); 1H NMR (CDCl3) δ 7.30-
7.50 (m, 10 H, Ar), 6.78 (m, 4 H, OPMP), 5.75 (d, 1 H, J ) 7.6
Hz, NH), 5.37 (d, 1 H, J ) 8.4 Hz, H-1), 3.53 (d, 1 H, J ) 2.6
Hz, H-4′), 4.83, 4.32 (ABq, 1 H each, J ) 12.3 Hz, OBn), 4.72,
4.65 (ABq, 1 H each, J ) 12.2 Hz, Cl3CCH2), 4.63-4.68 (m, 1
H, H-3), 4.55, 4.42 (ABq, 1 H each, J ) 11.8 Hz, OBn), 4.25 (s,
1 H, OH), 4.17 (q, 1 H, J ) 9.5 Hz, H-3), 4.15 (d, 1 H, J ) 8.4
Hz, H-1′), 4.10 (d, 1 H, J ) 6.9 Hz, NH), 3.50-3.85 (m, 7 H,
H-2,5,6,2′,5′,6′), 3.77 (s, 3 H, OMe), 3.42 (dd, 1 H, J ) 9.1, 6.4
Hz, H-6′), 2.04, 2.02, 1.98 (s, 3 H each, OAc, NHAc); 13C NMR
(CDCl3) δ 171.0, 170.5, 155.8, 154.6, 151.8, 138.6, 137.6, 129.5,
129.3, 129.0, 128.5, 119.1, 114.9, 102.1, 99.9, 95.9, 81.5, 75.0,
74.1, 73.7, 72.6, 71.4, 70.6, 67.7, 67.0, 58.1, 56.1, 52.6, 24.1,
21.00, 20.97; HRMS calcd for C42H49O15N2Cl3Na (M + Na)
949.2096, found 949.2111.
4-Meth oxyp h en yl (3,4-d i-O-a cetyl-6-O-ben zyl-2-d eoxy-
2-[[(2,2,2-t r ich lor oet h oxy)ca r bon yl]a m in o]-â-D-ga la ct o-
p yr a n osyl)-(1f4)-[2,3,4-t r i-O-b e n zyl-r-L -fu cop yr a n o-
s y l ](1 f3 )-(2 -a c e t a m i d o -6 -O -b e n z y l -2 -d e o x y -â-D -
glu cop yr a n osid e) (19). Ethyl 2,3,4-tri-O-benzyl-1-thio-R-L-
fucopyranoside16 (18, 114 mg, 0.24 mmol) was dissolved in dry
CH2Cl2 (0.9 mL), and freshly distilled Br2 (0.011 mL in 0.140
mL CH2Cl2) was added. The mixture was stirred for 15 min,
and cyclohexene was added until the color of Br2 disappeared.
The solvent was removed, and the residue was dissolved in
dry CH2Cl2 (0.9 mL). The solution was added to a mixture of
17 (112 mg, 0.12 mmol), 4 A molecular sieves (450 mg), Bu4-

Analogs of Sialyl Lewis x Tetrasaccharide
J . Org. Chem., Vol. 63, No. 25, 1998 9333
NBr (70 mg), and 5:3 CH2Cl2-DMF (0.96 mL). The mixture
was stirred for 48 h, pyridine (0.35 mL) was added, and the
stirring was continued for another 3 h. The mixture was
filtered through Celite and co-concentrated with toluene. The
concentrated. The residue was chromatographed (SiO2, 20:1
toluene-EtOH) to give 21 (75 mg, 98%): [R]20 -42.1 (c 0.9
D
CHCl3). A sample of 21 was crystallized from EtOAc-hep-
1
tane: mp 167-168 °C; H NMR (CDCl3) δ 7.20-7.40 (m, 25
residue was chromatographed (SiO2, 1:1 heptane-EtOAc) to
H, Ar), 6.73-6.83 (m, 4 H, OPMP), 6.32 (d, 1 H, J ) 7.5 Hz,
NH), 5.45 (d, 1 H, J ) 6.4 Hz, NH), 5.20 (d, 1 H, J ) 3.6 Hz,
H-1′′), 5.17 (d, 1 H, J ) 5.8 Hz, H-1), 4.95, 4.62 (ABq, 1 H
each, J ) 11.5 Hz, OBn), 4.86, 4.73 (ABq, 1 H each, J ) 11.5
Hz, OBn), 4.71-4.74 (m, 2 H, OBn), 4.71, 4.57 (ABq, 1 H each,
J ) 12.0 Hz, OBn), 4.47, 4.43 (s, 2 H each, OBn, Cl3CCH2),
4.34 (d, 1 H, J ) 8.2 Hz, H-1′), 4.05-4.20 (m, 3 H, H-4′,2′′,5′′),
3.92-4.00 (m, 2 H, H-2,3′′), 3.89 (dd, 1 H, J ) 10.1, 2.5 Hz,
H-3′), 3.45-3.80 (m, 11 H, H-3,4,5,6,2′,5′,6′,4′′, OH), 3.76 (s, 3
H, OMe), 2.85 (s, 1 H, OH), 1.83 (s, 3 H, NHAc), 1.08 (d, 3 H,
J ) 6.5 Hz, H-6′′); 13C NMR (CDCl3): δ 170.7, 155.5, 151.7,
139.2, 139.1, 138.1, 137.9, 128.99, 128.95, 128.92, 128.8, 128.7,
128.6, 128.42, 128.36, 128.2, 128.1, 128.0, 127.9, 127.7, 118.7,
114.8, 100.0, 99.6, 97.9, 95.7, 79.7, 78.1, 75.4, 75.2, 74.7, 74.5,
74.1, 74.0, 73.9, 73.4, 73.0, 72.7, 70.6, 69.2, 68.4, 67.5, 56.1,
23.6, 17.2; HRMS calcd for C65H73O17N2Cl3Na (M + Na)
1281.3873, found 1281.3866.
1
give 19 (107 mg, 66%): [R]20 -62.2 (c 1.1 CHCl3); H NMR
D
(CDCl3) δ 7.20-7.45 (m, 25 H, Ar), 6.74-6.90 (m, 4 H, OPMP),
6.38 (d, 1 H, J ) 7.9 Hz, NH), 5.44 (d, 1 H, J ) 3.1 Hz, H-4′),
5.24 (d, 1 H, J ) 4.6 Hz, H-1), 5.17 (d, 1 H, J ) 3.6 Hz, H-1′′),
4.97, 4.66 (ABq, 1 H each, J ) 11.8 Hz, OBn), 4.75-4.85 (m,
4 H, OBn, H-3′), 4.71, 4.45 (ABq, 1 H each, J ) 12.1 Hz, OBn),
4.67 (AB, 1 H, J ) 11.8 Hz, OBn), 4.50 (AB, 1 H, J ) 12.0 Hz,
OBn), 4.30-4.42 (m, 4 H, OBn, Cl3CCH2, H-1′), 4.00-4.20 (m,
3 H, H-2,2′′,5′′), 3.97 (t, 1 H, J ) 4.7 Hz, H-3′′), 3.76 (s, 3 H,
OMe), 3.50-3.85 (m, 8 H, H-3,5,6,2′,5′,6′,4′′), 3.43 (t, 1 H, J )
8.4 Hz, H-6′), 2.00, 1.97, 1.90 (s, 3 H each, OAc, NHAc), 1.07
(d, 3 H, J ) 6.4 Hz, H-6′′); 13C NMR (CDCl3) δ 170.8, 170.6,
170.4, 155.4, 155.2, 151.7, 139.2, 139.1, 139.0, 138.2, 137.7,
129.1, 129.0, 128.9, 128.7, 128.6, 128.38, 128.35, 128.28, 128.1,
128.02, 127.97, 127.8, 118.4, 114.8, 100.9, 99.0, 97.5, 95.7, 79.6,
74.9, 74.7, 74.0, 73.8, 73.6, 73.32, 72.29, 70.4, 69.9, 67.3, 67.2,
67.0, 56.1, 53.1, 52.9, 23.5, 21.1, 21.0, 17.2; HRMS calcd for
C69H77O19N2Cl3Na (M + Na) 1365.4084, found 1365.4075.
A sample of 19 was conventionally de-O-benzylated (H2, Pd-
C, AcOH) and O-acetylated (Ac2O-pyridine): 1H NMR (CDCl3)
δ 6.80-6.95 (m, 4 H, OPMP), 6.04 (d, 1 H, J ) 6.2 Hz, NH),
5.50 (d, 1 H, J ) 3.9 Hz, H-1′′), 5.42 (d, 1 H, J ) 3.1 Hz, H-4′),
5.39 (d, 1 H, J ) 2.6 Hz, H-4′′), 5.34 (d, 1 H, J ) 9.4 Hz, H-1′),
5.25 (dd, 1 H, J ) 10.9, 3.3 Hz, H-3′′), 5.11 (dd, 1 H, J ) 10.8,
3.9 Hz, H-2′′), 5.09 (d, 1 H, J ) 4.0 Hz, H-1), 5.04 (dd, 1 H, J
) 11.7, 2.3 Hz, H-3′), 4.60-4.70 (m, 3 H, Cl3CCH2, H-5′′), 4.35-
4.50 (m, 3 H, H-6, 6′), 4.29 (dd, 1 H, J ) 12.8, 5.4 Hz, H-6),
3.80-4.20 (m, 5 H, H-2,3,4,5,2′), 3.77 (s, 3 H, OMe), 2.22, 2.17,
2.10, 2.08, 2.07, 2.04, 2.03, 1.99 (s, 3 H each, OAc, NHAc), 1.23
(d, 3 H, J ) 6.5 Hz, H-6′′).
4-Meth oxyp h en yl [Meth yl(5-a ceta m id o-4,7,8,9-tetr a -O-
a cet yl-3,5-d id eoxy-D-glycer o-r-D-ga la ct o-2-n on u lop yr a -
n osyl)on a t e ]-(1f3)-[4-O-a ce t yl-6-O-b e n zyl-2-d e oxy-2-
[ [ ( 2 , 2 , 2 -t r i c h l o r o e t h o x y ) c a r b o n y l ] a m i n o ] -â-D -
g a l a c t o p y r a n o s y l )-(1 f4 )-(2 ,3 ,4 -t r i -O -b e n z y l -r-L -
fu cop yr a n osyl)-(1f3)-(2-a ceta m id o-6-O-ben zyl-2-d eoxy-
â-D-glu cop yr a n osid e) (23). To a mixture of 21 (180 mg,
0.143 mmol), 2220 (255 mg, 0.428 mmol), and 3A molecular
sieves (200 mg) were added CH2Cl2 (1.25 mL) and MeCN (1.50
mL). The mixture was stirred for 10 min at room temperature
and for 5 min at -60 °C under Ar. A solution of dry AgOTf
(130 mg) in freshly distilled MeCN (0.93 mL) was added. After
5 min, a 4 M solution of methylsulfenyl bromide15 in 1,2-
dichloroethane (0.116 mL) was added during 30 min. The
mixture was stirred for 3 h at -60 °C, diisopropylamine (0.475
mL) was added, and the mixture was stirred for 2 h at -60
°C. The reaction mixture was filtered through a short column
(SiO2, 2:1 toluene-acetone). The crude product was conven-
tionally acetylated (Ac2O-pyridine), the mixture was co-
concentrated with three portions of toluene, and the residue
was chromatographed (SiO2, 1:3 CH2Cl2-EtOAc) to give 23
4-Met h oxyp h en yl (2-Acet a m id o-3,4-d i-O-a cet yl-6-O-
ben zyl-2-d eoxy-â-D-ga la ctop yr a n osyl)-(1f4)-(2,3,4-tr i-O-
ben zyl-r-L-fu copyr an osyl)-(1f3)-2-acetam ido-6-O-ben zyl-
2-d eoxy-â-D-glu cop yr a n osid e (20). Compound 19 (50 mg,
0.04 mmol) was dissolved in AcOH (1.5 mL), and freshly
activated zinc dust (200 mg) was added. After 1.5 h, the
reaction mixture was filtered through a short column (SiO2,
1:1 toluene-acetone plus 0.1% Et3N). The crude product was
dissolved in pyridine (3 mL), and Ac2O (2.5 mL) was added.
The mixture was stirred for 2.5 h, co-concentrated with
(148 mg, 58%) and 19 (26 mg, 13%). Compound 23: [R]20
D
1
-52.8 (c 1.1 CHCl3); H NMR (CDCl3) δ 7.05-7.45 (m, 26 H,
Ar, NH), 6.70-6.90 (m, 4 H, OPMP), 5.72 (d, 1 H, J ) 7.6 Hz,
NH), 5.44 (dt, 1 H, J ) 6.3, 2.5 Hz, H-8′′′), 5.36 (dd, 1 H, J )
9.3, 2.2 Hz, H-7′′′), 5.25 (d, 1 H, J ) 3.4 Hz, H-1′′), 5.17 (bs, 1
H, H-1), 5.11 (d, 1 H, J ) 2.6 Hz, H-4′), 5.09 (d, 1 H, J ) 7.6
Hz, NH), 4.97 (m, 1 H, H-4′′′), 4.95, 4.63 (ABq, 1 H each, J )
11.7, OBn), 4.87, 4.74 (ABq, 1 H each, J ) 11.7, OBn), 4.82,
4.66 (ABq, 1 H each, J ) 12.3 Hz, OBn), 4.78 (d, 1 H, J ) 11.7
Hz, OBn), 4.50-4.60 (m, 3 H, H-1′,2, OBn), 4.47, 4.37 (ABq, 1
H each, J ) 11.7 Hz, Cl3CCH2), 4.42 (bd, 1 H, J ) 12.0 Hz,
H-3′), 4.32 (dd, 1 H, J ) 12.3, 2.3 Hz, H-9′′′), 4.27 (AB, 1 H, J
) 12.4 Hz, OBn), 4.05-4.20 (m, 4 H, H-5′,2′′,5′′′, OBn), 4.00
(dd, 1 H, J ) 12.1, 6.0 Hz, H-9′′′), 3.94 (dt, 1 H, J ) 9.5, 8.6
Hz, H-6′), 3.87 (s, 3 H, OMe), 3.65-3.85 (m, 7 H, H-3,4,2′,6′,3′′,-
4′′,5′′), 3.75 (s, 3 H, OMe), 3.47 (dd, 1 H, J ) 9.7, 5.4 Hz, H-6),
3.35-3.43 (m, 2 H, H-5,6), 2.63 (dd, 1 H, J ) 12.8, 4.8 Hz,
H-3′′′eq), 2.20, 2.13, 2.09, 2.07, 2.04, 1.94, 1.87 (s, 3 H each,
OAc, NHAc), 1.83 (dd, 1 H, J ) 11.9, 2.9 Hz, H-3′′′ax), 0.95 (d,
3 H, J ) 6.3 Hz, H-6′′); 13C NMR (CDCl3): δ 171.4, 171.3, 171.2,
170.8, 170.6, 170.5, 168.0 (C-1′′′, J C-1′′′:H-3′′′ax 6.1 Hz),21 156.4,
154.9, 151.7, 139.5, 139.1, 139.1, 138.7, 138.3, 138.1, 128.91,
128.86, 128.80, 128.79, 128.7, 128.6, 128.4, 128.19, 128.16,
128.0, 127.9, 127.8, 127.6, 127.5, 117.9, 114.8, 100.9, 98.6, 97.8,
96.8, 95.9, 79.0, 77.8, 76.7, 75.1, 74.7, 74.3, 73.8, 73.5, 73.4,
73.2, 72.9, 72.1, 72.0, 71.1, 70.7, 69.4, 68.1, 67.9, 67.5, 67.4,
67.2, 63.1, 56.1, 53.8, 49.7, 48.9, 38.0, 30.1, 23.6, 23.4, 21.9,
21.5, 21.3, 21.2, 21.0, 18.7, 17.0; HRMS calcd for C87H102O30N3-
Cl3Na (M + Na) 1796.5511, found 1796.5559.
toluene, and chromatographed (SiO2, 1:1 toluene-acetone) to
1
give 20 (37 mg, 83%): [R]20 -102.2 (c 0.7, CHCl3); H NMR
D
(CDCl3) δ 7.10-7.45 (m, 25 H, Ar), 6.85 (bd, 1 H, J ) 9.2 Hz,
NH), 6.70-6.90 (m, 4 H, OPMP), 5.44 (d, 1 H, J ) 3.0 Hz,
H-4′), 5.39 (d, 1 H, J ) 8.9 Hz, NH), 5.25 (d, 1 H, J ) 3.5 Hz,
H-1′′), 5.15 (d, 1 H, J ) 3.7 Hz, H-1), 4.97, 4.66 (ABq, 1 H
each, J ) 11.8 Hz, OBn), 4.94 (dd, 1 H, J ) 11.4, 3.4 Hz, H-3′),
4.85, 4.66 (ABq, 1 H each, J ) 11.6 Hz, OBn), 4.81, 4.68 (ABq,
1 H each, J ) 12.2 Hz, OBn), 4.51, 4.37 (ABq, 1 H each, J )
11.8 Hz, OBn), 4.35-4.42 (m, 1 H, H-2), 4.31 (d, 1 H, J ) 8.4
Hz, H-1′), 4.29, 4.26 (ABq, 1 H each, J ) 13.0 Hz, OBn), 4.16-
4.22 (m, 1 H, H-2′), 4.11 (dd, 1 H, J ) 10.0, 3.6 Hz, H-2′′), 4.07
(bt, 1 H, J ) 3.5 Hz, H-3), 3.98 (bs, 1 H, H-4), 3.70-3.92 (m,
5 H, H-5,6,5′,3′′,5′′), 3.76 (s, 3 H, OMe), 3.63 (dd, 1 H, J ) 8.9,
4.0 Hz, H-6), 3.43-3.54 (m, 3 H, H-4,6′), 2.05, 2.04, 2.01, 1.86
(s, 3 H each, OAc, NHAc), 1.01 (d, 3 H, J ) 6.5 Hz, H-6′′); 13
C
NMR (CDCl3) δ 171.6, 171.5, 170.7, 170.5, 155.2, 151.7, 139.4,
139.1, 139.0, 138.5, 137.7, 128.93, 128.89, 128.81, 128.7, 128.6,
128.4, 128.3, 128.2, 128.0, 127.9, 127.8, 118.3, 114.8, 100.7,
99.2, 97.1, 79.2, 76.7, 75.0, 74.7, 74.1, 73.9, 73.8, 73.4, 73.1,
72.9, 72.6, 70.6, 70.5, 67.5, 67.4, 67.1, 56.1, 51.3, 23.9, 23.5,
21.2, 21.1, 17.1. HRMS calcd for C68H78O18N2Na (M+Na)
1233.5147, found 1233.5173.
4-Meth oxyph en yl (6-O-Ben zyl-2-deoxy-2-[[(2,2,2-tr ich lo-
r oeth oxy)ca r bon yl]a m in o]-â-D-ga la ctop yr a n osyl)-(1f4)-
[2,3,4-tr i-O-ben zyl-r-L-fu copyr an osyl]-(1f3)-(2-acetam ido-
6-O-ben zyl-2-d eoxy-â-D-glu cop yr a n osid e) (21). Compound
19 (81 mg, 0.15 mmol) was dissolved in the guanidinium
nitrate stock solution19 (5 mL), the mixture was stirred for 15
min, neutralized with Amberlite IR-120 H+, filtered, and
4-Meth oxyp h en yl [Meth yl(5-a ceta m id o-4,7,8,9-tetr a -O-
a cet yl-3,5-d id eoxy-D-glycer o-r-D-ga la ct o-2-n on u lop yr a -
n osyl)on a te]-(1f3)-(2-a ceta m id o-4-O-a cetyl-6-O-ben zyl-
2-d eoxy-â-D-ga la ctop yr a n osyl)-(1f4)-(2,3,4-tr i-O-ben zyl-

9334 J . Org. Chem., Vol. 63, No. 25, 1998
Ellervik et al.
r-L-fu cop yr a n osyl)-(1f3)-(2-a ce t a m id o-6-O-b e n zyl-2-
d eoxy-â-D-glu cop yr a n osid e) (24). Compound 23 (146 mg,
0.08 mmol) was dissolved in AcOH (5 mL), and freshly
activated zinc dust (1.0 g) was added. The mixture was stirred
overnight, filtered through Celite, and co-concentrated with
toluene. The crude product was dissolved in pyridine (4 mL),
and Ac2O (3 mL) was added. The mixture was stirred for 4.5
h, co-concentrated with toluene, and chromatographed (SiO2,
NaHCO3 solution and water, dried (Na2SO4), and concentrated.
The residue was chromatographed (SiO2, 3:1 heptane-EtOAc)
1
to give 28 (464 mg, 92%): [R]20 -38 (c 1.1, CHCl3); H NMR
D
(CDCl3) δ 7.05-7.45 (m, 9 H, Ar), 5.06 (t, 1 H, J ) 9.3 Hz,
H-3), 4.92 (dd, 1 H, J ) 9.9, 9.3 Hz, H-2), 4.65 (d, 1 H, J )
10.0 Hz, H-1), 4.61, 4.56 (ABq, 1 H each, J ) 11.7 Hz, OBn),
3.83, 3.79 (dABq, 1 H each, J ) 10.4, 4.9 Hz, H-6), 3.73 (dt, 1
H, J ) 9.5, 3.3 Hz, H-4), 3.57 (dt, 1 H, J ) 9.5, 4.8 Hz, H-5),
2.99 (d, 1 H, J ) 3.4 Hz, OH), 2.34 (s, 3 H, ArMe), 2.10, 2.08
(s, 3 H each, OAc); 13C NMR (CDCl3): δ 171.9, 170.0, 139.0,
137.9, 133.9, 130.2, 128.5, 128.4, 128.2, 86.4, 78.5, 77.4, 74.3,
71.1, 70.6, 70.3, 21.6, 21.30, 21.27; HRMS calcd for C24H28O7-
SNa (M + Na) 483.1453, found 483.1450.
4:1 f 1:1 toluene-acetone) to give 24 (95 mg, 70%): [R]20
D
1
-65.8 (c 0.9, CHCl3); H NMR (CDCl3) δ 7.10-7.45 (m, 26 H,
ArH, NH), 6.70-6.95 (m, 4 H, OPMP), 5.99 (d, 1 H, J ) 8.3
Hz, NH′), 5.58 (dt, 1 H, J ) 9.1, 2.6 Hz, H-8′′′), 5.35 (d, 1 H, J
) 3.5 Hz, H-1′′), 5.27 (dd, 1 H, J ) 9.9, 2.4 Hz, H-7′′′), 5.14 (d,
1 H, J ) 4.3 Hz, H-1), 5.13 (d, 1 H, J ) 5.1 Hz, NH′′′), 5.01 (d,
1 H, J ) 2.9 Hz, H-4′), 4.95, 4.62 (ABq, 1 H each, J ) 11.7 Hz,
OBn), 4.93, 4.72 (ABq, 1 H each, J ) 11.5 Hz, OBn), 4.89 (dd,
1 H, J ) 11.9, 4.6 Hz, H-4′′′), 4.82, 4.66 (ABq, 1 H each, J )
12.4 Hz, OBn), 4.58 (dd, 1 H, J ) 10.0, 3.5 Hz, H-2), 4.49 (d,
1 H, J ) 7.8 Hz, H-1′), 4.46, 4.36 (ABq, 1 H each, J ) 11.4 Hz,
OBn), 4.38 (dd, 1 H, J ) 12.1, 2.6 Hz, H-9′′′), 4.25-4.31 (m, 2
H, H-3′,3′′), 4.00-4.15 (m, 6 H, H-3,4,2′,2′′,4′′,5′′′), 3.60-3.90
(m, 7 H, H-5,6,5′,6′,5′′,6′′′,9′′′), 3.88 (s, 3 H, OMe), 3.75 (s, 3 H,
OMe), 3.33-3.45 (m, 2 H, H-6,6′), 2.61 (dd, 1 H, J ) 12.8, 4.6,
H-3eq′′′), 2.16, 2.14, 2.13, 2.08, 2.03, 2.00, 1.92, 1.87 (s, 3 H
each, OAc, NHAc), 1.79 (t, 1 H, J ) 12.6 Hz, H-3ax′′′), 0.91 (d,
3 H, J ) 6.5 Hz, H-6′′); 13C NMR (CDCl3) δ 172.2, 171.6, 171.4,
171.3, 170.8, 170.64, 170.57, 168.0, 154.9, 152.0, 139.6, 139.2,
139.1, 138.8, 138.1, 128.89, 128.86, 128.75, 128.59, 128.57,
128.50, 128.2, 128.1, 128.0, 127.9, 127.8, 127.6, 127.5, 127.4,
117.9, 114.7, 100.0, 99.0, 97.7, 96.6, 78.8, 78.1, 76.5, 75.0, 74.3,
73.9, 73.5, 73.2, 72.7, 72.5, 72.3, 71.6, 71.4, 70.7, 69.3, 68.1,
67.6, 67.43, 67.36, 67.0, 64.2, 56.1, 53.8, 51.2, 49.9, 49.5, 38.0,
23.8, 23.6, 23.5, 21.9, 21.3, 21.2, 20.8, 16.9; HRMS calcd for
4-Met h ylp h en yl 2,3-Di-O-a cet yl-6-O-b en zyl-4-O-(Tr i-
flu or om eth a n su lfon yl)-1-th io-â-D-glu cop yr a n osid e (29).
Compound 28 (345 mg, 0.75 mmol) was dissolved in CH2Cl2
(3.5 mL), and the mixture was cooled to -78 °C. Pyridine (0.25
mL) was added, and then trifluoromethansulfonic anhydride
(0.236 mL, 1.5 mmol) was added during 10 min. The temper-
ature was gradually raised to 20 °C during 3 h, the mixture
was diluted with CH2Cl2, washed with saturated aqueous
NaHCO3 solution, dried, and concentrated. The residue was
dried under vacuum and used, without further purification,
in the next step.
4-Meth ylp h en yl 2,3-Di-O-a cetyl-4-a zid o-6-O-ben zyl-4-
d eoxy-1-th io-â-D-ga la ctop yr a n osid e (30). The crude com-
pound 29 was dissolved in DMF (5 mL), NaN3 (1.0 g, 14.6
mmol) was added, and the mixture was stirred for 17 h at ∼22
°C. The mixture was diluted with CH2Cl2, filtered through a
short column (SiO2, 1:1 heptane-EtOAc), and concentrated.
The residue was chromathographed (SiO2, 3:1 heptane-
EtOAc), to give 30 (344 mg, 95%): [R]20 -34 (c 1.1, CHCl3);
D
1H NMR (CDCl3) δ 7.10-7.40 (m, 9 H, Ar), 5.23 (t, 1 H, J )
9.9 Hz, H-2), 5.11 (dd, 1 H, J ) 9.7, 3.7 Hz, H-3), 4.59 (d, 1 H,
J ) 9.9 Hz, H-1), 4.56, 4.53 (ABq, 1 H each, J ) 11.6 Hz, OBn),
4.15 (dd, 1 H, J ) 3.7, 1.2 Hz, H-4), 3.79 (ddd, 1 H, J ) 7.0,
5.6, 1.3 Hz, H-5), 3.70 (dABq, 1 H, J ) 9.3, 5.6 Hz, H-6), 3.65
(dABq, 1 H, J ) 9.3, 7.6 Hz, H-6), 2.34 (s, 3 H, ArMe), 2.11,
2.10 (s, 3 H each, OAc); 13C NMR (CDCl3) δ 170.5, 169.8, 138.8,
137.9, 133.5, 130.1, 128.93, 128.90, 128.4, 128.3, 87.3, 76.1,
74.4, 74.1, 68.6, 68.1, 60.8, 21.6, 21.3, 21.0; HRMS calcd for
C
86H103O29N3Na (M + Na) 1664.6575, found 1664.6559.
4-Meth ylp h en yl 4,6-O-Ben zylid en e-1-th io-â-D-glu cop y-
r a n osid e (26). 4-Methylphenyl 1-thio-â-D-glucopyranoside22
(25, 2.86 g, 10 mmol) was dissolved in MeCN (35 mL). R,R-
Dimethoxytoluene (2.80 mL) and p-toluenesulfonic acid (35
mg) were added, and the mixture was stirred for 17 h. Et3N
(5 mL) was added, and the mixture was co-concentrated with
toluene three times. The residue was chromatographed (SiO2,
1:1 heptane-EtOAc) to give 26 (3.61 g, 96%). A sample was
C
24H27O6N3SNa (M + Na) 508.1518, found 508.1518.
4-Meth ylp h en yl 2,3-Di-O-a cetyl-4-a m in o-6 O-ben zyl-4-
crystallized from EtOAc-heptane: [R]20 -40 (c 1.0, CHCl3);
D
1
mp 171-172 °C; H NMR (CDCl3) δ 7.14-7.50 (m, 9 H, Ar),
d eoxy-1-th io-â-D-ga la ctop yr a n osid e (31). Compound 30
(252 mg, 0.52 mmol) was dissolved in 6:1 pyridine-H2O (84
mL), and the solution was saturated with H2S at 0 °C for 1 h
and left for 42 h at ∼22 °C. Residual H2S was removed by
bubbling N2 through the mixture for 1 h, which was then co-
concentrated with toluene. The residue was dried under
vacuum and used, without further purification, in the next
step.
5.51 (s, 1 H, ArCH), 4.54 (broad d, 1 H, J ) 9.7 Hz, H-1), 4.36
(broad d, 1 H, J ) 10.1 Hz, H-6), 3.72-3.83 (m, 2 H, H-3,6),
3.47 (m, 2 H, H-4,5), 3.41 (t, 1 H, J ) 8.9 Hz, H-2), 2.92, 3.15
(broad s, 1 H each, OH), 2.37 (s, 3 H, Me); 13C NMR (CDCl3)
δ 137.3, 134.1, 130.3, 129.8, 128.8, 126.8, 102.3, 89.1, 80.6, 74.9,
72.9, 70.9, 69.0, 21.6; HRMS calcd for C20H22O5SNa (M + Na)
397.1086, found 397.1085.
4-Meth ylp h en yl 2,3-Di-O-a cetyl-4,6-O-ben zylid en e-1-
th io-â-D-glu cop yr a n osid e (27). Compound 26 (0.97 g, 2.59
mmol) was dissolved in pyridine (25 mL), and Ac2O (20 mL)
was added. The mixture was stirred for 18 h and then co-
concentrated with toluene. The residue was chromatographed
(SiO2, 1:1 heptane-EtOAc) to give 27 (1.15 g, 97%). A sample
4-Meth ylp h en yl 2,3-Di-O-a cetyl-6-O-ben zyl-4-d eoxy-4-
[[(2,2,2-t r ich lor oet h oxy)ca r b on yl]a m in o]-1-t h io-â-D-ga -
la ctop yr a n osid e (32). The crude compound 31 was dissolved
in pyridine (10 mL), and the solution was cooled to 0 °C. (2,2,2-
Trichloroethoxy)carbonyl chloride (0.210 mL, 1.56 mmol) was
added, and the mixture was stirred at room temperature for
1 h. MeOH (1 mL) was added, and the mixture was co-
concentrated with toluene. The residue was chromatographed
was crystallized from EtOAc-heptane: [R]20 -59 (c 1.2,
D
CHCl3): mp 181-185 °C; 1H NMR (CDCl3) δ 7.15-7.45 (m, 9
H, Ar), 5.50 (s, 1 H, ArCH), 5.35 (t, 1 H, J ) 9.0 Hz, H-3), 4.95
(dd, 1 H, J ) 10.0, 9.0 Hz, H-2), 4.75 (d, 1 H, J ) 10.0 Hz,
H-1), 4.40 (dd, 1 H, J ) 10.6, 4.9 Hz, H-6), 3.80 (t, 1 H, J )
10.0 Hz, H-6), 3.65 (t, 1 H, J ) 9.5 Hz, H-4), 3.57 (dt, 1 H, J
) 9.6, 4.8 Hz, H-5), 2.37 (s, 3 H, ArMe), 2.12, 2.04 (s, 3 H,
OAc); 13C NMR (CDCl3) δ 170.6, 170.0, 139.3, 137.2, 134.1,
126.6, 101.9, 87.2, 78.5, 73.4, 71.2, 71.1, 68.9, 21.7, 21.3, 21.2;
HRMS calcd for C24H26O7S (M + Na) 481.1297, found 481.1296.
4-Meth ylp h en yl 2,3-Di-O-a cetyl-6 O-ben zyl-1-th io-â-D-
glu cop yr a n osid e (28). Compound 27 (500 mg, 1.09 mmol)
was dissolved in THF (10 mL), and the mixture was cooled to
0 °C. NaBH3CN (750 mg) and molecular sieves (1.5 g, 3 Å)
were added. Et2O (nondried) was saturated with HCl and
added until pH was ∼2 (moist litmus paper). The mixture was
stirred for 40 min, diluted with Et2O, and filtered through
Celite. The mixture was washed with saturated aqueous
(SiO2, 1:1 heptane-EtOAc) to give 32 (280 mg, 85%): [R]20
D
1
+6 (c 1.1, CHCl3); H NMR (C6D6) δ 6.90-7.70 (m, 9 H, Ar),
5.54 (t, 1 H, J ) 10.0 Hz, H-2), 5.27 (d, 1 H, J ) 9.7 Hz, NH),
5.13 (dd, 1 H, J ) 9.6, 4.1 Hz; H-4), 5.00 (dd, 1 H, J ) 10.0,
4.1 Hz, H-3), 4.83, 4.49 (ABq, 1 H each, J ) 12.0 Hz, OBn),
4.53 (d, 1 H, J ) 10.0 Hz, H-1), 4.32, 4.27 (ABq, 1 H each, J )
12.1 Hz, Cl3CCH2), 3.40-3.47 (m, 2 H, H-5,6), 3.27 (dd, 1 H, J
) 8.3, 3.2 Hz, H-6), 2.07, 1.85 (s, 3 H each, OAc), 1.28 (s, 3 H,
ArMe); 13C NMR (CDCl3) δ 170.7, 169.7, 153.4, 139.2, 138.0,
134.0, 130.2, 128.9, 128.4, 128.29, 128.25, 94.7, 86.9, 78.2, 77.6,
77.2, 74.0, 69.1, 67.8, 48.3, 23.6, 21.6, 21.2; HRMS calcd for
C
27H30O8NCl3SNa (M + Na) 656.0655, found 656.0646.
4-Meth oxyp h en yl (2,3-Di-O-a cetyl-4-a zid o-6-O-ben zyl-
4-d eoxy-â-D-ga la ctop yr a n osyl)-(1f4)-6-O-ben zyl-2-d eoxy-
2-tetr a ch lor op h th a lim id o-â-D-glu cop yr a n osid e (33). To
a solution of 30 (314 mg, 0.65 mmol) and 151 (295 mg, 0.46

Analogs of Sialyl Lewis x Tetrasaccharide
J . Org. Chem., Vol. 63, No. 25, 1998 9335
mmol) in CH2Cl2 (3.7 mL) at -78 °C under Ar was added a
solution of silver trifluoromethanesulfonate (355 mg, 1.37
mmol) in CH3CN (1.9 mL). After 5 min, a 4 M solution of
methylsulfenyl bromide15 in 1,2-dichloroethane (0.295 mL) was
added during 10 min. The mixture was stirred for 2 h,
isopropylamine (0.5 mL) was added, and the stirring was
continued for 1.5 h at -78 °C. The mixture was filtered
H-5,4′,2′′,5′′), 3.96 (t, 1 H, J ) 5.8 Hz, H-4), 3.84-3.93 (m, 2
H, H-2,3′′), 3.76 (s, 3 H, OMe), 3.54-3.70 (m, 7 H, H-3,6,5′,6′,4′′),
2.13, 2.02, 1.85 (s, 3 H each, OAc, NHAc), 1.09 (d, 3 H, J ) 6.5
Hz, H-6′′); 13C NMR (CDCl3): δ 170.7, 170.5, 170.1, 155.5,
151.7, 139.29, 139.27, 139.1, 138.4, 137.8, 129.0, 128.92,
128.89, 128.7, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 127.7,
118.8, 114.8, 99.8, 99.0, 97.6, 79.9, 76.9, 75.3, 74.7, 74.0, 73.8,
73.71, 73.68, 73.2, 73.0, 72.9, 71.8, 69.7, 69.3, 67.9, 67.2, 60.5,
56.1, 23.6, 21.2, 21.0, 17.0; HRMS calcd for C66H74O17N4Na (M
+ Na) 1217.4947, found 1217.4948.
through
a short column (SiO2, 2:1 toluene-acetone) and
concentrated. The residue was chromatographed (SiO2, 2:1
heptane-EtOAc) to give 33 (366 mg, 78%) and 15 (63 mg,
21%). Compound 33: [R]20 -12 (c 0.9, CHCl3); 1H NMR
4-Met h oxyp h en yl (4-Acet a m id o-2,3-d i-O-a cet yl-6-O-
ben zyl-4-d eoxy-â-D-ga la ctop yr a n osyl)-(1f4)-[2,3,4-tr i-O-
ben zyl-r-L-fu copyr an osyl]-(1f3)-(2-acetam ido-6-O-ben zyl-
2-d eoxy-â-D-glu cop yr a n osid e) (36). H2S was bubbled
through a mixture of 35 (145 mg, 0.12 mmol) and 6:1 pyridine-
H2O (42 mL) at 0 °C for 1 h. The mixture was kept under
H2S at ∼22 °C for 48 h. Residual H2S was removed by
bubbling N2 through the mixture for 1 h. The mixture was
co-concentrated with toluene, and the residue was dissolved
in pyridine (3 mL), Ac2O (2 mL) was added, and the mixture
was stirred for 30 min and co-concentrated with toluene. The
residue was chromatographed (SiO2, 2:1 toluene-acetone) to
D
(CDCl3) δ 7.20-7.40 (m, 10 H, Ar), 6.70-6.90 (m, 4 H, OPMP),
5.64 (d, 1 H, J ) 8.3 Hz, H-1), 5.24 (dd, 1 H, J ) 10.3, 8.0 Hz,
H-2′), 5.03 (dd, 1 H, J ) 10.0, 3.8 Hz, H-3′), 4.70 (AB, 1 H, J
) 12.1 Hz, OBn), 4.49 (d, 1 H, J ) 8.0 Hz, H-1′), 4.45-4.55
(m, 4 H, H-3, and OBn), 4.41 (dd, 1 H, J ) 10.9, 8.3 Hz, H-2),
4.10 (d, 1 H, J ) 1.9 Hz, OH), 4.06 (dd, 1 H, J ) 3.6, 1.0 Hz,
H-4′), 3.55-3.80 (m, 7 H, H-4,5,6,5,6′), 3.74 (s, 3 H, OMe), 2.12,
2.02, (s, 3 H each, OAc); 13C NMR (CDCl3) δ 170.4, 169.5, 155.9,
150.9, 140.6, 138.4, 137.5, 129.0, 128.9, 128.8, 128.43, 128.39,
128.34, 128.24, 128.22, 127.9, 119.0, 114.9, 101.7, 97.4, 81.8,
74.8, 74.1, 74.0, 73.3, 72.4, 69.8, 69.5, 68.8, 68.3, 60.2, 56.8,
56.0, 21.1, 20.8; HRMS calcd for C45H42O14N4Cl4Na (M + Na)
1025.1349, found 1025.1335.
give 36 (145 mg, 99%): [R]20 -83 (c 1.1, CHCl3); 1H NMR
D
(CDCl3) δ 7.15-7.40 (m, 25 H, Ar), 6.74-6.87 (m, 4 H, OPMP),
6.36 (d, 1 H, J ) 8.8 Hz, NH), 5.89 (d, 1 H, J ) 9.5 Hz, NH),
4.90-5.00 (m, 3 H, H-2′,3′, and OBn), 4.85, 4.78 (ABq, 1 H
each, J ) 11.2 Hz, OBn), 4.80 (d, 1 H, J ) 4.4 Hz, H-1), 4.75
(s, 2 H, OBn), 4.71 (dd, 1 H, J ) 9.3, 2.3 Hz, H-4′), 4.59 (AB,
1 H, J ) 11.4 Hz, OBn), 4.54, 4.41 (ABq, 1 H each, J ) 12.2
Hz, OBn), 4.49 (d, 1 H, J ) 7.1 Hz, H-1′), 4.39, 4.34 (ABq, 1 H
each, J ) 12.2 Hz, OBn), 4.32 (dd, 1 H, J ) 8.5, 5.5 Hz, H-2),
4.13 (dd, 1 H, J ) 10.0, 3.5 Hz, H-2′′), 4.07, t, 1 H, J ) 5.1 Hz,
H-3), 3.42-3.95 (m, 10 H, H-4,5,6,5′,6′,3′′,4′′,5′′), 3.77 (s, 3 H,
OMe), 2.07, 2.01, 1.95, 1.92 (s, 3 H each, OAc, NHAc), 0.97 (d,
J ) 6.5 Hz, H-6′′); 13C NMR (CDCl3) δ 170.9, 170.8, 170.7,
170.4, 155.4, 151.8, 139.0, 138.9, 138.7, 138.3, 137.9, 129.1,
128.94, 128.90, 128.87, 128.71, 128.67, 128.65, 128.28, 128.25,
128.20, 128.13, 128.05, 128.0, 127.7, 118.5, 114.8, 100.4, 99.6,
97.7, 79.6, 75.3, 75.1, 74.6, 74.0, 73.8, 73.8, 73.4, 73.1, 73.0,
71.8, 70.3, 69.7, 68.1, 67.9, 56.1, 50.9, 48.4, 32.3, 23.8, 23.6,
23.1, 21.3, 21.2, 17.2, 14.6; HRMS calcd for C68H78O18N2Na (M
+ Na) 1233.5148, found 1233.5138.
A sample of 33 was conventionally acetylated, which gave
a
1H NMR signal at δ 5.63 (dd, 1 H, J ) 10.6, 8.9 Hz, H-3).
4-Meth oxyp h en yl (2,3-Di-O-a cetyl-4-a zid o-6-O-ben zyl-
4-d eoxy-â-D-ga la ct op yr a n osyl)-(1f4)-2-a cet a m id o-6-O-
ben zyl-2-d eoxy-â-D-glu cop yr a n osid e (34). Compound 33
(758 mg, 0.75 mmol) was dissolved in dry EtOH (34 mL), and
1,2-diaminoethane (0.099 mL, 1.43 mmol) was added.12 The
mixture was heated at 60 °C for 4 h and then co-concentrated
with toluene. The residue was dissolved in MeOH-H2O-Ac2O
(17.0, 3.4, 5.1 mL), and the mixture was stirred for 1 h and
co-concentrated with toluene. The residue was chromato-
graphed (SiO2, 2:1 toluene-acetone) to give 34 (540 mg,
92%): [R]20 -30 (c 0.9 CHCl3); 1H NMR (CDCl3): δ 7.25-
D
7.40 (m, 10 H, Ar), 6.76-6.99 (m, 4 H, OPMP), 5.86 (d, 1 H, J
) 8.1 Hz, NH), 5.32 (d, 1 H, J ) 8.5 Hz, H-1), 5.20 (dd, 1 H, J
) 10.3, 7.9 Hz, H-2′), 5.03 (dd, 1 H, J ) 10.2, 3.9 Hz, H-3′),
4.63, 4.48 (ABq, 1 H each, J ) 12.1 Hz, OBn), 4.57, 4.49 (ABq,
1 H, each, J ) 11.9 Hz, OBn), 4.51 (d, 1 H, J ) 7.8 Hz, H-1′),
4.16 (bt, 1 H, J ) 8.0 Hz, H-3), 4.09 (broad s, 1 H, OH), 3.84
(broad s, 1 H, H-4′), 3.77 (s, 3 H, OMe), 3.50-3.80 m, 8 H,
4-Meth oxyp h en yl (4-Azid o-6-O-ben zyl-4-d eoxy-â-D-ga -
la ct op yr a n osyl)-(1f4)-[2,3,4-t r i-O-b en zyl-r-L-fu cop yr a -
n osyl]-(1f3)-(2-a cet a m id o-6-O-b en zyl-2-d eoxy-â-D-glu -
cop yr a n osid e) (37). Compound 35 (50 mg, 0.04 mmol) was
dissolved in MeONa-MeOH (3 mL, 0.05 M), and the mixture
was stirred for 30 min and then neutralized with Amberlite
IR 120 H+ resin. The mixture was filtered and concentrated,
and the residue was chromatographed (SiO2, 2:1 toluene-
H-2,4,5,6,5′,6′), 2.13, 2.02, 2.01, (s, 3 H each, OAc, NHAc); 13
C
NMR (CDCl3): δ 170.9, 170.5, 169.6, 155.8, 151.8, 138.5, 137.7,
129.0, 128.8, 128.54, 128.46, 128.2, 119.0, 114.9, 101.6, 99.8,
81.6, 74.5, 74.2, 73.9, 73.2, 72.3, 71.7, 69.8, 68.6, 60.3, 57.5,
56.1, 24.1, 21.1, 20.9; HRMS calcd for C39H46O13N4Na (M +
Na) 801.2959, found 801.2960.
4-Meth oxyp h en yl (2,3-Di-O-a cetyl-4-a zid o-6-O-ben zyl-
4-d eoxy-â-D-ga la ctop yr a n osyl)-(1f4)-[2,3,4-tr i-O-ben zyl-
r-L-fu cop yr a n osyl]-(1f3)-(2-a ce t a m id o-6-O-b e n zyl-2-
d eoxy-â-D-glu cop yr a n osid e) (35). Ethylthio 2,3,4-tri-O-
benzyl-R-L-fucopyranoside16 (18, 172 mg, 0.36 mmol) was
dissolved in dry CH2Cl2 (1.44 mL), and a solution of distilled
Br2 (0.020 mL) in CH2Cl2 (0.20 mL) was added. The mixture
was stirred for 15 min, and cyclohexene was added until the
color of Br2 disappeared. The solvents were evaporated, and
the residue was dissolved in dry CH2Cl2 (1.44 mL). The fucosyl
bromide solution was added to a mixture of 34 (143 mg, 0.18
mmol), molecular sieves (580 mg, 4 Å), Bu4NBr (110 mg), and
5:3 CH2Cl2-DMF (1.64 mL). The mixture was stirred for 3 d,
pyridine (1.64 mL) was added, and the stirring was continued
for 3 h. The mixture was filtered through Celite and co-
concentrated with toluene. The residue was chromatographed
acetone) to give 37 (44 mg, 96%): [R]20 -67 (c 1.1, CHCl3);
D
1H NMR (CHCl3) δ 7.25-7.45 (m, 25 H, Ar), 6.75-6.95 (m, 4
H, OPMP), 6.05 (d, 1 H, J ) 7.2 Hz, NH), 5.29 (d, 1 H, J ) 7.6
Hz, H-1), 5.13 (d, 1 H, J ) 3.6 Hz, H-1′′), 4.97, 4.64 (ABq, 1 H
each, J ) 11.6 Hz, OBn), 4.93, 4.64 (ABq, 1 H each, J ) 11.7
Hz, OBn), 4.77, 4.73 (ABq, 1 H each, J ) 11.6 Hz, OBn), 4.61,
4.49 (ABq, 1 H each, J ) 12.0 Hz, OBn), 4.48, 4.44 (ABq, 1 H
each, J ) 11.9 Hz, OBn), 4.47 (d, 1 H, J ) 7.5 Hz, H-1′), 4.29-
4.35 (m, 2 H, H-3,5′′), 4.26 (broad s, 1 H, OH), 4.12 (dd, 1 H,
J ) 10.3, 3.7 Hz, H-2′′), 4.02 (t, 1 H, J ) 8.7 Hz, H-4), 3.96 (d,
1 H, J ) 3.4 Hz, H-4′), 3.95 (dd, 1 H, J ) 10.2, 3.4 Hz, H-3′′),
3.87 (dd, 1 H, J ) 11.4, 3.9 Hz, H-6′), 3.82 (dd, 1 H, J ) 11.1,
2.4 Hz, H-6′), 3.75 (s, 3 H, OMe), 3.72 (broad s, 1 H, H-4), 3.55-
3.67 (m, 6 H, H-5, 3′,5′,2,6), 3.50 (bt, 1 H, J ) 4.5 Hz, H-2′),
2.97 (d, 1 H, J ) 2.1 Hz, OH), 1.14 (d, 3 H, J ) 6.5 Hz, H-6′′);
13C NMR (CDCl3) δ 171.2, 155.8, 151.8, 138.9, 138.8, 138.4,
138.0, 129.1, 128.9, 128.8, 128.7, 128.5, 128.4, 128.3, 128.13,
128.09, 128.08, 127.7, 119.4, 114.8, 101.4, 99.9, 98.2, 80.1, 76.1,
75.4, 75.1, 75.0, 74.7, 74.1, 73.9, 73.8, 72.8, 72.6, 72.2, 69.2,
68.5, 67.5, 61.5, 57.8, 56.1, 23.7, 17.3; HRMS calcd for
(SiO2, 1:1 heptane-EtOAc) to give 35 (200 mg, 93%): [R]20
D
-71 (c 1.2 CHCl3); 1H NMR (CDCl3) δ 7.17-7.40 (m, 25 h, Ar),
6.72-6.91 (m, 4 H, OPMP), 6.05 (d, 1 H, J ) 8.1 Hz, NH),
5.37 (d, 1 H, J ) 5.2 Hz, H-1), 5.13 (dd, 1 H, J ) 10.3, 8.1 Hz,
H-2′), 5.11 (d, 1 H, J ) 3.9 Hz, H-1′′), 4.99 (dd, 1 H, J ) 10.3,
3.8 Hz, H-3′), 4.97, 4.67 (ABq, 1 H each, J ) 11.5 Hz, OBn),
4.85, 4.75 (ABq, 1 H each, J ) 11.6 Hz, OBn), 4.80, 4.71 (ABq,
1 H each, J ) 11 0.7 Hz, OBn), 4.42-4.47 (m, 4 H, H-1′, OBn),
4.32 (ABq, 1 H, J ) 11.9 Hz, OBn), 4.10-4.20 (m, 4 H,
C
62H70O15N4Na (M + Na) 1133.4736, found 1133.4745.
4-Meth oxyp h en yl [Meth yl (5-a ceta m id o-4,7,8,9-tetr a -
O-acetyl-3,5-dideoxy-3-(ph en ylth io)-D-glycer o-r-D-galacto-
2-n on u lop yr a n osyl)on a t e]-(1f3)-(4-a zid o-6-O-b en zyl-4-
d eoxy-â-D-ga la ctop yr a n osyl)-(1f4)-[2,3,4-tr i-O-ben zyl-r-

9336 J . Org. Chem., Vol. 63, No. 25, 1998
Ellervik et al.
L-fu copyr an osyl]-(1f3)-(2-acetam ido-6-O-ben zyl-2-deoxy-
â-D-glu cop yr a n osid e) (39). To a mixture of 37 (400 mg,
0.360 mmol), 3823 (459 mg, 0.713 mmol), and molecular sieves
(1.6 g, 3 Å) were added dry CH2Cl2 (0.92 mL) and freshly
distilled MeCN (8.0 mL). The mixture was stirred under Ar
for 5 min at ∼22 °C and for 5 min at -45 °C. A solution of
silver trifluoromethanesulfonate (200 mg, 0.78 mmol) in MeCN
(2.0 mL) was added, and after 5 min, a 4 M solution of
methylsulfenyl bromide15 in 1,2-dichloroethane (0.182 mL) was
added during 20 min. The mixture was stirred for 1.5 h at
-45 °C, and then diisopropylamine (2.10 mL) was added. The
mixture was stirred for 1 h at -45 °C and filtered through a
short column (SiO2, 1:1 toluene-acetone). The crude product
was chromatographed (SiO2, 4:1 f 2:1 toluene-acetone) to
stirred for 4 h, filtered through Celite, and co-concentrated
with toluene. The residue was dissolved in MeOH (15 mL),
and MeONa-MeOH (1 M) was added until the pH reached 9.
The mixture was stirred for 1 h, neutralized with AcOH, and
concentrated. The residue was chromatographed (SiO2, 2:1
toluene-acetone) to give 40 (78 mg, 52%): [R]20 -51 (c 1.0,
D
CHCl3); 1H NMR (CDCl3) δ 7.25-7.40 (m, 25 H, Ar), 6.85 (bs,
1 H, NH′), 6.75-6.95 (m, 4 H, OPMP), 6.10 (d, 1 H, J ) 6.9
Hz, NH), 5.43 (d, 1 H, J ) 7.4 Hz, H-1), 5.14 (d, 1 H, J ) 3.5
Hz, H-1′′), 4.95, 4.60 (ABq, 1 H each, J ) 11.2 Hz, OBn), 4.93,
4.67 (ABq, 1 H each, J ) 11.7 Hz, OBn), 4.81, 4.75 (ABq, 1 H
each, J ) 11.6 Hz, OBn), 4.63, 4.47 (ABq, 1 H each, J ) 12.0
Hz, OBn), 4.51 (s, 2 H, OBn), 4.43 (d, 1 H, J ) 8.3 Hz, H-1′),
4.42 (t, 1 H, J ) 8.6 Hz, H-3), 4.32, 4.17 (ABq, 1 H each, J )
16.8 Hz, OCH2CO), 4.29 (t, 1 H, J ) 7.4 Hz, H-5′′), 4.06-4.13
(m, 3 H, H-4,4′,2′′), 4.00 (dd, 1 H, J ) 10.5, 2.9 Hz, H-4′′), 3.50-
3.85 (m, 9 H, H-2,3,5,6,2′,5′,6′), 3.77 (s, 3 H, OMe), 3.14, (dd,
1 H, J ) 10.1, 2.7 Hz, H-3′), 2.45 (b s, 1 H, OH), 1.73 (s, 3 H,
NHAc), 1.10 (d, 3 H, J ) 6.5 Hz, H-6′′); 13C NMR (CDCl3) δ
170.8, 168.9, 155.7, 151.7, 139.2, 139.1, 139.0, 138.3, 138.0,
129.00, 128.98, 128.9, 128.8, 128.68, 128.65, 128.5, 128.4,
128.3, 128.2, 128.0, 99.4, 99.1, 97.6, 80.0, 77.1, 76.9, 76.1, 75.4,
75.0, 74.9, 74.4, 74.0, 73.9, 72.8, 69.2, 68.8, 68.4, 67.3, 66.5,
57.4, 56.1, 52.2, 23.7, 17.4; HRMS calcd for C64H72O16N2Na (M
+ Na) 1147.4780, found 1147.4778.
give 39 (446 mg, 73%): [R]20 -34 (c 0.9 CHCl3); 1H NMR
D
(CDCl3) δ 7.20-7.50 (m, 30 H, Ar), 6.73-6.95 (m, 4 H, OPMP),
5.94 (d, 1 H, J ) 7.8 Hz, NH), 5.46-5.53 (m, 2 H, H-4′′′, NH′′′),
5.39 (d, 1 H, J ) 6.9 Hz, H-1), 5.36 (ddd, 1 H, J ) 8.8, 5.9, 2.8
Hz, H-8′′′), 5.26 (dd, 1 H, J ) 8.8, 1.5 Hz, H-7′′′), 5.15 (d, 1 H,
J ) 3.7 Hz, H-1′′), 4.97, 4.65 (ABq, 1 H each, J ) 11.6 Hz,
OBn), 4.90, 4.72 (ABq, 1 H each, J ) 11.9 Hz, OBn), 4.76, 4.73
(ABq, 1 H each, J ) 11.5 Hz, OBn), 4.57 (d, 1 H, J ) 7.6 Hz,
H-1′), 4.42-4.53 (m, 4 H, OBn), 4.38 (dd, 1 H, J ) 9.4, 3.8 Hz,
H-3′), 4.28-4.35 (m, 3 H, H-3,4′,6′′′), 3.90-4.22 (m, 8 H,
H-4,6,2′′,3′′,5′′′,9′′′), 3.87 (s, 3 H, OMe′′′), 3.75 (s, 3 H, OMe),
3.60-3.72 (m, H-2,5,5′,6′,4′′), 3.52 (t, 1 H, J ) 8.5 Hz, H-2′),
3.47 (d, 1 H, J ) 11.0 Hz, H-3′′′), 3.07 (broad s, 1 H, OH), 2.08,
1.94 (s, 6 H each, OAc), 1.90, 1.72 (s, 3 H each, NHAc), 1.14
(d, 3 H, J ) 6.4 Hz, H-6′′); 13C NMR (CDCl3) δ 171.4, 170.8,
170.7, 170.4, 169.9, 167.8 (J C-1′′′:H-3′′′ax 6.1 Hz, C-1′′′),21 155.6,
151.9, 139.3, 139.2, 139.1, 138.9, 138.1, 135.5, 132.0, 129.4,
129.0, 128.91, 128.85, 128.7, 128.6, 128.4, 128.3, 128.2, 128.1,
128.0, 127.9, 127.8, 127.73, 127.65, 119.2, 114.8, 102.2, 100.8,
99.5, 98.0, 80.3, 75.3, 74.6, 74.4, 74.3, 73.8, 73.5, 73.3, 73.1,
72.9, 71.6, 71.0, 69.1, 68.6, 67.14, 67.08, 62.54, 62.46, 57.7, 56.0,
53.4, 50.3, 30.1, 23.8, 23.6, 21.3, 21.1, 21.0, 17.1; HRMS calcd
for C88H101O27N5SNa (M + Na) 1714.6302, found 1714.6273.
A sample of 40 was conventionally acetylated, which gave
a
1H NMR signal at δ 5.43 (bs, 1 H, H-4′).
4-Meth ylp h en yl 4,6-O-Ben zylid en e-3-O-(m eth oxyeth -
an oyl)-1-th io-â-D-glu copyr an oside (41). Compound 26 (3.80
g, 10.09 mmol) and Bu2SnO (2.89 g, 11.6 mmol) were dissolved
in MeOH (120 mL). The mixture was refluxed for 75 min and
then co-concentrated with toluene. The residue was dissolved
in toluene (40 mL), and tert-butyl bromoacetate (5.95 mL, 40.4
mmol), Bu4NBr (3.41 g, 10.6 mmol), and molecular sieves (500
mg, 3 Å, activated) were added. The mixture was refluxed
for 3 h, filtered, and concentrated. The residue was dissolved
in MeONa-MeOH (120 mL, 0.05 M), and the mixture was
stirred for 1 h and neutralized with Amberlite IR 120 H+. The
mixture was filtered and concentrated, and the residue was
chromatographed (SiO2, 40:1 f 20:1 toluene-acetone) to give
A sample of 39 was conventionally acetylated: [R]20 -18
D
(c 0.9, CHCl3); 1H NMR (CDCl3) δ 7.15-7.55 (m, 30 H, Ar),
6.70-6.92 (m, 4 H, OPMP), 6.17 (d, 1 H, J ) 8.1 Hz, NH),
5.47 (dt, 1 H, J ) 6.2, 3.1 Hz, H-8′′′), 5.39 (dd, 1 H, J ) 8.9,
2.6 Hz, H-7′′′), 5.37 (d, 1 H, J ) 5.5 Hz, H-1), 5.31 (dd, 1 H, J
) 11.4, 10.1 Hz, H-4′′′), 5.24 (d, 1 H, J ) 10.4 Hz, NH′′′), 5.14
(d, 1 H, J ) 3.9 Hz, H-1′′), 5.12 (dd, 1 H, J ) 9.9, 8.0 Hz, H-2′),
4.85 (dd, 1 H, J ) 10.1, 3.9 Hz, H-3′), 4.93, 4.63 (ABq, 1 H
each, J ) 11.8 Hz, OBn), 4.83, 4.78 (ABq, 1 H each, J ) 11.9
Hz, OBn), 4.77, 4.69 (ABq, 1 H each, J ) 12.0 Hz, OBn), 4.66
(d, 1 H, J ) 7.8 Hz, H-1′), 4.40, 4.29 (ABq, 1 H each, J ) 12.0
Hz, OBn), 4.35 (dd, 1 H, J ) 8.0, 2.6 Hz, H-9′′′), 4.19 (t, 1 H,
J ) 6.1 Hz, H-3), 3.60-4.15 (m, 15 H, H-2,4,5,6,4′,5′,6′,2′′,3′′,-
4′′,5′′,6′′′, 3.83 (s, 3 H, OMe), 3.75 (s, 3 H, OMe), 3.15 (d, 1 H,
J ) 11.3 Hz, H-3′′′), 2.17, 2.07, 2.06, 2.00, 1.95, 1.90, 1.86 (s,
3 H each, OAc, NHAc), 1.09 (d, 3 H, J ) 6.5 Hz, H-6′′); 13C
NMR (CDCl3) δ 171.5, 171.0, 170.8, 170.7, 170.4, 170.3, 170.1,
168.2, 155.3, 151.7, 139.34, 139.28, 139.0, 138.7, 138.2, 137.0,
132.1, 129.5, 128.9, 128.83, 128.81, 128.61, 128.59, 128.4,
128.3, 128.0, 127.93, 127.87, 127.8, 127.7, 127.6, 118.7, 114.8,
99.9, 99.5, 98.8, 97.4, 79.7, 76.8, 75.2, 74.6, 73.9, 73.7, 73.6,
73.5, 73.22, 73.15, 73.1, 72.9, 72.5, 71.5, 71.0, 69.9, 68.6, 68.3,
67.3, 62.5, 62.1, 59.5, 56.1, 53.5, 50.5, 23.61, 23.56, 21.6, 21.4,
21.3, 21.1, 16.9; HRMS calcd for C90H103O28N5SNa (M + Na)
1756.6408, found 1756.6387.
41 (3.23 g, 72%). A sample was crystallized from heptane-
1
EtOAc: [R]20 -11 (c 1.1, CHCl3); mp 122-124 °C; H NMR
D
(CDCl3) δ 7.10-7.50 (m, 9 H, Ar), 5.53 (s, 1 H, ArCH), 4.61
(m, 1 H, virtual coupling as in entry 19 in ref 26, H-1), 4.44,
4.37 (ABq, 1 H each, J ) 16.8 Hz, OCH2CO), 4.38 (d, 1 H, J )
5.5 Hz, H-6), 3.79 (t, 1 H, J ) 10.2 Hz, H-6), 3.73 (s, 3 H, OMe),
3.60-3.65 (m, 1 H, H-4), 3.55 (q, 1 H, J ) 8.3 Hz, H-3), 3.54
(d, 1 H, J ) 9.4 Hz, H-2), 3.46 (dt, 1 H, J ) 9.9, 5.0 Hz, H-5),
2.36 (s, 3 H, Me); 13C NMR (CDCl3) δ 173.3, 139.0, 137.5, 134.4,
130.1, 129.6, 129.5, 128.8, 128.7, 128.1, 126.4, 101.8, 88.9, 84.6,
81.3, 71.7, 70.8, 69.3, 69.0, 52.7, 21.6; HRMS calcd for
C
23H26O7SNa (M + Na) 469.1297, found 469.1296.
4-Meth ylph en yl2-O-Acetyl-4,6-O-ben zyliden e-3-O-(m eth -
oxyeth a n oyl)-1-th io-â-D-glu cop yr a n osid e (42). Compound
41 (1.95 g, 14.4 mmol) was dissolved in pyridine (80 mL), and
Ac2O (65 mL) was added dropwise, followed by (dimethylami-
no)pyridine (DMAP, 20 mg). The mixture was stirred for 40
min and co-concentrated with toluene. The residue was
chromatographed (SiO2, 40:1 toluene-acetone) to give 42 (2.09
g, 98%). A sample was crystallized from heptane-EtOAc:
[R]20 -11 (c 1.1, CHCl3); mp 147.5-148 °C; 1H NMR (CDCl3)
D
δ 7.13-7.46 (m, 9 H, Ar), 5.52 (s, 1 H, ArCH), 4.99 (dd, 1 H, J
) 10.1, 8.5 Hz, H-2), 4.70 (d, 1 H, J ) 10.1 Hz, H-1), 4.38 (dd,
1 H, J ) 10.5, 5.0 Hz, H-6), 4.37, 4.31 (ABq, 1 H each, J )
16.8 Hz, OCH2CO), 3.69-3.82 (m, 3 H, H-3,4,6), 3.61 (s, 3 H,
OMe), 3.44-3.51 (m, 1 H, H-5), 2.36 (s, 3 H, Me), 2.22 (s, 3 H,
OAc); 13C NMR (CDCl3) δ 170.04, 170.00, 139.1, 137.3, 134.2,
130.2, 129.6, 128.7, 128.3, 126.5, 101.7, 87.1, 81.7, 71.1, 70.5,
69.4, 69.0, 52.0, 21.6, 21.5; HRMS calcd for C25H28O8SNa (M
+ Na) 511.1403, found 511.1407.
4-Met h oxyp h en yl (2-Am in o-6-O-b en zyl-2-d eoxy-2,3-
N,O-(2-oxoeth yliden e)-â-D-galactopyr an osyl)-(1f4)-[2,3,4-
tr i-O-ben zyl-r-L-fu cop yr a n osyl]-(1f3)-(2-a ceta m id o-6-O-
ben zyl-2-d eoxy-â-D-glu cop yr a n osid e) (40). Compound 21
(167 mg, 0.13 mmol) was dissolved in toluene (2.0 mL) and
Bu2SnO (42 mg, 0.17 mmol), and molecular sieves (85 mg, 4
Å, activated) were added. The mixture was stirred at 80 °C
for 8 h, then Bu4NBr (50 mg, 0.16 mmol) and tert-butyl
bromoacetate (0.2 mL, 1.35 mmol) were added. The stirring
was continued at 80 °C for 4 h, and the mixture was filtered
through a short column (SiO2, 1:1 toluene-acetone plus 1%
Et3N). The crude product was dissolved in AcOH (15 mL),
activated zinc dust (2.0 g) was added, and the mixture was
4-Meth ylp h en yl 2-O-Acetyl-6-O-ben zyl-3-O-(m eth oxy-
eth a n oyl)-1-th io-â-D-glu cop yr a n osid e (43). Compound 42
(2.91 g, 6.0 mmol) was dissolved in THF (60 mL), and the
mixture was cooled to 0 °C. NaBH3CN (3.75 g, 60 mmol) and
molecular sieves (4.5 g, 4 Å) were added. Et2O (nondried)

Analogs of Sialyl Lewis x Tetrasaccharide
J . Org. Chem., Vol. 63, No. 25, 1998 9337
saturated with HCl (g) was added to the reaction mixture until
the pH (moist litmus paper) was approximately 2. The
mixture was stirred at 0 °C for 1.5 h, diluted with Et2O, and
filtered through Celite. The mixture was washed with satu-
rated aqueous NaHCO3 solution and H2O, dried (Na2SO4), and
concentrated. The residue was chromatographed (SiO2, 40:1
f 20:1 toluene-acetone) to give 43 (2.35 g, 80%). A sample
heated at 60 °C for 15 h and then co-concentrated with toluene.
The residue was dissolved in MeOH-H2O-Ac2O (8.5, 1.7, 2.6
mL), and the mixture was stirred for 1 h and then co-
concentrated with toluene. The residue was chromatographed
(SiO2, 4:1 toluene-acetone) to give 46 (161 mg, 70%): [R]20
D
1
-24 (c 0.9, CHCl3); H NMR (CDCl3) δ 7.25-7.40 (m, 10 H,
Ar), 6.75-6.97 (m, 4 H, OPMP), 5.69 (d, 1 H, J ) 8.1 Hz, NH),
5.21 (d, 1 H, J ) 8.0 Hz, H-1), 5.17 (dd, 1 H, J ) 9.9, 8.1 Hz,
H-2′), 4.67, 4.49 (ABq, 1 H each, J ) 12.0 Hz, OBn), 4.59, 4.53
(ABq, 1 H each, J ) 11.9 Hz, OBn), 4.37 (d, 1 H, J ) 8.0 Hz,
H-1′), 4.29, 4.17 (ABq, 1 H, J ) 17.1 Hz, OCH2CO), 4.26 (d, 1
H, J ) 3.5 Hz, H-4′), 4.03 (b dd, 1 H, J ) 9.2, 7.9 Hz, H-3),
3.57-3.77 (m, 10 H, H-2,4,5,6,3′,4′,5′,6′), 3.78 (s, 3 H, OMe),
3.76 (s, 3 H, OMe), 2.07, 2.00 (s, 3 H each, OAc, NHAc); 13C
NMR (CDCl3) δ 170.9, 169.7, 155.7, 151.8, 138.7, 137.7, 129.0,
128.8, 128.5, 128.4, 128.2, 128.1, 119.0, 114.9, 101.7, 100.1,
81.4, 81.3, 74.6, 74.2, 74.0, 72.5, 72.0, 71.5, 68.7, 68.4, 60.3,
57.0, 56.1, 52.5, 24.1, 21.3; HRMS calcd for C40H48O14N4Na (M
+ Na) 831.3065, found 831.3073.
was crystallized from heptane-EtOAc: [R]20 -49 (c 0.9,
D
1
CHCl3); mp 100-100.5 °C; H NMR (CDCl3) δ 7.00-7.45 (m,
9 H, Ar), 4.96 (dd, 1 H, J ) 10.0, 9.1 Hz, H-2), 4.60 (s, 2 H,
OBn), 4.57 (d, 1 H, J ) 10.0 Hz, H-1), 4.40, 4.14 (ABq, 1 H
each, J ) 17.6 Hz, OCH2CO), 3.92 (dd, 1 H, J ) 10.7, 2.3 Hz,
H-6), 3.79 (s, 3 H, OMe), 3.74 (dd, 1 H, J ) 10.8, 6.1 Hz, H-6),
3.64 (t, 1 H, J ) 8.9 Hz, H-4), 3.52 (dt, 1 H, J ) 7.9, 2.5 Hz,
H-5), 3.40 (t, 1 H, J ) 9.0 Hz, H-3), 2.31 (s, 3 H, Me), 2.18 (s,
3 H, OAc); 13C NMR (CDCl3) δ 173.5, 169.8, 138.8, 138.5, 133.2,
130.1, 129.5, 128.1, 128.0, 87.4, 86.6, 80.1, 74.0, 72.3, 70.3, 70.0,
68.8, 52.9, 21.6, 21.5; HRMS calcd for C25H30O8SNa (M + Na)
513.1559, found 513.1567.
4-Meth ylph en yl 2-O-Acetyl-4-azido-6-O-ben zyl-4-deoxy-
3-O-(m eth oxyeth an oyl)-1-th io-â-D-galactopyr an oside (44).
Compound 43 (2.15 g, 4.4 mmol) was dissolved in CH2Cl2 (21
mL), and the mixture was cooled to 0 °C. Pyridine (1.48 mL)
and trifluoromethansulfonic anhydride (1.37 mL, 9.9 mmol)
were added. The temperature was increased to ∼22 °C, and
the solution was stirred for 3 h and then diluted with CH2Cl2.
The organic phase was washed with saturated aqueous
NaHCO3 solution, dried (Na2SO4), concentrated, and dried
under vacuum. The residue was dissolved in DMF (9 mL),
and NaN3 (1.65 g, 25.4 mmol) was added. The mixture was
stirred for 15 h and then diluted with CH2Cl2, filtered through
a short column (SiO2, 1:1 heptane-EtOAc), and then chro-
matographed (SiO2, 3:1 heptane-EtOAc), to give 44 (1.76 g,
4-Met h oxyp h en yl (2-O-Acet yl-4-a zid o-6-O-b en zyl-4-
d e oxy-3-O-(m e t h oxye t h a n oyl)-â-D-ga la ct op yr a n osyl)-
(1f4)-[2,3,4-tr i-O-ben zyl-R-L-fu cop yr a n osyl]-(1f3)-(2-a c-
eta m id o-6-O-ben zyl-2-d eoxy-â-D-glu cop yr a n osid e) (47).
Ethyl 2,3,4-tri-O-benzyl-1-thio-R-L-fucopyranoside16 (18, 171
mg, 0.36 mmol) was dissolved in dry CH2Cl2 (2.0 mL), and a
solution of freshly distilled Br2 (0.050 mL) in CH2Cl2 (0.450
mL) was added. The mixture was stirred for 15 min, and
cyclohexene was added until the color of Br2 disappeared. The
solvent was evaporated, the residue was dissolved in dry CH2-
Cl2 (2.16 mL), and the solution was then added to a mixture
of 46 (126 mg, 0.15 mmol), molecular sieves (850 mg, 4 Å),
and Bu4NBr (126 mg, 0.39 mmol) in CH2Cl2-DMF (5:3, 2.16
mL). The mixture was stirred for 3 d, pyridine (1.2 mL) was
added, and the stirring was continued for 3 h. The mixture
was filtered through Celite and co-concentrated with toluene.
75%): [R]20 -28 (c 1.0, CHCl3); mp 92.5-93 °C; 1H NMR
D
(CDCl3) δ 7.07-7.40 (m, 9 H, Ar), 5.20 (t, 1 H, J ) 9.7 Hz,
H-2), 4.58, 4.55 (ABq, 1 H each, J ) 12.1 Hz, OBn), 4.52 (d, 1
H, J ) 10.0 Hz, H-1), 4.32 (d, 1 H, J ) 3.6 Hz, H-4), 4.30, 4.20
(ABq, 1 H each, J ) 16.9 Hz, OCH2CO), 3.76 (s, 3 H, OMe),
3.65-3.74 (m, 4 H, H-3,5,6), 2.33 (s, 3 H, Me), 2.17 (s, 3 H,
OAc); 13C NMR (CDCl3) δ 170.9, 169.9, 138.5, 138.1, 133.2,
130.1, 129.5, 128.9, 128.4, 87.4, 82.3, 76.4, 74.2, 70.1, 69.1, 68.2,
60.8, 52.4, 21.6, 21.5; HRMS calcd for C25H29O7N3SNa (M +
Na) 538.1624, found 538.1644.
The residue was chromatographed (SiO2, 1:1 heptane-EtOAc)
1
to give 47 (181 mg, 82%): [R]20 -57 (c 0.9, CHCl3); H NMR
D
(CDCl3) δ 7.15-7.40 (m, 25 H, Ar), 6.72-6-91 (m, 4 H,
OPMP), 6.15 (d, 1 H, J ) 7.8 Hz, NH), 5.34 (d, 1 H, J ) 4.7
Hz, H-1), 5.13 (d, 1 H, J ) 3.6 Hz, H-1′′), 5.10 (dd, 1 H, J )
9.7, 7.9 Hz, H-2′), 4.96, 4.65 (ABq, 1 H each, J ) 11.6 Hz, OBn),
4.83, 4.71 (ABq, 1 H each, J ) 11.9 Hz, OBn), 4.79, 4.70 (ABq,
1 H each, J ) 12.0 Hz, OBn), 4.50 (s, 2 H, OBn), 4.39, 4.28
(ABq, 1 H each, J ) 12.0 Hz, OBn), 4.36 (d, 1 H, J ) 8.2 Hz,
H-1′), 4.31 (s, 1 H, H-4′), 4.30, 4.18 (ABq, 1 H each, J ) 16.8
Hz, OCH2CO), 3.50-4.10 (m, 15 H, H-2,3,4,5,6,3′,4′,5′,6′,2′′,3′′,-
4′′,5′′), 3.79 (s, 3 H OMe), 3.75 (s, 3 H, OMe), 2.06 (s, 3 H,
4-Met h oxyp h en yl [2-O-Acet yl-4-a zid o-6-O-b en zyl-4-
d eoxy-3-O-(m et h oxy et h a n oyl)-â-D-ga la ct op yr a n osyl]-
(1f4)-[2-d eoxy-6-O-ben zyl-2-(tetr a ch lor op h th a lim id o)-â-
D-glu cop yr a n osid e] (45). To a solution of 44 (806 mg, 1.52
mmol) and 151 (651 mg, 1.01 mmol) in CH2Cl2 (7.8 mL) at -78
°C under Ar was added a solution of AgOTf (670 mg, 3.03
mmol) in MeCN (4.1 mL). After 5 min, a 4 M solution of
methylsulfenyl bromide15 in 1,2-dichloroethane (0.635 mL) was
added during 30 min, the mixture was stirred for 1.5 h, and
then isopropylamine (0.65 mL) was added. The mixture was
stirred at -78 °C for 1.5 h, filtered through a short column
(SiO2, 1:1 heptane-EtOAc), and concentrated. The residue
OAc), 1.86 (s, 3 H, NHAc), 1.06 (d, 3 H, J ) 6.4 Hz, H-6′′); 13
C
NMR (CDCl3) δ 170.9, 170.7, 170.1, 155.3, 151.7, 139.3, 139.2,
139.0, 138.5, 137.9, 129.0, 128.9, 128.82, 128.77, 128.6, 128.5,
128.4, 128.3, 128.1, 128.02, 127.99, 127.9, 127.7, 118.6, 114.8,
99.8, 98.9, 97.4, 80.9, 79.7, 76.8, 75.2, 74.6, 74.1, 73.7, 73.6,
73.4, 73.1, 72.8, 72.2, 71.8, 69.6, 68.5, 68.3, 67.3, 60.7, 56.1,
52.5, 23.6, 21.4, 16.9; HRMS calcd for C67H76O18N4Na (M +
Na) 1247.5053, found 1247.5045.
was chromatographed (SiO2, 30:1 toluene-acetone) to give 45
4-Met h oxyp h en yl (2-O-Acet yl-4-a m in o-6-O-b en zyl-4-
d eoxy-4,3-N,O-(2-oxoeth ylid en e)-â-D-ga la ctop yr a n osyl)-
(1f4)-[2,3,4-tr i-O-ben zyl-r-L-fu cop yr a n osyl]-(1f3)-(2-a c-
eta m id o-6-O-ben zyl-2-d eoxy-â-D-glu cop yr a n osid e) (48).
H2S(g) was bubbled through a solution of 47 (177 mg, 0.14
mmol) in pyridine-Et3N-MeOH (8.0, 4.0, 4.0 mL) at 0 °C for
1 h. The mixture was kept under H2S at room temperature
for 15 h. Residual H2S was removed by a stream of N2 for 1
h, and the mixture was co-concentrated with toluene. The
residue was chromatographed (SiO2, 4:1 toluene-acetone) to
1
(715 mg, 67%): [R]20 -6 (c 1.0, CHCl3); H NMR (CDCl3) δ
D
7.15-7.35 (m, 10, Ar), 6.70-6.90 (m, 4 H, OPMP), 5.63 (d, 1
H, J ) 8.4 Hz, H-1), 5.21 (dd, 1 H, J ) 9.9, 8.0 Hz, H-2), 4.70
(ABq, 1 H, J ) 12.0 Hz, OBn), 4.38-4.55 (m, 6 H, H-2,3,4′,-
OBn), 4.43 (d, 1 H, J ) 8.0 Hz, H-1′), 4.32, 4.17 (ABq, 1 H
each, J ) 16.9 Hz, OCH2CO), 4.26 (d, 1 H, J ) 3.1 Hz, H-4′),
3.60-3.75 (m, 8 H, H-4,5,6,3′,5′,6′), 3.77 (s, 3 H, OMe), 3.73
(s, 3 H, OMe), 2.10 (s, 3 H, OAc); 13C NMR (CDCl3) δ 170.9,
169.6, 155.9, 150.9, 140.6, 138.7, 137.6, 128.81, 128.77, 128.20,
128.15, 128.1, 127.9, 118.9, 114.8, 101.8, 97.4, 82.0, 81.4, 74.8,
74.03, 74.00, 72.6, 71.5, 69.9,69.3, 68.5, 68.4, 60.3, 56.8, 56.0,
52.5, 21.4; HRMS calcd for C46H44O15N4Cl4Na (M + Na)
1055.1455, found 1055.1463.
give 48 (165 mg, 98%): [R]20 -48 (c 1.0, CHCl3); 1H NMR
D
(CDCl3): δ 7.20-7.40 (m, 25 H, Ar), 6.75-6.95 (m, 4 H,
OPMP), 6.60 (bs, 1 H, NH), 6.01 (d, 1 H, J ) 8.2 Hz, NH),
5.40 (d, 1 H, J ) 5.6 Hz, H-1), 5.24 (dd, 1 H, J ) 9.9, 7.9 Hz,
H-2′), 5.11 (d, 1 H, J ) 3.4 Hz, H-1′′), 4.95, 4.65 (ABq, 1 H
each, J ) 11.4 Hz, OBn), 4.88, 4.74 (ABq, 1 H each, J ) 11.7
Hz, OBn), 4.76, 4.72 (ABq, 1 H each, J ) 12.0 Hz, OBn), 4.56,
4.43 (ABq, 1 H each, J ) 12.0 Hz, OBn), 4.54 (d, 1 H, J ) 8.1
Hz, H-1′), 4.49, 4.33 (ABq, 1 H each, J ) 11.8 Hz, OBn), 4.38,
4.17 (ABq, 1 H each, J ) 17.8 Hz, OCH2CO), 4.19-4.24 (m, 2
4-Met h oxyp h en yl [2-O-Acet yl-4-a zid o-6-O-b en zyl-4-
d eoxy-3-O-(m et h oxy et h a n oyl)-â-D-ga la ct op yr a n osyl]-
(1f4)-(2-a cet a m id o-6-O-b en zyl-2-d eoxy-â-D-glu cop yr a -
n osid e) (46). Compound 45 (292 mg, 0.28 mmol) was
dissolved in dry EtOH (20 mL), and diaminoethane12 (0.022
mL, 0.33 mmol) was added during 30 min. The mixture was

9338 J . Org. Chem., Vol. 63, No. 25, 1998
Ellervik et al.
H, H-3,5′′), 4.13 (dd, 1 H, J ) 10.0, 3.7 Hz, H-2′′), 4.02 (t, 1 H,
J ) 6.1 Hz, H-4), 3.65-3.95 (m, 10 H, H-2, H-5, 2*H-6, H-3′,
H-4′, H-6′, H-2′′, H-3′′, H-4′′), 3.76 (s, 3 H, OMe), 3.59 (dd, 1
H, J ) 10.2, 6.2 Hz, H-6′), 3.35 (bt, 1 H, J ) 5.5 Hz, H-5′),
2.10 (s, 3 H, OAc), 1.80 (s, 3 H, NHAc), 1.12 (d, 3 H, J ) 6.4
Hz, H-6′′); 13C NMR (CDCl3) δ 170.8, 170.3, 168.6, 155.5, 151.7,
139.2, 138.5, 137.0, 129.2, 128.94, 128.86, 128.79, 128.6,
128.21, 128.17, 128.1, 127.9, 127.7, 118.9, 114.8, 100.2, 99.1,
98.1, 79.8, 78.5, 76.9, 75.5, 74.7, 74.3, 74.1, 73.9, 73.7, 72.9,
72.0, 70.9, 69.4, 68.7, 67.4, 66.5, 62.9, 56.1, 52.4, 23.7, 21.2,
17.0; HRMS calcd for C66H74O17N2Na (M + Na) 1189.4885,
found 1189.4906.
Ack n ow led gm en t. This work was supported by the
Swedish Natural Science Research Council.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
all title compounds described in the Experimental Section (39
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
J O981204P