Synthesis of double-chain bis-sulfone neoglycolipids of the 2-, 3-, and 6-deoxyglobotrioses

Article abstract of DOI:10.1021/jo951914k

Partially protected 2-(trimethylsilyl)ethyl 2- and 3-deoxyglucosides and 6-deoxylactoside were synthesised via various routes and glycosylated with galabiosyl and galactosyl donors to give the corresponding deoxytrisaccharides. Removal of the protecting g

Full text of DOI:10.1021/jo951914k

J . Org. Chem. 1996, 61, 2383-2393
2383
Syn th esis of Dou ble-Ch a in Bis-Su lfon e Neoglycolip id s of th e 2-, 3-,
a n d 6-Deoxyglobotr ioses
Zhiyuan Zhang and Go¨ran Magnusson*
Organic Chemistry 2, Chemical Center, The Lund Institute of Technology, University of Lund,
P. O. Box 124, S-221 00 Lund, Sweden
Received October 26, 1995X
Partially protected 2-(trimethylsilyl)ethyl 2- and 3-deoxyglucosides and 6-deoxylactoside were
synthesised via various routes and glycosylated with galabiosyl and galactosyl donors to give the
corresponding deoxytrisaccharides. Removal of the protecting groups gave the 2-(trimethylsilyl)-
ethyl 2-, 3-, and 6-deoxyglobotriosides. Transformation of the protected trisaccharides into
trichloroacetimidates, via the corresponding hemiacetals, proceeded in ∼80% overall yield.
Glycosylation of 3-(hexadecylsulfonyl)-2-[(hexadecylsulfonyl)methyl]propanol with the trisaccharidic
trichloroacetimidates, in 72-79% yield, followed by removal of protecting groups, gave the title
neoglycolipids.
In tr od u ction
Resu lts a n d Discu ssion
I. Syn th esis of th e 2- a n d 3-Deoxyglu cosid e Ac-
cep tor s 13 a n d 19. Glycosyl acceptors carrying an
unprotected hydroxyl group in the 4-position are nor-
mally prepared by reductive ring-opening of the corre-
sponding 4,6-O-benzylidene derivative, using sodium
cyanoborohydride in the presence of hydrogen chloride
or trifluoroacetic acid.6 In order to avoid the strongly
acidic conditions that are potentially harmful to glyco-
sides, especially of deoxygenated sugars, we have devel-
oped an alternative method7 based on oxidative cleavage
of 4,6-O-p-methoxybenzylidene acetals under neutral or
slightly acidic conditions. The cleavage is regioselective
and leads preferentially to the corresponding 6-O-p-
methoxybenzoate, leaving HO-4 unprotected for the
ensuing glycosylation. In contrast to the 6-O-benzylated
acceptors obtained by the reductive cleavage route, the
oxidative route gives acylated acceptors, which often
means that the overall synthetic scheme can be shortened
by a hydrogenolysis and an ensuing acylation step. It
seems as if this oxidative cleavage is the first generally
useful route to fully acylated glycosyl acceptors.
2-(Trimethylsilyl)ethyl â-D-glucopyranoside8 was treated
with p-methoxy-R,R-dimethoxytoluene in the presence of
a catalytic amount of p-toluenesulfonic acid to give the
O-p-methoxybenzylidene-protected glycoside 7 (94%).
Partial benzoylation of 7, either directly with benzoyl
chloride or via the stannylene derivative,9 gave easily
separated mixtures of mono and dibenzoylated com-
pounds (8-10) in different ratios (Scheme 1).
The monobenzoates 8 and 9 were treated with thio-
carbonyldiimidazole to give the thiocarbamates10 11
(93%) and 16 (94%). Reductive cleavage of the 2-thio-
carbamoyl group of 11 with tributyltin hydride11 pro-
ceeded in quantitative yields to give the 2-deoxy glucoside
Globotriose (GalR1-4Galâ1-4Glc) is present as glo-
botriosylceramide (GbO3, Pk antigen, CD77; Figure 1) on
the outside of eucaryotic cells, where it plays important
biological roles, as summarized in our previous publica-
tion on the synthesis of deoxyglobotriosides.1
The present publication describes the synthesis of the
final three TMSEt deoxyglobotriosides and the corre-
sponding neoglycolipids, where deoxygenations were
performed in the reducing-end glucose moiety (com-
pounds 1, 3, 5 and 2, 4, 6, respectively, Figure 2). The
corresponding deoxyglobotriose derivatives, where deoxy-
genations were performed in the non-reducing-terminal2
and the central1 galactose moieties, were reported earlier.
The complete set of deoxyglobotriose derivatives consti-
tutes, together with the parent compounds, a valuable
collection of molecular probes useful for identification of
binding epitopes in GbO3-binding proteins. The collection
of deoxytrisaccharides constitutes an addition to the
deoxydisaccharides previously used by us for receptor
mapping of surface adhesive proteins of pathogenic
Escherichia coli and Streptococcus suis bacteria.3
Our bis-sulfone neoglycolipids4 were designed to emu-
late the natural glycosyl ceramides (cf. Figure 1) and
thereby constitute a standardized platform for the syn-
thesis and biological evaluations of receptor-active sac-
charides and their analogs. We have recently shown that
GbO3-bis-sulfone neoglycolipid and its natural counter-
part GbO3-ceramide were equally effective binders of the
bacterial protein verotoxin.5
X Abstract published in Advance ACS Abstracts, March 15, 1996.
(1) Zhang, Z.; Magnusson, G. J . Org. Chem. 1995, 60, 7304-7315.
(2) Zhiyuan, Z.; Magnusson, G. Carbohydr. Res. 1994, 262, 79-101.
(3) (a) Kihlberg, J .; Hultgren, S. J .; Normark, S.; Magnusson, G. J .
Am. Chem. Soc. 1989, 111, 6364-6368. (b) Haataja, S.; Tikkanen, K.;
Nilsson, U.; Magnusson, G.; Karlsson, K.-A.; Finne, J . J . Biol. Chem.
1994, 269, 27466-27472. (c) Magnusson, G.; Hultgren, S. J .; Kihlberg,
J . Methods in Enzymolology; Doyle, R. J .; Ofek, I., Eds.; Academic
Press, San Diego, 1995; Vol. 253, pp 105-114. (d) Striker, R.; Nilsson,
U.; Stonecipher, A.; Magnusson, G.; Hultgren, S.J . Mol. Microbiol.
1995, 16, 1021-1029. (e) Kihlberg, J .; Magnusson, G. Pure Appl.
Chem., in press.
(4) Magnusson, G.; Ahlfors, S.; Dahme´n, J .; J ansson, K.; Nilsson,
U.; Noori, G.; Stenvall, K.; Tjo¨rnebo, A. J . Org. Chem. 1990, 55, 3933-
3946.
(5) Boyd, B.; Magnusson, G.; Zhiuyan, Z.; Lingwood, C. A. Eur. J .
Biochem. 1994, 223, 873-878.
(6) (a) Garegg, P. J .; Hultberg, H.; Wallin, S. Carbohydr. Res. 1982,
108, 97-101. (b) J ohansson, R.; Samuelsson, B. J . Chem. Soc. Perkin
Trans. 1 1984, 2371-2374.
(7) Zhang, Z.; Magnusson, G. J . Org. Chem. 1996, 61, 2394.
(8) J ansson, K.; Ahlfors, S.; Frejd, T.; Kihlberg, J .; Magnusson, G.
J . Org. Chem. 1988, 53, 5629-5647.
(9) (a) David, S.; Hanessian, S. Tetrahedron 1985, 41, 643-663. (b)
Ogawa, T.; Kaburagi, T. Carbohydr. Res. 1982, 103, 53-64.
(10) Rasmussen, J . R.; Slinger, C. J .; Kordish, R. J .; Newman-Evans,
D. D. J . Org. Chem. 1981, 46, 4843-4846.
(11) Barton, D. H. R.; McCombie, S. W. J . Chem. Soc., Perkin Trans.
1 1975, 1574-1585.
0022-3263/96/1961-2383$12.00/0 © 1996 American Chemical Society

2384 J . Org. Chem., Vol. 61, No. 7, 1996
Zhang and Magnusson
F igu r e 1. Structure of globotriosylceramide (GbO3) and its double-chain bis-sulfone mimetic.
ment of the crude mixture with silver nitrate/potassium
fluoride caused the 4-O-p-methoxybenzoyl group to mi-
grate to the 6-position, and the ratio of 19 and 20 changed
to 14:1. Pure glycosyl acceptor 19 was obtained after
chromatography in 85% yield from 17.
II. Syn th esis of th e 6-Deoxyla ctosid e a ccep tor 25.
Since lactose is an integrated part of GbO3, we decided
to investigate the possibility of regioselective function-
alization of the 6-position in the known2 lactoside 21
(Scheme 2). If successful, one glycosylation step and
several protection/deprotection steps would be avoided
en route to 6-deoxy-GbO3 derivatives. Thus, treatment
of 21 with iodine/imidazole/triphenylphosphine13 fur-
nished the 6-deoxyiodolactoside 22 (80%) and hydro-
genolysis of the carbon-iodine bond gave the 6-deoxy-
lactoside 23 (92%). Treatment of 23 with benzoyl chloride
and pyridine/DMAP gave the tetrabenzoate 24 (91%).
Oxidative cleavage of the p-methoxybenzylidene group
of 24 with DDQ essentially as above but with an excess
of acetic acid, gave a mixture of the 6- and 4-p-methoxy-
benzoates 25 and 26 in the ratio 5:1. Pure 6-deoxylac-
toside acceptor 25 was obtained in 83% yield after
chromatography.
F igu r e 2. Structures of the synthetic deoxyglobotriosides.
III. Syn th esis of th e Ga la biosyl Don or s 36-38.
Synthesis of glycosyl donors requires that the anomeric
protecting group is compatible with the methods used in
carbohydrate synthesis and that it can be transformed
into suitable anomeric activating groups. The 2-(trim-
ethylsilyl)ethyl (TMSEt) group fulfills most of these
criteria in that it permits highly yielding and stereose-
lective transformations into the corresponding hemiac-
etal, 1-O-acyl, and chloro sugar.8,14 As an alternative,
we have investigated the p-methoxyphenyl glycosides and
their conversion into various anomerically activated
derivatives. It is known15 that the p-methoxyphenyl
group can be removed by treatment with ceric ammonium
nitrate (CAN). In addition, we have found that p-
methoxyphenyl glycosides can be converted directly into
the corresponding chloro and bromo sugars as well as
thioglycosides.
12. According to TLC analysis, the reduction was equally
efficient with compound 16, but on chromatography of
the reaction product consisting almost exclusively of 17,
the p-methoxybenzylidene group was partly removed to
give 18, probably due to the increased acid sensitivity
introduced by the 3-deoxy function. This problem was
circumvented by the addition of a small amount of
triethylamine to the eluent. Treatment of 18 with
p-methoxy-R,R-dimethoxytoluene as above restored the
desired compound 17 (99%).
Regioselective oxidative cleavage of the p-methoxyben-
zylidene groups of 12 and 17 was performed by treatment
with DDQ. Compound 12 gave a mixture of the 6- and
4-O-p-methoxybenzoates 13 and 14, together with a small
amount of 15 in the ratio 24:10:1, using DDQ and 0.2
equiv of acetic acid. It is known that acyl groups migrate
on treatment with silver fluoride.12 Treatment of 14 with
silver nitrate/potassium fluoride gave a 3:1 mixture of
13 and 14, and the pure glycosyl acceptor 13 was
obtained in 69% yield. Treatment of 17 with DDQ in the
absence of acetic acid gave a mixture of the 6- and 4-O-
p-methoxybenzoates 19 and 20 in the ratio 3:2. Treat-
Galactose â-pentaacetate was treated with p-methox-
yphenol in the presence of boron trifluoride etherate to
(13) Garegg, P. J .; J ohansson, R.; Ortega, C.; Samuelsson, B. J .
Chem. Soc., Perkin Trans. 1 1982, 681-683.
(14) J ansson, K.; Noori, G.; Magnusson, G. J . Org. Chem. 1990, 55,
3181-3185.
(15) (a) Murakata, C.; Ogawa, T. Carbohydr. Res. 1992, 235, 95-
114. (b) J acob, P., III; Callery, P. S.; Shulgin, A. T.; Castagnoli, N., J r.
J . Org. Chem. 1976, 41, 3627-3629. (c) Fukuyama, T., Laird, A. A.,
Hotchkiss, L. M. Tetrahedron Lett. 1985, 26, 6291-6292.
(12) Yasumori, T.; Sato, K.; Hashimoto, H.; Yoshimura, J . Bull.
Chem. Soc. J pn. 1984, 57, 2538-2542.

Synthesis of Double-Chain Bis-Sulfone Neoglycolipids
J . Org. Chem., Vol. 61, No. 7, 1996 2385
Sch em e 1a
a
(a) p-MeOC6H4CH(OMe)2, TsOH, MeCN; (b) BzCl, Et3N, CH2Cl2; (c) Bu2SnO, toluene/benzene, and then BzCl, toluene; (d) (imidaz)2CS,
benzene, reflux; (e) Bu3SnH, AIBN, toluene, reflux; (f) DDQ, AcOH (0.2 equiv), mol sieves (3 Å), toluene, 80 °C; (g) AgNO3, KF, pyridine,
H2O, 100 °C; (h) DDQ, mol sieves (3 Å), toluene, 80 °C, and then AgNO3, KF, pyridine, H2O, 100 °C.
furnish crystalline 2715a in 81% yield (Scheme 3). Deacety-
lation of 27 gave crude 2815a (99%), which was treated
with R,R-dimethoxytoluene and p-toluenesulfonic acid to
give the solid 4,6-O-benzylidene derivative 29, which was
isolated by precipitation. Compound 29 was benzoylated
to give crystalline 30 in 85% yield. Reductive opening6a
of the benzylidene ring of 30 gave the p-methoxyphenyl
glycoside acceptor 31 in 91% yield after chromatography.
In summary, galactose â-pentaacetate was transformed
in five steps into 31 in >60% overall yield and with only
one (the last step) chromatographic purification.
The acceptor 31 was glycosylated with 2,3,4,6-tetra-
O-benzyl-R-D-galactopyranosyl chloride16 in the presence
of silver triflate to give the galabioside 32 (81%). Hy-
drogenolysis of the benzyl groups of 32, followed by
acetylation of the crude material gave the fully acylated
glycoside 34 in 89% overall yield.
Compound 34 was converted into the three galabiose
donors 36, 37, and 38. Treatment of 34 with CAN gave
the hemiacetal 35 (88%), and treatment of the crude
hemiacetal with trichloroacetonitrile gave the trichloro-
acetimidate 36 (91%), suitable17 for use as a galabiosyl
donor. Compound 34 was easily converted in one step
and high stereoselectivity into the thioglycoside 37 (93%)
by treatment with thiophenol and boron trifluoride
etherate. Treatment of 34 with acetyl bromide and a
catalytic amount of zinc bromide gave the galabiosyl
bromide 38 in 93% yield.
the 2-position are quite sensitive to anomerization,
especially in the presence of acids. Initial attempts to
glycosylate acceptor 13 with the trichloroacetimidate 36
or the thio glycoside 37 were essentially unsuccessful
(Scheme 4). With donor 36 and TfOTMS,17 the desired
39 was not formed and most of 36 was converted into
the hemiacetal 35. Changing to silver triflate18 gave 39,
albeit in low yield, partly due to rapid anomerization at
the TMSEt-anomeric center. The sensitivity of 2-deox-
yglycosides to anomerization is further witnessed by the
anomerization of acceptor 13 into 40. Attempted glyco-
sylation of 13 with the thioglycoside donor 37 was also
largely unsuccessful, due to the propensity for anomer-
ization under the glycosylation conditions.
Finally, compound 39 was successfully prepared by
glycosylation of 13 with the galabiosyl bromide 38 with
silver silicate19 as promoter in 86% isolated yield. This
reagent is mild enough not to cause anomerization of the
TMSEt glycosides; unreacted 13 was isolated (12%)
without anomerization into 40. Deacetylation of 39 gave
the 2-deoxyglobotrioside 2 in 88% yield.
In contrast to the attempted preparations of 2-deoxy-
globotriosides, the 3-deoxy analog 41 could be prepared
from both the trichloroacetimidate 36 and the thiogly-
coside 37, using the acceptor 19. In the former case,
activation with 1 equiv of silver triflate18 gave 41 in 63%
yield. When an excess of silver triflate was used, the
furanoside 42 was also formed, probably due to the
IV. Syn th esis of th e 2-, 3-, a n d 6-d eoxyglobotr io-
sid es 1, 3, a n d 5. Glycosides with a deoxy function in
(17) Schmidt, R. R.; Michel, J . Angew. Chem., Int. Ed. Engl. 1980,
19, 731-732.
(18) Douglas, S. P.; Whitfield, D. M.; Krepinsky, J . J . J . Carbohydr.
Chem. 1993, 12, 131-136.
(16) Kihlberg, J .; Frejd, T.; J ansson, K.; Sundin, A.; Magnusson, G.
Carbohydr. Res. 1988, 176, 271-286.
(19) Paulsen, H.; Lockhoff, O. Chem. Ber. 1981, 114, 3102-3114.

2386 J . Org. Chem., Vol. 61, No. 7, 1996
Zhang and Magnusson
Sch em e 2a
Furthermore, this cleavage reaction proceeded without
problems in our previous preparations of deoxyglobot-
riosides.1,2 However, attempted cleavage of the TMSEt
group in the 2-deoxysaccharide 39 by treatment with
trifluoroacetic acid gave the desired hemiacetal in only
15% yield together with 78% of a mixture of the three
corresponding trehaloses (data not shown). Furthermore,
attempted conversion of a 2-deoxylactoside21 to the cor-
responding chlorosugar14 was somewhat unpredictable;
no attempt to transform 39 into the corresponding
1-chlorosugar was therefore made. In addition, the
expected low â/R-selectivity in the planned glycosyla-
tions made us consider an alternative route to the
neoglycolipid 2.
Addition22 of hydrogen chloride to 3,4,6-tri-O-benzoyl-
glucal23 gave the desired 3,4,6-tri-O-benzoyl-2-deoxy-R-
D-glucopyranosyl chloride in quantitative yield according
to 1H NMR analysis. When the same reaction was
attempted with 3,4,6-tri-O-acetylglucal, several byprod-
ucts were formed. Treatment of the chloro sugar with
3-(hexadecylsulfonyl)-2-[(hexadecylsulfonyl)methyl]pro-
pan-1-ol2 (46) and silver silicate gave an easily separated
anomeric mixture of 47 and 48 (69%) (Scheme 5).
Debenzoylation of 47 gave crude 49, which was converted
into the acceptor 50 by regioselective benzoylation via
the corresponding stannylene intermediate. When 2
equiv of dibutyltin oxide was used for the stannylation,
50 was obtained in only 30% yield together with the
corresponding tri-O-benzoate and other byproducts. How-
ever, increasing the amount of dibutyltin oxide to 4 equiv
raised the yield of 50 to 84%. It seems as if the latter
procedure leads to highly selective benzoylations, without
the need for rigorously dry reaction conditions. Glyco-
sylation of acceptor 50 with the galabiosyl bromide 38,
using silver silicate19 as promoter, gave 51 in 83% yield.
Finally, deacetylation of 51 furnished the desired 2-deox-
yglobotriosyl neoglycolipid 2 (98%).
VI. Syn th esis of th e 3- a n d 6-Deoxyglobotr iosyl
Neoglycolip id s 4 a n d 6. In contrast to the attempted
formation of hemiacetal from 39, the 3- and 6-deoxygly-
cosides 41 and 45 smoothly underwent trifluoroacetic
acid-induced cleavage8 of the TMSEt group to give the
hemiacetals 52 (98%) and 55 (94%), respectively (Scheme
6). Treatment of 52 with trichloroacetonitrile17 gave the
corresponding trichloroacetimidate 53 (79%) as an R/â
mixture (2:1), whereas the same conditions converted 55
into pure 56 (81%). Silver triflate-promoted18 glycosy-
lation of the lipid alcohol 46 with trichloroacetimidates
53 and 56 gave 54 (72%) and 57 (79%). Deacetylation of
54 and 57 then gave the desired 3- and 6-deoxyglobot-
riosyl neoglycolipids 4 (98%) and 6 (96%), respectively.
a
(a) I2, imidazole, Ph3P, toluene/MeCN (5:2), reflux; (b) H2, Pd/
C, EtOAc/EtOH/Et3N (1:5:0.01); (c) BzCl, pyridine, DMAP; (d)
DDQ, AcOH (5 equiv), H2O, mol sieves (3 Å), toluene, 80 °C.
flexibility of the pyranose ring of 19, which might permit
a boatlike conformation, where HO-4 can reach the
anomeric position. Glycosylation of 19 with the thiogly-
coside donor 37 at -30 °C gave the desired 41 in 92%
yield, using N-iodosuccinimide/silver triflate20 as pro-
moter. No anomerization occurred and the furanosidic
byproduct 42 was not detected in the reaction mixture.
Deacetylation of 41 gave the 3-deoxyglobotrioside 3 in
95% yield.
Clean R-galactosylation of the 6-deoxylactoside accep-
tor 25 with 2,3,4,6-tetra-O-benzyl-R-D-galactopyranosyl
chloride16 in the presence of silver triflate gave 43 in 76%
yield. Hydrogenolysis of the benzyl protecting groups
gave 44 (93%), and deacylation of 44 gave the 6-deoxy-
globotrioside 5 in 98% yield. Acetylation of 44 gave the
fully acylated 45 (99%).
V. Syn th esis of th e 2-Deoxyglobotr iosyl Neogly-
colip id 2. Cleavage of the TMSEt group by trifluoro-
acetic acid8 to produce hemiacetal sugars is widely used,
especially with large synthetic oligosaccharides, where
reliability and high yields are of crucial importance.
Exp er im en ta l Section
General experimental procedures were as previously re-
ported.4 Toluene and dichloromethane were distilled from
calcium hydride under N2. Activated molecular sieves and
silver silicate18 were flame-dried under vacuum for 5 min and
then kept under vacuum (oil pump) for approximately 1 h.
2-(Tr im eth ylsilyl)eth yl 2-Deoxy-4-O-[4-O-(r-D-ga la cto-
p yr a n osyl)-â-D-ga la ctop yr a n osyl]-â-D-a r a bin o-h exop yr a -
n osid e (1). Compound 39 (60 mg, 0.048 mmol) was treated
with MeONa/MeOH (1 M, 0.2 mL) in MeOH (5 mL) at room
(21) Ekberg, T.; Magnusson, G. Unpublished results.
(22) Lancelin, J .-M.; Morin-Allory, L.; Sinay¨, P. J . Chem. Soc., Chem.
Commun. 1984, 355-356.
(23) Lundt, I.; Pedersen, C. Acta Chem. Scand. 1966, 20, 1369-
1375.
(20) Konradsson, P.; Udodong, U. E.; Fraser-Reid, B. Tetrahedron
Lett. 1990, 31, 4313-4316.

Synthesis of Double-Chain Bis-Sulfone Neoglycolipids
J . Org. Chem., Vol. 61, No. 7, 1996 2387
Sch em e 3a
a
(a) MeOC6H4OH, BF3‚Et2O, CH2Cl2; (b) MeONa, MeOH; (c) C6H5CH(OMe)2, TsOH, MeCN; (d) BzCl, pyridine; (e) NaBH3CN, HCl,
THF, mol sieves (3 Å); (f) 2,3,4,6-tetra-O-benzyl-R-D-galactopyranosyl chloride, AgOTf, collidine, acid washed mol sieves (3 Å), CH2Cl2; (g)
H2, Pd/C, AcOH; (h) Ac2O, pyridine; (i) (NH4)2Ce(NO3)6, acetone, H2O; (j) Cl3CCN, DBU, CH2Cl2; (k) C6H5SH, BF3‚Et2O, ClCH2CH2Cl; (l)
AcBr, ZnBr2, CHCl3.
Sch em e 4a
a
(a) Ag-SiO2, CH2Cl2; (b) NIS, TfOH, CH2Cl2; (c) NIS, TfOAg, CH2Cl2; (d) TfOAg, CH2Cl2; (e) TfOTMS, MeCN; (f) MeONa, MeOH; (g)
2,3,4,6-tetra-O-benzyl-R-D-galactopyranosyl chloride, TfOAg, collidine, CH2Cl2; (h) H2, Pd/C, AcOH; (i) Ac2O, pyridine.
temperature. The reaction was monitored by TLC (SiO2,
EtOAc/MeOH 3:1). After 5 h, the mixture was neutralized
with Duolite (H+) resin, filtered, and concentrated. The
1.45 (bq, 1 H, J ) 11.6 Hz), 0.95 (m, 2 H), -0.02 (s, 9 H); 13C
NMR data (D2O): δ 106.1, 103.1, 101.6, 83.2, 83.1, 80.1, 78.1,
77.6, 74.9, 73.7, 73.6, 72.1, 71.9, 71.7, 71.3, 70.4, 63.3, 63.1,
40.5, 20.2, 0.2.
3-(Hexa d ecylsu lfon yl)-2-[(h exa d ecylsu lfon yl)m eth yl]-
p r op yl 2-Deoxy-4-O-[4-O-(r-D-ga la ctop yr a n osyl)-â-D-ga -
la ctop yr a n osyl]-â-D-a r a bin o-h exop yr a n osid e (2). Com-
residue was chromatographed (SiO2-C18, H2O/MeOH 1:0 f 0:1)
1
to give 1 (25 mg, 88%); [R]25 +47.4° (c 1.0, MeOH); H NMR
D
data (D2O): δ 4.90 (d, 1 H, J ) 3.4 Hz), 4.47 (d, 1 H, J ) 7.8
Hz), 4.31 (t, 1 H, J ) 6.1 Hz), 2.34 (bd, 1 H, J ) 5.2, 12.5 Hz),

2388 J . Org. Chem., Vol. 61, No. 7, 1996
Zhang and Magnusson
Sch em e 5a
graphed (SiO2-C18, H2O/MeOH 1:0 f 0:1) to give 3 (40 mg,
97%); [R]25D +50.0° (c 1.0, MeOH); 1H NMR data (D2O): δ 4.91
(d, 1 H, J ) 3.8 Hz), 4.52 (d, 1 H, J ) 8.0 Hz), 4.44 (d, 1 H, J
) 8.2 Hz), 4.32 (t, 1 H, J ) 5.9 Hz), 1.34 (d, 3 H, J ) 6.3 Hz),
1.00 (m, 2 H), -0.01 (s, 9 H); 13C NMR data (D2O): δ 106.2,
103.9, 103.1, 86.7, 80.2, 78.1, 77.2, 75.9, 74.9, 73.8, 73.7, 73.6,
71.9, 71.7, 71.3, 71.1, 63.3, 63.1, 20.4, 19.5, 0.2.
3-(Hexa d ecylsu lfon yl)-2-[(h exa d ecylsu lfon yl)m eth yl]-
p r op yl 6-Deoxy-4-O-[4-O-(r-D-ga la ctop yr a n osyl)-â-D-ga -
la ctop yr a n osyl]-â-D-glu cop yr a n osid e (6). Compound 57
(84 mg, 0.046 mmol) was deacylated as described above (51
f 2), and the crude product was chromatographed (SiO2-C18
,
H2O/MeOH 1:0 f 0:1) to give 6 (49 mg, 96%); [R]25 +24.7° (c
D
1.0, CHCl3/MeOH/H2O 13:7:1); 1H NMR data (CDCl3/CD3OD/
D2O 13:7:1): δ 4.95 (bd, 1 H, J ) 2.7 Hz), 4.39, 4.33 (d, 1 H
each, J ) 7.1 and 7.8 Hz), 4.00 (d, 1 H, J ) 2.1 Hz), 3.96 (bs,
1 H), 3.11 (m, 4 H), 3.01 (m, 1 H), 1.39 (d, 3 H, J ) 6.2 Hz),
0.89 (t, 6 H, J ) 6.4 Hz).
2-(Tr im eth ylsilyl)eth yl 4,6-O-p-Meth oxyben zylid en e-
â-D-glu cop yr a n osid e (7). A mixture of 2-(trimethylsilyl)-
ethyl â-D-glucopyranoside8 (3.8 g, 13.57 mmol), p-methoxy-R,R-
dimethoxytoluene (3.1 mL, 20.4 mmol), dry CH3CN (100 mL),
and p-toluenesulfonic acid (50 mg) was stirred at room
temperature for 3 h and then neutralized with Et3N (1 mL)
and concentrated. The residue was chromatographed (SiO2,
toluene/CH3CN 4:1) to give 7 (5.10g, 94%); [R]25 -44.2° (c 1.0,
D
CHCl3); 1H NMR data (CDCl3): δ 7.42, 6.89 (d, 2 H each, J )
8.7 Hz), 5.49 (s, 1 H), 4.41 (d, 1 H, J ) 7.8 Hz), 4.33 (dd, 1 H,
J ) 10.5, 4.6 Hz), 2.85, 2.67 (s, 1 H each), 0.03 (s, 3 H). 13C
NMR (CDCl3) δ 160.3, 129.5, 127.6, 113.7, 102.7, 101.9, 80.6,
74.6, 73.2, 68.7, 67.9, 66.4, 55.3, 18.3, -1.4. HRMS calcd for
a
C
19H31O7Si (M + H): 399.1839; found: 399.1847.
(a) HCl, toluene, 0 °C; (b) Ag-SiO2, CH2Cl2; (c) MeONa,
MeOH, and then Bu2SnO, BzCl, toluene, 100 °C, 2 min; (d)
MeONa, MeOH, CHCl3.
2-(Tr im eth ylsilyl)eth yl 3-O-Ben zoyl-4,6-O-(p-m eth oxy-
ben zylid en e)-â-D-glu cop yr a n osid e (8), 2-(Tr im eth ylsilyl)-
et h yl 2-O-Ben zoyl-4,6-O-(p -m et h oxyb en zylid en e)-â-D-
glu cop yr a n osid e (9), a n d 2-(Tr im eth ylsilyl)eth yl 2,3-Di-
O -b e n zo y l-4,6-O -(p -m e t h o x y b e n zy lid e n e )-â-D -g lu c o -
p yr a n osid e (10). (a) Compound 7 (1.5 g, 3.77 mmol) and
Et3N (5.23 mL, 37.7 mmol) were dissolved in CH2Cl2 (30 mL).
The mixture was cooled (ice-water bath), and benzoyl chloride
(2.21 mL, 18.84 mmol) was added dropwise under Ar. After 1
h, the reaction was quenched by adding MeOH (2 mL), and
the mixture was diluted with CH2Cl2 (100 mL) and washed
with saturated aqueous NaHCO3 (2 × 50 mL). The organic
phase was dried (Na2SO4), filtered, and concentrated. The
residue was chromatographed (SiO2, heptane/toluene/EtOAc
6:1:1 f 5:1:1) to give 10 (0.54 g, 23%), 8 (1.28 g, 68%), and 9
pound 51 (27 mg, 0.016 mmol) was dissolved in CHCl3/MeOH
(5 mL, 3:2), and MeONa/MeOH (1 M, 0.2 mL) was added. The
reaction was monitored by TLC (CHCl3/MeOH/BuOAc/H2O 12:
8:8:1). After 11 h, the mixture was neutralized with AcOH
and concentrated. The residue was chromatographed (SiO2,
CH2Cl2/MeOH f CH2Cl2/MeOH/H2O; 2:1 f 2:1:0.05) to give
2 (17.6 mg, 98%); [R]25 +37.5° (c 0.6, CHCl3/MeOH/H2O 13:
D
7:1); 1H NMR data (CDCl3/CD3OD/D2O 13:7:1): δ 4.97 (d, 1
H, J ) 2.5 Hz), 4.61 (dd, 1 H, J ) 9.5, 1.2 Hz), 4.42 (d, 1 H, J
) 7.3 Hz), 4.12 (dd, 1 H, J ) 10.1, 4.2 Hz), 4.42 (d, 1 H, J )
1.6 Hz), 3.95 (bs, 1 H), 3.12 (m, 4 H), 2.99 (m, 1 H), 2.25 (bdd,
1 H, J ) 10.2, 4.5 Hz), 0.89 (t, 6 H, J ) 6.8 Hz).
(0.16 g, 8%). Compound 10: [R]25 -4.5° (c 1.0, CHCl3); 1H
2-(Tr im eth ylsilyl)eth yl 3-Deoxy-4-O-[4-O-(r-D-ga la cto-
p yr a n osyl)-â-D-ga la ctop yr a n osyl]-â-D-r ibo-h exop yr a n o-
sid e (3). Compound 43 (60 mg, 0.048 mmol) was deacylated
as described above (39 f 1) and the crude product was
chromatographed (SiO2-C18, H2O/MeOH 1:0 f 0:1) to give 3
D
NMR data (CDCl3): δ 5.76 (t, 1 H, J ) 9.6 Hz), 5.51 (s, 1 H),
5.46 (dd, 1 H, J ) 9.5, 7.9 Hz), 4.81 (d, 1 H, J ) 7.9 Hz), 4.43
(dd, 1 H, J ) 10.3, 5.0 Hz), 3.77 (s, 3 H), -0.07 (s, 9 H); HRMS
calcd for C33H38O9SiNa (M + Na): 629.2183; found: 629.2186.
Compound 8: [R]25 -83.0° (c 1.5, CHCl3); 1H NMR data
(27 mg, 95%); [R]25 +51.5° (c 1.0, MeOH); 1H NMR data
D
D
(CDCl3): δ 5.49 (s, 1 H), 5.48 (t, 1 H, J ) 9.5 Hz), 4.55 (d, 1 H,
J ) 7.7 Hz), 4.38 (dd, 1 H, J ) 10.5, 5.0 Hz), 3.76 (s, 3 H), 0.04
(s, 9 H); HRMS calcd for C26H35O8Si (M + H): 503.2109;
(D2O): δ 4.91 (d, 1 H, J ) 3.8 Hz), 4.48 (d, 1 H, J ) 7.6 Hz),
4.38 (d, 1 H, J ) 7.7 Hz), 2.52 (m, 1 H), 1.60 (q, 1 H, J ) 12.0
Hz), 1.00 (m, 2 H), -0.02 (s, 9 H); 13C NMR data (D2O): δ
106.7, 106.1, 102.9, 81.0, 79.4, 77.9, 76.6, 74.9, 73.6, 71.9, 71.7,
71.5, 70.8, 70.3, 63.2, 62.6, 40.5, 20.3, 0.2.
found: 503.2101. Compound 9: [R]25 -34.2° (c 2.0 CHCl3);
D
1H NMR data (CDCl3): δ 5.53 (s, 1 H), 5.17 (dd, 1 H, J ) 9.2,
7.9 Hz), 4.69 (d, 1 H, J ) 7.8 Hz), 4.38 (dd, 1 H, J ) 10.5, 4.9
Hz), 4.02 (t, 1 H, J ) 9.1 Hz), 3.80 (s, 3 H), -0.07 (s, 9 H);
3-(Hexa d ecylsu lfon yl)-2-[(h exa d ecylsu lfon yl)m eth yl]-
p r op yl 3-Deoxy-4-O-[4-O-(r-D-ga la ctop yr a n osyl)-â-D-ga -
la ctop yr a n osyl]-â-D-r ibo-h exop yr a n osid e (4). Compound
54 (65 mg, 0.037 mmol) was deacylated as described above
(51 f 2). After 12 h, the mixture was neutralized with Duolite
(H+) resin, filtered, and concentrated. The crude product was
chromatographed (SiO2-C18, H2O/MeOH 1:0 f 0:1) to give 4
HRMS calcd for
503.2101.
C26H35O8Si (M + H): 503.2109; found:
(b) Compound 7 (2.0 g, 5.03 mmol) and dibutyltin oxide (2.00
g, 8.04 mmol) were dissolved in toluene/benzene (120 mL 5:1),
the mixture was refluxed under Ar for 1 h, and approximately
30 mL of the solvent was distilled off. The mixture was cooled
to -25 °C, and benzoyl chloride (875 µL, 7.54 mmol) was
added. The mixture was kept at -25 °C overnight, a second
portion of benzoyl chloride (875 µL, 7.54 mmol) was added,
the mixture was stirred at room temperature for 2 h and at
40 °C for 1 h, MeOH (5 mL) was added, and the mixture was
concentrated. The residue was dissolved in hot CH3CN (50
mL), and the mixture was allowed to cool to room temperature.
The resulting precipitate was filtered off, and the filtrate was
concentrated. The residue was chromatographed (SiO2, hep-
(40 mg, 98%); [R]25 +27.8° (c 1.0, CHCl3/MeOH/H2O 13:7:1);
D
1H NMR data (CDCl3/CD3OD/D2O 13:7:1): δ 5.00 (d, 1 H, J )
2.4 Hz), 4.43, 4.29 (d, 1 H each, J ) 7.6 and 7.5 Hz), 4.03 (d,
1 H, J ) 1.6 Hz), 3.97 (bs 1 H), 3.11 (m, 4 H), 3.00 (m, 1 H),
2.52 (m, 1 H), 1.63 (q, 1 H, J ) 12.0 Hz), 0.89 (t, 6 H, J ) 6.8
Hz).
2-(Tr im eth ylsilyl)eth yl 6-Deoxy-4-O-[4-O-(r-D-ga la cto-
pyr an osyl)-â-D-galactopyr an osyl]-â-D-glu copyr an oside (5).
Compound 44 (80 mg, 0.070 mmol) was deacylated as de-
scribed above (39 f 1), and the crude product was chromato-

Synthesis of Double-Chain Bis-Sulfone Neoglycolipids
J . Org. Chem., Vol. 61, No. 7, 1996 2389
Sch em e 6a
a
(a) TFA, CH2Cl2, 0 °C; (b) Cl3CCN, DBU, CH2Cl2; (c) 46, TfOAg, CH2Cl2; (d) MeONa, MeOH, CHCl3.
tane/toluene/EtOAc 6:1:1) to give 10 (0.44 g, 14%), 8 (1.00 g,
39%), and 9 (1.15 g, 46%).
pound 15: [R]25 -15.6° (c 0.8, CHCl3); 1H NMR data (CDCl3):
D
δ 5.12 (m, 1 H), 4.68 (dd, 1 H, J ) 9.7, 2.0 Hz), 3.79 (t, 1 H, J
) 9.1 Hz), 3.44 (m, 1 H), 2.40 (ddd, 1 H, J ) 12.5, 5.2, 1.9 Hz),
1.78 (dt, 1 H, J ) 12.1, 9.8 Hz), 0.03 (s, 9 H); HRMS calcd for
C18H28O6 SiNa (M + Na): 391.1553; found: 391.1546.
2-(Tr im eth ylsilyl)eth yl 3-O-Ben zoyl-2-O-(im id a zol-1-
ylt h ioca r b on yl)-4,6-O-(p -m et h oxyb en zylid en e)-â-D-glu -
cop yr a n osid e (11). A mixture of compound 8 (1.16 g, 2.31
mmol), 1,1'-thiocarbonyldiimidazole (>97%, 847 mg, 4.61
mmol), and dry benzene (20 mL) was refluxed for 4 h and
concentrated. The residue was chromatographed (SiO2, hep-
14 f 13. To a solution of compound 14 (219 mg, 0.44 mmol)
in pyridine/H2O (4 mL, 5:1) were added AgNO3 (30 mg, 0.18
mmol) and KF (50 mg, 0.86 mmol). The mixture was stirred
at 100 °C for 8 h, poured into a stirred mixture of EtOAc/H2O
(115 mL, 75:40), and filtered through Celite. The water phase
was extracted with EtOAc (20 mL), and the combined organic
phases were dried (Na2SO4), filtered, and concentrated. The
residue was chromatographed (SiO2, heptane/EtOAc 5:1 f 1:2)
to give 13 (152 mg, 69%) and 14 (47 mg, 22%).
tane/EtOAc 5: 2) to give 11 (1.31 g, 93%); [R]25 -31.6° (c 1.0,
D
CHCl3); 1H NMR data (CDCl3): δ 8.27, 7.55, 6.99 (s, 1 H each),
6.03 (dd, 1 H, J ) 9.5, 7.8 Hz), 5.81 (t, 1 H, J ) 9.5 Hz), 5.51
(s, 1 H), 4.86 (d, 1 H, J ) 7.8 Hz), 4.43 (dd, 1 H, J ) 10.4, 4.9
Hz), 3.76 (s, 3 H), -0.04 (s, 9 H); HRMS calcd for C30H36O8N2-
SSiNa (M + Na+): 635.1859; found: 635.1864.
2-(Tr im et h ylsilyl)et h yl 2-O-Ben zoyl-3-O-(im id a zol-1-
ylt h ioca r b on yl)-4,6-O-(p -m et h oxyb en zylid en e)-â-D-glu -
cop yr a n osid e (16). Compound 9 (1.21 g, 2.41 mmol) was
treated as described in the preparation of 11. The crude
product was chromatographed (SiO2, heptane/EtOAc 2:1) to
2-(Tr im eth ylsilyl)eth yl 3-O-Ben zoyl-2-d eoxy-4,6-O-(p-
m eth oxyben zylid en e)-â-D-a r a bin o-h exop yr a n osid e (12).
A solution of compound 8 (1.28 g, 2.10 mmol) and a catalytic
amount of azobis(isobutyronitrile) in toluene (20 mL) was
added dropwise to a boiling solution of Bu3SnH (98%, 1.48 mL,
5.50 mmol) in toluene (35 mL) under Ar. The mixture was
refluxed for 4 h and concentrated. The residue was chromato-
graphed (SiO2, toluene 250 mL f heptane/EtOAc 3: 1) to give
give 16 (1.38 g, 94%): [R]25 -10.8° (c 1.5, CHCl3); 1H NMR
D
data (CDCl3): δ 6.32 (t, 1 H, J ) 9.3 Hz), 5.52 (m, 2 H, H-2),
4.85 (d, 1 H, J ) 7.6 Hz), 4.45 (dd, 1 H, J ) 10.6, 4.9 Hz), 3.89
(t, 1 H J ) 10.2 Hz), 3.78 (s, 3 H), -0.07 (s, 9 H). Anal. Calcd
for C30H36O8N2SSi: C 58.8, H 5.9, N 4.6; found: C 59.0, H 5.8,
N 4.5.
12 (1.01 g, 99%); [R]25 -97.9° (c 1.0 CHCl3); 1H NMR data
D
(CDCl3): δ 5.55 (s, 1 H), 5.35 (m, 1 H), 4.75 (dd, 1 H, J ) 9.6,
2.2 Hz), 4.36 (dd, 1 H, J ) 10.5, 4.9 Hz), 3.77 (s, 3 H), 2.51
(ddd, 1 H, J ) 12.4, 5.3, 1.9 Hz), 1.80 (bq, 1 H, J ) 11.8 Hz),
0.02 (s, 9 H); Anal. calcd for C26H34O7Si: C 64.2, H 7.1;
found: C 63.8, H 7.1.
2-(Tr im eth ylsilyl)eth yl 2-O-Ben zoyl-3-d eoxy-4,6-O-(p-
m eth oxyben zylid en e)-â-D-r ibo-h exop yr a n osid e (17) a n d
2-(Tr im et h ylsilyl)et h yl 2-O-Ben zoyl-3-d eoxy-â-D-r ibo-
h exop yr a n osid e (18). Compound 16 (1.36 g, 2.22 mmol) was
treated with Bu3SnH and AIBN as described in the prepara-
tion of 12. The crude product was chromatographed (SiO2,
toluene/EtOAc 7:1) to give 17 (312 mg, 29%) and 18 (568 mg,
70%). Compound 17: [R]25D -50.0° (c 1.0, CHCl3); 1H NMR data
(CDCl3): δ 5.08 (m, 1 H), 4.71 (d, 1 H, J ) 7.9 Hz), 4.36 (dd,
1 H, J ) 10.5, 4.8 Hz), 3.80 (s, 3 H), 2.66 (m, 1 H), 1.88 (q, 1
H, J ) 11.6 Hz), -0.04 (s, 9 H); HRMS calcd for C26H35O7Si
2-(Tr im et h ylsilyl)et h yl 3-O-Ben zoyl-2-d eoxy-6-O-(p -
m eth oxyben zoyl)-â-D-a r a bin o-h exop yr a n osid e (13), 2-(T-
r im eth ylsilyl)eth yl 3-O-Ben zoyl-2-d eoxy-4-O-(p-m eth ox-
yb en zoyl)-â-D-a r a bin o-h exop yr a n osid e (14), a n d 2-
(Tr im eth ylsilyl)eth yl 3-O-Ben zoyl-2-d eoxy-â-D-a r a bin o-
h exop yr a n osid e (15). A mixture of compound 12 (779 mg,
1.60 mmol), DDQ (751 mg, 3.21 mmol), AcOH (17 µL, 0.48
mmol), molecular sieves (300 mg, 4 Å), and toluene (30 mL)
was stirred at 80 °C overnight. The mixture was diluted with
EtOAc (150 mL), filtered, and washed with saturated aqueous
NaHCO3 (2 × 70 mL) and saturated aqueous NaCl (50 mL).
The organic phase was dried (NaSO4), filtered, and concen-
trated. Column chromatography (SiO2, heptane/EtOAc 6:1 f
4:1) of the residue gave 13 (533 mg, 66%), 14 (220 mg, 27%),
and 15 (16 mg, 3%). Compound 13: [R]25D -12.4° (c 1.4, CHCl3);
1H NMR data (CDCl3): δ 5.17 (m, 1 H), 4.74 (dd, 1 H, J )
12.0, 4.6 Hz), 4.67 (dd, 1 H, J ) 9.7, 2.0 Hz), 4.58 (dd, 1 H J
) 12.0, 2.2 Hz), 3.87 (s, 3 H), 2.41 (ddd, 1 H, J ) 12.5, 5.3, 1.8
Hz), 1.80 (dt, 1 H, J ) 12.0, 9.7 Hz), 0.02 (s, 9 H); HRMS calcd
for C26H34O8 SiNa (M + Na): 525.192; found: 525.1938;
(M + H): 487.2152; found: 487.2146. Compound 18: [R]25
D
1
-61.6° (c 1.5, CHCl3); H NMR data (CDCl3): δ 4.93 (m, 1 H),
4.64 (d, 1 H, J ) 7.8 Hz), 3.59 (m, 2 H), 3.43 (m, 1 H), 2.57 (dt,
1 H, J ) 12.2, 5.1 Hz), 1.72 (q, 1 H, J ) 11.5 Hz), -0.07 (s, 9
H); HRMS calcd for C18H29O6Si (M + H+): 369.1733; found:
369.1733.
18 f 17. Compound 18 (450 mg, 1.22 mmol) was treated
as described in the preparation of 7. The crude product was
chromatographed (SiO2, toluene/Et3N 100: 1) to give 17 (587
mg, 99%).
2-(Tr im et h ylsilyl)et h yl 2-O-Ben zoyl-3-d eoxy-6-O-(p -
m eth oxyben zoyl)-â-D-r ibo-h exop yr a n osid e (19) a n d 2-(T-
r im eth ylsilyl)eth yl 2-O-Ben zoyl-3-d eoxy-4-O-p-m eth ox-
yb en zoyl-â-D-r ibo-h exop yr a n osid e (20). A mixture of
compound 17 (150 mg, 0.31 mmol), DDQ (192 mg, 0.82 mmol),
molecular sieves (50 mg, unactivated), and toluene (5 mL) was
stirred at 80 °C for 24 h, diluted with EtOAc (70 mL), washed
Compound 14: [R]25 -103.3° (c 1.5, CHCl3); 1H NMR data
D
(CDCl3): δ 5.48 (m, 1 H), 5.33 (t, 1 H, J ) 9.6 Hz), 4.76 (dd, 1
H, J ) 9.7, 2.0 Hz), 3.81 (s, 3 H), 2.60-2.48 (m, 2 H), 1.91
(ddd, 1 H, J ) 9.6, 9.1, 9.7 Hz), 0.03 (s, 9 H); HRMS calcd for
C26H34O8 SiNa (M + Na): 525.1921; found: 525.1938. Com-

2390 J . Org. Chem., Vol. 61, No. 7, 1996
Zhang and Magnusson
with saturated aqueous NaHCO3 (2 × 40 mL), dried (Na2SO4),
and concentrated. The 1H-NMR spectrum of the crude product
showed a mixture of 19 and 20 (3:2). The mixture was
dissolved in pyridine/H2O (4.5 mL 10:1), and AgNO3 (55 mg,
0.32 mmol) and KF (19 mg, 0.33 mmol) were added. The
mixture was stirred at 100 °C for 16 h and concentrated. The
residue was chromatographed (SiO2, toluene/CH2Cl2/THF 20:
10:3) to give 19 (132 mg, 85%) and 20 (10 mg, 6.4%).
O-(p -m e t h oxyb e n zoyl)-â-D-ga la ct op yr a n osyl]-â-D-glu -
cop yr a n osid e (26). Compound 24 (259 mg, 0.27 mmol) was
treated with DDQ (134 mg, 0.57 mmol), AcOH (81.5 µL, 1.43
mmol), molecular sieves (250 mg), and H2O (10 µL, 0.57 mmol),
as described in the preparation of 13. The crude product was
chromatographed (SiO2, heptane/EtOAc 3:1 f 1:1) to give 25
(218 mg, 83%) and 26 (43.9 mg, 16%). Compound 25: [R]25
D
+34.0° (c 1.0, CHCl3); 1H NMR data (CDCl3): δ 5.71 (dd, 1 H,
J ) 10.4, 7.9 Hz), 5.65 (t, 1 H, J ) 9.0 Hz), 5.36 (dd, 1 H, J )
9.9, 8.0 Hz), 5.20 (dd, 1 H, J ) 10.4, 3.2 Hz), 4.80, 4.61 (d, 1 H
each, J ) 7.9 and 8.0 Hz), 3.87 (s, 3 H), 1.25 (d, 3 H, J ) 6.0
Hz), -0.11 (s, 9 H); HRMS calcd for C53H56O16SiNa (M +
Compound 19: [R]25 -70.5° (c 2.0, CHCl3); 1H NMR data
D
(CDCl3): δ 4.95 (m, 1 H), 4.75 (dd, 1 H, J ) 12.1, 4.4 Hz), 4.64
(d, 1 H, J ) 7.7 Hz), 4.50 (dd, 1 H, J ) 12.0, 2.4 Hz), 3.85 (s,
3 H), 2.60 (dt, 1 H, J ) 12.3, 4.7 Hz), 1.75 (q, 1 H, J ) 11.2
Hz), -0.06 (s, 9 H); HRMS calcd for C26H34O8SiNa (M + Na+):
525.1921; found: 525.1929. Compound 20: [R]25D -33.3° (c 0.9,
CHCl3); 1H NMR data (CDCl3): δ 5.20-5.00 (m, 2 H), 4.76 (d,
1 H, J ) 7.1 Hz), 3.86 (s, 3 H), 2.79 (dt, 1 H, J ) 12.7, 4.9 Hz),
1.97 (ddd, 1 H, J ) 10.2, 7.1, 10.1 Hz), -0.03 (s, 9 H); HRMS
calcd for C26H34O8SiNa (M + Na): 525.1921; found: 525.1938.
Na+): 999.3235; found: 999.3245. Compound 26: [R]25
D
+91.9° (c 1.0, CHCl3); 1H NMR data (CDCl3): δ 5.78 (dd, 1 H,
J ) 10.4, 7.9 Hz), 5.62 (t, 1 H, J ) 9.0 Hz), 5.53 (d, 1 H, J )
3.2 Hz), 5.42 (dd, 1 H, J ) 10.4, 3.4 Hz), 5.38 (dd, 1 H, J )
9.9, 8.0 Hz), 4.87, 4.62 (d, 1 H each, J ) 7.8 and 7.9 Hz), 3.91
(s, 3 H), 2.90, 2.72 (m, 1 H each), 1.27 (d, 3 H, J ) 6.1 Hz),
-0.11 (s, 9 H); HRMS calcd for C53H56O16SiNa (M + Na+):
999.3235; found: 999.3224.
2-(Tr im eth ylsilyl)eth yl 6-Deoxy-6-iod o-4-O-[4,6-O-(p-
m eth oxyben zyliden e)-â-D-galactopyr an osyl]-â-D-glu copy-
r a n osid e (22). Compound 212 (500 mg, 0.89 mmol), Ph3P (463
mg, 1.77 mmol), and imidazole (243 mg, 0.51 mmol) were
dissolved in toluene/CH3CN (70 mL 5:2). I2 (408 mg, 1.61
mmol) was carefully added, and the mixture was refluxed.
After 5 h, the mixture was cooled to room temperature, MeOH
(20 mL) was added, and the mixture was concentrated. The
residue was extracted with hot EtOAc (3 × 30 mL), and the
organic phase was concentrated. The residue was chromato-
graphed (SiO2, EtOAc/toluene 15:1 f 1:0 and then EtOAc/
p-Meth oxyp h en yl 2,3,4,6-Tetr a -O-a cetyl-â-D-ga la ctop y-
r a n osid e (27). Galactose pentaacetate (10.0 g, 25.64 mmol)
and p-methoxyphenol (3.38 g, 30.77 mmol) were dissolved in
CH2Cl2 (50 mL), the mixture was cooled (ice-water bath), and
BF3‚Et2O (3.85 mL, 28.11 mmol) was added dropwise. After
7 h, the mixture was diluted with CH2Cl2 (250 mL) and washed
with water (200 mL), saturated aqueous NaHCO3 (200 mL),
and water (2 × 150 mL), dried (Na2SO4), filtered, and
concentrated. The crude product was kept under vacuum (oil
pump) for 5 h. The partly crystalline residue was recrystal-
lized from EtOAc/heptane first at room temperature and then
at -20 °C overnight. Filtration gave crystalline 27 (9.40 g,
MeOH 20:1) to give 22 (480 mg, 80%); [R]25 -17.9° (c 1.0,
D
1
CHCl3); H NMR data (CDCl3): δ 5.42 (s, 1 H), 4.40, 4.31 (d,
1 H each, J ) 7.9 and 7.8 Hz), 4.22 (d, 1 H, J ) 12.0 Hz), 4.08
(d, 1 H, J ) 3.4 Hz), 3.78 (s, 3 H), 3.57 (dd, 1 H, J ) 9.8, 3.5
Hz), 0.03 (s, 9 H); 13C NMR data (CDCl3): δ 160.3, 129.9, 127.7,
113.7, 103.0, 101.6, 101.2, 82.4, 75.2, 74.1, 74.0, 73.4, 72.4, 70.4,
68.9, 67.6, 66.8, 55.4, 18.2, 6.51, -1.4; HRMS calcd for
81%): mp 109-110 °C; [R]25 +3.2° (c 0.9, CHCl3), [lit.15a [R]D
D
+9.6° (c 0.54)]; 1H NMR data (CDCl3): δ 6.96, 6.82 (d, 2 H
each, J ) 9.2 Hz), 5.50 (dd, 1 H, J ) 10.5, 8.0 Hz), 5.48 (dd, 1
H, J ) 3.5, 1.0 Hz), 5.09 (dd, 1 H, J ) 10.5, 3.4 Hz), 4.92 (d,
1 H, J ) 8.0 Hz), 4.24 (dd, 1 H, J ) 11.3, 7.0 Hz), 4.16 (dd, 1
H, J ) 11.2, 6.4 Hz), 4.01 (m, 1 H), 3.77 (s, 3 H), 2.18, 2.09,
2.06, 2.01 (s, 3 H each).
C
25H39O11SiINa (M + Na+): 693.1204; found: 693.1212.
2-(Tr im eth ylsilyl)eth yl 6-Deoxy-4-O-[4,6-O-(p-m eth oxy-
b e n zylid e n e )-â-D-ga la ct op yr a n osyl]-â-D-glu cop yr a n o-
sid e (23). Compound 22 (450 mg, 0.67 mmol) was dissolved
in EtOH/EtOAc/Et3N (50 mL 5:1:0.01), and the mixture was
hydrogenated (H2, Pd/C 10%, 250 mg). After 3 h, the mixture
was filtered through Celite, the solid residue was washed with
EtOAc (30 mL), and the filtrate was concentrated. The residue
was chromatographed (SiO2, EtOAc/toluene 20:1 f 1:0 and
then EtOAc/EtOH 10:1) to give 23 (337 mg, 92%); [R]25D -28.7°
p-Meth oxyp h en yl 4,6-O-Ben zylid en e-â-D-ga la ctop yr a -
n osid e (29). Compound 27 (14.25 g, 31.39 mmol) was
deacetylated as described in the preparation of 1 to give 28
(18.91 g, 99%). The crude product (4.15 g, 14.51 mmol) was
dissolved in dry acetonitrile (100 mL), and R,R-dimethoxytolu-
ene (7.9 mL, 29.02 mmol) and a catalytic amount of PTSA were
added. The mixture was stirred at room temperature for 30
min and then cooled (ice-water bath), and the crystalline
material was collected. The mother liquid was concentrated,
and the residue was triturated with hot heptane/EtOAc (60
mL 5:2). The solution was cooled to room temperature, and
the crystalline material was collected. The combined crystal-
line material was washed with heptane/EtOAc (5:2) and dried
1
(c 1.5, CHCl3); H NMR data (CDCl3): δ 5.44 (s, 1 H), 4.34,
4.28 (d, 1 H each, J ) 7.6 and 7.8 Hz), 4.24 (d, 1 H, J ) 12.0
Hz), 4.12 (d, 1 H, J ) 4.1 Hz), 3.80 (s, 3 H), 3.18 (t, 1 H, J )
9.0 Hz), 1.38 (d, 3 H, J ) 6.2 Hz), 0.02 (s, 9 H); 13C NMR data
(CDCl3): δ 160.3, 130.0, 127.8, 113.7, 103.4, 101.8, 101.2, 85.6,
75.0, 74.5, 73.9, 72.6, 71.2, 70.7, 68.8, 67.4, 66.9, 55.3, 18.3,
to give 29 (5.28 g, 98%): mp 229-231 °C; [R]25 -88.4° (c 1.0,
D
17.7, -1.4; HRMS calcd for
567.2238; found: 567.2249.
C
25H40O11SiNa (M + Na+):
MeOH/CHCl3 1:1); 1H NMR data (CDCl3): δ 5.58 (s, 1 H), 4.80
(d, 1 H, J ) 7.7 Hz), 4.38 (dd, 1 H, J ) 12.5, 1.5 Hz), 4.28 (dd,
1 H, J ) 3.8, 1.2 Hz), 4.12 (dd, 1 H, J ) 12.5, 1.9 Hz), 4.01
(dd, 1 H, J ) 9.3, 7.9 Hz), 3.59 (m, 1 H). HRMS calcd for
C20H22O7Na (M + Na): 397.1263; found: 397.1273.
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-ben zoyl-6-d eoxy-4-O-
[2,3-d i-O-ben zoyl-4,6-O-(p-m eth oxyben zylid en e)-â-D-ga -
la ctop yr a n osyl]-â-D-glu cop yr a n osid e (24). Compound 23
(308 mg, 0.57 mmol) and a catalytic amount of DMAP were
dissolved in pyridine (10 mL), and the mixture was cooled (ice-
water bath). Benzoyl chloride (437 µL, 3.75 mmol) was added
dropwise, and the mixture was left at room temperature
overnight. The solvent was removed, and the residue was
redissolved in CH2Cl2 (70 mL), washed with saturated aqueous
NaHCO3 (2 × 50 mL), dried (Na2SO4), filtered, and concen-
trated. The residue was chromatographed (SiO2, heptane/
p-Meth oxyp h en yl 2,3-Di-O-ben zoyl-4,6-O-ben zylid en e-
â-D-ga la ctop yr a n osid e (30). Compound 29 (5.08 g, 13.58
mmol) was benzoylated as described in the preparation of 24.
The crude product was recrystallized from MeOH to give 30
(6.68 g, 85%): mp 198-199 °C; [R]25 +115.6° (c 1.0, CHCl3);
D
1H NMR data (CDCl3): δ 6.10 (dd, 1 H, J ) 9.5, 8.1 Hz), 5.58
(s, 1 H), 5.43 (dd, 1 H, J ) 10.5, 3.5 Hz), 5.20 (d, 1 H, J ) 8.0
Hz), 4.65 (d, 1 H, J ) 2.9 Hz), 4.46 (dd, 1 H, J ) 12.5, 1.5 Hz),
4.17 (dd, 1 H, J ) 12.5, 1.7 Hz), 3.74 (s, 1 H); HRMS calcd for
C34H30O9Na (M + Na): 605.1788; found: 605.1770.
EtOAc 3:2) to give 24 (491 mg, 91%): [R]25 +125.0° (c 1.1,
D
CHCl3); 1H NMR data (CDCl3): δ 5.81-5.72 (m, 2 H), 5.27
(dd, 1 H, J ) 9.7, 8.0 Hz), 5.24 (s, 1 H), 5.15 (dd, 1 H, J ) 3.6,
10.4 Hz), 4.86, 4.62 (d, 1 H each, J ) 7.9 and 8.0 Hz), 4.28 (d,
1 H, J ) 3.6 Hz), 3.80 (s, 3 H), 1.15 (d, 3 H, J ) 6.0 Hz), 0.12
(s, 9 H).
p-Meth oxyp h en yl 2,3-Di-O-ben zoyl-6-O-ben zyl-â-D-ga -
la ctop yr a n osid e (31). To a mixture of compound 30 (6.00
g, 10.31 mmol), NaCNBH3 (85%, 5.75 g, 77.72 mmol), molec-
ular sieves (7 g), and dry THF (150 mL) was added dropwise
a cold saturated solution of HCl in Et2O until no more gas
was formed. The reaction was stopped after 2 h by adding
solid NaHCO3 (∼10 g). The mixture was diluted with CH2Cl2
(300 mL) and H2O (100 mL) and filtered through Celite. The
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-ben zoyl-6-d eoxy-4-O-
[2,3-d i-O-ben zoyl-6-O-(p-m eth oxyben zoyl)-â-D-ga la ctop y-
r a n osyl]-â-D-glu cop yr a n osid e (25) a n d 2-(Tr im eth ylsilyl)-
eth yl 2,3-Di-O-ben zoyl-6-d eoxy-4-O-[2,3-d i-O-ben zoyl-4-

Synthesis of Double-Chain Bis-Sulfone Neoglycolipids
J . Org. Chem., Vol. 61, No. 7, 1996 2391
organic phase was washed with saturated aqueous NaHCO3
(150 mL) and saturated aqueous NaCl (150 mL), dried (Na2-
SO4), filtered, and concentrated. The residue was chromato-
Crude 35 (250 mg, 0.329 mmol) was dissolved in CH2Cl2
(10 mL), the mixture was cooled (ice-water bath), and
trichloroacetonitrile (1.09 mL) and DMU (53.9 µL, 0.36 mmol)
were added. After 5 h, the mixture was concentrated, and the
residue was chromatographed (SiO2, heptane/EtOAc/Et3N 20:
10:0.1 f 10:10:0.1) to give 36 (270 mg, 91%); [R]25D +145.0° (c
1.0, CHCl3); 1H NMR data (CDCl3): δ 8.64 (s, 1 H), 6.80 (d, 1
H, J ) 3.6 Hz), 5.92 (dd, 1 H, J ) 11.0, 3.7 Hz), 5.77 (dd, 1 H,
J ) 11.0, 2.7 Hz), 5.26 (dd, 1 H, J ) 10.7, 3.5 Hz), 5.14 (d, 1
H, J ) 3.6 Hz), 4.39 (dd, 1 H, J ) 11.2, 6.9 Hz), 4.25 (dd, 1 H,
J ) 11.2, 6.1 Hz), 3.82 (dd, 1 H, J ) 11.0, 7.8 Hz), 3.53 (dd, 1
H, J ) 11.1, 6.2 Hz), 2.15, 2.09, 2.06, 2.00, 1.79 (s 3 H each).
HRMS calcd for C38H40O18Cl3NNa (M + Na): 926.1209;
found: 926.1215.
graphed (SiO2, heptane/EtOAc 4:1 f 3:2) to give 31 (5.56 g,
1
92%): [R]25 +71.4° (c 1.0, CHCl3); H NMR data (CDCl3): δ
D
6.01 (dd, 1 H, J ) 10.3, 8.0 Hz), 5.35 (dd, 1 H, J ) 10.3, 3.2
Hz), 5.13 (d, 1 H, J ) 8.0 Hz), 4.61 (s, 2 H), 4.44 (bt, 1 H, J )
3.8 Hz), 3.74 (s, 1 H); 13C NMR data (CDCl3): δ 165.9, 165.6,
119.0, 114.5, 101.4, 74.4, 73.9, 73.7, 69.6, 69.3, 69.2, 68.0, 55.6;
HRMS calcd for C34H32O9Na (M + Na): 607.1944; found:
607.1933.
p -Met h oxyp h en yl 2,3-Di-O-b en zoyl-6-O-b en zyl-4-O-
(2,3,4,6-tetr a -O-ben zyl-r-D-ga la ctop yr a n osyl)-â-D-ga la c-
top yr a n osid e (32). A mixture of 31 (1.28 g, 2.19 mmol),
TfOAg (817 mg, 3.15 mmol), CH2Cl2 (40 mL), and activated
acid-washed molecular sieve AW-300 (4 g) was stirred at -70
°C for 30 min. Collidine (626 µL, 4.73 mmol) and a solution
of 2,3,4,6-tetra-O-benzyl-R-D-galactopyranosyl chloride17 (1.60
g, 2.87 mmol) in CH2Cl2 (10 mL) was added. The mixture was
kept at -40 °C for 2 h and allowed to attain room tempera-
ture. After 4 h, the temperature was lowered to -40 °C and
an additional portion of TfOAg (371 mg, 0.46 mmol) was added.
The mixture was stirred at room temperature overnight, and
solid NaHCO3 (2 g) was added. The mixture was diluted with
CH2Cl2/H2O (250 mL 4:1) and filtered through Celite. The
organic phase was washed with saturated aqueous NaHCO3
(70 mL), dried (Na2SO4), filtered, and concentrated. The
residue was chromatographed (SiO2, toluene/Et2O 30:1) to give
P h en yl 6-O-Acetyl-2,3-d i-O-ben zoyl-4-O-(2,3,4,6-tetr a -
O-a cet yl-r-D-ga la ct op yr a n osyl)-1-t h io-â-D-ga la ct op yr a -
n osid e (37). Compound 34 (800 mg, 0.92 mmol) was dissolved
in ClCH2CH2Cl/toluene (20 mL 1:1), and thiophenol (379 µL,
3.70 mmol) and BF3‚Et2O (127 µL) were added. The mixture
was heated at 65 °C for 10 h and then poured into a mixture
of CH2Cl2 (150 mL) and saturated aqueous Na2CO3 (75 mL).
The organic phase was washed with saturated aqueous NaCl
(2 × 70 mL), dried (Na2SO4), filtered, and concentrated. The
residue was chromatographed (SiO2, heptane/EtOAc 2:1 f 1:1)
to give 37 (â:R ∼42:1, 721 mg, 93%). 37â had [R]25 +97.3° (c
D
1
1.0, CHCl3); H NMR data (CDCl3): δ 5.52 (t, 1 H, J ) 10.1
Hz), 5.37 (bd, 1 H, J ) 3.2 Hz), 5.15 (dd, 1 H, J ) 11.0, 3.4
Hz), 4.99 (d, 1 H, J ) 3.6 Hz), 4.90 (d, 1 H, J ) 9.7 Hz), 4.52
(dd, 1 H, J ) 11.4, 7.0 Hz), 2.15, 2.13, 2.07, 2.02, 1.97 (s, 3 H
each). HRMS calcd for C42H44O17SNa (M + Na): 875.2197;
found: 875.2197.
1
32 (1.95 g, 81%): [R]25 +78.0° (c 1.5, CHCl3); H NMR data
D
(CDCl3): δ 6.02 (dd, 1 H, J ) 10.7, 7.8 Hz), 5.28 (dd, 1 H, J )
10.7, 2.8 Hz), 5.15 (d, 1 H, J ) 7.8 Hz), 4.96 (d, 1 H, J ) 3.5
Hz), 4.46 (dd, 1 H, J ) 2.9 Hz), 4.39 (dd, 1 H, J ) 9.5, 5.5 Hz),
4.49 (dd, 1 H, J ) 10.3, 2.5 Hz), 3.74 (s, 1 H), 3.43 (t, 1 H, J )
9.2 Hz), 3.02 (dd, 1 H, J ) 8.3, 5.1 Hz); 13C NMR data
(CDCl3): δ 166.5, 165.4, 155.5, 151.4, 118.9, 114.5, 101.23,
101.20, 101.16, 100.7, 100.6, 79.0, 76.5, 75.51, 75.47, 75.0, 74.8,
74.8, 74.4, 73.9, 73.2, 73.0, 72.5, 69.7, 69.6, 68.7, 67.6, 67.5,
6-O-Acetyl-2,3-d i-O-ben zoyl-4-O-(2,3,4,6-tetr a -O-a cetyl-
r-D-galactopyr an osyl)-â-D-galactopyr an osyl Br om ide (38).
Compound 34 (100 mg, 0.12 mmol) was dissolved in CH2Cl2
(3 mL), and AcBr (26 mL, 0.35 mmol) and a catalytic amount
of ZnBr2 (∼2 mg) were added. The mixture was stirred at room
temperature for 4.5 h and chromatographed (SiO2, heptane/
EtOAc 5:1 f 3:2) to give 38 (88 mg, 93%); [R]25 +201.8° (c
D
55.64, 55.59; HRMS calcd for
1129.4350; found: 1129.4358.
C68H66O14Na (M + Na):
1.0, CHCl3); 1H NMR data (CDCl3): δ 6.89 (d, 1 H, J ) 3.9
Hz), 5.74 (dd, 1 H, J ) 10.8, 2.5 Hz), 5.60 (dd, 1 H, J ) 10.7,
3.9 Hz), 5.48 (bd, 1 H, J ) 2.9 Hz), 5.42 (dd, 1 H, J ) 11.0, 3.2
Hz), 5.25 (dd, 1 H, J ) 10.7, 3.7 Hz), 5.11 (d, 1 H, J ) 3.6 Hz),
4.39 (dd, 1 H, J ) 11.5, 7.1 Hz), 4.28 (dd, 1 H, J ) 11.5, 5.6
Hz), 3.82 (dd, 1 H, J ) 11.0, 7.6 Hz), 3.54 (dd, 1 H, J ) 11.0,
6.3 Hz), 2.14, 2.11, 2.08, 1.99, 1.95 (s, 3 H each); HRMS calcd
for C36H39O17BrNa (M + Na): 845.1268; found: 845.1262.
2-(Tr im et h ylsilyl)et h yl 3-O-Ben zoyl-2-d eoxy-6-O-(p -
m et h oxyb en zoyl)-4-O-[6-O-a cet yl-2,3-d i-O-b en zoyl-4-O-
(2,3,4,6-t et r a -O-a cet yl-r-D-ga la ct op yr a n osyl)-â-D-ga la c-
top yr a n osyl]-â-D-a r a bin o-h exop yr a n osid e (39). Acceptor
13 (139 mg, 0.28 mmol), donor 38 (342 mg, 0.42 mmol), acid-
washed molecular sieves (AW-300, 500 mg), and CH2Cl2 (5 mL)
were stirred for 40 min under Ar. Silver silicate (400 mg) was
added, and the mixture was stirred at room temperature under
protection from light. After 24 h, an additional portion of silver
silicate (50 mg) was added, and stirring was continued for
another 24 h. The mixture was filtered through Celite, and
the solid residue was washed with hot CH2Cl2 (25 mL). The
combined filtrate was concentrated, and the residue was
chromatographed (SiO2, heptane/EtOAc 2:1 f 1:1) to give 39
p-Met h oxyp h en yl 2,3-Di-O-b en zoyl-4-O-(r-D-ga la ct o-
p yr a n osyl)-â-D-ga la ctop yr a n osid e (33) a n d p-Meth ox-
yp h en yl 6-O-Acetyl-2,3-d i-O-ben zoyl-4-O-(2,3,4,6-tetr a -O-
a cetyl-r-D-ga la ctop yr a n osyl)-â-D-ga la ctop yr a n osid e (34).
A mixture of compound 32 (1.47 g, 1.33 mmol) and AcOH (5
mL) was hydrogenated (H2, Pd/C 10%, 210 mg) for 6.5 h. The
mixture was filtered and concentrated to give crude 33: [R]25
D
1
+111.9° (c 1.0, CHCl3); H NMR data (CDCl3): δ 5.86 (dd, 1
H, J ) 10.1, 8.3 Hz), 5.46 (bd, 1 H, J ) 10.5 Hz), 5.13 (d, 1 H,
J ) 7.8 Hz), 5.00 (s, 1 H), 4.49 (s, 1 H), 3.68 (s, 1 H); HRMS
calcd for C33H36O14Na (M + Na+): 679.2003; found: 679.2023.
Crude 33 was acetylated with Ac2O/pyridine (8 mL, 1:1).
The mixture was coconcentrated with toluene (2 × 3 mL), and
the residue was chromatographed (SiO2, heptane/EtOAc 2:1
f 1:1) to give 34 (1.023 g, 89%); [R]25 +115.3° (c 0.9, CHCl3);
D
1H NMR data (CDCl3): δ 5.90 (dd, 1 H, J ) 10.5, 7.8 Hz), 5.51
(dd, 1 H, J ) 3.2, 1.4 Hz), 5.47 (dd, 1 H, J ) 10.8, 3.3 Hz),
5.31 (dd, 1 H, J ) 10.5, 2.8 Hz), 5.23 (dd, 1 H, J ) 10.7, 3.6
Hz), 5.17 (d, 1 H, J ) 7.7 Hz), 5.12 (d, 1 H, J ) 3.7 Hz), 4.39
(d, 1 H, J ) 2.4 Hz), 3.76 (s, 1 H), 2.14, 2.11, 2.08, 1.99 and
1.91 (s, 3 H each). Anal. Calcd for C43H46O19: C 59.6, H 5.4.
Found: C 59.9, H 5.4.
(297 mg, 86%); [R]25 +83.8° (c 1.0, CHCl3); 1H NMR data
D
(CDCl3): δ 5.64 (dd, 1 H, J ) 10.7, 7.8 Hz), 5.43 (dd, 1 H, J )
3.1, 1.3 Hz), 5.36 (m, 1 H), 5.30 (dd, 1 H, J ) 11.0, 3.4 Hz),
5.16-5.06 (m, 2 H), 4.95 (d, 1 H, J ) 3.5 Hz), 4.89 (d, 1 H, J
) 7.8 Hz), 4.19 (d, 1 H, J ) 2.5 Hz), 2.51 (bdd, 1 H, J ) 12.9,
5.5 Hz), 2.09 (m, 1 H), 2.02, 1.98, 1.96, 1.91, 1.86 (s, 3 H each).
Anal. Calcd for C62H72O25Si: C 59.8, H 5.8. Found: C 59.7,
H 5.6.
6-O-Acetyl-2,3-d i-O-ben zoyl-4-O-(2,3,4,6-tetr a -O-a cetyl-
r-D-ga la ctop yr a n osyl)-D-ga la ctop yr a n ose (35) a n d 6-O-
Acet yl-2,3-d i-O-b en zoyl-4-O-(2,3,4,6-t et r a -O-a cet yl-r-D-
ga la ct op yr a n osyl)-r-D-ga la ct op yr a n osyl Tr ich lor oa c-
etim id a te (36). Compound 34 (960 mg, 1.11 mmol) was
dissolved in acetone-H2O (40 mL 3:1), and the mixture was
cooled (ice-water bath). A solution of CAN (4.3 g, 7.84 mmol)
in acetone/H2O (5 mL 3:1) was added, and the mixture was
stirred at room temperature for 30 min. The mixture was
concentrated to a volume of 20 mL, diluted with CH2Cl2 (150
mL), washed with saturated aqueous NaHCO3 (2 × 70 mL),
dried (Na2SO4), filtered, and concentrated. The residue was
chromatographed (SiO2, heptane/EtOAc 1:1 f 1:2) to give
crude 35 (740 mg, 88%).
2-(Tr im et h ylsilyl)et h yl 3-O-Ben zoyl-2-d eoxy-6-O-(p -
m eth oxyben zoyl)-r-D-a r a bin o-h exopyr an oside (40). Com-
pound 40 was obtained as a byproduct (presumably via
anomerization of acceptor 13) during the largely unsuccessful
attempts to prepare 39 from 36 or 37 (see text). Compound
40: [R]25D +57.0° (c 0.4, CHCl3); 1H NMR data (CDCl3): δ 5.46
(m, 1 H), 5.01 (d, 1 H, J ) 3.2 Hz), 5.54 (dd, 1 H, J ) 12.0, 4.9
Hz), 4.56 (dd, 1 H, J ) 12.0, 2.0 Hz), 4.03 (m, 1 H), 3.68 (m, 1

2392 J . Org. Chem., Vol. 61, No. 7, 1996
Zhang and Magnusson
H), 2.32 (bdd, 1 H, J ) 13.4, 5.5 Hz), 1.92 (bddd, 1 H, J ) 3.4,
3.1, 3.2 Hz); HRMS calcd for C26H34O8SiNa (M + Na+):
525.1921; found: 525.1938.
55.52, 55.48, 18.1, 17.7, -1.40, -1.42; HRMS calcd for C87H90O21-
SiNa (M + Na+): 1521.5642; found: 1521.5654.
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-ben zoyl-6-d eoxy-4-O-
[2,3-d i-O-b en zoyl-6-O-(p -m et h oxyb en zoyl)-4-O-(r-D-ga -
la ctop yr a n osyl)-â-D-ga la ctop yr a n osyl]-â-D-glu cop yr a n o-
sid e (44). Compound 43 (300 mg, 0.20 mmol) was dissolved
in AcOH (5 mL), and the mixture was hydrogenated (H2, Pd/C
10%, 50 mg) for 2 h. The mixture was filtered and concen-
trated. The residue was chromatographed (SiO2, heptane/
2-(Tr im et h ylsilyl)et h yl 2-O-Ben zoyl-3-d eoxy-6-O-(p -
m et h oxyb en zoyl)-4-O-[6-O-a cet yl-2,3-d i-O-b en zoyl-4-O-
(2,3,4,6-t et r a -O-a cet yl-r-D-ga la ct op yr a n osyl)-â-D-ga la c-
t op yr a n osyl]-â-D-r ibo-h exop yr a n osid e (41) a n d 2-(Tr i-
m eth ylsilyl)eth yl 2-O-Ben zoyl-3-d eoxy-6-O-p-m eth oxy-
ben zoyl-r-D-r ibo-h exofu r a n osid e (42). (a) A mixture of
compound 36 (305 mg, 0.34 mmol), 19 (203 mg, 0.41 mmol),
acid-washed molecular sieves (AW-300, 300 mg), and CH2Cl2
(5 mL) was cooled (ice-water bath), and the mixture was
stirred under Ar for 20 min. Silver triflate (76 mg, 0.34 mmol)
was added under protection from light. The mixture was
stirred at 0 °C for 4.5 h. The cooling bath was removed, and
stirring was continued for 20 h. An additional portion of silver
triflate (30 mg, 0.13 mmol) was added, and the mixture was
stirred for 3 h. The reaction was quenched by adding Et3N
(250 µL), and the mixture was diluted with CH2Cl2 (75 mL),
filtered through Celite, washed with saturated aqueous NaH-
CO3 (30 mL), dried (Na2SO4), filtered, and concentrated. The
residue was chromatographed (SiO2, heptane/EtOAc 3:2) to
EtOAc 1:20 f 0:1) to give 44 (212 mg, 93%); [R]25 +51.0° (c
D
1.0, CHCl3); 1H NMR data (CDCl3): δ 5.70 (dd, 1 H, J ) 10.7,
7.8 Hz), 5.65 (t, 1 H, J ) 9.5 Hz), 5.36 (dd, 1 H, J ) 9.8, 8.0
Hz), 5.23 (dd, 1 H, J ) 10.7, 2.7 Hz), 4.93 (d, 1 H, J ) 3.2 Hz),
4.83 (d, 1 H, J ) 7.8 Hz), 4.61 (d, 1 H, J ) 8.1 Hz), 4.25 (d, 1
H, J ) 2.7 Hz), 3.84 (s, 3 H), 1.24 (d, 3 H, J ) 5.9 Hz), -0.12
(s, 9 H); 13C NMR data (CDCl3): δ 166.0, 165.6, 165.4, 165.2,
102.04, 102.01, 101.98, 100.13, 100.08, 100.00, 82.6, 18.0, 17.4,
-1.49, -1.51; HRMS calcd for C59H66O21SiNa (M + Na+):
1161.3764; found: 1161.3740.
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-ben zoyl-6-d eoxy-4-O-
[2,3-d i-O-b en zoyl-6-O-(p -m et h oxyb en zoyl)-4-O-(2,3,4,6-
tetr a -O-a cetyl-r-D-ga la ctop yr a n osyl)-â-D-ga la ctop yr a n o-
syl]-â-D-glu cop yr a n osid e (45). Compound 44 (105 mg, 0.092
mmol) was acetylated as described in the preparation of 34.
The crude product was chromatographed (SiO2, heptane/EtOAc
give 42 (37 mg, 18%) and 41 (264 mg, 63%). Compound 42:
1
[R]25 -17.5° (c 1.0, CHCl3); H NMR data (CDCl3): δ 5.36 (d,
D
1 H, J ) 5.1 Hz), 5.14 (s, 1 H), 4.62 (dt, 1 H, J ) 7.6, 3.9, Hz),
4.44 (dd, 1 H, J ) 11.7, 4.6 Hz), 4.35 (dd, 1 H, J ) 11.7, 6.6
Hz), 4.18 (bq, 1 H, J ) 4.4 Hz), 3.86 (s, 3 H), 3.21 (s, 1 H), 2.57
(m, 1 H), 2.18 (dd, 1 H, J ) 14.2, 7.1 Hz), 0,03 (s, 9 H); 13C
NMR δ 166.4, 165.8, 163.6, 122.1, 113.7, 105.4, 81.0, 78.7, 71.2,
66.1, 65.3, 55.5, 29.5, 18.2, -1.4; HRMS calcd for C26H34O8-
1:1) to give 45 (119 mg, 99%); [R]25 +77.5° (c 1.0, CHCl3); 1H
D
NMR data (CDCl3): δ 5.73-5.63 (m, 2 H), 5.47 (dd, 1 H, J )
3.1, 1.0 Hz), 5.03 (d, 1 H, J ) 3.4 Hz), 4.87 (d, 1 H, J ) 7.8
Hz), 4.60 (d, 1 H, J ) 8.0 Hz), 4.46 (bt, 1 H, J ) 7.3 Hz), 4.22
(d, 1 H, J ) 2.4 Hz), 3.86 (s, 3 H), 2.04, 2.00, 1.96, 1.90 (s, 3 H
each), 1.25 (d, 3 H, J ) 6.1 Hz), -0.12 (s, 9 H). Anal. Calcd
for C67H74O25Si: C 61.5, H 5.7. Found: C 61.3, H 5.6.
SiNa (M + Na): 525.1921; found: 525.1908.
1
Compound 41: [R]25 +68.8° (c 1.0, CHCl3); H NMR data
D
(CDCl3): δ 5.64 (dd, 1 H, J ) 10.6, 7.9 Hz), 5.49 (dd, 1 H, J )
3.0, 1.0 Hz), 5.42 (dd, 1 H, J ) 11.0, 3.2 Hz), 5.18 (dd, 1 H, J
) 11.0, 3.4 Hz), 5.01 (d, 1 H, J ) 3.8 Hz), 4.97 (m, 1 H), 4.81,
4.60 (d, 1 H each, J ) 7.8 and 7.9 Hz), 4.29 (d, 1 H, J ) 2.3
Hz), 2.88 (dt, 1 H, J ) 12.6, 5.1 Hz), 2.09, 2.05, 2.01, 1.96,
1.88 (s, 3 H each). Anal. Calcd for C62H72O25Si: C 59.8, H
5.8. Found: C 59.8, H 5.7.
(b) A mixture of compound 37 (224 mg, 0.26 mmol), 19 (88
mg, 0.18 mmol), NIS (77 mg, 0.342 mmol), acid-washed
molecular sieves (AW-300, 300 mg), and CH2Cl2 (5 mL) was
cooled to -50 °C. The mixture was stirred under Ar for 60
min, and then silver triflate (6.8 mg, 0.026 mmol) was added
under protection from light. The mixture was stirred at -50
°C for 40 min and at -30 °C for 3 h. Et3N (200 µL) was added,
and the mixture was diluted with CH2Cl2 (75 mL), filtered
through Celite, washed with 10% aqueous Na2S2O3 (40 mL),
dried (Na2SO4), filtered, and concentrated. The residue was
chromatographed (SiO2, heptane/EtOAc 3:2) to give 41 (201
mg, 92%).
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-ben zoyl-6-d eoxy-4-O-
[2,3-d i-O-b en zoyl-6-O-(p -m et h oxyb en zoyl)-4-O-(2,3,4,6-
t et r a -O-b en zyl-r-D-ga la ct op yr a n osyl)-â-D-ga la ct op yr a -
n osyl]-â-D-glu cop yr a n osid e (43). A mixture of compound
25 (300 mg, 0.31 mmol), silver trifluoromethanesulfonate (120
mg, 0.46 mmol), collidine (92 mL, 0.69 mmol), acid-washed
molecular sieves (AW-300, 150 mg), and CH2Cl2 (5 mL) was
cooled to -60 °C. A solution of 2,3,4,6-tetra-O-benzyl-R-D-
galactopyranosyl chloride16 (265 mg, 0.64 mmol) in CH2Cl2 (3
mL) was added under Ar and protection from light. The
mixture was kept at -50 °C for 2 h and at room temperature
for 20 h. The mixture was diluted with CH2Cl2 (70 mL),
filtered through Celite, washed with saturated aqueous NaH-
CO3 (40 mL), dried (Na2SO4), filtered, and concentrated. The
3-(Hexa d ecylsu lfon yl)-2-[(h exa d ecylsu lfon yl)m eth yl]-
p r op yl 3,4,6-Tr i-O-ben zoyl-2-d eoxy-â-D-a r a bin o-h exop y-
r a n osid e (47) a n d 3-(Hexa d ecylsu lfon yl)-2-[(h exa d ecyl-
su lfon yl)m eth yl]p r op yl 3,4,6-Tr i-O-ben zoyl-2-d eoxy-r-D-
a r a bin o-h exop yr a n osid e (48). HCl (g) was bubbled into a
cold (ice-water bath) solution of 3,4,6-tri-O-benzoyl-D-glucal23
(100 mg, 0.22 mmol) in dry toluene (4 mL) for 40 min. The
mixture was coconcentrated with CHCl3 (2 × 2 mL) to remove
unreacted HCl. The crude product was kept under vacuum
(oil pump) overnight. A mixture of the crude 3,4,6-O-tri-
benzoyl-2-deoxy-R-D-arabino-hexopyranosyl chloride, com-
pound 46 (150 mg, 0.23 mmol), acid-washed molecular sieves
(3 Å, 300 mg), and CH2Cl2 (8 mL) was stirred for 30 min under
Ar and then cooled (ice-water bath), and silver silicate (200
mg) was added under protection from light. The mixture was
stirred at 0 °C for 0.5 h and at room temperature for 30 h and
then filtered through Celite using hot CH2Cl2 (30 mL). The
filtrate was concentrated, and the residue was chromato-
graphed (SiO2, heptane/EtOAc/CH2Cl2 8:1:2 f 5:1:2) to give
48 (50 mg, 21%) and 47 (115 mg, 48%). Compound 47: [R]25
D
-5.3° (c 1.0, CHCl3); 1H NMR data (CDCl3): δ 5.58 (t, 1 H, J )
9.6 Hz), 5.42 (m, 1 H), 4.83 (dd, 1 H, J ) 9.4, 1.9 Hz), 4.65 (dd,
1 H, J ) 12.1, 2.8 Hz), 4.46 (dd, 1 H, J ) 12.0, 5.3 Hz), 2.62
(ddd, 1 H, J ) 12.3, 5.2, 1.8 Hz), 0.88 (t, 6 H, J ) 6.4 Hz); 13
C
NMR data (CDCl3): δ 166.1, 165.7, 165.5, 99.7. Anal. Calcd
for C63H96O12S2: C 68.2, H 8.7. Found: C 68.3, H 8.6.
1
Compound 48: [R]25 +19.4° (c 1.0, CHCl3); H NMR data
D
(CDCl3): δ 5.64 (m, 1 H), 5.57 (t, 1 H, J ) 9.5 Hz), 5.11 (d, 1
H, J ) 3.1 Hz), 4.58 (dd, 1 H, J ) 12.1, 3.1 Hz), 4.47 (dd, 1 H,
J ) 12.2, 5.2 Hz), 4.36 (m, 1 H), 4.06 (dd, 1 H, J ) 10.0, 4.6
Hz), 3.77 (dd, 1 H, J ) 10.0, 4.8 Hz), 3.46 (dd, 2 H, J ) 14.1,
6.4 Hz), 3.25 (dq, 2 H, J ) 13.7, 6.0, 3.4 Hz), 3.12-2.98 (m, 5
H), 2.55 (dd, 1 H, J ) 13.4, 4.9 Hz), 2.04 (m, 1 H), 0.88 (t, 6 H,
J
) 6.4 Hz); HRMS calcd for C63H96O12S2Na (M + Na+):
residue was chromatographed (SiO2, toluene/Et2O 20:1) to give
1
43 (350 mg, 76%); [R]25 +35.7° (c 1.0 CHCl3); H NMR data
1131.6241; found: 1131.6251.
D
(CDCl3): δ 5.77-5.68 (m, 2 H), 5.31 (dd, 1 H, J ) 9.8, 7.9 Hz),
5.10 (dd, 1 H, J ) 10.7, 2.7 Hz), 4.89 (d, 1 H, J ) 7.9 Hz), 4.61
(d, 1 H, J ) 8.0 Hz), 3.98 (dd, 1 H, J ) 10.5, 2.2 Hz), 3.76 (t,
1 H, J ) 9.2 Hz), 3.35 (t, 1 H, J ) 9.4 Hz), 2.98 (dd, 1 H, J )
5.2 and 8.3 Hz), 1.28 (d, 3 H, J ) 6.1 Hz), 0.10 (s, 9 H); 13C
NMR data (CDCl3): δ 166.6, 165.4, 165.3, 165.1, 163.6, 122.3,
113.9, 101.8, 101.72, 101.68, 101.3, 101.2, 100.3, 100.2, 82.1,
79.1, 75.8, 75.5, 75.01, 74.95, 74.9, 74.5, 73.54, 73.47, 73.42,
73.39, 73.3, 73.0, 72.8, 72.72, 72.65, 71.2, 70.3, 69.8, 67.5, 61.7,
3-(Hexa d ecylsu lfon yl)-2-[(h exa d ecylsu lfon yl)m eth yl]-
p r op yl 2-Deoxy-â-D-a r a bin o-h exop yr a n osid e (49) a n d
3-(Hexadecylsu lfon yl)-2-[(h exadecylsu lfon yl)m eth yl]pr o-
p yl 3,6-Di-O-ben zoyl-2-d eoxy-â-D-a r a bin o-h exop yr a n o-
sid e (50). Compound 47 (129 mg, 0.12 mmol) was debenzoy-
lated to give 49, as described in the preparation of 1. Without
further characterization, the crude 49 and dibutyltin oxide
(123 mg, 0.49 mmol) were refluxed in toluene/benzene (13 mL,
10:3); approximately 2 mL of the solvent was removed by

Synthesis of Double-Chain Bis-Sulfone Neoglycolipids
J . Org. Chem., Vol. 61, No. 7, 1996 2393
distillation. Benzoyl chloride (36 µL, 0.31 mmol) was added,
and after 3 min, the mixture was cooled and diluted with CH2-
Cl2 (20 mL) and then cooled with an ice-water bath to
crystallize the stannylene byproducts, filtered and concen-
trated. The residue was chromatographed (SiO2, heptane/
then filtered through Celite using hot CH2Cl2 (5 mL). The
combined organic phase was washed with aqueous 10%
NaHCO3/10% NaCl (25 mL), dried (Na2SO4), filtered, and
concentrated. The residue was chromatographed (SiO2, hep-
tane/EtOAc 3:2) to give 54 (90.5 mg, 72%): [R]25 +48.5° (c
D
EtOAc 4:1 f 3:1) to give 50 (98.2 mg, 84%): [R]25 -2.7° (c
1.0, CHCl3); 1H NMR data (CDCl3): δ 5.65 (dd, 1 H, J ) 10.6,
7.8 Hz), 5.49 (dd, 1 H, J ) 2.9, 1.0 Hz), 5.43 (dd, 1 H, J )
11.0, 3.3 Hz), 5.19 (m, 2 H), 5.04 (d, 1 H, J ) 3.4 Hz), 4.97 (m,
1 H), 4.82 (d, 1 H, J ) 7.8 Hz), 4.63 (d, 1 H, J ) 7.8 Hz), 4.56
(bt, 1 H, J ) 6.6 Hz), 4.30 (d, 1 H, J ) 2.7 Hz), 3.50-2.72 (m,
10 H), 2.10, 2.06, 2.02, 1.96, 1.89 (s, 3 H each), 0.87 (t, 6 H, J
) 6.5 Hz); HRMS calcd for C93H132O29S2Na (M + Na+):
1799.8193; found: 1799.8234.
D
1.0, CHCl3); 1H NMR data (CDCl3): δ 5.15 (m, 1 H), 4.77 (dd,
1 H, J ) 12.2, 4.2 Hz), 4.72 (dd, 1 H, J ) 9.6, 1.9 Hz), 4.63
(dd, 1 H, J ) 12.1, 2.0 Hz), 4.02, 3.96 (dd, 1 H each, J ) 10.0,
5.0, 4.8 Hz), 2.45 (ddd, 1 H, J ) 12.3, 5.1, 1.7 Hz), 0.88 (t, 6 H,
J
) 6.6 Hz); HRMS calcd for C56H92O11S2Na (M + Na+):
1027.5979; found: 1027.5958.
3-(Hexa d ecylsu lfon yl)-2-[(h exa d ecylsu lfon yl)m eth yl]-
p r op yl 3,6-Di-O-b en zoyl-2-d eoxy-4-O-[6-O-a cet yl-2,3-d i-
O-ben zoyl-4-O-(2,3,4,6-tetr a -O-a cetyl-r-D-ga la ctop yr a n o-
syl)-â-D -ga la ct op yr a n osyl]-â-D -a r a bin o-h e xop yr a n o-
sid e (51). Compound 50 (86 mg, 0.086 mmol) and compound
38 (100 mg, 0.12 mmol) were treated with silver silicate (240
mg) in CH2Cl2 (5 mL) as described in the preparation of 41.
After 48 h, the reaction mixture was worked up, and the crude
product was chromatographed (SiO2, heptane/EtOAc/CH2Cl2
2,3-Di-O-ben zoyl-6-d eoxy-4-O-[2,3-d i-O-ben zoyl-6-O-(p-
m eth oxyben zoyl)-4-O-(2,3,4,6-tetr a -O-a cetyl-r-D-ga la cto-
p yr a n osyl)-â-D-ga la ctop yr a n osyl]-D-glu cop yr a n ose (55).
Compound 45 (122 mg, 0.093 mmol) was treated with trifluo-
roacetic acid as described in the preparation of 52. The crude
product was chromatographed (SiO2, heptane/EtOAc 1:1) to
give 55 (106 mg, 94%), which was used without further
characterization. HRMS calcd for C62H62O25Na (M + Na+):
1229.3478; found: 1229.3447.
2:1:1 f 3:2:2) to give 51 (124 mg, 83%): [R]25 +65.5° (c 1.0,
D
CHCl3); 1H NMR data (CDCl3): δ 5.65 (dd, 1 H, J ) 10.8, 7.8
Hz), 5.44 (dd, 1 H, J ) 3.1, 1.2 Hz), 5.35 (m, 1 H), 5.32 (dd, 1
H, J ) 11.2, 3.2 Hz), 5.14 (dd, 1 H, J ) 11.2, 3.5 Hz), 4.96 (d,
1 H, J ) 3.4 Hz), 4.92 (d, 1 H, J ) 7.8 Hz), 4.6 (bd, 1 H, J )
9.8 Hz), 4.19 (d, 1 H, J ) 2.7 Hz), 3.51 (bt, 1 H, J ) 6.8 Hz),
2.54 (bdd, 1 H, J ) 12.2, 5.1 Hz), 2.03, 1.97, 1.96, 1.94, 1.85
(s, 3 H each), 0.88 (t, 6 H, J ) 6.6 Hz); HRMS calcd for
C92H130O28S2Na (M + Na+): 1769.8089; found: 1760.8059.
2-O-Ben zoyl-3-d eoxy-6-O-(p -m et h oxyb en zoyl)-4-O-[6-
O-a cetyl-2,3-d i-O-ben zoyl-4-O-(2,3,4,6-tetr a -O-a cetyl-r-D-
ga la ctop yr a n osyl)-â-D-ga la ctop yr a n osyl]-D-r ibo-h exop y-
r a n ose (52). To a cold (-10 °C) solution of compound 41 (135
mg, 0.11 mmol) in CH2Cl2 (0.5 mL) was added trifluoroacetic
acid (1 mL).8 The mixture was stirred at -10 °C for 30 min,
at 0 °C for 60 min, and 10 °C for 30 min, n-propyl acetate (3
mL) was added, and the mixture was coconcentrated with
toluene (3 × 1 mL). The residue was chromatographed (SiO2,
heptane/EtOAc/CH2Cl2 4:3:2 f 2:3:1) to give 52 (121 mg, 98%),
which was used without full characterization. HRMS calcd
for C59H60O25Na (M + Na): 1167.3321; found: 1167.3333.
2-O-Ben zoyl-3-d eoxy-6-O-p-m eth oxyben zoyl-4-O-[6-O-
a cetyl-2,3-d i-O-ben zoyl-4-O-(2,3,4,6-tetr a-O-a cetyl-r-D-ga -
lactopyr an osyl)-â-D-galactopyr an osyl]-r,â-D-r ibo-h exopy-
r an osyl Tr ich lor oacetim idate (53). To a cold (0 °C) solution
of compound 52 (113 mg, 0.099 mol) in CH2Cl2 (2 mL) was
added trichloroacetonitrile (0.347 mL) and diazabicyclounde-
cane (DMU, 0.014 mL). The reaction was monitored by TLC
(heptane/EtOAc 1:1). The solvent was removed, and the
residue was chromatographed (SiO2, heptane/EtOAc/Et3N 30:
20:1) to give 53 (101 mg, 79% R/â ∼2:1): 1H NMR data
(CDCl3): δ 8.61 (s), 8.56 (s), 6.50 (d, J ) 4.4 Hz), 5.99 (d, J )
7.9 Hz); HRMS calcd for C59H60OSiNa (M + Na): 1310.2418;
found: 1310.2412.
2,3-Di-O-ben zoyl-6-d eoxy-4-O-[2,3-d i-O-ben zoyl-6-O-(p-
m eth oxyben zoyl)-4-O-(2,3,4,6-tetr a -O-a cetyl-r-D-ga la cto-
p yr a n osyl)-â-D-ga la ct op yr a n osyl]-â-D-glu cop yr a n osyl
Tr ich lor oa cetim id a te (56). Compound 55 (102 mg, 0.085
mmol) was treated with trichloroacetonitrile (0.274 mL) and
DBU (0.011 mL) as described in the preparation of 53. The
residue was chromatographed (SiO, heptane/EtOAc/Et3
N 1:1:
0.05) to give 56 (92 mg, 81%); [R]25 +96.8° (c, 1.3 CHCl3); 1H
D
NMR data (CDCl3): δ 8.49 (s, 1 H), 6.59 (d, 1 H, J ) 3.9 Hz),
6.09 (t, 1 H, J ) 9.3 Hz), 5.70 (dd, 1 H, J ) 10.9, 7.8 Hz), 5.46
(bd, 1 H, J ) 2.1 Hz), 5.40 (dd, 1 H, J ) 10.2, 3.4 Hz), 5.14
(dd, 1 H, J ) 11.2, 3.0 Hz), 5.15 (m, 2 H), 5.05 (d, 1 H, J ) 3.5
Hz), 4.93 (d, 1 H, J ) 8.0 Hz), 4.47 (bt, 1 H, J ) 6.4 Hz), 4.23
(d, 1 H, J ) 2.0 Hz), 3.50-2.72 (m, 10 H), 2.04, 2.00, 1.95,
1.89 (s, 3 H each), 1.24 (d, 3 H, J ) 6.6 Hz); HRMS calcd for
C64H62O25SiNa (M + Na): 1372.2574; found: 1372.2566.
3-(Hexa d ecylsu lfon yl)-2-[(h exa d ecylsu lfon yl)m eth yl]-
p r op yl 2,3-Di-O-ben zoyl-6-d eoxy-4-O-[2,3-d i-O-ben zoyl-6-
O-(p-m eth oxyben zoyl)-4-O-(2,3,4,6-tetr a -O-a cetyl-r-D-ga -
l a c t o p y r a n o s y l ) -â-D -g a l a c t o p y r a n o s y l ] -â-D -g l u -
cop yr a n osid e (57). Compound 56 (82 mg, 0.061 mmol) was
treated with 46 (119 mg, 0.18 mmol) and TfOAg (48 mg, 0.061
mmol) as described in the preparation of 54. The crude
product was chromatographed (SiO2, heptane/EtOAc/CH2Cl2
14:7:4) to give 57 (88 mg, 79%): [R]25 +53.2° (c 1.0, CHCl3);
D
1H NMR data (CDCl3): δ 5.74-5.62 (m, 2 H), 5.46 (dd, 1 H, J
) 3.0, 1.2 Hz), 5.03 (d, 1 H, J ) 3.7 Hz), 4.86 (d, 1 H, J ) 7.7
Hz), 4.62 (d, 1 H, J ) 8.1 Hz), 4.46 (bt, 1 H, J ) 6.7 Hz), 4.23
(d, 1 H, J ) 2.3 Hz), 3.15 (m, 2 H), 2.89 (m, 4 H), 2.68 (m, 1
H), 2.05, 2.00, 1.96, 1.90 (s, 3 H each), 0.88 (t, 6 H, J ) 6.4
Hz); HRMS calcd for C98H134O29S2Na (M + Na+): 1861.8450;
found: 1861.8301.
3-(Hexa d ecylsu lfon yl)-2-[(h exa d ecylsu lfon yl)m eth yl]-
p r op yl 2-O-Ben zoyl-3-d eoxy-6-O-(p -m eth oxyben zoyl)-4-
O-[6-O-a cetyl-2,3-d i-O-ben zoyl-4-O-(2,3,4,6-tetr a -O-a cetyl-
r-D-ga la ct op yr a n osyl)-â-D-ga la ct op yr a n osyl]-â-D-r ibo-
-h exop yr a n osid e (54). A mixture of compound 53 (91 mg,
0.71 mmol), 46 (140 mg, 0.22 mmol), acid-washed molecular
sieves (AW-300, 250 mg), and CH2Cl2 (5 mL) was stirred for
30 min under Ar and then cooled (ice-water bath), and TfOAg
(56 mg, 0.070 mmol) was added. The mixture was stirred at
0 °C for 1 h under protection from light and then at room
temperature for 5 h. Solid NaHCO3 (0.5 g) and CH2Cl2 (25
mL) were added, and the mixture was stirred for 10 min and
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
and 1H NMR data with peak assignments for all title com-
pounds described in the Experimental Section (73 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 O951914K