Multivalent Templated Saccharides: Convenient Syntheses of Spacer-Linked 1,1′-Bis -and 1,1′,1″-Tris-β-glycosides by the Glycal Epoxide Glycosidation Method

Full text of DOI:10.1021/jo961819r

J . Org. Chem. 1997, 62, 1543-1546
1543
We anticipated using similar methodology for our
constructs and began our investigation by attempting the
glycosidation of 1,6-hexanediol with 6-benzyl-â-D-galac-
tose 1,2,3,4-tetra-O-acetate.8 In this case, bis-coupling
took place; however, the product was a mixed R,â-bis-
glycoside. With lower order diols (C5, C4, C2) no glycosidic
products were obtained; moreover, debenzylation of the
glycosyl donor was observed. In model studies with â-D-
glucose pentaacetate, coupling gave rise to R,R-bis-
glycosides in modest yields (ca. <25%) with none of the
desired â,â-bis-glycosides being observed. Operating at
lower temperatures (<5 °C), as suggested by Honma et
al.,9 did not affect the stereochemical outcome of the
reaction. Clearly, the trans-directing ability of the 2-
phthalimido group10 does not extend to the 2-acetate
group under these reaction conditions. The use of tri-
methylsilyl triflate, under conditions described for â-gly-
cosylation with a primary alcohol by Ogawa,11 also failed
to provide the desired â,â-bis-glycoside. While Helferich-
catalyzed glycosylation in toluene and toluene/
nitromethane solvent mixtures12 and modified Koenigs-
Knorr glycosylations13 provided the desired â,â-bis-gly-
cosides in model reactions with R-D-acetobromoglucose
and 1,6-hexanediol, yields were again quite modest.
Thus, we turned our attention to alternative glycosida-
tion methods that would be compatible with the some-
what labile 6-benzylic ether functionality.
Mu ltiva len t Tem p la ted Sa cch a r id es:
Con ven ien t Syn th eses of Sp a cer -Lin k ed
1,1′-Bis -a n d 1,1′,1′′-Tr is-â-glycosid es by th e
Glyca l Ep oxid e Glycosid a tion Meth od
Raymond J . Patch,* Hang Chen, and
Chennagiri R. Pandit
Department of Rational Drug Design, Procept, Inc., 840
Memorial Drive, Cambridge, Massachusetts 02139
Received September 24, 1996
The importance of carbohydrates in mediating a host
of biological responses has become increasingly appreci-
ated in recent years. Cellular adhesion events rely on
carbohydrate-protein interactions and have implications
in a variety of disease states such as those involving
cellular proliferation, cellular differentiation, inflamma-
tory responses, pathogenic invasions, and tumor meta-
stasis.1 Furthermore, carbohydrates are believed to af-
fect protein folding2 and additionally may provide con-
formational stability to glycoprotein tertiary structure.3
Advances in synthetic methodology have allowed re-
searchers to prepare complex oligosaccharides as tools
for examining the binding modes of various protein-
carbohydrate interactions. In some cases, such studies
have given rise to important structure-function relation-
ships for oligosaccharide binding to target proteins.4
While advances continue to be made in the development
of synthetic methodologies for preparing complex oli-
gosaccharides, such molecules still pose formidable syn-
thetic challenges and, as such, are not widely viewed as
feasible candidates for drug development. However,
oligosaccharide mimics may offer reasonable alternatives
for therapeutic intervention.5
Danishefsky’s elegant glycal epoxide glycosidation
methodology seemed well suited to our needs for provid-
ing â-glycosides in a highly stereoselective fashion under
mild conditions.14 To our knowledge, application of this
method has been limited to monoglycosidation reactions.
In certain cases where primary and secondary hydroxyl
groups are present in the glycosyl acceptor, reactivity
differences between the two may be sufficient to favor
exclusive primary glycoside formation, thus obviating the
need for secondary alcohol protection.15 By contrast, in
at least one instance it has been postulated that the
presence of two hydroxyl groups may have “interfered
with the ability of zinc chloride to orchestrate glycosida-
tion”.16 Thus, the effectiveness of this methodology with
glycosyl acceptors containing more than one reactive
alcohol functionality has not been clearly established.
Herein, we report that the utility of this method does in
fact extend to single-step homologous bis- and even tris-
glycosidations through reaction with reactive diols and
triols affording bis- and tris-â-glycosides, respectively, in
good yields.
Along these lines, we recently required a series of
molecules 1a , wherein two carbohydrate moieties, benz-
ylated at the 6-hydroxyl position, were to be connected
via â-glycosidic linkages to an aliphatic spacer (X).
Similar molecules have been reported by Lehmann’s
group,6,7 wherein a homologous series of spacer-modified
disaccharides, 1b, were prepared to study the mechanism
of galactosylation by â-D-galactosyltransferase. In those
studies, N-phthalimidoglucosamine peracetate residues
were coupled to primary aliphatic diols (C6-C12) using
tin(IV) chloride as the coupling agent to provide bis-â-
glycosides in good yields.
Scheme 1 outlines the general synthesis of our target
bis-glycosides. Benzyl galactal carbonate 3 was prepared
in two steps (61%) from known silyl galactal carbonate
(8) Lee, E. E.; Keaveney, G.; Hartigan, A.; O’Colla, P. S. Carbohydr.
Res. 1976, 49, 475-478.
(9) Honma, K.; Nakazima, K.; Uematsu, T.; Hamada, A. Chem.
Pharm. Bull. 1976, 24, 394-399.
(1) Reviewed in: Fukuda, M. Bioorg. Med. Chem. 1995, 3, 207-
215.
(10) Lemieux, R. U.; Takeda, T.; Chung, B. Y. ACS Symp. Ser. 1976,
39, 90-115.
(2) Helenius, A. Mol. Biol. Cell 1994, 5, 253-265.
(3) Withka, J . M.; Wyss, D. F.; Wagner, G.; Arulanandum, A. R. N.;
Reinherz, E. L.; Recny, M. A. Structure 1993, 1, 69-81.
(4) For a leading reference, see: Bundle, D. R.; Young, N. M. Curr.
Opin. Struct. Biol. 1992, 2, 666-673 and references cited therein.
(5) Parekh, R. B.; Edge, C. J . Trends Biotechnol. 1994, 12, 339-
345.
(6) Lehmann, J .; Petry, S. Carbohydr. Res. 1990, 204, 141-144.
(7) Ats, S.-C.; Lehmann, J .; Petry, S. Carbohydr. Res. 1994, 252,
325-332.
(11) Ogawa, T.; Beppu, K.; Nakabayashi, S. Carbohydr. Res. 1981,
93, C6-C9.
(12) Helferich, B.; Weis, K. Chem. Ber. 1956, 89, 314-321.
(13) Schroeder, L. R.; Green, J . W. J . Chem. Soc. C 1966, 530-531.
(14) Halcomb, R. L.; Danishefsky, S. J . J . Am. Chem. Soc. 1989,
111, 6661-6666.
(15) Danishefsky, S. J .; Behar, V.; Randolph, J . T.; Lloyd, K. O. J .
Am. Chem. Soc. 1995, 117, 5701-5711.
(16) Liu, K. K.-C.; Danishefsky, S. J . J . Am. Chem. Soc. 1993, 115,
4933-4934.
S0022-3263(96)01819-1 CCC: $14.00 © 1997 American Chemical Society

1544 J . Org. Chem., Vol. 62, No. 5, 1997
Notes
Sch em e 1
2.17 Using the standard conditions described by Dan-
ishefsky, modified to include 3 Å molecular sieves, a
highly stereoselective R-epoxidation with 3,3-dimethyl-
dioxirane18 was realized. Subsequent treatment with
diols (0.45 equiv) and zinc chloride afforded the sym-
metrical bis-â,â′-glycosides 5 in yields ranging from 36
to 80% (unoptimized). Deprotection of the cyclic carbon-
ates was accomplished by methanolysis to provide target
bis-glycosides 6 in satisfactory overall yield.
molecules, in and of themselves or with minor modifica-
tions, may find biological utility as “cluster-type ligands”20
and additionally may help to elucidate binding specificity
of carbohydrate-protein interactions. Clustering effects
have been observed with a number of lectin systems;
multivalent compounds such as those above may prove
useful as functional ligands for these systems.21 Finally,
differentially protected molecules similar to model com-
pounds 5, 7, and 8 may be further elaborated selectively
into oligosaccharide mimetics of increased complexity
including, for example, carbohydrate-based dendrim-
ers.22,23 Results from such studies will be reported in due
course.
Anomeric configurations of cyclic carbonates 5 are
readily assigned by inspection of H1 and H2 resonances
1
in their H NMR spectra. With the exception of 5c, the
anomeric proton signals lie between δ 4.4-4.5 ppm with
the expected coupling (J 1,2 ≈ 6-6.5 Hz).17 Interestingly,
the anomeric proton of butyne analog 5c is significantly
deshielded. Its resonance signal is shifted downfield to
δ 4.98 ppm and exhibits an apparent reduced coupling
to H2 (J 1,2 ≈ 4.5 Hz) due to broadening of the signal.
However, examination of the H2 resonance signal of 5c
(δ 4.19 ppm) reveals the true coupling between these
protons (J ) 6.3 Hz), confirming the assignment of
â-configuration to this bis-glycoside.
Encouraged by these results, we next explored the
possibility of extending the methodology to single-step
tris-glycosidation reactions. In this case, galactal epoxide
4 (3.3 equiv based on galactal precursor 3) was reacted
with 1,3,5-benzenetrimethanol19 to afford the tris-â-
galactoside 7 in 25% yield along with bis-â-galactoside 8
(46%) (Scheme 2). Use of 4.8 equiv of galactal 3 led to
an increased yield (66%) of tris-galactoside 7. No R-
galactoside-containing products were isolated from the
reaction, again due to the high stereoselectivity of the
reaction process. Methanolysis as before afforded 9 in
59% isolated yield.
Exp er im en ta l Section
Gen er a l P r oced u r es. All reactions were carried out in
flame-dried vessels under an inert argon atmosphere. Molecular
sieves were flame-dried under vacuum immediately prior to use.
Anhydrous THF and dichloromethane were used as supplied by
Aldrich. Flash chromatography was performed with silica gel
60 (EM, 0.040-0.063 mm). Radial chromatography was per-
formed on a chromatotron (Harrison Research Co.) using pre-
coated silica gel rotors (Analtech). 1H NMR (250 MHz, Bruker)
spectra were obtained as solutions in CDCl3 with chemical shifts
reported in parts per million (ppm, δ) downfield from internal
Me4Si (TMS) or in DMSO-d6, referencing DMSO at 2.49 ppm.
13C NMR spectra were obtained as solutions in DMSO-d6,
referencing the solvent at 39.50 ppm. Infrared spectra were
recorded on a Perkin-Elmer 1605 series FTIR spectrophotometer.
Negative ion FAB MS spectra were obtained at the Harvard
University Chemistry department24 on samples dissolved in
methanol using an SX102A mass spectrometer (J EOL Ltd.) with
a glycerol matrix-coated probe. Elemental analyses were carried
out by Atlantic Microlab Inc. Melting points are uncorrected.
6-O-Ben zyl-3,4-(oxom eth ylen e)-D-ga la cta l (3). To an ice-
cooled solution of 6-O-tert-butyldiphenylsilyl-3,4-(oxomethylene)-
The relative ease with which bis-glycosides 5, 6, and 8
and tris-glycosides 7 and 9 can be assembled is particu-
larly noteworthy. As oligosaccharide mimetics, such
(20) Lee, Y. C. Carbohydr. Res. 1978, 67, 509-514.
(21) Lee, Y. C.; Lee, R. T. Acc. Chem. Res. 1995, 28, 321-327.
(22) Toyokuni, T.; Hakomori, S-i.; Singhal, A. K. Bioorg. Med. Chem.
1994, 2, 1119-1132.
(23) Zanini, D.; Park, W. K. C.; Meunier, S. J .; Wu, Q.; Aravind, S.;
Kratzer, B.; Roy, R. Polym. Mater. Sci. Eng. 1995, 73, 82-83.
(24) We acknowledge Dr. Andrew Tyler for obtaining mass spectral
data. The Harvard University Chemistry Department Mass Spectrom-
etry Facility is supported by grants from NSF (CHE-9020043) and NIH
(S10-RR06716).
(17) Gervay, J .; Peterson, J . M.; Oriyama, T.; Danishefsky, S. J . J .
Org. Chem. 1993, 58, 5465-5468.
(18) Murray, R. W.; J eyaraman, R. J . Org. Chem. 1985, 50, 2847-
2853.
(19) Cochrane, W. P.; Paulson, P. L.; Stevens, T. S. J . Chem. Soc. C
1968, 630-632.

Notes
J . Org. Chem., Vol. 62, No. 5, 1997 1545
Sch em e 2
D-galactal 217 (3.30 g; 8.0 mmol) in THF (40 mL) was added 1 M
tetrabutylammonium fluoride in THF (8.2 mL; 8.2 mmol), and
the resulting solution was stirred for 0.5 h. The solution was
then concentrated, and the residue was purified by flash
chromatography eluting with chloroform and then chloroform/
methanol (25:1) to afford 3,4-(oxomethylene)-D-galactal (1.18 g;
85%) as a colorless syrup. A solution of this syrup in DMF
(10ml) was treated with silver(I) oxide (4 g) and benzyl bromide
(2 mL), and the resulting mixture was stirred at room temper-
ature. After 3 days, the mixture was diluted with toluene (15
mL), filtered through Celite, and concentrated. Purification of
the residue by flash chromatography eluting with hexane/ethyl
acetate (4:1) afforded 6-O-benzyl-3,4-(oxomethylene)-D-galactal
(3) (1.10g; 61%) as a colorless syrup: 1H NMR (CDCl3) δ 7.5-
7.2 (m, 5H), 6.70 (d, J ) 6.2 Hz, 1H), 5.18 (dd, J ) 8.0, 3.2 Hz,
1H), 5.0-4.9 (m, 2H), 4.60 (s, 2H), 4.15-4.05 (m, 1H), 3.82 (q, J
) 9.6 Hz, 1H), 3.78 (q, J ) 9.6 Hz, 1H).
4.81 (dd, J ) 7.7, 2.0 Hz, 2H), 4.67 (dd, J ) 7.9, 6.1 Hz, 2H),
4.58 (s, 4H), 4.39 (d, J ) 6.6 Hz, 2H), 4.02 (td, J ) 6.6, 2.0 Hz,
2H), 3.90 (dt, J ) 9.9, 6.0 Hz, 2H), 3.80-3.65 (m, 6H), 3.50 (dt,
J ) 9.9, 6.0 Hz, 2H), 3.05 (br d, J ) 3.3 Hz, 2H), 1.70-1.50 (m,
4H), 1.50-1.30 (m, 4H).
1,3-Bis[[6-O-b e n zyl-3,4-(oxom e t h yle n e )-â-D -ga la ct o-
p yr a n osyloxy)p r op a n e (5b). According to the above proce-
dure described for 5a , galactal 3 (220 mg; 0.84 mmol) was
converted to epoxide 4 and subsequently reacted with 1,3-
propanediol (24 uL; 0.33 mmol) to afford after purification by
radial chromatography [chloroform; chloroform/methanol (25:
1)] bis-galactoside 5b (75mg; 36%) as a white foam: 1H NMR
(CDCl3) δ 7.5-7.2 (m, 10H), 4.81 (dd, J ) 7.7, 2.0 Hz, 2H), 4.67
(dd, J ) 7.7, 5.5 Hz, 2H), 4.58 (s, 4H), 4.45 (d, J ) 6.4 Hz, 2H),
4.04 (td, J ) 6.4, 2.0 Hz, 2H), 3.93 (dt, J ) 9.9, 5.5 Hz, 2H),
3.80-3.60 (m, 8H), 3.07 (br d, J ) 3.3 Hz, 2H), 1.90 (quint, J )
7.2 Hz, 2H).
1,6-Bis[[6-O-b e n zyl-3,4-(oxom e t h yle n e )-â-D -ga la ct o-
p yr a n osyl]oxy]h exa n e (5a ). To an ice-cooled solution of
galactal 3 (147 mg; 0.56 mmol) and 3 Å molecular sieves (0.25
g) in dichloromethane (12 mL) was added a solution of 3,3-
dimethyldioxirane18 (6 mL; >0.6 mmol) in a steady, dropwise
fashion. Upon complete addition, the ice bath was removed and
stirring was continued at room temperature. After 1 h, the
reaction was concentrated and briefly dried in vacuo. The
residue was taken up in anhydrous THF (4 mL) and treated with
1,6-hexanediol (30 mg; 0.25 mmol) and additional sieves (0.25
g), and the resulting mixture was stirred at room temperature.
After 15 min, the mixture was cooled to -78 °C, 1 M ZnCl2 in
ether (0.67mL) was added, and the reaction was maintained at
this temperature for 2 h and then overnight at room tempera-
ture. Ethyl acetate (10 mL) was added, the mixture was filtered
through Celite and the filtrate was quenched with saturated
aqueous KHCO3. The organic phase was separated and con-
centrated under reduced pressure, and the residue was purified
by radial chromatography eluting with chloroform and then
chloroform/methanol (25:1) to afford bis-galactoside 5a (136 mg;
80%) as a white foam: 1H NMR (CDCl3) δ 7.5-7.2 (m, 10H),
1,4-Bis-[[6-O-b e n zyl-3,4-(oxom e t h yle n e )-â-D -ga la ct o-
p yr a n osyl]oxy]bu t-2-yn e (5c). According to the above pro-
cedure described for 5a , galactal 3 (220 mg; 0.84 mmol) was
converted to epoxide 4 and subsequently reacted with 1,4-
butynediol (28 mg; 0.33 mmol) to afford after purification by
radial chromatography [chloroform; chloroform/methanol (25:
1)] bis-galactoside 5c (89 mg; 42%) as a white foam: 1H NMR
(CDCl3) δ 7.5-7.2 (m, 10H), 4.98 (br d, J ) 4.5 Hz, 2H), 4.76
(dd, J ) 8.1, 1.8 Hz, 2H), 4.66 (dd, J ) 8.1, 3.8 Hz, 2H), 4.58 (s,
4H), 4.38 (s, 4H), 4.18 (td, J ) 6.3, 1.8 Hz, 2H), 3.8-3.6 (m, 8H).
1,3-Bis-(6-O-b e n zyl-3,4-(oxom e t h yle n e )-â-D -ga la c t o-
p yr a n osyl]oxy]m eth yl]ben zen e (5d ). According to the above
procedure described for 5a , galactal 3 (190 mg; 0.73 mmol) was
converted to epoxide 4 and subsequently reacted with 1,3-
benzenedimethanol (45.5 mg; 0.33 mmol) to afford after purifica-
tion by radial chromatography [chloroform; chloroform/methanol
(25:1)] bis-galactoside 5d (121 mg; 53%) as a white foam: 1H
NMR (CDCl3) δ 7.5-7.1 (m, 14H), 4.88 (d, J ) 12.1 Hz , 2H),
4.81 (dd, J ) 7.7, 2.0 Hz , 2H), 4.62 (dd, J ) 7.7, 5.5 Hz , 2H),
4.60 (s, 4H), 4.58 (d, J ) 12.1 Hz , 2H), 4.51 (d, J ) 5.7 Hz , 2H),

1546 J . Org. Chem., Vol. 62, No. 5, 1997
Notes
4.04 (td, J ) 6.1, 2.0 Hz , 2H), 3.90-3.70 (m, 6H), 3.05 (br d, J
) 3.5 Hz , 2H).
the residue was purified by flash chromatography, eluting with
chloroform/methanol (20:3) to afford 6d (65 mg; 58%) as a white
solid: mp 132-149 °C (gradual melting); FTIR (KBr) 3405 (br),
2919, 2870, 1498, 1453, 1368, 1070, 908, 782, 736, 696 cm-1; 1H
NMR (DMSO-d6) δ 7.5-7.2 (m, 14H), 4.76 (d, J ) 12.15 Hz ,
2H), 4.7-4.4 (m, 8H), 4.22 (d, J ) 7.0 Hz , 2H), 3.8-3.5 (m, 10H),
3.5-3.1 (m, 6H); 13C NMR (DMSO-d6) δ 138.59, 137.92, 128.18,
127.93, 127.35, 127.31, 126.89, 126.71, 102.73, 73.45, 73.16,
72.16, 70.46, 69.53, 69.50, 68.64; MS (FAB (M-)) m/ e 641 [M -
H], 651 [M - CH2Ph], 389 [M - (6-benzyl-1-deoxygalactose)].
Anal. Calcd for C34H42O12‚0.5 H2O: C, 62.66; H, 6.65. Found:
C, 62.62; H, 6.68.
1,3,5-Tr is-[[[6-O-ben zyl-3,4-(oxom eth ylen e)-â-D-ga la cto-
p yr a n osyl]oxy]m eth yl]ben zen e (7). According to the above
procedure described for 5a , galactal 3 (220 mg; 0.84 mmol) was
converted to epoxide 4 and subsequently reacted with 1,3,5-
benzenetrimethanol19 (38 mg; 0.23 mmol) to afford after puri-
fication by radial chromatography [chloroform/methanol (15:1)]
tris-galactoside 7 (52 mg; 25%) and bis-galactoside 8 (65 mg;
43%), each as a white foam. When the reaction was performed
using 4.8 equivalents of galactal 3, tris-galactoside 7 was isolated
in 66% yield: 1H NMR (CDCl3) δ 7.5-7.2 (m, 18H), 4.81 (d, J )
12.0 Hz , 3H), 4.72 (dd, J ) 7.8, 2.0 Hz , 2H), 4.62-4.52 (m,
3H), 4.58 (s,6H), 4.48 (d, J ) 5.5 Hz , 2H), 4.44 (d, J ) 12.0 Hz
, 2H), 4.05 (br td, J ) 6.0, 2.0 Hz , 2H), 3.9-3.8 (br hump, 3H,
exch), 3.8-3.6 (m, 9H).
1,6-Bis[6-O-ben zyl-â-D-galactopyr an osyl)oxy]h exan e (6a).
To a solution of bis-galactoside 5a (136 mg; 0.20 mmol) in
anhydrous methanol (5 mL) was added a pinch of sodium
methoxide, and the resulting mixture was stirred at room
temperature. After 2 h, the product, which formed as a white
precipitate, was filtered and dried under vacuum to provide pure
6a (67 mg; 54%): mp 174.5-176 °C; FTIR (KBr) 3513, 3446,
3260 (br), 2935, 2866, 1377, 1152, 1091, 1076, 1057, 1022, 948,
1
921, 908, 857, 786, 739, 699 cm-1; H NMR (DMSO-d6) δ 7.5-
7.2 (m, 10H), 4.84 (br d, J ) 4.0 Hz , 2H), 4.72 (br d, J ) 4.5 Hz
, 2H), 4.49 (s, 4H), 4.46 (d, J ) 5.0 Hz , 2H), 4.07 (br d, J ) 7.0
Hz , 2H), 3.75-3.15 (m, 16H), 1.60-1.40 (m, 4H), 1.40-1.20 (m,
4H); 13C NMR (DMSO-d6) δ 138.60, 128.16, 127.32, 127.30,
103.36, 73.31, 73.24, 72.13, 70.41, 69.53, 68.66, 68.50, 29.32,
25.39; MS (FAB (M-)) m/ e 621 [M - H], 531 [M - CH2Ph], 439,
369 [M
32H46O12: C, 61.72; H, 7.45. Found: C, 61.62; H, 7.49.
1,3-Bis[6-O-b en zyl-â-D-ga la ct op yr a n osyl)oxy]p r op a n e
- (6-benzyl-1-deoxygalactose)]. Anal. Calcd for
C
(6b). To a solution of bis-galactoside 5b (91 mg; 0.14 mmol) in
anhydrous methanol (5 mL) was added a pinch of sodium
methoxide and the resulting mixture was stirred at room
temperature. After 2 h, the solvent was evaporated and the
residue was purified by flash chromatography, eluting with
chloroform/methanol (4:1) to afford 6b (41 mg; 49%) as a white
solid: mp 118.5-120 °C; FTIR (KBr) 3497, 3426 (br), 2923, 2869,
Bis-ga la ctosid e (8): 1H NMR (CDCl3) δ 7.5-7.2 (m, 13H),
4.84 (d, J ) 12.0 Hz , 2H), 4.77 (dd, J ) 7.8, 2.0 Hz , 2H), 4.65-
4.55 (m, 8H), 4.53 (d, J ) 5.5 Hz , 2H), 4.49 (s, 2H), 4.05 (br td,
J ) 6.0, 2.0 Hz , 2H), 3.85-3.65 (m, 6H), 3.65-3.45 (br, 3H,
exch). 13C NMR (CDCl3) δ 154.60, 141.41, 137.48, 137.26,
128.54, 128.02, 127.92, 127.34, 126.73, 99.44, 77.20, 77.10, 74.58,
73.75, 70.33, 69.65, 68.57, 64.48; MS (FAB (M+)) m/ e 747 [M +
Na]; HRMS (FAB (M-)) calcd for C37H40O15 723.2289 [M - H],
found 723.2293.
1,3,5-[[Tr is-(6-O-ben zyl-â-D-ga la ctop yr a n osyl]oxy]m eth -
yl]ben zen e (9). To a solution of tris-galactoside 7 (98 mg; 0.098
mmol) in anhydrous methanol (5 mL) was added a pinch of
sodium methoxide, and the resulting mixture was stirred
overnight at room temperature. The solvent was evaporated,
and the residue was crystallized from water/EtOH, affording
pure 9 (53 mg; 59%) as a tan amorphous powder: mp > 150 °C,
dec; FTIR (KBr) 3406 (br), 2913, 2868, 1604, 1497, 1454, 1368,
1074, 908, 858, 785, 737, 697 cm-1; 1H NMR (DMSO-d6) δ 7.5-
7.2 (m, 18H), 5.15-5.0 (br hump, 3H), 4.95-4.75 (br hump, 3H),
4.79 (d, J ) 12.4 Hz , 3H), 4.65-4.40 (m, 12H), 4.24 (d, J ) 7.0
Hz , 3H), 3.7-3.5 (m, 12H), 3.5-3.2 (m, 6H); 13C NMR (DMSO-
d6) δ 138.59, 137.86, 128.22, 127.39, 127.35, 126.15, 102.85,
73.48, 73.21, 72.19, 70.49, 69.63, 69.48, 68.66; MS (FAB (M-))
m/ e 923 [M - H], 833 [M - CH2Ph], 671 [M - (6-benzyl-1-
deoxygalactose)]; HRMS (FAB) calcd for C48H60O18 923.3701 [M
- H], found 923.3731.
1452, 1376, 1144, 1097, 1072, 1058, 949, 923, 851, 742, 697 cm-1
;
1H NMR (DMSO-d6) δ 7.5-7.2 (m, 10H), 4.86 (br d, J ) 4.4 Hz
, 2H), 4.72 (br d, J ) 5.0 Hz , 2H), 4.49 (s, 4H), 4.47 (d, J ) 5.5
Hz , 2H), 4.09 (br d, J ) 7.1 Hz , 2H), 3.77 (dt, J ) 9.9, 6.6 Hz
), 3.65-3.40 (m, 10H), 3.30-3.20 (m, 4H), 1.80 (quint, J ) 7.2
Hz , 2H); 13C NMR (DMSO-d6) δ 138.56, 128.17, 127.35, 127.29,
103.52, 73.26, 73.21, 72.13, 70.42, 69.45, 68.62, 65.82, 29.92; MS
(FAB (M-)) m/ e 579 [M - H], 489 [M - CH2Ph], 397, 327 [M -
(6-benzyl-1-deoxygalactose)]. Anal. Calcd for C29H40O12
59.99; H, 6.94. Found: C, 59.77; H, 6.88.
: C,
1,4-Bis-(6-O-b e n zyl-â-D -ga la ct op yr a n osyl)oxy]b u t -2-
yn e (6c). To a solution of bis-galactoside 5c (89 mg; 0.14 mmol)
in anhydrous methanol (5 mL) was added a pinch of sodium
methoxide, and the resulting mixture was stirred at room
temperature. After 2 h, the solvent was evaporated and the
residue was treated with water (2 mL). The white crystalline
product that resulted was filtered and dried under vacuum,
affording pure 6c (43 mg; 53%): mp 160-161.5 °C; FTIR (KBr)
3481, 3436, 3344, 3251, 2908, 2862, 1453, 1343, 1272, 1206,
1100, 1055, 1008, 923, 905, 888, 782, 753, 734, 697 cm-1 1H
;
NMR (DMSO-d6) δ 7.5-7.2 (m, 10H), 5.02 (br d, J ) 3.8 Hz ,
2H), 4.75 (br d, J ) 4.4 Hz , 2H), 4.55-4.45 (m, 6H), 4.40 (d, J
) 13.6 Hz , 2H), 4.28 (d, J ) 13.6 Hz , 2H), 4.23 (br d, J ) 7.0
Hz , 2H), 3.65-3.40 (m, 8H), 3.40-3.20 (m, 4H); 13C NMR
(DMSO-d6) δ 138.54, 128.19, 127.39, 127.32, 101.41, 82.18, 73.48,
73.08, 72.18, 70.23, 69.40, 68.54, 55.00; MS (FAB (M-)) m/ e 589
[M - H], 499 [M - CH2Ph], 337 [M - (6-benzyl-1-deoxygalac-
tose)]. Anal. Calcd for C30H38O12: C, 61.01; H, 6.49. Found:
C, 60.81; H, 6.46.
1,3-Bis-[[6-O-ben zyl-â-D-ga la ctop yr a n osyl)oxy]m eth yl)-
ben zen e (6d ). To a solution of bis-galactoside 5d (121 mg; 0.17
mmol) in anhydrous methanol (5 mL) was added a pinch of
sodium methoxide, and the resulting mixture was stirred at
room temperature. After 2 h, the solvent was evaporated, and
Su p p or tin g In for m a tion Ava ila ble: Copies of the 1H
NMR spectra for compounds 3, 5a -d , and 7-9 (15 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 O961819R