A practical synthesis of benzyl α- and allyl β-D-glucopyranosides regioselectively substituted with (CH2)3OH groups: Stereocontrolled β- galactosidation by cation π-interaction

Article abstract of DOI:10.1055/s-1999-3566

In a simple and efficient two-step reaction, the 2,3- and 4,6-di-O- hydroxypropyl regioselectively-functionalized glucose derivatives, 5, 12 and 13 were synthesized by reaction of the allyl 4,6-O-benzylidene-β-D- glucopyranoside (1), allyl 2,3-di-O-benzyl

Full text of DOI:10.1055/s-1999-3566

PAPER
1625
A Practical Synthesis of Benzyl a- and Allyl b-D-Glucopyranosides
Regioselectively Substituted with (CH2)3OH Groups: Stereocontrolled b-
Galactosidation by Cation p-Interaction
Ion Neda,a* Peyman Sakhaii,a Anke Waßmann,b Ulf Niemeyer,c Eckhard Günther,c Jürgen Engelc
a Institut für Anorganische und Analytische Chemie der Technischen Universität, Postfach 3329, D-38023 Braunschweig, Germany
b Gesellschaft für Biotechnologische Forschung (GBF), Mascheroder Weg 1, D-38124 Braunschweig, Germany
c ASTA Medica AG, Weismüllerstr. 45, D-60314 Frankfurt, Germany
Received 4 January 1999; revised 12 April 1999
Dedicated to Professor Reinhard Schmutzler on the occasion of his 65th birthday
has not yet been investigated. This is due to the lack of ef-
ficient methods for the preparation of glycosyl acceptors
bearing HO(CH2)3O-groups and allyl- or aminopropyl
groups, the latter bonded stereoselectively to the anomeric
Abstract: In a simple and efficient two-step reaction, the 2,3- and
4,6-di-O-hydroxypropyl regioselectively-functionalized glucose
derivatives, 5, 12 and 13 were synthesized by reaction of the allyl
4,6-O-benzylidene-b-D-glucopyranoside (1), allyl 2,3-di-O-benzyl-
b-D-glucopyranoside (6) and benzyl 2,3-di-O-benzyl-a-D-glucopy- center and acting as spacer groups for the binding to the
ranoside (7) with 2-(3-bromopropoxy)tetrahydro-2H-pyran
(BPTHP), followed by removal of the tetrahydropyranyl groups us-
ing pyridinium p-toluenesulfonate (PPTS). Reaction of 1 with 2-(3-
solid phase.
In general, there are many strategies for the substitution of
glucose with (CH2)nOH groups; for example: allylation
with allyl chloride under the conditions of inverse phase
transfer catalysis3f,8 and subsequent hydroboration with
bis[3-methylbut-2-yl]borane,3f,9 treatment of glucose with
allyl alcohol and BF3•OEt2 and ozonolysis,3f,10a,b reaction
of glucose derivatives with alkyl dichlorides and subse-
quent basic hydrolysis to hydroxy compounds6a or the flu-
orination of 1,2-O-ethanediyl-b-D-glucopyranoside with
bromopropoxy)tetrahydro-2H-pyran led to a mixture of three reac-
tion products 2–4. The major product 2 separated by column chro-
matography, was treated with PPTS to give allyl 4,6-O-
benzylidene-2,3-di-O-(3-hydroxypropyl)-b-D-glucopyranoside (5).
In contrast to 3 and 4, the regioisomers 10 and 11 could be separated
and isolated in high yield. Compound 15 was synthesized by selec-
tive protection of the O-6 position with tert-butyldiphenylsilyl chlo-
ride and functionalization with BPTHP. Subsequent deprotection
using TBAF led to 11. The highly b-stereoselective galactosylation
of 12 with 2,3,4,6-tetra-O-benzyl-b-D-galactopyranosyl difluoro- HF and subsequent basic solvolysis with sodium metha-
nolate.6b However, our attempt to use these strategies for
the preparation of allyl 4,6-di-O-benzylidene-2,3-di-O-
phosphate 16 led to the allyl 2,3-di-O-benzyl-4,6-di-O-[3-(2,3,4,6-
tetra-O-benzyl-b-D-galactopyranosyl-oxypropyl)]-b-D-glucopyra-
noside (17).
(3-hydroxypropyl)-b-D-glucopyranoside (5) or allyl 2,3-
Key words: carbohydrates, spacer groups, glucopyranosides
di-O-benzyl-4,6-di-O-(3-hydroxypropyl)-b-D-glucopyra-
noside (12) failed, because the conversion of the allyl
groups of the perallylated glucoside derivative3f into 3-hy-
droxypropyl spacers by the methods mentioned above
could not be performed regioselectively.
Specific interactions of carbohydrate ligands and lectin
receptors have recently received much attention,1 because
they represent a key step in many biological recognition
processes.1 As a direct consequence of these properties,
considerable attention has been focused on the develop-
ment of carbohydrate-centered multivalent glycomimet-
ics, such as glycoclusters and glycodendrimers2 or spacer-
modified oligosaccharides3 in many different forms with
species whose molecular structures are comparable, in
their sites and shapes, to biomolecules. These have recent-
ly been shown to serve as high affinity ligands in many
carbohydrate-protein interactions due to the “multivalen-
cy effect”,4 their spacing and flexibility1,5 playing a cen-
tral role in such interactions.
We report here the substitution of anomerically pure allyl
4,6-O-benzylidene-b-D-glucopyranoside (1),11 allyl 2,3-
di-O-benzyl-b-D-glucopyranoside (6)12 and benzyl 2,3-di-
O-benzyl-a-D-glucopyranoside (7)13,14 with (CH2)3OH
groups, using 2-(3-bromopropoxy)tetrahydro-2H-pyran
(BPTHP).15 In order to investigate spacer-modified oli-
gosaccharides as affinity ligands in the isolation of tumor
cell lectins via affinity chromatography, the synthesis of a
prototype 17 has been described.
It is known that glycosyl donors having phosphorous con-
taining groups at the anomeric center allow the glycosyla-
tion of glycosyl acceptors under mild conditions without
the use of strong Lewis acids.16 In the present case we de-
scribe an efficient method for the highly b-stereoselective
galactosylation of 12 using 2,3,4,6-tetra-O-benzyl-b-D-
galactopyranosyl difluorophosphate (16) as galactosyl do-
nor.
The chemistry of spacer-modified monosaccharides or
multiantennary oligosaccharides from O-protected and O-
unprotected sugars has been employed in many cases and
is well described.2g,3,6 However, the synthesis of (1Æ4)–
(1Æ6)-linked di- or multiantennary oligosaccharides in
which the glucose backbone involves multiple O-attach-
ment of the sugar moiety through (CH2)3O-spacers7 and
allyl- or aminoalkyl groups located at the anomeric center,
According to Scheme 1, compound 2 was prepared from
111 using an excess of BPTHP15 in DMF in the presence of
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1626
I. Neda et al.
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Scheme 1
sodium hydride at room temperature. TLC investigation tions with (CH2)3OTHP groups permits the efficient
of the reaction solution exhibited a mixture of three reac- separation of both regioisomers 10 and 11.
tion products 2–4 (Scheme 1) with different degrees of
substitution. HPLC measurements revealed the derivative
The O-6 selective silylation of the known 4,6-O-unpro-
tected derivative 713,14 with tert-butyldiphenylsilyl chlo-
2 as the major product in the mixture mentioned above.
ride (TBDS)17a,b,d in the presence of imidazole leads to 14.
The allyl b-D-glucopyranoside derivative 2 was separated
By O-4 alkylation of 14 with BPTHP in the presence of
in high yield by silica gel column chromatography
NaH and subsequent O-6 desilylation with (Bu)4N+F-, the
regioisomer 11 (via 15, Scheme 3) is formed exclusively.
(Table 1), whereas the compounds 3 and 4 could only be
isolated as a mixture.
The structures of spacer-modified glucopyranosides 5, 12
and 13 could be unequivocally confirmed by means of
Treatment of 2 with PPTS (acidic catalyst) in methanol at
room temperature did not yield the expected allyl 2,3-di-
NMR spectroscopy and MS spectrometry. According to
O-(3-hydroxypropyl)-b-D-glucopyranoside A, instead the
4,6-benzylidene-protected derivative 5 was obtained in
high yield via chemoselective removal of the terminal
THP-groups which was purified by column chromatogra-
phy (Table 1).
1H and 13C NMR evidence, compounds 5, 12 and 13 show
doublets in the range of d = 4.2–4.8 for the anomeric pro-
ton. The coupling constants (3JHH ª 8 Hz) confirmed the b-
configuration. By 2D-COLOC investigations, cross peaks
(3JCH) between the protons of the spacer groups (in the
Similarly, the known derivatives 612 and 713,14 were con- case of 10 to the 6-C and in the case of 11 to the 4-C atom
verted by reaction with BPTHP15 under the conditions de- of the glucose backbone) could be observed. Thus, a spe-
scribed above into compounds 8–11 (Scheme 2). The cific assignment of the molecular structure via the connec-
products 12 and 13 were obtained by acid-catalyzed tivity of the spacer groups to the glucose backbone was
(PPTS15) removal of the THP-groups in 8 and 9. After col- now possible. In most cases, the protons of the propyl
umn chromatography purification, either the b- or the a- groups of the diols mentioned above are strongly coupled
form of the glucopyranosides 8–13 were obtained exclu- and are diastereotopic, leading to a general spin system
sively in good yields (Table 1). In contrast to 3 and 4 [ABCDEF]. For the assignment of all protons, CH-corre-
(Scheme 1), the regioisomers 10 and 11 (Scheme 2) could lation or HMQC spectra were used, because overlapping
be separated by silica gel column chromatography in high multiplets did not allow a simple assignment from routine
yield (Table 1). The marked difference in the polarity gen- 1D NMR spectra. Compounds 5, 12 and 13 are not only
erated by unsymmetrically substituted O-4 and O-6 posi- attractive building blocks in the synthesis of asymmetric
diantennary or tetraantennary oligosaccharides, but also
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Stereocontrolled b-Galactosidation by Cation p-Interaction
1627
Table 1 Experimental Data for the Preparation of 2–5, 9–13
Starting Materials:a
g (mmol)
Product(s)
Yield
g (%)
Rf-values
(solvents)b
1: 0.5 (1.5),
BPTHP: 1.0 (4.6),
NaH: 0.2 (9.3)
2, 3 and 4
2: 0.7 (75)
3: 0.05 (5)
4: 0.05 (5)
2: 0.4 (Et2O/PE, 2:1)
3: 0.3 (Et2O/PE, 2:1)
4: 0.3 (Et2O/PE, 2:1)
6: 6.0 (15.0),
8
4.7 (46)
0.6 (Et2O/PE, 2:1)
BPTHP: 10.0 (45.0),
NaH: 2.2 (90.0)
7: 0.5 (1.1),
BPTHP: 0.7 (3.3),
NaH: 0.2 (9.3)
9, 10 and 11
9: 0.6 (70)
10: 0.04 (5)
11: 0.04 (5)
9: 0.5 (Et2O/PE, 2:1)
10: 0.4 (Et2O/PE, 2:1)
11: 0.3 (Et2O/PE, 2:1)
2: 0.3 (0.5),
PPTS: 0.4 (1.4)
5
12
13
0.2 (85)
2.4 (95)
1.1 (75)
0.1 (Et2O)
0.9 (EtOH)
0.2 (Et2O)
8: 3.4 (5.0),
PPTS: 4.0 (15.7)
9: 2.0 (2.7),
PPTS: 2.1 (8.2)
a cf. Schemes 1 and 2. BPTHP = 2-(3-bromopropoxy) tetrahydro-2H-pyran. PPTS: pyridinium p-toluenesulfonate.
b PE = petroleum ether.
should be a suitable precursor for the preparation of We have already described the synthesis of allyl 2,3-di-O-
neoglycoconjugates by solid-phase synthesis or for a sol- benzyl-4,6-di-O-[3-(b-D-galactopyranosyloxypropyl)]-b-
id-phase carbohydrate library.17d It is our aim to D-glucopyranoside (17),7a using 2,3,4,6-tetra-O-benzyl-a-
synthesize diantennary, b, b-selectively functionalized D-galactopyranosyl trichloroacetimidate19 as galactosyl
oligosaccharides from 12.
donor and 12 as glucosyl acceptor.7a However, by this
method a mixture of anomers of 17 was formed (b,b,b/
Scheme 2
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1628
I. Neda et al.
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Scheme 3
b,b,a/b,a,b), which could not be separated by column display typical coupling constants (3JHH ª 8 Hz) for the
chromatography. Therefore, we have synthesized the new anomeric protons due to the exclusively b-configuration
galactosyl donor 16 employing difluorophosphate20 as at all anomeric centers. The modification of allyl group
anomeric leaving group by reaction of trimethylsilyl functions by galactosylation reaction was not observed.
2,3,4,6-tetra-O-benzyl-b-D-galactopyranoside17c
with
This highly efficient b-stereoselectivity may be explained
by the complexation ability of TOPC through cation-p-in-
teraction.22 However, due to the intramolecular complex-
phosphorus oxyfluoride in the presence of phosphorus
pentafluoride.
By using 16 as galactosyl donor, with AgClO4 added to ation-decomplexation equilibrium22 in the cone-TOPC-
activate the leaving group and tetra-O-propylated cone- AgClO4 complex, Ag+ is capable of activating the leaving
calix[4]arene21 (TOPC) for its stabilizing effect by cation- group.
p-interaction,22 a b-stereoselective galactosylation of the
anomerically pure compound 12 to 17 could be conducted
The results of the investigations of the TOPC-oxonium
complex by computional studies and NMR spectroscopy
successfully (Scheme 4). The crude product was purified
indicate that the cationic guest is selectively included in
by silica gel column chromatography leading exclusively
the cone cavity and that the preorganization of the ben-
to the b,b,b-isomer.
zene rings is indispensable to the formation of the “cation-
According to 1H and 13C NMR evidence, a stereospecific p- and p-p-interactions”.23
course of galactosylation was observed. Compound 17
Scheme 4
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Stereocontrolled b-Galactosidation by Cation p-Interaction
1629
residue was dissolved in anhyd THF (20 mL) and molecular sieves
(4 Å) were added. After stirring for 30 min at r.t., AcOH (0.05 mL)
and a solution of Bu4NF in THF (1 mL, 1 M) was added at –20 °C.
After stirring for 10 h at this temperature, the mixture was poured
onto ice water (10 mL) and extracted with CH2Cl2 (3 x 20 mL). The
combined organic solutions were dried and the solvent was evapo-
rated in vacuo. The residue was purified by silica gel column chro-
matography (eluent: Et2O/hexane, 2:1, v/v), leading to the expected
product 11 with oily consistency; yield:4.2 g (47%).
We assume that the reaction involves a b-nucleophilic at-
tack on the anomeric center, probably due to two fac-
tors:1) the stabilization of the glycosyl cation by
complexation at the a-face and 2) the p-p-interaction be-
tween O-2 benzyl group of the oxocarbenium cation and
TOPC by the electron-rich faces of host aromatic rings.
In conclusion, the results presented here provide an effi-
cient synthesis of the 2,3- or 4,6-di-O-hydroxypropyl-
functionalized glucose derivatives 5, 12 and 13. These
compounds represent potential precursors for the synthe-
sis of multiantennary oligosaccharides as for example 17.
We have developed a new method for the b-stereoselec-
tive galactosylation bearing galactosyl difluorophosphate
as galactosyl donor and TOPC as stabilizator for the oxo-
carbenium ion. The latter compound is intended to serve
(via immobilization on solid phase and subsequent depro-
tection) as affinity ligand in the isolation of tumour cell
lectins via affinity chromatography.
Deprotection of 2, 8 and 9 with Pyridinium p-Toluenesulfonate
(PPTS); General Procedure
In a three-necked round-bottom flask, fitted with a reflux-condens-
er, the starting compound (2, 8 and 9, respectively) and PPTS15
(amounts, see Table) were dissolved in anhyd MeOH (40 mL). The
solution was stirred for 3 h at 60 °C. Subsequently, satd aq NaHCO3
solution (50 mL) was added. The reaction product was extracted
with CHCl3 (3 x 100 mL). The organic layer was separated and
dried (Na2SO4). The solvent was evaporated in vacuo and the oily
residue was purified by silica gel column chromatography (eluent:
Et2O). In this manner, all byproducts were removed from the col-
umn. The products 5, 12 and 13 were obtained by washing the silica
gel with ethanol. Subsequently, the solvent was removed in vacuo.
The oily reaction products remained in pure form (Table 1).
NMR spectra were recorded on a Bruker AC 400 spectrometer and
on a Bruker DMX 600 spectrometer with inverse probe head.
Chemical shifts (d) are given in ppm downfield from TMS. Cou-
pling constants are given in Hz. Many assignments were made with
support of DEPT, 1H1H-COSY, 1H13C-COSY, HMQC, HMBC and
TOCSY experiments. Mass spectra (ESI) were recorded using a
Finnigan MAT TSQ 700 triple quadrupole mass spectrometer
equipped with a NanoES ion source. Elemental analyses were con-
ducted at the Institut für Anorganische und Analytische Chemie der
Technischen Universität Braunschweig. TLC was performed on sil-
ica gel 60 F254 coated foil (Merck). Preparative column chromato-
graphy was performed with silica gel 60 (63–200 mm, Merck).
Allyl 4,6-O-Benzylidene-2,3-di-O-[3-(tetrahydro-2H-pyra-
nyl)oxypropyl]-b-D-glucopyranoside (2)
1H NMR (400.1 MHz, CDCl3): d = 7.41–7.20 (m, 20 H, arom), 5.85
(mc ª dddd, 4 H, OCHaHbCH = CHcHd), 5.45 (s, 4 H, CHPh), 5.24
(mc ª dddd, 4 H, OCHaHbCH = CHcHd), 5.13 (mc ª dddd, 4 H,
OCHaHbCH = CHcHd), 4.41 and 4.51 (mc ª t, 8 H, 1-CTHPH), 4.36
3
(d, JHH = 7.7 Hz, 4 H, 1-Hgluc), 4.29 (mc ª dddd, 4 H,
OCHaHbCH = CHcHd), 4.24 (mc, 4 H, 6-CglucHaHb), 4.05 (mc ª
dddd, 4 H, OCHaHbCH = CHcHd), 3.77 (mc, 8 H, 5-CTHPHaHb), 3.75
(mc,
8
H, THPOCHaHbCH2CH2O), 3.74 (mc, 16 H,
THPOCH2CH2CH2O), 3.68 (mc, 4 H, 6-CglucHaHb), 3.47 (mc ª t, 4
H, 4-Hgluc), 3.44 (mc, 8 H, 5-CTHPHaHb), 3.38 (mc ª t, 4 H, 3-Hgluc),
3.42 (mc, 8 H, THPOCHaHbCH2CH2O), 3.27 (mc ª ddd, 4 H, 5-
Hgluc), 3.12 (mc ª t, 4 H, 2-Hgluc), 1.81 (mc ª quin, 8 H,
THPOCH2CH2CH2O), ª 1.75 (mc, 8 H, 3-CTHPHaHb), ª 1.70 (mc ª
quin, 8 H, THPOCH2CH2CH2O), ª 1.60 (mc, 8 H, 2-CTHPHaHb), ª
1.50 (mc, 8 H, 2-CTHPHaHb), 1.48 (mc, 8 H, 4-CTHPHaHb), 1.44 (mc,
8 H, 4-CTHPHaHb), ª 1.40 (mc, 8 H, 3-CTHPHaHb).
13C NMR (100.61 MHz, CDCl3): d = 133.76 (4 C,
OCH2CH = CH2), 128.79–125.90 (20 C, CH, arom), 117.36, 117.35
(4 C, OCH2CH = CH2), 103.04, 102.98 (4 C, 1-Cgluc), 101.10,
101.00 (4 C, CHPh), 98.75, 98.73, 98.68 (8 C, 1-CTHP), 82.37, 82.28
(4 C, 2-Cgluc), 81.36, 81.31 (4 C, 3-Cgluc), 81.29, 81.21 (4 C, 4-Cgluc),
70.54, 70.52 (4 C, OCH2CH = CH2), 70.46, 70.45, 70.43, 70.40,
70.24, 70.21 (8 C, THPOCH2 CH2CH2O), 68.71 (4 C, 6-Cgluc),
65.98, 65.95 (4 C, 5-Cgluc), 64.50, 64.41 (8 C,
THPOCH2CH2CH2O), 62.14, 62.11, 62.01 (8 C, 5-CTHP), 30.65,
30.62 (8 C, 2-CTHP), 30.55, 30.69, 30.61 (8 C,
THPOCH2CH2CH2O), 25.46, 25.44 (8 C, 4-CTHP), 19.54, 19.48 (8
C, 3-CTHP).
Estherification of Glucosides 1, 6 and 7 with 2-(3-Bromopro-
poxy)tetrahydro-2H-pyran (BPTHP); General Procedure
Under N2 atmosphere, compounds 111, 612 and 713,14 (Table) were
dissolved in anhyd DMF (60 mL). To these solutions, the corre-
sponding amounts of NaH [freshly washed with anhyd hexane (20
mL), Table] were added. The suspensions were stirred at r.t. for 30
min. After cooling to 0 °C, BPTHP15 was added within 2 min (Ta-
ble). After stirring at r.t. for 12 h, EtOH (10 mL) and H2O (20 mL)
were added. The products were extracted with CH2Cl2 (3 x 100
mL). The organic layers were separated and dried (Na2SO4). After
filtration, the solvents were evaporated in vacuo. The residues were
purified by silica gel column chromatography (eluent: Et2O/hexane,
3:1, v/v), leading to the expected products 2, 8–11 in oily consis-
tence (Table 1). Compounds 3 and 4 could only be isolated as a mix-
ture of regioisomers.
Regioselective Synthesis of Compound 11
A solution of 713,14 (6.0 g, 15.0 mmol), imidazole (2.0 g, 30 mmol)
and tert-butyldiphenylsilyl chloride (4.9 g, 18 mmol) in CH2Cl2 (20
mL) was stirred for 8 h at r.t. under N2 atmosphere. Subsequently,
H2O (40 mL) were added and the two layers were separated. The or-
ganic layer was dried (Na2SO4). After filtration, the solvent was
evaporated in vacuo and the oily residue was dissolved in anhyd
DMF (10 mL). To this solution, the corresponding amount of NaH
(0.7 g, 30 mmol, freshly washed with dry hexane (20 mL)) was add-
ed. The suspension was stirred at r.t. for 30 min. Subsequently, it
was cooled to 0 °C and BPTHP15 (4.5 g, 20 mmol) was added within
2 min. After stirring for 12 h, EtOH (10 mL) and H2O (20 mL) were
added to the reaction mixture. The product was extracted with
CH2Cl2 (3 x 100 mL). The organic layer was separated and dried
(Na2SO4). After filtration, the solvent was evaporated in vacuo. The
MS (ESI): m/z = 614 (M+Na+).
Anal. calcd for C33H50O10 (606.8): C, 65.33; H 8.30. Found C,
65.79; H, 8.43.
Allyl 4,6-O-benzylidene-2-O-[3-(tetrahydro-2H-pyranyl)oxypro-
pyl]-b-D-glucopyranoside (3) and allyl 4,6-benzylidene-3-O-[3-
(tetrahydro-2H-pyranyl)oxypropyl]-b-D-glucopyranoside (4) could
only be isolated as a mixture by column chromatography using
Et2O/hexane (2:1) as solvent. Characterization was done by mass
spectrometry.
MS (ESI): m/z = 486 (M+Na+).
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H, 5-CTHPHaHb), 3.72 (mc, H,
THPOCHaHbCH2CH2O), 3.62 (mc ª ddd, 4 H, 5-Hgluc), 3.56 (mc, 8
H, 6-CglucH2) ª 3.55 (mc, 8 H, THPOCH2CH2CHaHbO), 3.39 (mc ª
t, 4 H, 2-Hgluc), 3.38 (mc, 8 H, THPOCHaHbCH2CH2O), 3.37 (m, 8
H, 5-CTHPHaHb), 3.31 (mc ª t, 4 H, 4-Hgluc), 1.82 (mc ª quin., 8 H,
THPOCH2CH2CH2O), 1.76 (mc ª quin., 8 H, THPOCH2CH2CH2O),
1.69 (m, 8 H, 2-CTHPHaHb), ª 1.51 (m, 8 H, 3-CTHPHaHb), ª 1.48 (m,
8 H, 3-CTHPHaHb), 1.45 (m, 8 H, 4-CTHPHaHb), 1.41 (m, 8 H, 4-CTH-
PHaHb), ª 1.40 (m, 8 H, 2-CTHPHaHb).
13C NMR (100.61 MHz, CDCl3): d = 138.95, 138.24, 137.24 (12 C,
quart, arom), 128.43–127.48 (60 C, CH, arom), 98.88, 98.85 (8 C,
1-CTHP), 95.47 (4 C, 1-Cgluc), 81.96 (4 C, 3-Cgluc), 79.75 (4 C, 2-
Cgluc), 77.88 (4 C, 4-Cgluc), 75.61, 75.58 (4 C, CH2Ph), 72.99 (4 C,
CH2Ph), 70.45 (4 C, 5-Cgluc), 69.99–68.66 (12 C, THPOCH2
CH2CH2O, 6-Cgluc), 68.94 (4 C, CH2Ph), 64.55, 64.53, 64,46 (8 C,
THPOCH2 CH2CH2O), 62.37, 62.32, 62.26, 62.22 (8 C, 5-CTHP),
30.75, 29.99 (8 C, THPOCH2CH2CH2O), 25.46 (8 C, 4-CTHP),
30.70, 30.06 (8 C, 2-CTHP), 19.69, 19.65, 19.62,19.59 (8 C, 3-CTHP).
Anal. calcd for C25H35O8 (463.6): C, 64.78; H, 7.61. Found C,
64.79; H, 7.43.
Hgluc), 3.74 (m,
8
8
Allyl 4,6-O-Benzylidene-2,3-di-O-(3-hydroxypropyl)-b-D-glu-
copyranoside (5)
1H NMR (400.1 MHz, CDCl3): d = 7.49–7.25 (m, 5 H, arom), 5.85
(mc ª dddd, 1 H, OCHaHbCH = CHcHd), 5.53 (s, 1 H, CHPh), 5.30
(mc ª dddd, 1 H, OCHaHbCH = CHcHd), 5.20 (mc ª dddd, 1 H,
3
OCHaHbCH = CHcHd), 4.42 (d, JHH = 7.8 Hz, 1 H, 1-Hgluc), 4.18
(mc, 1 H, 6-CglucHaHb), 3.80 (mc, 1 H, 6-CglucHaHb), 3.70 (mc, 4 H,
HOCH2CH2CH2O), 3.65 (mc, 4 H, HOCH2CH2CH2O), 3.49 (mc ª t,
1 H, 4-Hgluc), 3.35 (mc ª t, 1 H, 3-Hgluc), 3.29 (mc ª ddd, 1 H, 5-
Hgluc), 3.09 (mc ª t, 1 H, 2-Hgluc), 2.28 (s, 2 H, HOCH2CH2CH2O),
1.82 (mc ª quin, 2 H, HOCH2CH2CH2O), 1.78 (mc ª quin, 2 H,
HOCH2CH2CH2O).
13C NMR (100.61 MHz, CDCl3): d = 137.12 (1 C, quart, arom),
133.51 (1 C, OCH2CH = CH2), 129.14–126.00 (5 C, CH, arom),
117.80 (1 C, OCH2CH = CH2), 102.50 (1 C, 1-Cgluc), 101.31 (1 C,
CHPh), 81.88 (1 C, 2-Cgluc), 81.69 (1 C, 3-Cgluc), 81.06 (1 C, 4-
Cgluc), 71.88, 71.15 (2 C, HOCH2CH2CH2O), 70.60 (1 C,
OCH2CH = CH2), 68.50 (1 C, 6-Cgluc), 65.99 (1 C, 5-Cgluc), 61.14,
60.97 (2 C, HOCH2CH2CH2O), 32.43, 32.34 (2 C,
HOCH2CH2CH2O).
MS (ESI): m/z = 757 (M+Na+).
Anal. calcd for C43H58O10 (734.9): C, 70.28; H, 7.95. Found C,
70.19; H, 8.00.
Benzyl 2,3-Di-O-benzyl-6-O-[3-(tetrahydro-2H-pyranyl)oxy-
propyl]-a-D-glucopyranoside (10)
MS (ESI): m/z = 447 (M+Na+).
Anal. calcd for C22H32O8 (424.5): C, 62.25; H, 7.59. Found C,
62.88; H, 7.78.
1H NMR (400.1 MHz, CDCl3): d = 7.34–7.17 (m, 30 H, arom), 4.94
(AB, 1 H, CHaHbPh), 4.92 (AB, 1 H, CHaHbPh), 4.76 (mc ª d, 1 H,
1-Hgluc), 4.75 (mc ª d, 1 H, 1-Hgluc), 4.71 (AB, 1 H, CHaHbPh), 4.68
(AB, 1 H, CHaHbPh), 4.59 (AB, 2 H, CHaHbPh), 4.56 (AB, 1 H,
CHaHbPh), 4.55 (AB, 1 H, CHaHbPh), 4.50 (mc ª t, 1 H, 1-CTHPH),
4.49 (AB, 2 H, CHaHbPh), 4.48 (AB, 1 H, CHaHbPh), 4.47 (AB, 1
H, CHaHbPh), 4.41 (mc ª t, 1 H, 1-CTHPH), 3.83 (mc, 1 H,
THPOCHaHbCH2CH2OÆ6-Cgluc), 3.78 (mc ª t, 2 H, 3-Hgluc), 3.76
(mc, 1 H, 5-CTHPHaHb), 3.74 (mc, 1 H, 5-CTHPHaHb), 3.72 (mc, 1 H,
THPOCHaHbCH2CH2OÆ6-Cgluc), 3.67 (mc ª t, 1 H, 4-Hgluc), 3.65
(mc ª t, 1 H, 4-Hgluc), 3.56 (mc, 2 H, 6-CglucHaHb), 3.55 (mc, 1 H,
THPOCH2CH2CHaHbOÆ6-Cgluc), 3.54 (mc ª ddd, 2 H, 5-Hgluc),
3.54 (mc, 1 H, THPOCH2CH2CHaHbOÆ6-Cgluc), 3.52 (mc, 2 H, 6-
Allyl 2,3-Di-O-benzyl-4,6-di-O-[3-(tetrahydro-2H-pyranyl)oxy-
propyl]-b-D-glucopyranoside (8)
1H NMR (600.13 MHz, CDCl3): d = 7.34–7.20 (m, 40 H, arom),
5.87 (mc ª dddd, 4 H, OCH2CH = CH2), 5.26 (mc ª dddd, 4 H,
OCH2CH = CHaHb), 5.11 (mc ª dddd, 4 H, OCH2CH = CHaHb),
4.85 (AB, 4 H, CHaHbPh), 4.80 (AB, 4 H, CHaHbPh), 4.69 (AB, 4
H, CHaHbPh), 4.61 (AB, 4 H, CHaHbPh), 4.48 (mc ª t, 4 H, 1-CTH-
PH), 4.46 (mc ª t, 2 H, 1-CTHPH), 4.43 (mc ª t, 2 H, 1-CTHPH), 4.34
(mc ª dddd, 4 H, OCHaHbCH = CH2), 4.33 (mc, 8 H, 5-CTHPHaHb),
3
4.32 (d, JHH = 7.7 Hz, 4 H, 1-Hgluc), 4.05 (mc ª dddd, 4 H,
OCHaHbCH = CH2), 3.81 (mc, 4 H, THPOCH2CH2CHaHbO), 3.56
(mc, 4 H, THPOCH2 CH2CHaHbO), ª 3.55 (mc, 8 H, 6-CglucH2), 3.45
(mc ª t, 4 H, 3-Hgluc), 3.54 (mc, 4 H, THPOCH2CH2CHaHbO), 3.49
(mc, 4 H, THPOCH2CH2CHaHbO), 3.39 (mc, 8 H, 5-CTHPHaHb),
3.37 (mc, 8 H, THPOCHaHbCH2CH2O), 3.33 (mc ª t, 4 H, 2-Hgluc),
C
glucHaHb), 3.46 (mc, 1 H, THPOCH2CH2CHaHbOÆ6-Cgluc), 3.44
(mc, 1 H, THPOCH2CH2CHaHbOÆ6-Cgluc), 3.43 (mc ª t, 2 H, 2-
Hgluc), 3.42 (mc, 1 H, THPOCHaHbCH2CH2OÆ6-Cgluc), 3.39 (mc, 1
H, 5-CTHPHaHb), 3.36 (mc, 1 H, THPOCHaHbCH2CH2OÆ6-Cgluc),
3.33 (mc,
1
H, 5-CTHPHaHb), 1.79 (mc,
8
H,
3.25 (mc,
8
H, 4-Hgluc
,
5-Hgluc), 1.81 (mc,
8
H,
THPOCH2CH2CH2OÆ6-Cgluc, 2-CTHPH2), 1.71 (mc, 2 H, 2-CTH-
PHaHb), 1.45 (mc, 2 H, 4-CTHPHaHb), 1.42 (mc, 2 H, 3-CTHPHaHb),
1.40 (mc, 2 H, 4-CTHPHaHb).
THPOCH2CH2CH2O), 1.75 (mc, 8 H, THPOCH2 CH2CH2O), ª 1.45
(mc, 16 H, 3-CTHPH2), 1.44 (mc, 16 H, 4-CTHPH2), 1.43 (mc, 16 H, 2-
CTHPH2).
13C NMR (100.61 MHz, CDCl3): d = 139.03–137.17 (6 C, quart,
arom), 128.44–127.58 (30 C, CH, arom), 99.63, 98.76 (2 C, 1-
CTHP), 95.64, 95.51 (2 C, 1-Cgluc), 81.69, 81.55 (2 C, 3-Cgluc), 79.57,
79.52 (2 C, 2-Cgluc), 75.52, 75.37 (2 C, CH2Ph), 72.95, 72.78 (2 C,
CH2Ph), 70.91 (2 C, 5-Cgluc), 70.44, 70.05 (2 C, 4-Cgluc), 70.12,
69.86 (2 C, 6-Cgluc), 69.01 (2 C, CH2Ph), 68.81, 68.25 (2 C,
13C NMR (150.92 MHz, CDCl3): d = 138.71, 138.55 (8 C, quart,
arom), 134.12 (4 C, OCH2CH = CH2), 128.82–127.55 (40 C, CH,
arom), 117.36, 117.21 (4 C, OCH2CH = CH2), 102.64 (4 C, 1-Cgluc),
98.94, 98.90, 98.84 (8 C, 1-CTHP), 84.59, 84.51 (4 C, 3-Cgluc), 82.19
(4 C, 2-Cgluc), 78.27 (4 C, 4-Cgluc), 75.61, 75.54 (4 C, CH2Ph), 75.06
(4 C, 5-Cgluc), 74.88, 74.71 (4 C, CH2Ph), 69.86 (4 C, 6-Cgluc),
70.60–68.72 (8 C, THPOCH2CH2CH2O), 64.56, 64.48, 64.41 (8 C,
THPOCH2CH2CH2O), 62.55–61.00 (8 C, 5-CTHP), 32.81–30.13 (16
C, THPOCH2CH2CH2O, 2-CTHP), 25.48 (8 C, 4-CTHP), 19.64 (8 C,
3-CTHP).
THPOCH2CH2CH2OÆ6-Cgluc),
64.21,
64.11
(2
C,
THPOCH2CH2CH2OÆ 6-Cgluc), 63.23, 62.33 (2 C, 5-CTHP), 30.88,
30.60, 29.75, 29.64 (4 C, 2-CTHP, THPOCH2CH2CH2OÆ6-Cgluc),
25.38, 25.36 (2 C, 4-CTHP), 20.23, 19.57 (2 C, 3-CTHP).
MS (ESI): m/z = 614 (M+Na+).
MS (ESI): m/z = 707 (M+Na+).
Anal. calcd for C35H43O8 (591.7): C, 71.04; H, 7.32. Found C,
71.02; H, 7.84
Anal. calcd for C39H56O10 (684.9): C, 68.40; H, 8.24. Found C,
68.80; H, 8.42.
Benzyl 2,3-Di-O-benzyl-4-O-[3-(tetrahydro-2H-pyranyl)oxy-
propyl]-a-D-glucopyranoside (11)
Benzyl 2,3-Di-O-benzyl-4,6-di-O-[3-(tetrahydro-2H-pyranyl)-
oxypropyl]-a-D-glucopyranoside (9)
1H NMR (400.1 MHz, CDCl3): d = 7.34–7.17 (m, 30 H, arom), 4.86
(AB, 2 H, CHaHbPh), 4.73 (AB, 2 H, CHaHbPh), 4.60 (AB, 2 H,
CHaHbPh), 4.56 (AB, 2 H, CHaHbPh), 4.51 (AB, 2 H, CHaHbPh),
4.49 (AB, 2 H, CHaHbPh), 4.48 (mc ª d, 2 H, 1-Hgluc), 4.47 (mc ª t,
2 H, 1-CTHPH), 3.89 (mc, 1 H, THPOCH2CH2CHaHbOÆ4-Cgluc),
1H NMR (400.1 MHz, CDCl3): d = 7.34–7.16 (m, 60 H, arom), 4.86
(m, AB, 4 H, CHaHbPh), 4.73 (mc ª d, 4 H, 1-Hgluc), 4.72 (m, AB, 4
H, CHaHbPh), 4.58 (m, AB, 4 H, CHaHbPh), 4.55 (m, AB, 4 H,
CHaHbPh), 4.48 (m, AB, 8 H, CHaHbPh), 4.45 (mc ª t, 8 H, 1-CTH-
PH), ª 3.85 (mc, 8 H, THPOCH2CH2CHaHbO), 3.84 (mc ª t, 4 H, 3-
Synthesis 1999, No. 9, 1625–1632 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Stereocontrolled b-Galactosidation by Cation p-Interaction
1631
3.88 (mc
ª
t,
2
H, 3-Hgluc), 3.86 (mc,
1 H,
13C NMR (100.61 MHz, CDCl3): d = 138.8, 138.0, 137.1 (3 C,
THPOCH2CH2CHaHbOÆ4-Cgluc), 3.75 (mc, 1 H, 5-CTHPHaHb), 3.73
(mc, 1 H, 5-CTHPHaHb), 3.72 (mc, 2 H, THPOCHaHbCH2CH2O Æ4-
Cgluc), 3.66 (mc, 2 H, 6-CglucHaHb), 3.63 (mc, 2 H, 6-CglucHaHb), 3.62
(mc, 1 H, THPOCH2CH2CHaHbOÆ4-Cgluc), 3.61 (mc, 1 H,
THPOCH2CH2CHaHbOÆ4-Cgluc), 3.58 (mc, 1 H, 5-Hgluc), 3.57 (mc,
1 H, 5-Hgluc), 3.39 (mc, 2 H, 5-CTHPHaHb), 3.38 (mc, 2 H,
THPOCHaHbCH2CH2OÆ4-Cgluc), 3.34 (mc ª t, 2 H, 2-Hgluc), 3.30
(mc ª t, 1 H, 4-Hgluc), 3.27 (mc ª t, 1 H, 4-Hgluc), 1.76 (mc, 8 H,
THPOCH2CH2CH2OÆ 4-Cgluc, 2-CTHPH2), 1.45 (mc, 4 H, 4-
CTHPH2), 1.43 (mc, 4 H, 3-CTHPH2).
quart, arom), 128.4–127.5 (15 C, CH, arom), 95.5 (1 C, 1-Cgluc),
81.8 (1 C, 3-Cgluc), 79.9 (1 C, 2-Cgluc), 78.0 (1 C, 4-Cgluc), 75.5 (1 C,
CH2Ph), 72.9 (1 C, CH2Ph), 71.1 (1 C, 5-Cgluc), 70.1 (1 C, CH2Ph),
69.5 (2 C, HOCH2CH2CH2O, 6-Cgluc), 69.1 (1 C,
HOCH2CH2CH2O), 60.7 (1 C, HOCH2CH2CH2O), 60.6 (1 C,
HOCH2CH2CH2O), 32.8 (1 C, HOCH2CH2CH2O), 31.9 (1 C,
HOCH2CH2 CH2O).
MS (ESI): m/z = 589 (M+Na+).
Anal. calcd for C33H42O8 (566.7): C, 69.94; H, 7.47. Found C,
69.43; H, 7.42.
13C NMR (100.61 MHz, CDCl3): d = 138.84–137.09 (6 C, quart,
arom), 128.35–127.47 (30 C, CH, arom), 98.98, 98.91 (2 C, 1-
Allyl 2,3-Di-O-benzyl-4,6-di-O-[3-(2,3,4,6-tetra-O-benzyl-b-D-
galactopyranosyl- oxypropyl)]-b-D-glucopyranoside (17)
A solution of 12 (0.1 g, 0.19 mmol) in CH2Cl2 (2 mL) was added to
a mixture of the galactosyl donor 1620 (0.25 g, 0.40 mmol), AgClO4
(1.24 g, 6 mmol, dried before use for 1 d at 160 °C/0.02 Torr), pow-
dered molecular sieves 4 Å (0.4 g), TOPC21 (0.23 g, 0.39 mmol) and
CH2Cl2 (4 mL) at –10 °C. After stirring for 4 days at r.t. under N2
(the progress of the reaction was monitored by TLC), the mixture
was diluted with CH2Cl2 (50 mL), the precipitated silver salt was re-
moved by filtration through Celite and washed with satd aq solution
of Na2S2O3 (20 mL) and then with H2O (20 mL). The organic layer
was dried (Na2SO4) and concentrated in vacuo. The residue was pu-
rified by silica gel column chromatography (eluent: hexane/Et2O/
CH2Cl2, 3:1:0.2, v/v), leading to the expected product with oily con-
sistency; yield:0.10 g (35%).
C
THP), 95.52 (2 C, 1-Cgluc), 81.85, 81.71 (2 C, 3-Cgluc), 79.88 (2 C,
2-Cgluc), 78.11, 78.00 (2 C, 4-Cgluc), 75.53, 75.46 (2 C, CH2Ph),
73.02, 73.00 (2 C, CH2Ph), 71.18, 71.08 (2 C, 5-Cgluc), 70.07, 69.97
(2 C, THPOCH2CH2CH2OÆ4-Cgluc), 69.13, 69.11 (2 C, CH2Ph),
64.30, 64.21 (2 C, THPOCH2CH2CH2OÆ4-Cgluc), 62.61, 62.31 (2
C, 5-CTHP), 61.86, 61.67 (2 C, 6-Cgluc), 30.70, 30.61, 30.52 (4 C,
THPOCH2CH2CH2OÆ4-Cgluc, C, 2-CTHP), 25.39, 25.36 (2 C, 4-
CTHP), 19.76, 19.58 (2 C, 3-CTHP).
MS (ESI): m/z = 614 (M+Na+).
Anal. calcd for C35H43O8 (591.7): C, 71.04; H, 7.32. Found C,
71.13; H, 7.55.
Allyl 2,3-Di-O-benzyl-4,6-di-O-(3-hydroxypropyl)-b-D-glucopy-
ranoside (12)
1H NMR (400.1 MHz, CDCl3): d = 7.18–7.24 (m, 10 H, arom), 5.87
(mc ª dddd, 1 H, OCHaHbCH = CHcHd), 5.33 (mc ª dddd, 1 H,
1H NMR (600.13 MHz, CD2Cl2): d = 7.94–7.04 (m, 50 H, arom),
6.02 (mc ª dddd, 1 H, OCH2CH = CH2), 5.39 (mc ª dddd, 1 H,
OCH2CH = CHaHb), 5.24 (mc ª dddd, 1 H, OCH2CH = CHaHb),
4.98 (m, AB, 2 H, CHaHbPh), 4.97 (m, AB, 1 H, CHaHbPh), 4.96 (m,
AB, 1 H, CHaHbPh), 4.91 (m, AB, 2 H, CHaHbPh), 4.90 (m, AB, 2
H, CHaHbPh), 4.81 (m, AB, 2 H, CHaHbPh), 4.80 (m, AB, 1 H,
CHaHbPh), 4.76 (m, AB, 2 H, CHaHbPh), 4.73 (m, AB, 1 H, CHaH-
bPh), 4.62 (m, AB, 2 H, CHaHbPh), 4.54 (m, AB, 2 H, CHaHbPh),
4.49 (m, AB, 2 H, CHaHbPh), 4.43 (mc ª dddd, 1H, OCHaHb-
OCHaHbCH = CHcHd),
5.19
(mc
ª
dddd,
1
H,
OCHaHbCH = CHcHd), 4.93 (mc, 1H, CHaHbPh), 4.89 (mc, 1H,
CHaHbPh), 4.74 (mc, 1H, CHaHbPh), 4.68 (mc, 1H, CHaHbPh), 4.41
(d, 3JHH = 7.7 Hz,
1
H, 1-Hgluc), 3.71 (mc,
HOCHaHbCH2CH2O),ª 4.40 (mcª dddd,
OCHaHbCH = CHcHd), 4.15 (mc
1
H,
H,
H,
1
ª
ª
dddd,
1
OCHaHbCH = CHcHd), 3.95 (mc, 1 H, 6-CHaHb), 3.75 (mc ª t, 2 H,
HOCH2 CH2CH2O), 3.70 (mc, 1 H, 6-CHaHb), 3.69 (mc, 1 H,
HOCH2CH2CHaHbO), 3.68 (mc,
HOCH2CH2CH2O), 3.66 (mc, 1 H, HOCH2CH2CHaHbO), 3.52 (mc
ª t, 1 H, 3-Hgluc), 3.41 (mc ª t, 1 H, 2-Hgluc), 3.35 (mc ª t, 1 H, 4-
H
HOCH2CH2CH2O), 1.82 (mc ª quin, 2 H, HOCH2CH2CH2O), 1.75
(mc ª quin, 2 H, HOCH2CH2CH2O).
13C NMR (100.61 MHz, CDCl3): d = 138.51, 138.33 (2 C, quart,
arom), 133.88 (1 C, OCH2CH = CH2), 127.58–128.32 (10 C, CH,
arom), 117.36 (1 C, OCH2CH = CH2), 102.57 (1 C, 1-Cgluc), 84.35
(1 C, 3-Cgluc), 82.12 (1 C, 2-Cgluc), 78.34 (1 C, 4-Cgluc), 75.49 (1 C,
CH2Ph), 74.82 (1 C, CH2Ph), 74.55 (1 C, 5-Cgluc), 71.23 (1 C, 6-
3
CH = CH2), 4.43 (d, JHH = 7.77 Hz, 1 H, 1-Hgluc), 4.41 (d,
3
H, HOCH2CH2CH2O,
3JHH = 7.74 Hz, 1 H, 1-Hgal 1), 4.35 (d, 3JHH = 7.64 Hz, 1 H, 1-Hgal 2),
4.16 (mc ª dddd, 1 H, OCHaHb-CH = CH2), 3.99 (mc ª t, 1 H, 4-Hgal
1), 3.99 (m, 1 H, Gal2CHaHbCH2CH2OÆ6-Gluc), 3.98 (m, 1 H,
Gal1CHaHbCH2CH2OÆ4-Gluc), 3.97 (mc ª t, 1 H, 4-Hgal 2), 3.88
(m, 1 H, Gal1CH2 CH2CHaHbOÆ4-Gluc), 3.73 (mc ª t, 1 H, 2-Hgal
2), 3.70 (m,1H, Gal1CH2CH2CHaHbO Æ4-Gluc), 3.69 (m, 1 H,
gluc), 3.33 (mc ª ddd, 1 H, 5-Hgluc), 2.25 (s, 2 H,
Gal2CHaHbCH2CH2OÆ6-Gluc),
3.68
(m,1
H,
Gal2CH2CH2CHaHbOÆ6-Gluc), 3.66 (m, 1 H, 6-CglucHaHb), 3.65
(m, 1 H, Gal2CH2CH2CHaHbO Æ6-Gluc), 3.63 (m, 2 H, 6-Cgal 1, gal
2HaHb), 3.62 (m, 1 H, 6-CGlucHaHb), 3.61 (mc, 2 H, 5-Hgal 1, 2), 3.59
(m, 1 H, Gal1CHaHbCH2CH2OÆ4-Gluc),3.58 (mc, 1 H, 3-Hgal 1),
3.57 (m, 2 H, 6-Cgal 1, gal 2HaHb), 3.55 (mc, 1 H, 3-Hgal 2), 3.53 (mc ª
t, 1 H, 3-Hgluc), 3.48 (mc ª t, 1 H, 2-Hgal 1), 3.41 (mc ª t, 1 H, 2-Hgluc),
3.38 (mc ª t, 1 H, 4-Hgluc), 3.34 (mc ª t, 1 H, 5-Hgluc), 1.96 (mc ª quin,
1 H, Gal2CH2CHaHbCH2OÆ6-Gluc), 1.93 (mc ª quin, 1H,
Gal2CH2CHaHbCH2OÆ6-Gluc), 1.92 (mc ª quin, 1 H, Gal1CH2
Cgluc), 70.28 (1 C, OCH2CH = CH2), 70.13 (1 C,
HOCH2CH2CH2O), 69.95 (1 C, HOCH2CH2CH2O), 61.06 (1 C,
HOCH2CH2CH2O), 60.73 (1 C, HOCH2CH2CH2O), 32.72 (1 C,
HOCH2CH2CH2O), 31.94 (1 C, HOCH2CH2CH2O).
MS (ESI): m/z = 539 (M+Na+).
CHaHbCH2 OÆ4-Gluc),
1.89
(mc
ª
quin,
1
H,
Anal. calcd for C29H40O8∑0.5 MeOH (516.6•MeOH): C, 66.52; H,
7.95. Found C, 66.82; H, 7.90.
Gal1CH2CHaHbCH2OÆ4-Gluc).
13C NMR (150.92 MHz, CD2Cl2): d = 139.97–139.07 (10 C, quart,
arom), 135.13 (1 C, OCH2CH = CH2), 129.11–128.13 (50 C, CH,
arom), 117.41 (1 C, OCH2CH = CH2), 104.75 (1 C, 1-Cgal 1), 104.69
(1 C, 1-Cgal 2), 103.40 (1 C, 1-Cgluc), 85.13 (1 C, 3-Cgluc), 82.98 (2 C,
3-Cgal 1, 2), 82.97 (1 C, 2-Cgluc), 80.35 (1 C, 2-Cgal 1), 80.32 (1 C, 2-
Cgal 2), 78.92 (1 C, 4-Cgluc), 75.60 (1 C, 5-Cgluc), 75.59–74.14 (10 C,
CH2Ph), 74.95 (2 C, 4-Cgal 1, 2), 73.92 (2 C, 5-Cgal 1, 2), 70.74 (1 C,
OCH2CH = CH2), 70.43 (1 C, 6-Cgluc),70.40 (1 C,
Gal1CH2CH2CH2OÆ4-Gluc), 69.48 (1 C, Gal2CH2CH2CH2OÆ6-
Gluc), 69.15 (2 C, 6-Cgal 1, 2), 67.75 (1 C, Gal2CH2CH2CH2OÆ6-
Gluc), 67.67 (1 C, Gal1CH2CH2 CH2OÆ4-Gluc), 31.61 (1 C,
Benzyl 2,3-Di-O-benzyl-4,6-di-O-(3-hydroxypropyl)-a-D-gluco-
pyranoside (13)
1H NMR (400.1 MHz, CDCl3): d = 7.41–7.25 (m, 15 H, arom), 4.97
(mc, 1 H, 6-CHaHb), 4.82 (d, 3JHH = 3.9 Hz, 1 H, 1-Hgluc), 4.76 (mc,
1 H, 6-CHaHb), 4.65 (AB, 2 H, CH2Ph), 4.52 (AB, 2 H, CH2Ph),
3.98–3.89 (m, 2 H), 3.77–3.57 (m, 8 H), 3.55 (dd, JHH = 10.8 Hz,
3
3
J
HH = 1.7 Hz, 1 H), 3.48 (dd, JHH = 9.8 Hz, JHH = 3.9 Hz, 1 H, 2-
Hgluc), 3.39 (m, 1 H, 4-Hgluc), 2.62 (s, 2 H, OH), 1.92–1.69 (mc, 4 H,
HOCH2CH2CH2O).
Synthesis 1999, No. 9, 1625–1632 ISSN 0039-7881 © Thieme Stuttgart · New York

1632
I. Neda et al.
PAPER
Gal1CH2CH2CH2OÆ4-Gluc), 31.06 (1 C, Gal2CH2CH2 CH2OÆ6-
Chem. 1996, 1313.
(e) Rademann, J.; Schmidt, R. R. J. Org. Chem. 1997, 62,
3650.
(f) Barresi, F.; Hindsgaul, O. J. Carbohyd. Chem. 1995, 14,
1043, and references cited therein.
Gluc).
MS (ESI): m/z = 1583 (M+Na+).
Anal. calcd for C97H108O18•CH2Cl2 (1561.9•CH2Cl2): C, 71.47; H,
6.73.646.85. Found C, 71.90; H, 6.94.
(7) (a) Sakhaii, P.; Melnicky, C., Neda, I. submitted for
publication.
(b) Gschrey, M. PhD. Thesis, Krebsforschungszentrum
Heidelberg, Germany, 1995.
Acknowledgement
(8) Nouguier, R.; Mchich, M. J. Org. Chem. 1985, 50, 3296.
(9) Brown H. C. Organic Synthesis via Boranes, J. Wiley: New
York, 1975.
(10) (a) Kim, J. M.; Roy, R. Tetrahedron Lett. 1997, 38, 3487.
(b) Fuchs, T.; Schmidt, R. R. Synthesis 1998, 753.
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We thank the Bundesministerium für Bildung, Wissenschaft, For-
schung und Technologie and ASTA Medica AG for financial sup-
port, Prof. R. Schmutzler (Technische Universität Braunschweig)
for his support of this research and Prof. M. Wiessler (Krebsfor-
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Article Identifier:
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Synthesis 1999, No. 9, 1625–1632 ISSN 0039-7881 © Thieme Stuttgart · New York