Synthesis of linear β-(1→4)-galacto-hexa- and heptasaccharides and studies directed towards cyclogalactans

Article abstract of DOI:10.1016/S0008-6215(02)00081-2

Synthesis of an exclusively β-(1→4)-linked galactohexa- and heptasaccharide is described by coupling a 2-O-pivaloyl-3,6-O-allyl-protected thiogalactobioside donor with an equally protected, yet terminally 4-OH-free galactopentaoside. The same approach though failed to elaborate cyclic oligomers, as neither cyclodimerization of the correspondingly protected thiogalactotriosides with a 4″-OH could be effected, nor intramolecular glycosidation of the respective hexa- and heptagalactosides with an unprotected 4-OH at one, and phenylthio or sulfoxido groups at the reducing end. The causative factors underlying this are attributed to an inadequate predisposition of the linear β-(1→4)-galactan chains to adopt the tightly coiled molecular geometry necessary for cyclization - at least at the hexa- and heptasaccharide stage.

Full text of DOI:10.1016/S0008-6215(02)00081-2

Carbohydrate Research 337 (2002) 2171–2180
www.elsevier.com/locate/carres
Synthesis of linear b-(1“4)-galacto-hexa- and heptasaccharides
and studies directed towards cyclogalactans
Markus Oberthu¨r, Siegfried Peters, Saibal Kumar Das, Frieder W. Lichtenthaler*
Institut fu¨r Organische Chemie, Technische Uni6ersita¨t Darmstadt, Petersenstraße 22, D-64287 Darmstadt, Germany
Received 14 December 2001; accepted 15 March 2002
Dedicated to Professor Derek Horton on the occasion of his 70th birthday
Abstract
Synthesis of an exclusively b-(1“4)-linked galactohexa- and heptasaccharide is described by coupling a 2-O-pivaloyl-3,6-O-al-
lyl-protected thiogalactobioside donor with an equally protected, yet terminally 4-OH-free galactopentaoside. The same approach
though failed to elaborate cyclic oligomers, as neither cyclodimerization of the correspondingly protected thiogalactotriosides with
a 4%%-OH could be effected, nor intramolecular glycosidation of the respective hexa- and heptagalactosides with an unprotected
4-OH at one, and phenylthio or sulfoxido groups at the reducing end. The causative factors underlying this are attributed to an
inadequate predisposition of the linear b-(1“4)-galactan chains to adopt the tightly coiled molecular geometry necessary for
cyclization—at least at the hexa- and heptasaccharide stage. © 2002 Elsevier Science Ltd. All rights reserved.
Keywords: b-(1“4)-galacto-Oligosaccharides; Galactosylations; Thioglycosides; Galactosyl phenylsulfoxides
1. Introduction
residues. Thus, both have a pronounced predisposition
for coiling toward a helical molecular geometry.
This analogy, which has been corroborated by simple
calculations,8 can be carried even further. Amylose, due
Linear chains of b-(1“4)-linked galactopyranose
residues of varying lengths are the major carbohydrate
components of pectins, either as part of arabinogalac-
tans or galactans.1 The chain length of these galactans
appears to depend on the source, as well as the isola-
tion procedure, with the number of galactose units
varying from four (wood,2 willow bark,3 citrus fruits4),
six (soy bean5), 28 (aloe6) to 33 (citrus pectin,4 garlic7).
The conformational similarity of a b-(1“4)-
tan to its amylose a-(1“4)- -glucan analog, is striking
(Fig. 1), as only the orientation of the intersaccharidic
linkages—axial at one side of the pyranoid ring and
equatorial at the other—is interchanged, entailing
kinks at every glycosidic bond in both cases, as well as
2-O···HO-3% hydrogen bonds between contiguous
to the six glucose units per helix turn, forms a distinctly
9
,
hydrophobic channel of about 5.4 A in diameter —di-
mensions that are similar to those found for the cavity
of a-cyclodextrin (1) (Fig. 2).10 Molecular modelings on
the hexameric b-(1“4)-cyclogalactan (2) revealed simi-
lar cavity dimensions,11,12 yet the distribution of hydro-
phobic and hydrophilic surface regions is different, such
that the hydrophobic areas extend significantly over the
cavities narrower rim toward the outside (Fig. 2, bot-
tom entries). Accordingly, the inclusion complexation
behavior of 2 is expected to be quite different from that
of its glucose analog (Fig. 2, bottom entries). Similar
differences are to be inferred for a b-(1“4)-galactan, as
it may be considered a tubular-extended analog of 2.
We surmise that further insights into the molecular
D-galac-
D
architecture of b-(1“4)-D-galactans would result from
* Corresponding author. Tel.: +49-6151-162376; fax: +
49-6151-166674
E-mail address: fwlicht@sugar.oc.chemie.tu-darmstadt.de
(F.W. Lichtenthaler).
study of pure oligomers, but their isolation from pectic
cell-wall material has proved exceedingly cumbersome
and has not provided well-defined products larger than
0008-6215/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(02)00081-2

2172
M. Oberthu¨r et al. / Carbohydrate Research 337 (2002) 2171–2180
2. Results and discussion
tetrasaccharide. Generation of oligo-b-(1“4)-galac-
tosides by b-galactosidase-induced galactosyl transfer
has, despite its simplicity, not even passed the b-(1“4)-
galactobiose level.13 Chemical synthesis14–16 has proved
a formidable task also, since the axially disposed 4-OH
of a galactosyl acceptor—a priori comparatively unre-
active, and necessarily carrying blocking groups at O-6
and O-3—is sterically less accessible for glycosylation
than primary or equatorial OHs. Most recently though,
a straightforward, preparatively efficient methodology
for construction of b-(1“4)-intergalactosidic linkages
has been developed,16 key elements being the use of
phenylthio and/or phenyl sulfoxide donor functionali-
ties for glycosylations and a judiciously designed block-
ing group pattern for donor and acceptor alike:
pivaloyl protection at O-2 for securing b-selectivity,
sterically undemanding allyl or benzyl groups at O-3
and O-6 to minimize the steric bulk around the unreac-
tive galactosyl-4-OH, the p-methoxyphenyl moiety,
readily replaceable by SPh, as an intermediate anomeric
substituent, and an acetyl group for temporary protec-
tion of the terminal Gal-4-OH.16 In this paper, we
document the application of this strategy to the synthe-
sis of linear b-(1“4)-galacto-heptaosides, and report
on protocols designed to lead to cyclic hexa- and
heptamers.
A deceptively simple approach to a cyclo-b-(1“4)-
galactohexaoside, such as 2, comprises the cyclodimer-
ization of a suitably blocked b-(1“4)-galactotrioside
with a terminal 4-OH and a donor functionality at the
reducing end. Two trisaccharides meeting these require-
ments, i.e., 5 and 6, could readily be prepared in two
respective three steps from the well accessible17 p-
methoxyphenyl galactotrioside 3: replacement of the
anomeric blocking group with a phenylthio residue by
exposure to TMS–thiophenol/BF3 (“4, 88%) and sub-
sequent liberation of the terminal 4-OH (“5, 90%).
Oxidation of 5 to the respective phenylsulfoxide deriva-
tive 6 was best effected (87% yield) by peracetic acid,
generated in situ from acetic anhydride and hydrogen
peroxide, inasmuch as employing the usually used m-
chloroperbenzoic acid resulted in sluggish, incomplete
conversion, with yields not exceeding 50% (Scheme 1).
The trimeric precursors 5 and 6 thus obtained were
then submitted to cyclization experiments under a vari-
ety of conditions. In detail, thioglycoside 5 and sulfox-
ide 6 were activated using 1–5 M equiv of methyl
triflate and triflic anhydride, respectively, while the
dilution of the reaction mixture (0.1–0.001 M) and the
mode of addition (normal: addition of activator to a
diluted solution of 5 or 6; inverse: addition of 5 or 6 to
Fig. 1. Top: Sketch representation of a left-handed, single stranded helix of Vh-amylose (left), and of a-cyclodextrin (1) (right),
which represents the excision of a single helix turn and its reconnection by CGTases. Bottom: depiction of a right-handed
b-(1“4)-
D
-galactan helix (left), as predicted by early computational studies,8 and its galactose analog 2, a cyclo-b-(1“4)-
D
-galac-
tohexaoside, as free of steric constraints as a-cyclodextrin (1).10,11 Conversely, amylose and its b-(1“4)-
be considered as tubular extensions of 1 and 2.
D-galactan analog may

M. Oberthu¨r et al. / Carbohydrate Research 337 (2002) 2171–2180
2173
Fig. 2. MOLCAD program-generated molecular lipophilicity patterns (MLPs), projected onto the respective contact surfaces of
a-cyclodextrin (1, top entry) and the respective cyclo-b-(1“4)-
-galactohexaoside (2, bottom).11,12 The pictures on the left are
D
viewed through the larger openings of the conically shaped molecules exposing the intensively hydrophilic (blue) 2-OH/3-OH side,
whereas the representations in the middle depict the opposite, smaller aperture with the 6-CH2OH groups facing the viewer,
thereby clearly revealing the hydrophobic (yellow) surface areas. The side view MLPs on the right, in closed and bisected form
each, are oriented in such a way that the 2-OH/3-OH side is aligned upward (larger opening of the torus) with the 6-CH2OH
groups pointing down. The substantially enlarged hydrophobic surface area in the cyclogalactoside 2 as compared to a-CD is
clearly apparent.
terminal 4-OAc with sodium methoxide–methanol
smoothly led to 11 (91%). The oxidation of the
phenylthio to the phenylsulfoxido group, i.e., 10“11,
was again best performed using in situ generated per-
acetic acid (89%). Both thioglycoside 11 and sulfoxide
12 were activated under the same set of reaction condi-
tions as outlined for trisaccharides 5 and 6. Distinctly
fewer side-products were observed in these reactions,
yet here too, no cyclization products could be detected
by either TLC or NMR. In the case of thioglycoside 11,
monitoring the reactions by TLC revealed the slow
appearance of the corresponding lactol when 10 equiv
of methyl triflate were used, yet no spot attributable to
cyclization product 8. Whereas the formation of the
lactol proved that activation at the anomeric center had
taken place, albeit rather slow, it obviously was not
followed by intramolecular glycosidation of the termi-
nal 4-OH. Sulfoxide 12, on the other hand, disappeared
nearly completely after activation with 5–10 equiv of
triflic anhydride under a range of concentrations (0.1–
a solution of activating agent) was systematically
varied. The reactions were then monitored by TLC, and
the mixture was quenched when no further change of
product distribution could be detected. Whereas both 5
and 6 partly dimerized to linear hexamers (as judged by
TLC using reference compounds, and NMR spectra of
fractions obtained after column chromatography), and
may also contain higher oligomers, no cyclic product
such as 7 was detectable.
As an alternate approach to cyclic galacto-oligosac-
charides, the cyclization of a suitably functionalized
b-(1“4)-galactohexaoside was attempted next. Starting
with hexagalactoside 9, readily accessible from b-(1“
4)-galactobioside building blocks by iterative exten-
sion,16 the required hexameric precursors 11 and 12
were obtained using the reaction sequence elaborated at
the trisaccharide stage for 3“5 and 3“6, respectively.
Thus, exposure of the hexameric p-methoxyphenyl gly-
coside 9 to TMS-protected thiophenol under BF3-catal-
ysis gave thioglycoside 10 (84%), and the removal of the

2174
M. Oberthu¨r et al. / Carbohydrate Research 337 (2002) 2171–2180
0.002 M), yet again furnished exclusively, the lactol
upon aqueous work-up. In fact, in high dilution, both
donor types turned out to be essentially inert, even
when using 10 equiv of activating agent.
The reluctance of hexamers 11 and 12 to cyclize
could be due to steric constraints of the comparatively
bulky pivaloyl ester groups, one of which is situated
next to the anomeric center to be activated, thereby
obstructing the adoption of the pre-coiled shape re-
quired for joining terminal ends. Thus, an attempt was
made towards lowering the steric bulk by two means:
enlargement of ring size to be generated by using
galactoheptaoside precursors and exchange of the bulky
2-O-pivaloyl groups by acetyl residues, despite their
greater propensity to form orthoester side-products.16,17
Accordingly, the respective b-(1“4)-galactoheptaoside
21 was synthesized using various standard methodolo-
gies. At first, the pivaloylated p-methoxyphenyl hep-
Scheme 1. Galacto-oligosaccharides used for cyclization experiments. Reagents and conditions: (a) PhSSiMe3, BF3·OEt2,
ClCH2CH2Cl, 50 °C, 3 h; (b) NaOMe, MeOH–CH2Cl2, 25 °C, 16 h: (c) Ac2O, H2O2, SiO2, CH2Cl2, 25 °C, 16 h. Yields
throughout were in the 90% range.

M. Oberthu¨r et al. / Carbohydrate Research 337 (2002) 2171–2180
2175
Scheme 2. Generation of galactoheptaosides and exchange of the bulky 2-OPiv for 2-OAc. Reagents and conditions: (a) MeOTf,
,
2,6-di-tBu-pyridine, mol. sieve 4 A, CH2Cl2, 25 °C, 16 h, 72%; (b) PhSSiMe3, BF3·OEt2, ClCH2CH2Cl, 50 °C, 3 h, 72%; (c)
NaOMe, MeOH–CH2Cl2, 25 °C, 16 h, 86%; (d) SEMCl, iPr2NEt, CH2Cl2, 25 °C, 24 h, 86%; (e) LiOH, MeOH, reflux, 12 h, 70%;
(f) Ac2O, DMAP, pyridine, 25 °C, 16 h, 77%; (g) HF–pyridine, THF, 25 °C, 30 min, 77%. SEM=Me3Si(CH2)2OCH2.
tasaccharide 15 was prepared by methyl triflate-
promoted coupling of the readily accessible17 disaccha-
ride thiophenyl donor 13 and galactopentaoside accep-
tor 14 (72%), followed by exchange of the anomeric
substituent for a phenylthio group (“16, 72%) and
de-O-acetylation (“17, 86%). Replacement of the 2-O-
pivaloyl blocking groups for the less bulky acetyl
residue was then effected in a four-step sequence: tem-
porary protection of the terminal 4-OH position with
the (trimethylsilyl)ethoxymethyl (SEM) group18 by ex-
posure to SEM chloride (17“18, 86%), removal of the
pivaloates by use of lithium hydroxide in refluxing
methanol (“19, 70%), acetylation (“20, 77%) and
cleavage of the SEM-group using hydrogen fluoride–
pyridine19 (“21, 77%) (Scheme 2).
Numerous experiments to induce the heptameric
thiogalactosides 17 (with its bulky 2-O-pivaloyl ester
groups) and the sterically less demanding 2-O-acety-
lated analog 21 to cyclization were not met with suc-
cess, despite extensive variation of reaction conditions
(methyl triflate activation, 5–10 equiv; dilution, 0.1–
0.001 M; temperature, 20–40 °C).

2176
M. Oberthu¨r et al. / Carbohydrate Research 337 (2002) 2171–2180
3. Conclusions
ried out on Fluka Silica Gel 60 (70–230 mesh); eluents
1
are given in brackets. H and 13C NMR spectra were
The previously developed strategy for the construc-
tion of b-(1“4)-intergalactosidic linkages16 can readily
be applied to the generation of linear heptasaccharides,
e.g., coupling of a 2-O-pivaloyl-3,6-di-O-allyl protected
thiogalactobioside donor with a terminally 4-OH-free
galactopentaoside proceeded efficiently (72% yield).
However, the same approach failed to produce cyclic
oligomers and cyclodimerization could not be induced
with trigalactosides carrying an unprotected 4%%-OH. In
addition hexa- and heptasaccharides blocked respec-
tively by phenylthio or sulfoxido groups at the reducing
end and 4-OH at the other did not yield cycloglycosyla-
tion. The causative factors underlying this are multi-
faceted, but seem to narrow down to an inadequate
predisposition to adopt the appropriate coiled geometry
for effecting a head–tail reaction—at least at the hexa-
and heptasaccharide stage. Preliminary molecular dy-
namics studies on ‘‘infinite’’ b-(1“4)-galactan poly-
mers in periodic tetragonal boxes filled with water
molecules show a pronounced tendency to elaborate
recorded on Bruker WM-300, AC-300, and Avance 500
spectrometers. The structures of all new compounds
were confirmed by COSY, HETCOR, TOCSY, and
decoupling experiments. Chemical shifts are reported
relative to Me4Si as an internal reference. Coupling
constants are listed separately if an assignment was
possible.
In the listings of 1H and 13C NMR data for the
individual compounds, signals originating from block-
ing groups are omitted if well separated from the
galactose–CH and CH2 protons, i.e., pivaloyl groups (9
H-singlets between 1.18–1.26 ppm, carbon resonances
at 27–28 ppm for CH3, 38–39 ppm for CMe3, 176–178
ppm for CO), the aromatic protons and carbons of
phenyl, p-methoxyphenyl, and benzyl moieties, and
most allyl resonances, i.e., All-H-2 multiplets (5.60–
6.00 ppm), All-H-3 multiplets (5.00–5.40 ppm), All-C-2
signals (134–136 ppm) and All-C-3 signals (116–118
ppm). Protons and carbons of the galactose moieties
are designated alphabetically starting from that con-
taining the aglycon, i.e., 1-Ha, 1-Hb, …up to 1-Hf for
1H NMR, C-1a, C-1b, etc. for 13C NMR data.
right-handed helices with an average pitch per turn of
20
,
about 15–17 A. Compared to the single-stranded,
left-handed Vh-form of amylose (cf. Fig. 1, top left),
Phenyl (4-O-acetyl-3,6-di-O-allyl-2-O-pi6aloyl-i-
galactopyranosyl)-(1“4)-(3,6-di-O-allyl-2-O-pi6aloyl-
i- -galactopyranosyl)-(1“4)-3,6-di-O-allyl-2-O-pi6a-
loyl-1-thio-i- -galactopyranoside (4).—p-Methoxy-
D-
,
which has a repeating height of only 8–9 A, the sizably
larger end-to-end distance of the b-(1“4)-galactose
oligomers appears to indicate a substantially lower
tendency for cyclization than in the respective a-(1“4)-
glucose analogs. Accordingly, the unfeasibility of induc-
D
D
phenyl galactotrioside 316 (2.86 g, 2.5 mmol) in
ClCH2CH2Cl (30 mL) was exposed to PhSSiMe3 (1.88
mL, 10 mmol) in the presence of BF3·Et2O (223 mL,
1.75 mmol) for 3 h at 50 °C. After diluting with CH2Cl2
(200 mL), the mixture was washed with satd aq
NaHCO3 (250 mL), and the NaHCO3-layer was ex-
tracted with CH2Cl2 (100 mL), and the combined or-
ganic layers were dried (MgSO4), filtered and
evaporated in vacuo. Purification of the residue by
elution from a silica gel column (8:1 toluene–EtOAc)
gave 4 (2.5 g, 88%) as a syrup; Rf 0.42 (4:1 toluene–
ing
a
head-to-tail reaction in suitably blocked
b-(1“4)-galactohexa- and heptaosides is likely to be
due to coiling characteristics inherent in a b-(1“4)-
galactan chain, rather than in insufficiently reactive
donor substituents or too bulky blocking groups. Siz-
ably higher oligogalactosides may in fact be required to
chemically effect cyclization, despite the fact that the
cyclohexamer, b-(1“4)-cyclogalactin 2, can elaborate
an essentially unstrained macrocycle with a cavity (cf.
Fig. 2) somewhat wider than that of a-cyclodextrin.
1
EtOAc); [h]2D0 −7.1° (c 0.96, CHCl3); H NMR (300
MHz, CDCl3): l 2.12 (s, 3 H, AcCH3), 3.44 (m, 6 H,
H-3 (a–c), H-5c, 2 H-6), 3.59 (m, 2 H, H-5, H-6), 3.70
(m, 4 H, H-5a, 3 H-6), 3.83–4.17 (m, 12 H, 12 All-H-1),
4.32 (d, 1 H, H-4a), 4.42 (d, 1 H, H-4b), 4.62 (d, 1 H,
H-1a), 4.90 (d, 1 H, H-1b), 4.98–5.11 (m, 4 H, H-1c,
H-2 (a–c)), 5.42 (d, 1 H, H-4c), J1a,2a 10.0, J3a,4a 2.4,
J1b,2b 7.9, J3b,4b 2.0, J3c,4c 2.9 Hz; 13C NMR (75.5 MHz,
CDCl3): l 20.8 (AcCH3), 67.0 (C-4c), 67.5 (C-4b), 68.5
(C-6c), 69.1, 69.2, 69.3 (C-2a, C-4a, C-6), 70.1 (C-6),
70.7, 70.8 (C-2b,c), 71.0, 71.1 (All-C-1), 72.4, 72.5, 72.6
(C-5c, All-C-1), 73.7 (C-5b), 77.0 (C-3c), 78.4 (C-5a),
80.6 (C-3b), 81.2 (C-3a), 87.2 (C-1a), 99.1 (C-1c), 99.9
(C-1b), 170.2 (COMe); MS (ESI): m/z 1153.6
[M−H+Na]+. Anal. Calcd for C59H86O19S (1131.38):
C, 62.64; H, 7.66. Found: C, 62.44; H, 7.46.
4. Experimental
General.—Reactions were carried out under Ar. All
solvents were of reagent grade and were further dried;
reagents were used as received. Optical rotations were
measured on a Perkin–Elmer 241 polarimeter at 20 °C
using a cell of 1 dm path length. Mass spectra were
recorded on Varian MAT 311 and MAT 212 spectrom-
eters. Microanalyses were determined on a Perkin–
Elmer 240 elemental analyzer. Analytical thin-layer
chromatography (TLC) was performed on precoated
Merck plastic sheets (0.2 mm Silica Gel 60 F254) with
detection by UV (254 nm) and/or spraying with H2SO4
(50%) and heating. Column chromatography was car-

M. Oberthu¨r et al. / Carbohydrate Research 337 (2002) 2171–2180
2177
The use of thiophenol instead of its TMS-derivative
gave considerably lower yields.
68.3 (C-2a), 69.0, 69.3 (C-6 (a–c)), 70.2 (C-4a), 70.6,
70.7 (C-2b,c), 70.9, 71.1, 71.6, 72.2, 72.5, 72.6 (6 All-C-
1), 73.5, 73.8 (C-5b,c), 78.8 (C-3c), 79.2, 80.0 (C-3a,
C-5a), 80.7 (C-3b), 94.1 (C-1a), 99.0 (C-1c), 100.6 (C-
1b).
Phenyl (3,6-di-O-allyl-2-O-pi6aloyl-i-
ranosyl)-(1“4)-(3,6-di-O-allyl-2-O-pi6aloyl-i-
actopyranosyl)-(1“4)-3,6-di-O-allyl-2-O-pi6aloyl-1-
thio-i- -galactopyranoside (5).—Trisaccharide 4 (2.3 g,
D-galactopy-
D-gal-
D
Diastereomer 6 II. Rf 0.21 (1:1 toluene–EtOAc); [h]D20
1
2.0 mmol) was dissolved in 4:1 MeOH–CH2Cl2 (20
mL) and treated with NaOMe (0.5 M in MeOH, 1 mL)
for 16 h. The solution was neutralized with Amberlite
IR 120 (H+ form), filtered and concentrated in vacuo.
Purification of the residue by elution from a silica gel
column (4:1 toluene–EtOAc) gave 5 (1.96 g, 90%) as a
colorless foam; Rf 0.21 (4:1 toluene–EtOAc); [h]D20
+11.6° (c 0.95, CHCl3); H NMR (300 MHz, CDCl3):
l 2.45 (bs, 1 H, 4c-OH), 3.41 (dd, 1 H, H-3b), 3.46–
3.60 (m, 6 H, H-3c, H-5 (a–c), 2 H-6), 3.62–3.75 (m, 5
H, H-3a, 4 H-6), 3.78–4.15 (m, 12 H, 12 All-H-1), 4.00
(m, 1 H, H-4c), 4.16 (d, 1 H, H-1a), 4.30 (d, 1 H, H-4a),
4.38 (d, 1 H, H-4b), 4.83 (d, 1 H, H-1b), 4.97 (dd, 1 H,
H-2b), 5.02 (m, 2 H, H-1c, H-2c), 5.09–5.35 (m, 13 H,
H-2a, 12 All-H-3), J1a,2a 9.8, J3a,4a 2.3, J1b,2b 7.9, J2b,3b
10.1, J3b,4b 3.1, J2c,3c 10.2 Hz; 13C NMR (75.5 MHz,
CDCl3): l 66.5 (C-4c), 67.1 (C-2a), 67.8 (C-4b), 69.0
(C-6c), 69.3 (C-4a), 69.6, 69.8 (C-6a,b), 70.6, 70.7 (C-
2b,c), 71.0, 71.1, 71.2, 72.5, 72.6 (6 All-C-1), 73.5, 74.0
(C-5b,c), 78.8 (C-3c), 80.0 (C-5a), 80.6 (C-3b), 80.7
(C-3a), 91.9 (C-1a), 99.0 (C-1c), 100.0 (C-1b); MS (FD):
m/z 1129 [M+H+Na]+. Anal. Calcd for C57H84O19S
(1105.34): C, 61.94; H, 7.66. Found: C, 61.54; H, 7.55.
Phenyl (4-O-acetyl-3-O-allyl-6-O-benzyl-2-O-pi6al-
1
−13.5° (c 1.1, CHCl3); H NMR (300 MHz, CDCl3): l
2.49 (bs, 1 H, 4c-OH), 3.45 (m, 3 H, H-3 (a–c)),
3.51–3.68 (m, 8 H, H-5 (a–c),5 H-6), 3.74 (dd, 1 H,
H-6), 3.90–4.17 (m, 12 H, 12 All-H-1), 4.00 (m, 1 H,
H-4c), 4.32 (d, 1 H, H-4a), 4.41 (d, 1 H, H-4b), 4.62 (d,
1 H, H-1a), 4.90 (d, 1 H, H-1b), 5.02–5.11 (m, 4 H,
H-1c, H-2 (a–c)), J1a,2a 10.0, J3a,4a 2.4, J1b,2b 7.9, J3b,4b
1.9, J5,6b 5.9 Hz; 13C NMR (75.5 MHz, CDCl3): l 66.5
(C-4c), 67.6 (C-4b), 69.0 (C-6c), 69.1, 69.4 (C-2a, C-4a),
69.6, 70.2 (C-6a,b), 70.6, 70.8 (C-2b,c), 71.0, 71.1, 72.4,
72.5 (6 All-C-1), 73.5, 74.0 (C-5b,c), 78.4 (C-5a), 78.9
(C-3c), 80.7 (C-3b), 81.2 (C-3a), 87.2 (C-1a), 99.0 (C-
1c), 99.9 (C-1b); MS (ESI): m/z 1112.6 [M+Na]+.
Anal. Calcd for C57H84O18S (1089.34): C, 62.85; H,
7.77. Found: C, 62.90; H, 7.87.
oyl - i -
benzyl-2-O-pi6aloyl-i-
O-allyl-6-O-benzyl-2-O-pi6aloyl-1-thio-i-
D
- galactopyranosyl) - (1“4) - [(3 - O - allyl - 6 - O-
-galactopyranosyl)-(1“4)]4-3-
-galactopy-
D
D
ranoside (10).—Galactohexaoside 916 (970 mg, 0.4
mmol) was treated with PhSSiMe3 (0.3 mL, 1.6 mmol)
as described above for 3“4. The resulting residue was
subjected to chromatography on silica gel (10:1 tolu-
ene–EtOAc) to give thiogalactoside 10 (810 mg, 84%)
as a colorless foam; Rf 0.56 (4:1 toluene–EtOAc); [h]D20
Phenyl (3,6-di-O-allyl-2-O-pi6aloyl-i-
ranosyl)-(1“4)-(3,6-di-O-allyl-2-O-pi6aloyl-i-
actopyranosyl)-(1“4)-3,6-di-O-allyl-2-O-pi6aloyl-i-
galactopyranosyl sulfoxide (6).—To solution of
D-galactopy-
D-gal-
D-
a
1
phenylthio galactotrioside 5 (610 mg, 0.56 mmol) in
CH2Cl2 (3 mL) was added silica gel 60 (230–400 mesh,
110 mg), Ac2O (59 mL, 0.62 mmol), and H2O2 (30% aq
solution, 68 mL, 0.68 mmol). After 8 h of stirring at rt,
the mixture was diluted with CH2Cl2 (100 mL), filtered
through a sintered frit, washed with satd aq KHSO3 (50
mL), satd aq NaHCO3 (50 mL), and brine (50 mL)
followed by drying (MgSO4), and concentration in
vacuo. The solid residue was subjected to column chro-
matography (7:4 toluene–EtOAc) to afford 6 (540 mg,
87%) as a colorless powder, comprising an approximate
1:1 mixture of the two sulfoxide diastereomers. Their
separation may be achieved by another elution from a
silica gel column (4:1 toluene–EtOAc).
+4.0° (c 0.65, CHCl3); H NMR (300 MHz, CDCl3): l
2.00 (s, 3 H, AcCH3), 3.38 (m, 5 H, 5 H-3), 3.47–3.78
(m, 19 H, H-3, H-5 (a–f), 2 H-6 (a–f)), 3.82–4.14 (m,
12 H, 12 All-H-1), 4.24, 4.30, 4.33 (3 bs, 5 H, H-4
(a–e)), 4.37–4.55 (m, 12 H, 6 CH2Ph), 4.60 (d, 1 H,
H-1a), 4.84 (d, 1 H, J1,2 7.7 Hz, H-1), 4.86 (d, 1 H, J1,2
7.6 Hz, H-1), 4.90 (d, 1 H, J1,2 7.9 Hz, H-1), 4.95–5.24
(m, 20 H, 2 H-1, H-2 (a–f), 12 All-H-3), 5.48 (d, 1 H,
H-4f), J1a,2a 10.9 Hz; 13C NMR (75.5 MHz, CDCl3): l
20.8 (AcCH3), 66.6 (C-4f), 67.7, 68.1 (2 C-4), 68.1
(C-6f), 68.8, 69.0, 69.4 (3 C-4), 69.8, 70.5, 70.6, 70.7
(C-6 (a–e)), 70.8, 71.1, 71.3 (6 C-2, 6 All-C-1), 72.3
(C-5f), 73.4, 73.5, 73.6, 73.7 (6 CH2Ph), 73.9, 74.3, 74.4,
(C-5 (b–e)), 77.2 (C-3f), 78.5 (C-5a), 80.0, 80.1, 80.4,
81.0 (C-3 (a–e)), 87.2 (C-1a), 99.4, 99.8, 100.0 (C-1
(b–f)), 170.2 (COMe); MS (ESI): m/z 2433.1 [M+
Na]+. Anal. Calcd for C134H176O37S (2410.91): C,
66.76; H, 7.36. Found: C, 66.66; H, 7.35.
Diastereomer 6 I. Rf 0.28 (1:1 toluene–EtOAc); [h]D20
1
−39.3° (c 0.82, CHCl3); H NMR (300 MHz, CDCl3):
l 2.45 (b, 1 H, 4c-OH), 3.36–3.57 (m, 8 H, H-3 (a–c),
H-5 (a–c), 2 H-6), 3.60–3.76 (m, 4 H, 4 H-6), 3.81–
4.19 (m, 12 H, 12 All-H-1), 4.00 (m, 1 H, H-4c), 4.08 (d,
1 H, H-1a), 4.18 (d, 1 H, H-4a), 4.40 (d, 1 H, H-4b),
4.71 (d, 1 H, H-1b), 4.91 (dd, 1 H, H-2b), 4.97–5.07 (m,
2 H, H-1c, H-2c), 5.37 (t, 1 H, H-2a), J1a,2a 9.4, J2a,3a
9.4, J3a,4a 1.8, J1b,2b 7.8, J2b,3b 10.1, J3b,4b 2.3 Hz; 13C
NMR (75.5 MHz, CDCl3): l 66.5 (C-4c), 67.2 (C-4b),
Phenyl
galactopyranosyl)-(1“4)]5-3-O-allyl-6-O-benzyl-2-O-
pi6aloyl-1-thio-i- -galactopyranoside (11).—Thio-
[(3-O-allyl-6-O-benzyl-2-O-pi6aloyl-i-D-
D
galactoside 10 (600 mg, 0.25 mmol) was de-O-acety-
lated as described above for 4“5. Purification of the
residue by elution from a silica gel column (6:1 tolu-

2178
M. Oberthu¨r et al. / Carbohydrate Research 337 (2002) 2171–2180
ene–EtOAc) gave 11 (536 mg, 91%) as a colorless
syrup; Rf 0.36 (4:1 toluene–EtOAc); [h]2D0 −1.6° (c
0.82, CHCl3); H NMR (300 MHz, CDCl3): l 2.44 (bs,
CH2Cl2 (20 mL) was stirred with freshly activated
,
molecular sieve (4 A) for 15 min. Then, MeOTf (0.78
1
mL, 6.9 mmol) was added and the mixture was stirred
at rt for 16 h, diluted with CH2Cl2 (250 mL), washed
with satd aq NaHCO3 (250 mL), which after separation
was reextracted with CH2Cl2 (250 mL). The combined
organic layers were then dried (MgSO4), filtered and
concentrated to a syrup which was purified by elution
from a silica gel column (10:1 toluene–EtOAc) to af-
ford heptasaccharide 15 (3.35 g, 72%) as a colorless
foam; Rf 0.52 (4:1 toluene–EtOAc); [h]2D0 −6.0° (c 1.0,
1 H, 4f-OH), 3.33–3.47 (m, 6 H, H-3 (a–f)), 3.51 (m, 4
H, 4 H-5), 3.56–3.67 (m, 6 H, 2 H-5, 4 H-6), 3.68–3.79
(m, 8 H, 8 H-6), 3.81–4.14 (m, 12 H, 12 All-H-1), 4.05
(m, 1 H, H-4f), 4.24 (d, 1 H, J3,4 2.3 Hz, H-4), 4.30 (m,
4 H, 4 H-4), 4.40–4.56 (m, 12 H, 6 CH2Ph), 4.60 (d, 1
H, H-1a), 4.82–4.97 (m, 5 H, H-1 (b–f)), 5.09–5.30 (m,
18 H, H-2 (a-f), 12 All-H-3), J1a,2a 10.0 Hz; 13C NMR
(75.5 MHz, CDCl3): l 66.3 (C-4f), 67.8, 68.4, 69.0, 69.3,
69.4 (C-4 (a–e)), 70.0, 70.1, 70.3, 70.6, 70.7, 70.8, 71.0,
71.1, 71.3 (C-2 (a–f), C-6 (a–f), 6 All-C-1), 73.6, 73.7,
73.8 (6 CH2Ph), 74.1, 74.2, 74.4, 74.6 (C-5 (b–f)), 78.8
(C-5a), 79.1, 80.3, 80.5, 81.3 (C-3 (a–f)), 87.3 (C-1a),
99.6, 100.0, 100.2 (C-1 (b–f)); MS (ESI): m/z 2391.4
[M+Na]+. Anal. Calcd for C132H174O36S (2368.87): C,
66.93; H, 7.40. Found: C, 66.52; H, 7.50.
1
CHCl3); H NMR (300 MHz, CDCl3): l 2.11 (s, 3 H,
AcCH3), 3.34–3.71 (m, 28 H, H-3 (a–g), H-5 (a–g), 2
H-6 (a–g)), 3.74 (s, 3 H, OCH3), 3.82–4.22 (m, 28 H,
28 All-H-1), 4.23–4.35 (m, 6 H, H-4 (a–f)), 4.74 (d, 1
H, H-1a), 4.82–5.04 (m, 12 H, H-1 (b–g), H-2 (b–g)),
5.09–5.35 (m, 29 H, H-2a, 28 All-H-3), 5.42 (d, 1 H,
H-4g), J1a,2a 7.9, J3g,4g 3.1 Hz; 13C NMR (75.5 MHz,
CDCl3): l 20.8 (AcCH3), 55.6 (OCH3), 67.0 (C-4g),
68.5, 68.9, 70.7, 70.8, 71.0, 73.9, 74.2, 74.5, 75.0, 77.3,
80.5 (C-2 (a–g), C-3 (a–g), C-5 (a–g), C-4 (a–f)), 68.6,
69.5, 70.0, 70.3, 70.4, 70.5, 71.1, 71.2, 71.3, 71.4, 72.6,
72.7 (C-6 (a–g), 14 All-C-1), 99.6, 99.9 (C-1 (b–g)),
101.2 (C-1a), 170.3 (COMe); MS (ESI): m/z 2473.7
[M+Na]+. Anal. Calcd for C128H192O45 (2450.90): C,
62.73; H, 7.90. Found: C, 63.07; H, 7.95.
Phenyl [(3-O-allyl-6-O-benzyl-2-O-pi6aloyl-i-
actopyranosyl) - (1“4)]5 - 3 - O - allyl - 6 - O - benzyl - 2 - O-
pi6aloyl-i- -galactopyranosyl sulfoxide (12).—Phenyl
D-gal-
D
galactohexaoside 11 (543 mg, 0.23 mmol) in CH2Cl2 (2
mL) was treated with Ac2O (24 mL, 0.25 mmol) and
H2O2 (30%, 28 mL, 0.28 mmol) in the presence of silica
gel (230–400 mesh, 50 mg) for 24 h, followed by
workup as described above for 5“6. The resulting
syrup was subjected to chromatography on silica gel
(3:1 toluene–EtOAc) to give sulfoxide 12 (485 mg,
89%) as a single diastereomer; Rf 0.19 (4:1 toluene–
Phenyl (4-O-acetyl-3,6-di-O-allyl-2-O-pi6aloyl-i-
galactopyranosyl)-(1“4)-[(3,6-di-O-allyl-2-O-pi6aloyl-
i- -galactopyranosyl)-(1“4)-]5 -3,6-di-O-allyl-2-O-
pi6aloyl-1-thio-i- -galactopyranoside (16).—p-
D-
D
1
EtOAc); [h]2D0 +6.0° (c 1.51, CHCl3); H NMR (300
D
MHz, CDCl3): l 2.20–2.50 (b, 1 H, 4f-OH), 3.35 (m, 4
H, H-3 (b–e)), 3.43–3.58 (m, 10 H, H-3a,f, H-5 (a–f),
2 H-6), 3.60–3.73 (m, 10 H, 10 H-6), 3.76–3.97 (m, 6
H, 6 All-H-1), 4.05 (m, 7 H, H-4f, 6 All-H-1), 4.08 (d,
1 H, H-1a), 4.13 (b, 1 H, H-4), 4.24 (d, 1 H, J3,4 2.6 Hz,
H-4), 4.29 (m, 3 H, 3 H-4), 4.32–4.56 (m, 12 H, 6
CH2Ph), 4.71 (d, 1 H, J1,2 7.8 Hz, H-1), 4.82 (d, 1 H,
J1,2 8.0 Hz, H-1), 4.86–4.98 (m, 3 H, 3 H-1), 4.90–5.10
(m, 5 H, H-2 (b–f)), 5.00–5.28 (m, 12 H, 12 All-H-3),
5.37 (t, 1 H, H-2a), J1a,2a 9.3, J2a,3a 9.2 Hz; 13C NMR
(75.5 MHz, CDCl3): l 66.4 (C-4f), 67.3, 68.3, 68.8, 69.0
(C-4 (b–e)), 70.2 (C-6), 70.4 (C-4a), 70.6, 70.7 (5 C-6),
70.8, 71.0, 71.1, 71.2 (C-2 (a–f)), 71.3, 71.4 (6 All-C-1),
73.7, 73.8, 73.9 (6 CH2Ph), 74.0, 74.1, 74.2, 74.5 (C-5
(b–f)), 77.2, 79.0, 79.3, 80.0, 80.2, 80.5 (C-3 (a–f),
C-5a), 94.0 (C-1a), 99.4, 99.6, 99.8, 100.1, 100.5 (C-1
(b–f)); MS (ESI): m/z 2407.5 [M+Na]+. Anal. Calcd
for C132H174O37S (2384.87): C, 66.48; H, 7.35. Found:
C, 66.32; H, 7.53.
Methoxyphenyl galactoheptaoside 15 (2.46 g, 1.0
mmol) in ClCH2CH2Cl (30 mL) was treated with
PhSSiMe3 (0.76 mL, 4.0 mmol) in the presence of
BF3·Et2O (90 mL, 0.7 mmol) as described above for
3“4. Purification of the residue by chromatography on
silica gel (6:1 toluene–EtOAc) gave 16 (1.76 g, 72%) as
a colorless syrup; Rf 0.49 (4:1 toluene–EtOAc); [h]D20
1
−3.5° (c 1.0, CHCl3); H NMR (300 MHz, CDCl3): l
1.19, 1.20, 1.22, 1.24, 1.26 (5 s, 63 H, 7 C(CH3)3), 2.11
(s, 3 H, AcCH3), 3.35–3.70 (m, 28 H, H-3 (a–g), H-5
(a–g), 2 H-6 (a–g)), 3.83–4.15 (m, 28 H, 28 All-H-1),
4.25 (bd, 1 H, H-4), 4.32 (m, 5 H, H-4 (a–f)), 4.61 (d,
1 H, H-1a), 4.82–5.02 (m, 12 H, H-1 (b–g), H-2 (b–g)),
5.09–5.35 (m, 29 H, H-2a, 28 All-H-3), 5.42 (d, 1 H,
H-4g), J1a,2a 9.9, J3g,4g 3.4 Hz; 13C NMR (75.5 MHz,
CDCl3): l 20.9 (AcCH3), 67.1 (C-4g), 68.1, 68.5, 69.0,
69.3, 70.8, 71.0, 71.1, 73.9, 74.2, 74.5, 74.6, 77.3, 78.8,
80.3, 80.4, 80.5, 81.3 (C-2 (a–g), C-3 (a–g), C-5 (a–g),
C-4 (a–f)), 68.6, 69.4, 70.0, 70.3, 70.4, 70.5, 71.2, 71.3,
71.4, 72.5, 72.7 (C-6 (a–g), 14 All-C-1), 87.3 (C-1a),
99.7, 100.1 (C-1 (b–g)), 170.3 (COMe); MS (ESI): m/z
2459.4 [M+Na]+. Anal. Calcd for C127H190O43S
(2436.93): C, 62.59; H, 7.86. Found: C, 62.60; H, 7.84.
4-Methoxyphenyl (4-O-acetyl-3,6-di-O-allyl-2-O-pi-
6aloyl-i-
O-pi6aloyl-i-
allyl-2-O-pi6aloyl-i-
D
-galactopyranosyl)-(1“4)-[(3,6-di-O-allyl-2-
D
-galactopyranosyl)-(1“4)-]5-3,6-di-O-
D-galactopyranoside (15).—A so-
lution of pentasaccharide acceptor 1416 (3.10 g, 1.9
mmol), galactobioside donor 1314 (2.80 g, 3.4 mmol),
and 2,6-di-tbutylpyridine (2.05 mL, 8.7 mmol) in
Phenyl [(3,6-di-O-allyl-2-O-pi6aloyl-i-
D-galactopy-
ranosyl)-(1“4)-]6-3,6-di-O-allyl-2-O-pi6aloyl-1-thio-

M. Oberthu¨r et al. / Carbohydrate Research 337 (2002) 2171–2180
2179
i-
D
-galactopyranoside (17).—Galactoheptaoside 16
rt, the mixture was filtered and the residue was thor-
oughly washed with MeOH (100 mL). The combined
filtrates were neutralized with Amberlite IR 120 (H+
form), filtered, and concentrated. The resulting syrup
was subjected to a silica gel column (2:1 toluene–
EtOAc) to give 19 (640 mg, 70%) as a colorless foam;
Rf 0.34 (1:1 toluene–EtOAc); [h]2D0 +4.7° (c 1.0,
(1.71 g, 0.7 mmol) was de-O-acetylated as described
above for 4“5. The resulting residue was subjected to
column chromatography (3:1 toluene–EtOAc) to give
17 (1.43 g, 86%) as a colorless syrup; Rf 0.47 (2:1
toluene–EtOAc); [h]2D0 −8.3° (c 1.0, CHCl3); H NMR
1
(300 MHz, CDCl3): l 2.20–2.50 (bs, 1 H, 4g-OH),
3.35–3.75 (m, 28 H, H-3 (a–g), H-5 (a–g), 2 H-6
(a–g)), 3.86–4.16 (m, 29 H, H-4g, 28 All-H-1), 4.23–
4.35 (m, 6 H, H-4 (a–f)), 4.61 (d, 1 H, H-1a), 4.81–5.09
(m, 13 H, H-1 (b–g), H-2 (a–g)), J1a,2a 10.0 Hz; 13C
NMR (75.5 MHz, CDCl3): l 66.6 (C-4g), 68.1, 68.6,
69.0, 69.3, 69.5 (C-4 (a–f)), 69.1, 69.8, 70.1, 70.4, 70.5,
71.1, 71.2, 71.3, 71.5, 72.7 (C-6 (a–g), 14 All-C-1), 70.7,
71.1 (C-2 (a–g)), 73.6, 74.2, 74.3, 74.5 (C-5 (a–g)), 78.8,
79.1, 80.3, 80.5, 81.3 (C-3 (a–g)), 99.5, 99.6, 100.0,
100.1 (C-1 (b–g)); MS (ESI): m/z 2417.2 [M+Na]+.
Anal. Calcd for C126H188O42S (2394.90): C, 62.69; H,
7.91. Found C, 62.28; H, 7.60.
1
CHCl3); H NMR (300 MHz, CDCl3): l 0.00 (s, 9 H,
Si(CH3)3), 0.92 (m, 2 H, SiCH2), 3.28–3.87 (m, 44 H,
H-2 (a–g), H-3 (a–g), H-5 (a–g), 2 H-6 (a–g), OCH2,
7 OH], 3.90–4.42 (m, 41 H, H-1 (b–g), H-4 (a–g), 28
All-H-1), 4.47 (d, 1 H, H-1a), 4.72, 4.96 (2d, 1 H each,
JOCH O 7.0 Hz, OCH2O), J1a,2a 9.6 Hz; 13C NMR (75.5
2
MHz, CDCl3): l −1.4 (Si(CH3)3), 18.1 (SiCH2), 65.7
(OCH2), 68.8, 69.0, 69.2, 69.3, 69.7 (C-6 (a-g)), 70.4,
72.0, 72.1, 72.2, 72.3, 72.6 (14 All-C-1), 69.4, 72.8, 73.4,
73.6, 73.8, 74.2, 75.4, 76.8, 76.6, 76.7, 77.0, 77.5, 78.5,
80.3, 80.4, 80.6, 81.2, 81.8 (C-2 (a–g), C-3 (a–g), C-4
(a–g), C-5 (a–g)), 88.5 (C-1a), 95.6 (OCH2O), 105.0,
105.4, 105.7, 105.78, 105.8, 107.0 (C-1 (b–g)); MS
(ESI): m/z 1959.7 [M+Na]+. Anal. Calcd for
C96H146O36SSi (1936.33): C, 59.55; H, 7.60. Found: C,
59.15; H, 7.52.
Phenyl (3,6-di-O-allyl-2-O-pi6aloyl-4-O-trimethylsi-
lylethoxymethyl-i-
O-allyl-2-O-pi6aloyl-i-
3,6-di-O-allyl-2-O-pi6aloyl-1-thio-i-
D
-galactopyranosyl)-(1“4)-[(3,6-di-
-galactopyranosyl)-(1“4)-]5-
-galactopyranoside
D
D
(18).—A solution of 4g-OH free heptaoside 17 (1.36 g,
0.57 mmol), EtN(iPr)2 (0.17 mL, 1.0 mmol) and 2-
(trimethylsilyl)ethoxymethyl chloride (0.12 mL, 0.68
mmol) in CH2Cl2 (1 mL) was stirred at rt for 24 h.
After dilution with CH2Cl2 (250 mL), the mixture was
washed with 2 N HCl (250 mL) and satd aq NaHCO3
(250 mL), dried (MgSO4), filtered, and concentrated to
a syrup. Chromatography on silica gel (5:1 toluene–
EtOAc) afforded, after the evaporation of the appropri-
ate fractions, 18 (1.23 g, 86%) as a colorless syrup; Rf
0.80 (2:1 toluene–EtOAc); [h]2D0 −11.9° (c 1.0, CHCl3);
1H NMR (300 MHz, CDCl3): l −0.01 (s, 9 H,
Si(CH3)3), 0.90 (m, 2 H, SiCH2), 3.33–3.73 (m, 30 H,
H-3 (a–g), H-5 (a–g), 2 H-6 (a–g), OCH2), 3.85–4.14
(m, 29 H, H-4g, 28 All-H-1), 4.29 (m, 6 H, H-4 (a–f)),
4.59 (d, 1 H, H-1a), 4.72 (d, 1 H, JOCH O 6.8 Hz, 0.5
OCHaHbO), 4.81–5.00 (m, 13 H, H-1 (b–2g), H-2 (b–g),
0.5 OCHaHbO), 5.04–5.34 (m, 29 H, H-2a, 28 All-H-3),
J1a,2a 9.8 Hz; 13C NMR (75.5 MHz, CDCl3): l −1.4
(Si(CH3)3), 17.8 (SiCH2), 65.7 (OCH2), 67.8, 68.0, 68.3,
68.7, 69.0, 69.2 (C-4 (a–g)), 70.8 (C-2 (a–g)), 69.5, 69.9,
70.2, 70.3, 70.9, 71.0, 71.3, 72.4 (C-6 (a–g), 14 All-C-1),
73.9, 74.1, 74.2, 74.3 (C-5 (a–g)), 78.5, 79.8, 80.0, 80.3,
81.0 (C-3 (a–g)), 87.1 (C-1a), 95.6 (OCH2O), 99.4, 99.5,
99.8 (C-1 (b–g)); MS (ESI): m/z 2548.2 [M+Na]+.
Anal. Calcd for C131H202O43SSi (2525.16): C, 62.31; H,
8.06. Found: C, 62.45; H, 7.94.
Phenyl
lylethoxymethyl-i-
acetyl-3,6-di-O-allyl-i-
2-O-acetyl-3,6-di-O-allyl-1-thio-i-
(2-O-acetyl-3,6-di-O-allyl-4-O-trimethylsi-
-galactopyranosyl)-(1“4)-[(2-O-
-galactopyranosyl)-(1“4)-]5-
-galactopyranoside
D
D
D
(20).—A solution of 19 (600 mg, 0.31 mmol), pyridine
(0.78 mL, 9.8 mmol), Ac2O (0.62 mL, 6.5 mmol), and a
catalytic amount of DMAP in CH2Cl2 (4 mL) was
stirred at rt for 16 h. CH2Cl2 (100 mL) was added and
the mixture was washed with 2 N HCl (100 mL) and
satd aq NaHCO3 (100 mL), dried (MgSO4), filtered,
and evaporated in vacuo. The residue was purified by
elution from a silica gel column (2:1 toluene–EtOAc) to
give 20 (540 mg, 77%); Rf 0.79 (1:1 toluene–EtOAc);
[h]2D0 −24.6° (c 1.0, CHCl3); 1H NMR (300 MHz,
CDCl3): l 0.00 (s, 9 H, Si(CH3)3), 0.91 (m, 2 H, SiCH2),
2.04, 2.06, 2.14, 2.15, 2.15 (6s, 21 H, 7 AcCH3), 3.35–
3.73 (m, 30 H, H-3 (a–g), H-5 (a–g), 2 H-6 (a–g),
OCH2), 3.93–4.15 (m, 29 H, H-4, 28 All-H-1), 4.20 (m,
6 H, 6 H-4), 4.55 (d, 1 H, H-1a), 4.72 (d, 2 H, J1,2 7.2,
JOCH O 7.2 Hz, 1-H, OCHaHbO), 4.86 (m, 6 H, 5 H-1,
2
OCHaHbO), 5.09–5.34 (m, 35 H, H-2 (a–g), 28 All-H-
3), J1a,2a 10.0 Hz; 13C NMR (75.5 MHz, CDCl3): l
−1.4 [Si(CH3)3], 18.1 (SiCH2), 20.8, 20.9 (7 AcCH3),
65.7 (OCH2), 68.7, 69.1, 69.3, 69.9, 70.2, 71.1, 71.6 (C-2
(a–g), C-4 (a–g)), 69.2, 69.4, 69.5, 69.6 (C-6 (a–g)),
70.8, 70.9, 71.0, 72.4, 72.5 (14 All-C-1), 73.8, 73.9, 78.2,
79.5, 79.7, 79.9, 80.0, 81.1 (C-3 (a–g), C-5 (a–g)), 86.4
(C-1a), 95.7 (OCH2O), 99.5, 99.8, 100.2 (C-1 (b–g)),
169.3, 169.8, 169.9, 170.0 (7 COMe); MS (ESI): m/z
2253.2 [M+Na]+. Anal. Calcd for C110H160O43SSi
(2230.59): C, 59.23; H, 7.23. Found: C, 59.09; H, 7.30.
Phenyl
methyl-i-
(3,6-di-O-allyl-4-O-trimethylsilylethoxy-
-galactopyranosyl)-(1“4)-[(3,6-di-O-allyl-
D
i-
i-
D
-galactopyranosyl)-(1“4)-]5-3,6-di-O-allyl-1-thio-
D-galactopyranoside (19).—A suspension of 18 (1.19
g, 0.47 mmol) and LiOH·H2O (1.38 g, 32.9 mmol) in
MeOH (10 mL) was refluxed for 16 h. After cooling to

2180
M. Oberthu¨r et al. / Carbohydrate Research 337 (2002) 2171–2180
(b) Stephen, A. M. In The Polysaccharides; Aspinall, G.
O., Ed.; Academic Press: New York, 1983; Vol. 2, pp
122–193.
Phenyl (2-O-acetyl-3,6-di-O-allyl-i-
osyl)-(1“4)-[(2-O-acetyl-3,6-di-O-allyl-i-
pyranosyl)-(1“4)-]5 -2-O-acetyl-3,6-di-O-allyl-1-thio-
i- -galactopyranoside (21).—A mixture of galactohep-
taoside 20 (450 mg, 0.2 mmol) in THF (0.5 mL) and
D
-galactopyran-
D
-galacto-
2. Bouveng H. O.; Meier H. Acta Chem. Scand. 1959, 13,
1884–1889.
3. Toman R.; Kara´csonyi S.; Kubackova´ M. Carbohydr.
Res. 1975, 43, 111–116.
4. Labavitch J. M.; Freeman L. E.; Albersheim P. J. Biol.
Chem. 1976, 251, 5904–5910.
5. Fransen C. T. M.; Van Laere K. M. J.; van Wijk A. A.
V.; Bru¨ll L. P.; Dignum M.; Thomas-Oates J. E.;
Haverkamp J.; Schols H. A.; Voragen A. G. J.; Kamer-
ling J. P.; Vliegenthart J. F. G. Carbohydr. Res. 1998,
314, 101–114.
D
,
freshly activated molecular sieve (4 A) was treated with
HF–pyridine (3 mL) at rt for 30 min. The resulting
slurry was extracted with CH2Cl2 (100 mL), washed
with satd aq NaHCO3 (100 mL), dried (MgSO4), and
filtered. Concentration of the filtrate in vacuo and
chromatography of the residue on a silica gel column
(3:2 toluene–EtOAc) afforded 21 (350 mg, 77%) as a
colorless foam; Rf 0.53 (1:1 toluene–EtOAc); [h]D20
6. Mandal G.; Das A. Carbohydr. Res. 1980, 86, 247–257.
7. Das N. N.; Das A.; Mukherjee A. K. Carbohydr. Res.
1977, 56, 337–349.
1
−19.0° (c 1.0, CHCl3); H NMR (300 MHz, CDCl3): l
2.06, 2.08, 2.16, 2.18, 2.19, 2.22 (6s, 21 H, 7 AcCH3),
2.30 (bs, 1 H, 4g-OH), 3.36–3.79 (m, 28 H, H-3 (a–g),
H-5 (a–g), 2 H-6 (a–g)), 3.95–4.18 (m, 29 H, H-4, 28
All-H-1), 4.19–4.24 (m, 6 H, 6 H-4), 4.56 (d, 1 H,
H-1a), 4.75 (d, 1 H, H-1), 4.89 (m, 5 H, 5 H-1), 5.05 (m,
6 H, H-2 (b–g)), 5.11–5.34 (m, 29 H, H-2a, 28 All-H-
3), J1a,2a 10.0, J1,2 7.8 Hz; 13C NMR (75.5 MHz,
CDCl3): l 21.0, 21.1, 21.2 (7 AcCH3), 66.8, 68.9, 69.2,
69.5, 70.1, 70.3, 71.3 (C-2 (a–g), C-4 (a–g)), 69.1, 69.3,
69.5, 69.6, 69.8 (C-6 (a–g)), 71.0, 71.1, 71.2, 72.6, 72.7
(14 All-C-1), 73.6, 73.8, 73.9, 78.4, 78.6, 79.9, 80.0,
80.2, 81.3 (C-3 (a–g), C-5 (a–g)), 86.4 (C-1a), 99.7,
99.8, 99.9, 100.1, 100.4 (C-1 (b–g)), 169.5, 170.0, 170.1,
170.2 (7 COMe); MS (ESI): m/z 2122.8 [M−H+Na]+
, 2123.7 [M+Na]+. Anal. Calcd for C104H146O42S
(2100.33): C, 59.47; H, 7.01. Found C, 59.23; H, 7.07.
8. (a) Sundararajan P. R.; Rao V. S. R. Biopolymers 1970,
9, 1239–1247;
(b) Rees D. A.; Scott W. E. J. Chem. Soc. B 1971,
469–479;
(c) Brant, D.A. Structure and Function of Carbohy-
drates. In The Biochemistry of Plants; Preiss, J., Ed.;
Academic Press: New York, 1980; Vol. 3, pp 425–472;
(d) Burton B. A.; Brant D. A. Biopolymers 1983, 22,
1784–1786;
(e) Tanaka F.; Mizoguchi Y.; Shuto Y.; Okamura K.;
Ogawa K.; Koshijima T. Mokuzai Kenkyu Shiryo (Wood
Res. Notes) 1986, 22, 37–45 Chem. Abstr. 1987, 107,
35367e.
9. Immel S.; Lichtenthaler F. W. Starch/Sta¨rke 2000, 52,
1–8 and literature cited therein.
10. (a) Szejtli J. Chem. Re6. 1998, 98, 1743–1753;
(b) Lipkowitz K. B. Chem. Re6. 1998, 98, 1829–1873;
(c) Immel S.; Lichtenthaler F. W. Liebigs Ann. Chem.
1996, 27–37.
11. Lichtenthaler F. W.; Immel S. Tetrahedron: Asymmetry
1994, 5, 2045–2060.
12. Lichtenthaler F. W.; Immel S. J. Inclusion Phenom. Mol.
Recogn. Chem. 1996, 25, 3–16.
13. (a) Farkas E.; Thiem J. Eur. J. Org. Chem. 1999, 3073–
3077;
(b) Hart J.; Falshaw E.; Thiem J. Synlett 2001, 329–332.
14. Kova´c P; Taylor R. B. Carbohydr. Res. 1987, 167, 153–
157.
15. El-Shenawy H. A.; Schuerch C. Carbohydr. Res. 1984,
131, 239–246.
Acknowledgements
This work was funded by the Fonds der Chemischen
Industrie, Frankfurt, and the Su¨dzucker AG,
Mannheim/Ochsenfurt, to whom our thanks are due.
We are also indebted to Dr. Stefan Immel of this
institute for providing Figs. 1 and 2.
16. Lichtenthaler F. W.; Oberthu¨r M.; Peters S. Eur. J. Org.
Chem. 2001, 3849–3869.
17. Kunz H.; Harreus A. Liebigs Ann. Chem. 1982, 41–48.
18. Lipshutz B. H.; Pegram J. J. Tetrahedron Lett. 1980, 21,
3343–3346.
References
19. Lipshutz B. H.; Pegram J. J.; Morey M. C. Tetrahedron
Lett. 1981, 22, 4603–4606.
20. Immel S. In Cyclodextrin News; Szejtli J., Ed.; Cyclolab:
Budapest, 2001; Vol. 15, pp 226–228.
1. (a) Aspinall, G. O. Chemistry of Cell Wall Polysaccha-
rides. In The Biochemistry of Plants; Preiss, J., Ed.;
Academic Press: New York, 1980; Vol. 3, pp 473–500;