Synthesis and mesogenic properties of glycosyl diacylglycerols.

Article abstract of DOI:10.1016/S0009-3084(01)00202-X

We synthesised glycosyl diacylglycerols bearing unsaturated or chiral methyl branched fatty acid chains. The thermotropism was measured with polarising microscopy and additionally the lyotropism with the contact preparation method. The synthesised compoun

Full text of DOI:10.1016/S0009-3084(01)00202-X

Chemistry and Physics of Lipids
114 (2002) 55–80
www.elsevier.com/locate/chemphyslip
Synthesis and mesogenic properties of glycosyl
diacylglycerols
H.M. von Minden a, M. Morr b, G. Milkereit a, E. Heinz c, V. Vill a,*
a Institut fu¨r Organische Chemie, Uni6ersita¨t Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany
b Gesellschaft fu¨r Biotechnologische Forschung mbh, Mascheroder Weg 1, 38124 Braunschweig, Germany
c Institut fu¨r Allgemeine Botanik, Uni6ersta¨t Hamburg, Ohnhorststr. 18, 22609 Hamburg, Germany
Received 8 March 2001; received in revised form 12 November 2001; accepted 23 November 2001
Dedicated to Professor Joachim Thiem for the occasion of his 60th birthday
Abstract
We synthesised glycosyl diacylglycerols bearing unsaturated or chiral methyl branched fatty acid chains. The
thermotropism was measured with polarising microscopy and additionally the lyotropism with the contact prepara-
tion method. The synthesised compounds displayed thermotropic SA (lamellar), cubic and columnar phases and
investigation of the lyotropic phase behaviour led to the observation of inverted bicontinuous cubic VII phases,
lamellar La phases and normal bicontinuous cubic VI phases. The phases are discussed with respect to the chemical
structures that have been varied systematically to derive structure–property relationships. © 2002 Elsevier Science
Ireland Ltd. All rights reserved.
Keywords: Glycosyl diacylglycerols; Cubic phases; Columnar phases
1. Introduction
(Ishizuka and Yamakawa, 1985). Glycosyl diacyl-
glycerols with a sugar headgroup of 1–3 glycosyl
residues are major structural components of the
cell membrane while the more complex examples
with bigger carbohydrate headgroups are involved
in cell surface recognition processes (Curatolo,
1987).
Despite the great importance of this class of
glycolipids, very little data is available in the
literature concerning their physical properties,
which hampers a clear understanding of the way
in which their structure is related to their unique
Glycosyl diacylglycerols are known to be im-
portant constituents of many cell membranes.
These lipids (e.g. b glucosyl glycerols, Fig. 1)
consist of a carbohydrate polar headgroup (con-
taining 1–8 sugar moieties) attached to a 1,2-di-
O-acyl-sn-glycerol via an a or b glycosidic linkage
* Corresponding author. Tel.: +49-40-42838-4269; fax: +
49-40-42838-4325.
E-mail address: vill@chemie.uni-hamburg.de (V. Vill).
0009-3084/02/$ - see front matter © 2002 Elsevier Science Ireland Ltd. All rights reserved.
PII: S0009-3084(01)00202-X

56
H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
with a statistical mix of different chain lengths
and degree of unsaturation dependent on the
source, environmental/growing conditions and
the exact extracting procedure. Hence it was im-
possible to analyse the mesogenic properties of
well-defined compounds and thus to understand
the properties of a given membrane on the basis
of its constituting components.
Fig. 1. 1,2-Di-O-acyl-3-O-(b-D-glucopyranosyl)-sn-glycerol.
To circumvent these problems, chemical syn-
thesis was used to obtain pure compounds, but
this was hampered by difficulties encountered in
synthesising optically active compounds of high
anomeric purity. Several strategies have been
used to solve this problem:
– glycolipids that have been extracted from nat-
ural sources have been used as starting mate-
rials and by means of classical synthesis
semisynthetic compounds with a defined acyl
chain structure were obtained (Heinz, 1971;
Heinz et al., 1979). Since sources of large
quantities of natural glycolipids with a wide
range of headgroup structures are scarce, this
approach is still rather limited and not help-
ful for this work, i.e. performing a systematic
structure variation to elucidate structure
property relationships.
– another solution to the problem of glycoglyc-
erolipid synthesis was to avoid some of the
difficulties inherent in the synthesis of glyco-
syl diacylglycerols by preparing the corre-
sponding dialkyl analogues. Based on this
approach, the synthesis of glucosyl (Six et al.,
1983; Hinz et al., 1991, 1996), glucuronosyl
(Koynova et al., 1993), galactosyl (Kuttenre-
ich et al., 1988; Hinz et al., 1991, 1996), man-
nosyl (Hinz et al., 1991, 1996), maltosyl (Six
et al., 1983; Hinz et al., 1991) and maltotrio-
syl (Hinz et al., 1996) dialkylglycerols was de-
scribed and except for the glucosyl
compounds (Six et al., 1983), mesogenic
properties were also investigated. However,
the properties of the dialkyl compounds differ
from the properties of the diacyl compounds.
The former are therefore of limited value as
model compounds for the naturally occurring
glycosyl diacylglycerols only of limited value
(Lewis et al., 1990 and references cited
therein).
role in biomembranes. In a review article about
the mesogenic properties of glycosyl diacylglyc-
erols published in 1994 by Caffrey (Koynova
and Caffrey, 1994) most of the entries refer only
to glucosyl diacylglycerols and their ether ana-
logues followed by a less comprehensive group
of galactosyl diacyl- and dialkylglycerols. Be-
sides these ‘bigger’ compilations only a few
other entries can be found concerning glycoglyc-
erolipids with disaccharide or larger headgroups,
and all of them belong to the dialkylglycerol
type with the aliphatic chains bound by ether
instead of ester bonds to the glycerol moiety.
The reason for the aforementioned lack of in-
formation might be the difficulty to obtain suffi-
cient amounts of glycosyl diacylglycerols
necessary for a thorough physical characterisa-
tion. Traditionally the lipids have mostly been
isolated from natural sources. For example,
monogalactosyl and digalactosyl diacylglycerols
with polyunsaturated fatty acid chains have
been extracted from plants and algae where they
account for more than 80% of the polar lipids
in the photosynthetic membranes (Quinn and
Williams, 1983). The investigation of the meso-
genic properties of these extracted lipids also
improved the understanding of their role in the
structure and function of photosynthetic mem-
branes (review: Quinn and Williams, 1983), e.g.
that the activity of enzymes of the photosyn-
thetic process strongly depends on the presence
of these lipids (Pick et al., 1987).
Unfortunately, it is impossible to obtain gly-
colipids with a homogeneous fatty acid composi-
tion by extraction from natural sources. After
purification and separation, the extracted glycol-
ipids have a common sugar headgroup but al-
ways a heterogeneous fatty acid composition,

H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
57
Fig. 2. Synthesis of glucosyl diacylglycerols according to Mannock et al. (1987).
Finally, Mannock et al. (1987, 1990) presented
2. Results and discussion
a convenient synthetic pathway to saturated a and
b glucosyl diacylglycerols and determined their
mesogenic properties in detail but hitherto neither
the synthesis nor the mesogenic properties of sim-
ilar compounds with other carbohydrate head-
groups have been described, and no data on
synthesised glycosyl diacylglycerols with unsatu-
rated chains are available.
To derive structure–property relationships, a
systematic variation of the carbohydrate head-
group will be presented. Whereas, alkylglycosides
are the simpler model compounds, glycosyl dia-
cylglycerols are more complex and closer to na-
ture. Because of the experiences made while
analysing the mesogenic properties of alkyl gly-
cosides (Vill et al., 2000; Minden et al., in press),
glycosyl diacylglycerols with unsaturated cis-9-oc-
tadecanoyl chains were chosen as model systems
to prevent crystallisation, as these compounds are
intended for use in binary mixtures where crys-
tallisation may cause problems because of inho-
mogeneities in the mixture.
2.1. Synthesis of glycosyl diacylglycerols
The well-elaborated procedure from Mannock
et al. (1987)) for the synthesis of glucosyl diacyl-
glycerols had to be modified for glycosyl diacyl-
glycerols bearing unsaturated fatty acid chains.
The synthetic strategy used by Mannock et al. is
sketched in Fig. 2. The first step is a condensation
of 2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl bro-
mide (1) with 1,2-di-O-benzyl-sn-glycerol (12) un-
der well-established Koenigs–Knorr conditions to
obtain the b-glucoside 2. The optically pure agly-
con 12 is prepared in a 6-step procedure (Fig. 3)
starting with
D
-mannitol 6 (Van Boeckel et al.,
1985; Mannock et al., 1987). In this respect it is
noteworthy that the easily accessible and optically
pure 1,2-O-isopropylidene-sn-glycerol racemises
during the Koenigs–Knorr condensation proce-
dure (Wickberg, 1958; Wehrli and Pomeranz,
1969), due to intramolecular migration of the
isopropylidene group and cannot be used thus.

58
H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
After hydrogenolytic removal of the benzyl protec-
tive groups of compound 2, the glycerol 3 is
afforded which yields after esterification and subse-
quent reductive deacetylation the glucosyl diacyl-
glycerol 5.
The final selective removal of the acetyl protect-
ing groups of 4 in the presence of the fatty acyl
groups esterified to the glycerol moiety is only
possible under reductive conditions using hydra-
zine hydrate and it is this final step which is
troublesome in the case of unsaturated fatty acids
(Nagatsu et al., 1994). For example, on treat-
because linoleoyl groups were reduced to oleoyl
groups, other monounsaturated and/or saturated
acyl groups. Thus, Nagatsu later exchanged the
acetyl groups, which are necessary as neighbouring
groups in the glycosylation step, for 4-methoxyben-
zyl groups, which can easily be cleaved under mild
conditions.
In the literature only a few cases of the synthesis
of glycosyl diacylglycerols with unsaturated fatty
acids can be found (Nagatsu et al., 1994; Chupin
et al., 1994; Van Boeckel et al., 1985). Nagatsu et
al. described the synthesis of some galactosyl dia-
cylglycerols with unsaturated acyl chains and the
investigation of their anti-tumor-promoting activ-
ity. The inhibitory activity of the synthesised com-
ing 1,2-di-O-linoleoyl-3-O-(b-D-galactopyranos-
yl)-sn-glycerol with hydrazine hydrate Nagatsu
observed only a low yield of the desired product,
Fig. 3. Synthesis of 1,2-di-O-benzyl-sn-glycerol.

H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
59
pounds on Epstein–Barr virus early antigen activa-
tion was evaluated as anti-tumor-promoting activ-
ity, with 1,2-di-O-oleoyl-3-O-(b-D-galactopyrano-
syl)-sn-glycerol showing the strongest activity. Un-
fortunately, no attempts have been made in the
course of these investigations to characterise the
liquid crystalline properties of the synthesised com-
pounds, and the same holds true for the work of
Van Boeckel et al. (1985), who reported the synthe-
1978) and DMAP, yielding the ester 19 which upon
removal of the 4-methoxybenzyl groups with ceric
ammonium nitrate (Classon et al., 1984; Johansson
and Samuelsson, 1984; Oikawa et al., 1982) gave
the desired glyco lipid 1,2-di-O-oleoyl-3-O-(b-D-
glucopyranosyl)-sn-glycerol (20) as a waxy solid.
Due to its liquid crystallinity at ambient temper-
ature, the glycolipid 20 could not be recrystallised
as additional purification after silica gel chro-
matography. To ensure the high purity which is
necessary for the exact determination of the liquid
crystalline transition temperatures, 20 was purified
by means of an additional gel filtration. The same
procedure as described above for the synthesis of
the glucosyl compound 20 was also applied to the
synthesis of the maltobiosyl and cellobiosyl com-
pounds 31 and 42. In the case of the disaccharide
derivatives, the final deprotection step turned out
to be troublesome since the end product was more
or less insoluble in the solvent system and precip-
itated together with small amounts of partially
deprotected intermediates, rendering the purifica-
tion more difficult. For this reason, as well as to
shorten the lengthy procedure by two steps, the
chloroacetate protecting group was subsequently
used instead of the 4-methoxybenzyl group. The
chloroacetate group can be cleaved under very mild
conditions using thio urea as reagent in ethanolic
solution (Ziegler, 1990; Van Boeckel and Beetz,
1983; Bertolini and Glaudemans, 1970). This new
route is depicted in Figs. 6 and 7. It was decided
not to take advantage of the even shorter synthetic
route starting with the perchloracetylated sugar as
the glycosyl donor precursor, because of the well-
known low stability of perchloracetylated sugars as
well as because of the significantly lower anomeric
selectivity using this glycosyl donor in the glycosy-
lation step (Ziegler, 1990). It was believed that the
reactivity of the chloro acetates could easily have
caused problems in a multistep synthesis.
sis of 1,2-di-O-oleoyl-3-O-(b-D-glucopyranosyl)-
sn-glycerol used as a building block for the
synthesis of a complex phospholipid. These efforts
have been made by Chupin et al. (1994), who also
synthesised 1,2-di-O-oleoyl-3-O-(b-D-galactopyra-
nosyl)-glycerol, using however a synthetic strategy
which only led to the formation of a product with
a racemic glycerol moiety. Since the naturally
occurring glyerol derivatives are never racemic, it
seems unwise to use this strategy to synthesise
model compounds.
In a first approach, the route and reaction
conditions outlined in Figs. 4 and 5 have been used
in this work, and are a combination of the works
from Nagatsu and Van Boeckel. For example,
glucose 13 was peracetylated and transformed into
the sugar bromide 1 by the action of hydrogen
bromide in glacial acetic acid. The bromide 1 was
condensed with optically pure 1,2-di-O-benzyl-sn-
glycerol (12) under well-established Helferich con-
ditions (Helferich and Ost, 1962) giving the
glucosylglycerol
2
in excellent yield. Hy-
drogenolytic removal of the benzyl groups afforded
the diol 3, which was protected as isopropylidene
ketal 15 by treatment with 2,2-dimethoxypropane
in the presence of a catalytic amount of 4-toluene-
sulfonic acid. Deprotection of the acetylated sugar
moiety using the Zemplen procedure yielded the
glucoside 16.
The free hydroxyl groups of compound 16 were
protected with p-methoxybenzyl groups (Classon et
al., 1984; Johansson and Samuelsson, 1984;
Oikawa et al., 1982), which can easily be cleaved
in the final step under mild conditions, avoiding
any interference with the double bonds. In the
following synthetic steps, the glycerol moiety was
deprotected by treatment with aqueous acetic acid,
giving the diol 18. This was esterified with oleic acid
using the DCC method (Hassner and Alexanian,
Acetobrom galactose 45 was prepared as out-
lined in Fig. 6 using standard procedures, and
condensed with 1,2-di-O-benzylglycerol (12) af-
fording the b galactoside 46, which was deacety-
lated using the Zemplen procedure to obtain
compound 47. The free hydroxyl groups of 47

60
H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
Fig. 4. Synthesis of compounds 16, 27 and 38.

H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
61
Fig. 5. Synthesis of compounds 20, 31 and 42.
40 °C decomposed completely and even at 20 °C
to some extent. This decomposition can be pre-
vented by using ethyl acetate as solvent, and
demonstrates the aforementioned and sometimes
troublesome reactivity of the chloroacetate pro-
tecting group. The diol 49 was esterified with oleic
acid using the procedure developed by Hassner
were chloracetylated with chloroacetic acid anhy-
dride in the presence of sodium hydrogen carbon-
ate in absolute dimethylformamide (Ziegler, 1990;
Chittenden and Regeling, 1987). The hy-
drogenolytic removal of the benzyl protecting
groups of derivative 48 in ethanol afforded com-
pound 49, which on evaporation of the solvent at

62
H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
Fig. 6. Synthesis of compounds 49 and 57.

H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
63
and Alexanian (1978), and the ester 50 was
dechloroacetylated in the final step by treatment
with thio urea (Ziegler, 1990; Van Boeckel and
Beetz, 1983; Bertolini and Glaudemans, 1970).
The same procedure was also used for the
analogous maltoside 24 starting from the per-
acetylated sugar, using the Koenigs–Knorr proce-
dure requiring the intermediate synthesis of the
aceto brom sugar. Compared to the initial strat-
egy (Figs. 4 and 5) this last strategy, with only six
steps starting from the peracetylated sugar, is
shorter by three steps.
The decision to synthesise glycolipids with un-
saturated chains was initially made to prevent
crystallisation, which might have rendered the use
of the compounds in binary mixtures difficult.
Another aspect was that an easy procedure for the
synthesis of these interesting compounds was
missing, and therefore little was known about
their physical properties. With the synthetic route
outlined in Figs. 6 and 7, this problem has been
synthesis of 1,3-di-O-(b-D-glucopyranosyl)-2-O-
oleoyl-sn-glycerol (65) (Fig. 8) using commercially
available 2-benzyloxy-1,3-propanediol as aglycon.
In a further attempt to shorten the lengthy
procedure, the peracetylated saccharide 53 was
treated directly with the protected glycerol 12 in
absolute dichloromethane in the presence of
boron trifluoride ethyl etherate. Using these con-
ditions, the glycoside 54 was achieved in an excel-
lent yield of 71%, especially in comparison with
an overall yield of 52% for the synthesis of the
Fig. 7. Synthesis of compounds 51 and 59.

64
H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
Fig. 8. 1,3-Di-O-(b-D-glucopyranosyl)-sn-glycerol (65).
solved. Another well-known possibility in liquid
crystal chemistry to prevent crystallisation is to
disturb the molecular packing by branching of the
aliphatic chains. To date only a few phospholipids
with branched fatty acid chains (Morr et al., 1997
and references cited therein) have been synthe-
sised besides some thermotropic ferro- and anti-
ferro-electric liquid crystals (Heppke et al., 1997),
and nothing is known about glycolipids with
methyl branched fatty acid chains. Thus, some
glucosyl diacylglycerols of this kind have been
synthesised here to investigate the exact influence
of the highly methyl substituted chiral fatty acid
chains on the mesophase behaviour in comparison
to the analogous, non-methyl-substituted com-
pounds. The chiral methyl branched fatty acids
used for this synthesis have been isolated from
rump glands of Cairina moschata (Fortkamp,
1994) and Anser a. f. domesticus (Morr et al.,
1992), and for the preparation of these com-
pounds the above-mentioned procedure developed
by Mannock et al. (1987) (Fig. 9) was utilised.
mostly formed SA phases due to their rod-like
molecular shape. The introduction of unsatura-
tion into the fatty acid chains (compound 20)
lowered the clearing temperature of the columnar
phase by 21 K. It is interesting to compare this
result with the structure–property relationships
derived for alkyl glycosides (Vill et al., 2000) since
the same value (20.8 K) was found for the lower-
ing of the clearing temperature of the SA phase in
the case of the stearyl monoglucoside (compound
73, Table 2), upon introduction of a double bond
into the alkyl chain (compound 74). The effect of
the introduction of an unsaturation can be at-
tributed to the disturbance in the alkyl chain
packing. The size of this disturbance seems to be
the same regardless if the sugar bears one chain
(alkyl glucosides) or two chains (glucosyl diacyl-
glycerols), since in both cases the clearing temper-
ature was depressed by 21 K. Due to the
unsaturation of the fatty acid chains in compound
20 the m.p. is also lowered relative to compound
72, causing the former to be liquid crystalline even
at ambient temperature. Hence the m.p. is de-
pressed by more than 70 K due to the disturbed
packing of the alkyl chains and as in the case of
the alkyl glucoside 74, the effect of the unsatura-
tion on the m.p. is also much stronger than the
effect on the clearing point (Fig. 10).
2.2. Mesogenic properties of glycosyl
diacylglycerols
2.2.1. Thermotropic properties
Fig. 10 depicts a systematic structure variation
of a well-known glycosyl diacylglycerol, 1,2-di-
O-stearoyl-3-O-(b-
D
-glucopyranosyl)-sn-glycerol
2.2.2. Influence of the configuration of the
hydroxyl groups of the sugar residue
(glucopyranosyl 6s. galactopyranosyl)
(72), the mesogenic properties of which were re-
ported first by Mannock et al. (1987). Due to its
wedge shaped structure compound 72 and similar
glycosyl diacylglycerols form columnar meso-
phases of type II with the hydrophilic/hydropho-
bic interface being curved towards the sugar
component (the minor component), while the
mono-tailed alkyl glycosides described in previous
papers (Vill et al., 2000; Minden et al., in press)
If the b-
D
-glucopyranosyl residue of compound
-galactopyranosyl residue
20 is replaced by a b-
D
(compound 51), the clearing point increases by
about 5 K. Therefore, it can be concluded that the
configuration of the hydroxyl groups in the head-
group has a small effect of on the mesophase
stability, but this effect is much smaller for glyco-

H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
65
syl diacylglycerols than for the mono-tailed alkyl-
glycosides. For example, in the case of alkyl gly-
cosides the exchange of a gluco- (compound 74,
Table 2) for a galyctopyranosyl moiety (com-
pound 75, Table 2) increased the stability of the
SA phase by 19 K.
ence in stability between compound 31 and 42.
Hence, the kind of interglycosidic linkage—a1“
4 in the former and b1“4 in the latter—seems to
have no significant influence on the stability of the
columnar mesophase.
2.2.4. Influence of the position of linkage between
the two sugar moieties in the disaccharide
headgroup (1“6 6s. 1“4)
2.2.3. Influence of the type of linkage between the
two sugar residues (h 6s. i)
In the next step, the glucose headgroup of
compound 20 was replaced by the disaccharides
maltobiose (compound 31) and cellobiose (com-
pound 42). In both cases the clearing temperature
was raised by about 107 K due to increased
hydrogen bonding in the headgroup region, at-
tributable to the increased number of hydroxyl
groups. However, there is more or less no differ-
If the position of the linkage between the two
sugar moieties in the disaccharide headgroup was
changed (1“4–1“6), a complex polymorphism
was found. Compound 59 with a b1“6 linked
diglucoside headgroup displayed a SA phase up to
82 °C, followed by a broad cubic phase, which
transformed at 149 °C into
a
columnar
mesophase and cleared at 200 °C. The reason for
Fig. 9. Synthesis of glucosyl diacylglycerols with chiral methyl branched fatty acids.

66
H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
Fig. 10. Systematic structure variation of glycosyl diacylglycerols.
statistical degree of unsaturation of the various
fatty acids linked to the glycerol, the following
mesogenic behaviour was found by means of po-
larising microscopy:
this complex behaviour is the broad structure of
the 1“6 linked disaccharide headgroup, giving
compound 59 at low temperatures a rod-like
shape and hence a SA phase is found as the low
temperature phase. With increasing temperature
the molecule becomes more and more wedge-like
due to an increased motion of the aliphatic
chains, and thus at 149 °C a columnar phase is
found. In the temperature range between 82 and
149 °C a cubic phase is formed as a compromise,
since both other phases are destabilised by the
other molecular moiety. This result proves again
the interesting and important influence of 1“6
linked disaccharide headgroups on the mesogenic
properties of glycolipids (Minden et al., in press).
A similar mesogenic behaviour was found in the
case of a glycosyl diacylglycerol with a 1“6
linked digalactoside headgroup that has been ex-
tracted from Heinz (unpublished results) from
natural sources. After hydrogenation to reduce at
least the heterogeneity of the sample due to a
Cr 85 SA 130 cub 180 col 233
I
Hence, it seems very likely that broad 1“6
linked carbohydrate headgroups as a general
structural principle lead to the formation of a
broad polymorphism in glycosyl diacylglycerols
and that nature possibly uses the demanding
stereochemistry of carbohydrates to control bio-
logical processes.
To investigate the effect of very broad hy-
drophilic headgroups, the neoglycolipid 65 with
two b-D-glycopyranosyl moieties linked to posi-
tions 1 and 3 of the glycerol and only one oleic
acid chain linked to position 2 was synthesised.
This compound exhibited as low temperature
phase a columnar phase up to 72 °C, followed by
a very broad cubic phase up to a temperature of

H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
67
156 °C. The high temperature phase was a SA
phase with a clearing temperature of 217 °C (Fig.
10). This phase sequence is exactly of the opposite
order to that found for compound 59. Because of
the very broad structure of the hydrophilic head-
group compared to that of the single fatty acid
chain, compound 65 forms a columnar phase of
type I, i.e. the hydrophilic/hydrophobic interface
curves towards the fluid hydrocarbon chain region
(the minor component). With increasing tempera-
ture, the spacial demand of the hydrophobic region
increases again due to an increased motion of the
fatty acid chain, and the molecule becomes finally
rod-shaped and forms as high temperature phase a
SA phase. In the temperature range between 72 and
156 °C a cubic phase (also type I) is formed as a
fact of frustration from compound 65, since the
columnar phase is already destabilised due to the
increased volume of the fluid hydrocarbon chain
region, but a SA cannot yet accommodate the
hydrophilic headgroup, which is too broad com-
pared to the hydrocarbon chain. To obtain further
structural information and to prove the phase type,
X-ray experiments were also performed. In good
accordance with the results of the polarising mi-
croscopy, the columnar to cubic transition at 72 °C
turned out to be a transition from a 2-d hexagonal
,
phase with a lattice parameter of 51 A to a cubic
phase of the space group Ia3d with a lattice
,
parameter of 99 A. This space group is frequently
described in the literature for lyotropic cubic phases
and was also found in at least one case for a
thermotropic cubic phase, i.e. that of dodecyl-a-D-
gentiobioside (Fischer et al., 1994).
Table 1 summarises the mesogenic properties of
some glycosyl diacylglycerols and alkyl glycosides.
Depending on the number of alkyl chains linked to
the hydrophilic headgroup (1 vs. 2) and the position
of linkage between the two sugar moieties in the
disaccharide headgroup (1“6 vs. 1“4), all differ-
ent phases (bicontinuous cubic, columnar and
lamellar) and types of phases (normal and inverted)
Table 1
Mesogenic properties of some carbohydrate amphiphiles depending on the number of alkyl chain and position of linkage

68
H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
Table 2
Mesogenic properties of some alkylglycosides for comparison (Vill et al., 1999; Minden et al., in press)
can be found on heating in this system as they can
be found in lyotropic systems depending on concen-
tration. Compound 65 forms a columnar phase of
type I, due to the very broad headgroup and the
single chain. This phase transforms with increasing
temperature, for the reasons discussed above, to a
cubic phase and finally to a SA phase. If the very
broad headgroup of compound 65 is exchanged for

H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
69
On the introduction of a stiff and linear b-cel-
lobiose headgroup (compound 78) the cubic phase
disappears also and only the SA phase remains.
Compound 42 with the same carbohydrate head-
group displays a columnar phase of type II, because
of its wedge-shaped structure due to the introduc-
tion of a second chain. Finally, the exchange of the
a somewhat smaller 1“6 linked diglucoside head-
group (compounds 76 and 77), the columnar phase
disappears. Moreover, depending on the chain
length the bicontinous cubic phase eventually be-
comes monotropic (compound 76; C-18), while the
dodecyl glycoside 77 displays a ‘ordinary’ enan-
tiotropic cubic phase (Table 2).
Fig. 11. Mesogenic properties of some glucosyl diacylglycerols bearing chiral methyl branched fatty acids and literature data
(Mannock et al., 1987) of unbranched compounds for comparison.

70
H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
Fig. 12. Lyotropic properties of the synthesised glycosyl diacylglycerols. *, Myelin figures beyond the SA phase in the contact
preparation with water.
no data are available about the physical properties
of the analogous compounds with the same chain
length, but without the methyl branching. One
reason might be that the glucosyl diacylglycerols
with octanoyl and decanoyl chains are not liquid
crystalline, because of the too short fatty acid
chains. This idea is strongly supported by the
changes in the transition temperatures of the liquid
crystalline compounds 72, 79, 80 and 81 (Fig. 11).
It is also interesting to compare the transition
temperatures of the methyl branched compounds
69 and 71 (Fig. 11) with those of compounds 79 and
80 with unbranched fatty acid chains having the
same total number of carbon atoms. While the
compounds 79 and 80 have a crystal to liquid
b1“4 linked cellobiose headgroup for a broader
b1“6 linked gentobiose headgroup (compound
59) again introduces a broad polymorphism with a
SA phase, a bicontinous cubic phase of type II and
a columnar phase of type II.
According to our knowledge, we were the first to
synthesise glycoglycerolipids with chiral fatty acid
chains, while the synthesis of some phospholipids
with this chiral fatty acid chains has been described
previously (Morr et al., 1997). In addition to the
introduction of unsaturation, the introduction of
lateral branches is a well-known method in liquid
crystal chemistry to prevent crystallisation.
All these compounds displayed a columnar
mesophase at ambient temperature. Unfortunately,

H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
71
crystal transition at 80 and 83 °C, the compounds
69 and 71 are already liquid crystalline at room
temperature. The clearing point of compound 69
(four methyl branches) is lowered in comparison to
79 by 73.8 K and in the case of compound 71 (three
methyl branches) in comparison to 80 by 56 K,
yielding in both cases an average lowering of the
clearing point of about 18 K per methyl branch, if
the total number of carbon atoms is kept constant.
Compounds 67–69 differ in that, the terminal
methyl group of 67 has been replaced by a 1-
methylpropyl group. Normally, one should have
expected in the case of these short chain com-
pounds an increase of the clearing point upon
elongation of the acyl chain (e.g. 67 and 71), but
this effect is overcompensated by the effect of the
additional methyl branch, giving a lowering of the
clearing point of 4.9 K. If at a constant chain
length one methyl group is removed (69, 71) the
clearing point rises up by 17.8 K.
It can be concluded that the methyl branching
disturbs the interaction in the hydrophobic tail
region and therefore destabilises the mesophase,
but enlarges the mesophase range, since the crystal
to liquid crystal interconversion is depressed much
more strongly. Hence, the methyl branching has
the same effect on the mesogenic properties as the
introduction of double bonds into the fatty acid
chains. Since these branched compounds are much
more stable, e.g. they cannot be degraded by
b-oxidation, they might be interesting for future
application in drug carriers or the development of
cubic phases derived nano porous materials, since
they could substitute unsaturated lipids while still
maintaining favourable transition temperatures.
pound 88) or cellobiose (compound 100) a much
more complex polymorphism is found in the con-
tact preparation with water (Fig. 12). In both
cases, three phases are formed with increasing
water concentration: a HII phase, a bicontinous
cubic VII phase and a La phase. Furthermore,
beyond the lamellar region towards higher water
concentration myelin figures (Jeffrey and Wingert,
1992; Bouligand, 1998) can be found. These are
very interesting results, since it was believed until
now that the introduction of a second or third
sugar moiety in the headgroup region strongly
simplifies the phase behaviour and suppresses the
ability of these lipids to form non-lamellar struc-
tures (Hinz et al., 1996). However, the observed
mesogenic behaviour seems to be reasonable, since
the size of the headgroup should increase with
increasing hydration, and hence the molecule
should become less wedge-shaped and finally even
rod-shaped. This corresponds exactly with the
observation of a cubic and finally a lamellar phase
(rod-like shape of the molecules) at the highest
water concentration.
Compound 116 with a b1“6 linked diglucoside
headgroup displayed, interestingly, only myelin
figures besides the lamellar La phase. The next
phase that might have been expected to be formed
on hydration is in this case a VI phase with the
polar/unpolar interface being curved towards the
fluid hydrocarbon chain region. Since this phase
cannot be found, the amount of hydration of the
gentobiose headgroup seems to be not sufficient to
increase its size as much as necessary to become the
major component and to force the polar/unpolar
interface to curve towards the chain region. The
opposite is true for compound 122, with two
glucopyranosyl moieties linked to the position 1
and 3 of the glycerol moiety and bearing only a
single fatty acid chain at C-2. This compound
forms, even without hydration, a columnar phase
of type I and in the contact preparation with water
two additional cubic phases, separated from one
another by a sharp boundary, can be found. At
present it is difficult to speculate about their exact
structure, but two different micellar cubic phases
of type I seem to be quite probable and only
further X-ray experiments can help to unravel the
exact structures.
2.2.5. Lyotropic properties
The glucosyl diacylglycerols 77, 124, 126, and
128 displayed in a contact preparation with water
exclusively a columnar phase, as in the anhydrous
state. The same holds true for compound 108 with
a galactopyranosyl headgroup, and there seems
therefore to be no difference between the glucoside
77 and the galactoside 108 despite the different
configuration of the hydroxyl group at C-4, influ-
encing e.g. the ability to form hydrogen bonds.
If the glucose headgroup of compound 77 is
replaced by the disaccharides maltobiose (com-

72
H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
3. Experimental section
and sodium methoxide was added (pH 8–9). The
solution was stirred at ambient temperature until
TLC revealed the reaction to be complete,
neutralised using Amberlyst IR 120 ion-exchange
resign (protonated form), filtrated and evaporated
in vacuo.
3.1. Remark
Due to the length of the article, NMR-data has
been left out. It can be accquired from
http://liqcryst.chemie.uni-hamburg.de/pub/NMR1.
pdf.
3.3.3. Glycosylation II (general procedure 3)
To a solution of 1,2-di-O-benzyl-sn-glycerol
(12) (9.2 mmol), HgBr2 (5 mmol) and Hg(CN)2 (5
mmol) in 25 ml of dry acetonitrile was added
under nitrogen, over a period of 30 min at ambi-
ent temperature, a solution of the acetobromo
sugar (10 mmol) in 25 ml of dry acetonitrile.
When tlc revealed the reaction to be complete, the
reaction mixture was concentrated in vacuo to an
oil, redissolved in 150 ml chloroform, filtered,
washed three times with 100 ml of a 1 M aqueous
solution of KBr and subsequently once with 100
ml of water. The organic phase was dried with
MgSO4 and concentrated in vacuo to obtain a
viscous residue, which was purified by silica gel
chromatography.
3.2. Materials and methods
Thin-layer chromatography was performed on
silica gel (Merck GF254), and detection was effected
by spraying with a solution of ethanol–sulphuric
acid (9:1), followed by heating. Column
chromatography was performed using silica gel 60
(230–240 mesh, Machery & Nagel). NMR spectra
were recorded on a Bruker AMX-400 or a Bruker
DRX 5001 spectrometer (mc=centered multiplet,
d=doublet, t=triplet, dd double doublet,
dt=double triplet). An Olympus BH optical
polarising microscope equipped with a Mettler FP
82 hot stage and a Mettler FP 80 central processor
was used to identify thermal transitions and
characterise anisotropic textures.
3.3.4. Esterification using DCC (general procedure
4)
3.3. Synthesis
A solution of the carbonic acid (1.1 equivalent),
N,N-dicyclohexylcarbodiimide (1.1 equivalent),
the alcohol (1 equivalent) and a catalytic amount
of 4-(1-pyrrolidinyl)pyridin in dry dichlorometh-
ane was stirred at room temperature until tlc
revealed the reaction to be complete. During the
course of the reaction formed N,N%-dicyclohexy-
lurea was filtered off, the solution concentrated in
vacuo and the resulting residue purified by silica
gel chromatography.
3.3.1. Glycosylation I (general procedure 1)
The peracetylated saccharide (10 mmol) and the
alcohol (15 mmol) were dissolved in 100 ml
anhydrous dichloromethane under an atmosphere
of dry nitrogen and afterwards the Lewis acid (14
mmol boron trifluoride etherate) was added. The
mixture was stirred at ambient temperature until
TLC revealed the reaction to be complete. The
preparation of the b anomer required a reaction
time of 2–4 h. After the reaction had been
quenched with 100 ml of a saturated solution of
sodium hydrogen carbonate, the organic layer was
separated and the aqueous layer extracted two
times with dichloromethane. The combined organic
phases were washed twice with water (100 ml),
dried over magnesium sulphate, filtrated and
evaporated in vacuo. The resulting syrup was
purified by column chromatography.
3.3.5. 1,2-Di-O-benzyl-3-O-(2%,3%,4%,6%-tetra-O-a-
cetyl-i- -glucopyranosyl)-sn-glycerol (2)
D
General procedure 3 using 10 mmol of aceto-
bromo glucose and 9.17 mmol 1,2-di-O-benzyl-sn-
glycerol. Yield: 4.40 g (80%).
3.3.6. 3-O-(2%,3%,4%,6%-Tetra-O-acetyl-i-
D-glucop-
yranosyl)-sn-glycerol (3)
A mixture of 4.21 g (6.98 mmol) 61 and 0.4 g
Pd/C (10%) in 100 ml ethanol containing 2 ml
glacial acetic acid was stirred under one atmo-
3.3.2. Deacetylation (general procedure 2)
The compound was dissolved in dry methanol

H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
73
sphere of hydrogen until tlc showed the reaction to
be complete. The catalyst was removed by
filtration, the mother liquor evaporated in vacuo
and the resulting residue purified by silica gel
chromatography (chloroform–methanol 9:1).
Yield: 2.92 g (99%).
eum ether [50/70]–ethyl acetate 2:1). Yield: 2.15 g
(51%).
3.3.10. 3-O-[2%,3%,4%,6%-Tetra-O-(4¦-methoxybenz-
yl)-i- -glucopyranosyl]-sn-glycerol (18)
D
Compound 17 (1.64 g, 2.12 mmol) was dis-
solved in 20 ml 70% acetic acid and stirred for 3
h at 50 °C. The solvent was evaporated under
reduced pressure and the resulting oil was co-
evaporated twice with toluene and purified by
chromatography on silica gel (chloroform–
methanol 98:2). Yield: 967 mg (62%).
3.3.7. 1,2-O-Isopropylidene-3-O-(2%,3%,4%,6%-tetra-
O-acetyl-i- -glucopyranosyl)-sn-glycerol (15)
D
Compound 3 (2.85 g, 6.75 mmol) was dissolved
in 90 ml acetone and 11.3 ml (92.16 mmol)
2,2-dimethoxypropane and 225 mg (1.31 mmol)
p-toluenesulfonic acid were added. After stirring
for 1 h at room temperature the solution was
neutralised with triethylamine and evaporated to
dryness. The crude material was redissolved in 170
ml chloroform and washed twice with 100 ml of a
saturated solution of NaHCO3 and once with 100
ml water. The organic phase was dried (MgSO4),
the solvent removed in vacuo and the residue
recrystallised from diisopropyl ether. Yield: 3.03 g
(97%).
3.3.11. 1,2-Di-O-oleoyl-3-O-[2%,3%,4%,6%-tetra-O-
(4¦-methoxybenzyl)-i-
D-glucopyranosyl]-sn-glyce-
rol (19)
Compound 18 (930 mg, 1.27 mmol) was acy-
lated using general procedure 4. The crude product
was subjected to chromatographic purification on
silica gel (petroleum ether [50/70]–ethyl acetate
3:1) Yield: 1.04 g (65%).
3.3.8. 1,2-O-Isopropylidene-3-O-(i-D-glucopyran-
osyl)-sn-glycerol (16)
3.3.12. 1,2-Di-O-oleoyl-3-O-(i-D-glucopyranos-
Compound 15 (2.93 g, 6.33 mmol) was
deprotected using general procedure 2. Yield: 1.71
g (92%).
yl)-sn-glycerol (20)
Compound 19 (504 mg, 0.39 mmol) and ceric
ammonium nitrate (1.93 g, 3.51 mmol) were dis-
solved in 20 ml acetonitrile–water 18:1 and stirred
for 1 h at ambient temperature. After completion,
the reaction mixture was diluted with 100 ml
dichloromethane, washed with 50 ml water, 50 ml
sodium hydrogen sulfite, 50 ml sodium hydrogen
carbonate and again with water. The organic
layer was dried (MgSO4) and evaporated to dry-
ness. The crude material was purified by silica gel
chromatography (choroform–methanol 98:2) and
subsequent gel filtration on a column of Serva
LH-20 suspended in methanol. Yield: 180 mg
(58%).
3.3.9. 1,2-O-Isopropylidene-3-O-[2%,3%,4%,6%-tetra-
O-(4¦-methoxybenzyl)-i-
ycerol (17)
D-glucopyranosyl]-sn-gl-
Compound 16 (1.61 g, 5.47 mmol) was dissolved
under nitrogen in 50 ml dry N,N-dimethylform-
amide. The solution was cooled in an ice–water
bath and 1.05 g (43.8 mmol) NaH were added in
portionwise at 0 °C. The mixture was subsequently
brought to ambient temperature, 5.9 ml (43.8
mmol) p-methoxybenzylchloride were added
dropwise and the resulting mixture was stirred at
ambient temperature overnight. Methanol was
added carefully to destroy excess NaH and the
solvent was evaporated in vacuo. The residue was
dissolved in 150 ml ethyl acetate, washed twice with
50 ml of a saturated solution of NaHCO3 and once
with 50 ml water. The organic layer was dried
(MgSO4) and evaporated to dryness. The residue
was purified by column chromatography (petrol-
3.3.13. 1,2-Di-O-benzyl-3-O-[4%-O-(2¦,3¦,4¦,6¦-t-
etra-O-acetyl-h-
D
-glucopyranosyl)ꢀ2%,3%,6%-tri-O-
acetyl-i-
D
-glucopyranosyl]-sn-glycerol (24)
General procedure 3 using 12 mmol of aceto-
bromo maltose and 11.02 mmol 1,2-di-O-benzyl-
sn-glycerol. Yield: 6.37 g (65%).

74
H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
3.3.14. 3-O-[4%-O-(2¦,3¦,4¦,6¦-Tetra-O-acetyl-h-
-glucopyranosyl)ꢀ2%,3%,6%-tri-O-acetyl-i- -gluc-
opyranosyl]-sn-glycerol (25)
The organic layer was dried (MgSO4) and evapo-
rated to dryness. The residue was purified by
column chromatography (petroleum ether [50/70]–
ethyl acetate 7:5) to obtain compound 28. This was
added to 40 ml 70% acetic acid and stirred for 4
h at 50 °C. The solvent was evaporated under
reduced pressure and the resulting oil was co-evap-
orated twice with toluene and purified by chro-
matography on silica gel (petroleum ether
[50/70]–ethyl acetate 1:2). Yield: 1.92 g (28%).
D
D
A mixture of 5.90 g (6.62 mmol) 24 and 0.4 g Pd/C
(10%) in 130 ml ethanol containing 20 ml ethyl
acetate and 3.5 ml glacial acetic acid was stirred
under 1 atm of hydrogen until tlc showed the
reaction to be complete. The catalyst was filtered
off, the mother liquor evaporated in vacuo and the
resulting residue purified by silica gel chromatogra-
phy (chloroform–methanol 95:5). Yield: 4.35 g
(92%).
3.3.17. 1,2-Di-O-oleoyl-3-O-[4%-O-(2¦,3¦,4¦,6¦-t-
etra-O-{4-methoxybenzyl}-h-
2%,3%,6%-tri-O-{4-methoxybenzyl}-i-
D
-glucopyranosyl)ꢀ
-glucopyran-
3.3.15. 1,2-O-Isopropylidene-3-O-[4%-O-(2¦,3¦,4¦,
D
6¦-tetra-O-acetyl-h-
i-O-acetyl-i-
D
-glucopyranosyl)ꢀ2%,3%,6%-tr-
osyl]-sn-glycerol (30)
D
-glucopyranosyl]-sn-glycerol (26)
Compound 29 (1.54 g, 1.22 mmol) was acylated
using general procedure 4. The crude product was
subjected to chromatographic purification on silica
gel (petroleum ether [50/70]–ethyl acetate 4:1)
Yield: 1.48 g (68%).
Compound 25 (4.25 g, 5.98 mmol) was dissolved
in 60 ml acetone. 2,2-Dimethoxypropane (10.0 ml,
81.56 mmol) and p-toluenesulfonic acid (200 mg,
1.16 mmol) were added and the mixture stirred at
ambient temperature. After completion the solution
was neutralised with triethylamine and evaporated
to dryness. The crude material was re-
dissolved in 150 ml chloroform and washed twice
with 100 ml of a saturated solution of NaHCO3 and
once with 100 ml water. The organic layer was dried
(MgSO4) and the solvent evaporated under reduced
pressure. Yield: 4.18 g (93%).
3.3.18. 1,2-Di-O-oleoyl-3-O-[4%-O-(h-D-glucopyr-
anosyl)-i- -glucopyranosyl]-sn-glycerol (31)
D
Compound 30 (1.33 g, 0.74 mmol) and ceric
ammonium nitrate (6.25 g, 11.40 mmol) were
dissolved in a mixture of 22 ml acetonitrile and 1.2
ml water and stirred at ambient temperature. After
completion, the precipitate was filtered off and
dissolved in chloroform, washed with 50 ml water,
50 ml sodium hydrogen sulfite, 50 ml sodium
hydrogen carbonate and again with water. The
organic layer was dried (MgSO4) and evaporated
to dryness. The crude material was purified by silica
gel chromatography (choroform–methanol 95:5)
and a subsequent gel filtration on a column of Serva
LH-20 suspended in methanol. Yield: 265 mg (38%).
3.3.16. 3-O-[4%-O-(2¦,3¦,4¦,6¦-Tetra-O-{4-metho-
xybenzyl}-h- -glucopyranosyl)ꢀ2%,3%,6%-tri-O-{4-
D
methoxybenzyl}-i-
(29)
D -glucopyranosyl]-sn-glycerol
Compound 26 (4.08 g, 5.43 mmol) was depro-
tected using general procedure 2. Thus, the obtained
compound 27 was dissolved under nitrogen in 40
ml dry N,N-dimethylformamide. The solution was
cooled to 0 °C and 1.71 g (71.46 mmol) NaH were
added in portionwise at 0 °C. After the addition of
NaH was complete the mixture was brought to
ambient temperature, 9.72 ml (71.46 mmol) p-
methoxybenzyl chloride were added dropwise and
the resulting mixture was stirred at ambient temper-
ature overnight. Methanol was added carefully to
destroy excess NaH and the solvent was evaporated
in vacuo. The residue was dissolved in 150 ml ethyl
acetate, washed twice with 50 ml of a saturated
solution of NaHCO3 and once with 50 ml water.
3.3.19. 1,2-Di-O-benzyl-3-O-[4%-O-(2¦,3¦,4¦,6¦-t-
etra-O-acetyl-i-
D
-glucopyranosyl)ꢀ2%,3%,6%-tri-O-
acetyl-i-
D
-glucopyranosyl]-sn-glycerol (35)
General procedure 3 using 9.32 mmol of aceto-
bromo cellobiose and 9.32 mmol 1,2-di-O-benzyl-
sn-glycerol. Yield: 5.45 g (66%).
3.3.20. 3-O-[4%-O-(2¦,3¦,4¦,6¦-Tetra-O-a cetyl-i-
D-glucopyranosyl)ꢀ2%,3%,6%-tri-O-acetyl-i-D-gluco-
pyranosyl]-sn-glycerol (36)
A mixture of 5.26 g (5.90 mmol) 35 and 0.4 g Pd/C

H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
75
(10%) in 100 ml ethanol containing 9 ml ethyl
acetate and 2.5 ml glacial acetic acid was stirred
under 1 atm of hydrogen until tlc showed the
reaction to be complete. Chloroform was added
until the white precipitate was completly dissolved.
The catalyst was filtered off, the mother liquor
evaporated in vacuo, and the resulting residue
re-crystallised from ethanol. Yield: 3.80 g (91%).
pound 39. This was added to 40 ml 70% acetic
acid and stirred for 4 h at 50 °C. The solvent was
evaporated under reduced pressure and the result-
ing oil was co-evaporated twice with toluene and
chromatographed on silica gel (petroleum ether
[50/70]–ethyl acetate 1:2). Yield: 1.29 g (20%).
3.3.23. 1,2-Di-O-oleoyl-3-O-[4%-O-(2¦,3¦,4¦,6¦-te-
tra-O-{4-methoxybenzyl}-i-D-glucopyranosyl)ꢀ2%,
3%,6%-tri-O-{4-methoxybenzyl}-i-D-glucopyranos-
yl]-sn-glycerol (41)
Compound 40 (1.07 g, 0.85 mmol) was acylated
using general procedure 4. The crude product was
subjected to chromatographic purification on sil-
ica gel (petroleum ether [50/70]–ethyl acetate
4:1“3:1). Yield: 1.02 g (67%).
3.3.21. 1,2-O-Isopropylidene-3-O-[4%-O-(2¦,3¦,4¦,
6¦-tetra-O-acetyl-i-D-glucopyranosyl)ꢀ2%,3%,6%-
tri-O-acetyl-i-D-glucopyranosyl]-sn-glycerol (37)
Compound 36 (3.70 g, 5.21 mmol) was dissolved
in 60 ml acetone, 8.7 ml (71.40 mmol)
2,2-dimethoxypropane and 174 mg (1.01 mmol)
p-toluenesulfonic acid were added and the mixture
stirred at ambient temperature. After completion,
the solution was neutralised with triethylamine and
evaporated to dryness. The crude material was
redissolved in 150 ml chloroform and washed twice
with 100 ml of a saturated solution of NaHCO3 and
once with 100 ml water. The organic layer was dried
(MgSO4) and the solvent evaporated under reduced
pressure. Yield: 3.85 g (99%).
3.3.24. 1,2-Di-O-oleoyl-3-O-[4%-O-(i-D-glucopyr-
anosyl)-i-D-glucopyranosyl]-sn-glycerol (42)
Compound 41 (864 mg, 0.48 mmol) and ceric
ammonium nitrate (4.08 g, 7.45 mmol) were dis-
solved in a mixture of 22 ml acetonitrile and 1.2
ml water and stirred at ambient temperature.
After completion, the precipitate was filtered off
and dissolved in chloroform, washed with 50 ml
water, 50 ml sodium hydrogen sulfite, 50 ml
sodium hydrogen carbonate and again with water.
The organic layer was dried (MgSO4) and evapo-
rated to dryness. The crude material was purified
by silica gel chromatography (choroform–
methanol 95:5) and a subsequent gel filtration on
a column of Serva LH-20 suspended in methanol.
Yield: 175 mg (39%).
3.3.22. 3-O-[4%-O-(2¦,3¦,4¦,6¦-Tetra-O-{4-metho-
xybenzyl}-i-D-glucopyranosyl)ꢀ2%,3%,6%-tri-O-{4-
methoxybenzyl}-i-D-glucopyranosyl]-sn-glycerol
(40)
Compound 37 (3.75 g, 5.00 mmol) was depro-
tected using general procedure 2. Thus, the ob-
tained compound 38 was dissolved under nitrogen
in 40 ml dry N,N-dimethylformamide. The solu-
tion was cooled to 0 °C and 1.66 g (69.17 mmol)
NaH were added portionwise. After the addition
of NaH was complete the mixture was brought to
ambient temperature, 9.94 ml (73.12 mmol) p-
methoxybenzyl chloride were added dropwise and
the resulting mixture was stirred at ambient tem-
perature overnight. Methanol was added carefully
to destroy excess NaH and the solvent was evapo-
rated in vacuo. The residue was dissolved in 150
ml ethyl acetate, washed twice with 50 ml of a
saturated solution of NaHCO3 and once with 50
ml water. The organic layer was dried (MgSO4)
and evaporated to dryness. The residue was
purified by column chromatography (petroleum
ether [50/70]–ethyl acetate 7:5) to obtain com-
3.3.25. 1,2-Di-O-benzyl-3-O-(2%,3%,4%,6%-tetra-O-
acetyl-i-D-galactopyranosyl)-sn-glycerol (46)
General procedure 3 using 10 mmol of aceto-
bromo galactose and 9.17 mmol 1,2-di-O-benzyl-
sn-glycerol. Yield: 4.81 g (87%).
3.3.26. 1,2-Di-O-benzyl-3-O-(i-D-galactopyranos-
yl)-sn-glycerol (47)
Compound 46 (4.52 g, 7.51 mmol) was depro-
tected using general procedure 2. Yield: 3.10 g
(95%).

76
H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
3.3.27. 1,2-Di-O-benzyl-3-O-(2%,3%,4%,6%-tetra-O-
chloroacetyl-i-D-galactopyranosyl)-sn-glycerol
(48)
again evaporated to dryness. The residue was
purified by column chromatography on silica gel
(chloroform–methanol 95:5) and a subsequent gel
filtration on a column of Serva LH-20 suspended
in methanol. Yield: 0.88 g (50%).
Sodium hydrogen carbonate (1.37 g, 16.42 mmol)
was added under nitrogen to a solution of 3.0 g (6.90
mmol) 47 and 9.44 g (55.23 mmol) chloroacetic acid
anhydride in 35 ml dry N,N-dimethylformamide
and the suspension was stirred for 3.5 h at ambient
temperature. After tlc showed the reaction to be
complete, the suspension was diluted with 80 ml
ethyl acetate, poured into 150 ml of ice–water and
stirred for an additional 30 min. The phases were
separated and the aqueous layer was extracted twice
with 80 ml ethyl acetate and the combined organic
phases were washed twice with a saturated solution
of sodium hydrogen carbonate and once with water.
After drying (MgSO4) the solvent was removed in
vacuo and the resulting residue submitted to purifi-
cation by column chromatography (petroleum
ether [50/70]–diethyl ether 25:20). Yield: 4.15 g
(81%).
3.3.31. 1,2-Di-O-benzyl-3-O-[6%-O-(2¦,3¦,4¦,6¦-t-
etra-O-acetyl-i-D-glucopyranosyl)ꢀ2%,3%,4%-tri-O-
acetyl-i-D-glucopyranosyl]-sn-glycerol (54)
1,2-Di-O-benzyl-sn-glycerol (2.45 g, 9.00 mmol)
was glycosylated with 6.10 g (9.00 mmol) gentobiose
peracetate using general procedure 1. The product
was submitted to chromatographic purification
(petroleum ether [50/70]–ethyl acetate 1.5:1“
1.3:1). Yield: 5.69 g (71%).
3.3.32. 1,2-Di-O-benzyl-3-O-[6%-O-(i-D-glucopy-
ranosyl)-i-D-glucopyranosyl]-sn-glycerol (55)
Compound 54 (4.72 g, 5.30 mmol) was depro-
tected using general procedure 2. Yield: 3.09 g (98%).
3.3.33. 1,2-Di-O-benzyl-3-O-[6%-O-(2¦,3¦,4¦,6¦-t-
etra-O-chloroacetyl-i-D-glucopyranosyl)ꢀ2%,3%,4%-
tri-O-chloroacetyl-i-D-glucopyranosyl]-sn-glycer-
ol (56)
3.3.28. 3-O-(2%,3%,4%,6%-Tetra-O-chloroacetyl-i-D-
galactopyranosyl)-sn-glycerol (49)
A mixture of 3.65 g (4.93 mmol) 48 and 0.4 g Pd/C
(10%) in 120 ml ethyl acetate was stirred under 1
atm of hydrogen until tlc showed the reaction to be
complete. After 1 day the catalyst was filtered off
and the solvent evaporated to dryness. Yield: 2.68
g (97%).
Sodium hydrogen carbonate (1.16 g, 13.81 mmol)
was added under nitrogen to a solution of 3.0 g (5.02
mmol) 55 and 8.07 g (47.18 mmol) chloroacetic acid
anhydride in 30 ml dry N,N-dimethylformamide
and the suspension was stirred for 4.5 h at ambient
temperature. After tlc showed the reaction to be
complete, the suspension was diluted with 100 ml
ethyl acetate, poured into 150 ml of ice–water and
stirred for additional 30 min. The phases were
separated and the aqueous layer was extracted twice
with 100 ml ethyl acetate and the combined organic
phases were washed twice with a saturated solution
of sodium hydrogen carbonate and once with water.
After drying (MgSO4) the solvent was removed in
vacuo and the resulting residue submitted to purifi-
cation by column chromatography (petroleum
ether [50/70]–ethyl acetate 2:1). Yield: 4.71 g (83%).
3.3.29. 1,2-Di-O-oleoyl-3-O-( 2%,3%,4%,6%-tetra-O-
chloroacetyl-i-D-galactopyranosyl)-sn-glycerol (50)
Compound 49 (2.57 g, 4.59 mmol) was acylated
using general procedure 4. The crude product was
subjected to chromatographic purification on silica
gel (petroleum ether [50/70]–ethyl acetate 4:1)
Yield: 3.88 g (78%).
3.3.30. 1,2-Di-O-oleoyl-3-O-(i-D-galactopyrano-
syl)-sn-glycerol (51)
A solution of 0.866 g (11.37 mmol) thiourea in
15 ml methanol was added to a solution of 2.44 g
(2.24 mmol) 50 in 60 ml chloroform–methanol 3:1,
and the mixture was stirred for 18 h at ambient
temperature followed by 3 h at 50 °C. The solvent
was evaporated to dryness and the residue was
dissolved in chloroform, filtered and the solution
3.3.34. 3-O-[6%-O-(2¦,3¦,4¦,6¦-Tetra-O-chloroace-
tyl-i-D-glucopyranosyl)ꢀ2%,3%,4%-tri-O-chloroacet-
yl-i-D-glucopyranosyl]-sn-glycerol (57)
A mixture of 2.64 g (2.33 mmol) 56 and 0.15 g
Pd/C (10%) in 40 ml ethyl acetate was stirred

H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
77
under 1 atm of hydrogen until tlc showed the
reaction to be complete. After 1 day the catalyst
was filtered off and the solvent evaporated to
dryness. Yield: 2.20 g (99%).
mmol) was added under nitrogen to a solution of
2.16 g (4.26 mmol) 61 and 11.65 g (68.14 mmol)
chloroacetic acid anhydride in 45 ml dry N,N-
dimethylformamide and the suspension was stirred
for 5 h at ambient temperature. After tlc showed
the reaction to be complete, the suspension was
diluted with 100 ml ethyl acetate, poured into 150
ml of ice–water and stirred for an additional 30
min. The phases were separated and the aqueous
layer was extracted twice with 100 ml ethyl acetate
and the combined organic phases were washed
twice with a saturated solution of sodium hydrogen
carbonate and once with water. After drying
(MgSO4) the solvent was removed in vacuo and the
resulting residue submitted to purification by
column chromatography (petroleum ether [50/70]–
ethyl acetate 1.6:1). Yield: 2.20 g (46%).
3.3.35. 1,2-Di-O-oleoyl-3-O-[6%-O-(2¦,3¦,4¦,6¦- t -
etra-O-chloroacetyl-i-D-glucopyranosyl)ꢀ2%,3%,4%-
tri-O-chloroacetyl-i-D-glucopyranosyl]-sn-glycer-
ol (58)
Compound 57 (2.11 g, 2.21 mmol) were acylated
using general procedure 4. The crude product was
subjected to chromatographic purification on silica
gel (petroleum ether [50/70]–ethyl acetate 4:1)
Yield: 2.16 g (66%).
3.3.36. 1,2-Di-O-oleoyl-3-O-[6%-O-(i-D-glucopyr-
anosyl)-i-D-glucopyranosyl]-sn-glycerol (59)
A solution of 0.62 g (8.17 mmol) thiourea in 12
ml methanol was added to a solution of 1.24 g (0.84
mmol) 58 in 40 ml chloroform–methanol 3:1, and
the mixture was stirred for 20 h at ambient temper-
ature and finally for 3.5 h at 50 °C. The solvent was
evaporated to dryness and the residue was ex-
tracted with chloroform, filtered and the solution
again evaporated to dryness. The residue was
purified by column chromatography on silica gel
(chloroform–methanol 88:12) and a subsequent gel
filtration on a column of Serva LH-20 suspended
in methanol. Yield: 0.55 g (69%).
3.3.40. 1,3-Di-O-(2%,3%,4%,6%-tetra-O-chloroacetyl-
i-D-glucopyranosyl)-sn-glycerol (63)
A mixture of 2.09 g (1.87 mmol) 62 and 0.15 g
Pd/C (10%) in 40 ml ethyl acetate was stirred under
1 atm of hydrogen until tlc showed the reaction to
be complete. After 1 day the catalyst was filtered
off and the solvent evaporated to dryness. Yield:
1.83 g (95%).
3.3.41. 1,3-Di-O-(2%,3%,4%,6%-tetra-O-chloroacetyl-
i-D-glucopyranosyl)-2-O-oleoyl-sn-glycerol (64)
Compound 63 (1.72 g, 1.67 mmol) was acylated
using general procedure 4. The crude product was
subjected to chromatographic purification on silica
gel (petroleum ether [50/70]–ethyl acetate 2.1:1)
Yield: 1.21 g (56%).
3.3.37. 1,3-Di-O-(2%,3%,4%,6%-tetra-O-acetyl-i-D-
glucopyranosyl)-2-O-benzyl-sn-glycerol (60)
2-Benzyloxy-1,3-propanediol (2.00 g, 10.97
mmol) were glycosylated with 9.84 g (23.94 mmol)
acetobromo glucose using general procedure 3. The
product was purified by silica gel chromatography
(petroleum ether[50/70]–ethyl acetate 1:1). Yield:
4.23 g (46%).
3.3.42. 1,3-Di-O-(i-D-glucopyranosyl)-2-O-oleoy-
l-sn-glycerol (65)
A solution of 0.687 g (9.03 mmol) thiourea in 12
ml methanol was added to a solution of 1.15 g (0.89
mmol) 64 in 40 ml chloroform–methanol 3:1, and
the mixture was stirred for 24 h at ambient temper-
ature and followed by 3 h at 50 °C. The solvent was
evaporated to dryness and the residue was purified
by column chromatography on silica gel (chloro-
form–methanol 80:20) and a subsequent gel filtra-
tion on a column of Serva LH-20 suspended in
methanol. Yield: 0.23 g (38%).
3.3.38. 1,3-Di-O-(i-D-glucopyranosyl)-2-O-benz-
yl-sn-glycerol (61)
Compound 60 (4.07 g, 4.83 mmol) was depro-
tected using general procedure 2. Yield: 2.27 g
(93%).
3.3.39. 1,3-Di-O-(2%,3%,4%,6%-tetra-O-chloroacetyl-
i-D-glucopyranosyl)-2-O-benzyl-sn-glycerol (62)
Sodium hydrogen carbonate (1.69 g, 20.12

78
H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
3.3.43. 1,2-Di-O-[(2%R,4%R,6%R)-2%,4%,6%-trimethyl-
octanoyl]-3-O-(2¦,3¦,4¦,6¦-tetra-O-acetyl-i-D-gl-
ucopyranosyl)-sn-glycerol (66)
(chloroform–methanol 40:1“30:1) and gel filtra-
tion on a column of Serva LH-20 suspended in
methanol. Yield: 0.71 g (64%).
Compound 3 (1.00 g, 2.37 mmol) was acylated
with (2R,4R,6R)-2,4,6-trimethyloctanoic acid us-
ing general procedure 4. The crude product was
subjected to chromatographic purification on silica
gel (petroleum ether [50/70]–ethyl acetate 3:1)
Yield: 1.68 g (93%).
3.3.47. 1,2-Di-O-[(4%R,6%R,8%R)-4%,6%,8%-trimethyl-
decanoyl]-3-O-(2¦,3¦,4¦,6¦-tetra-O-acetyl-i-D-gl-
ucopyranosyl)-sn-glycerol (70)
Compound 3 (0.67 g, 1.59 mmol) was acylated
with (4R,6R,8R)-trimethyldecanoic acid using gen-
eral procedure 4. The crude product was subjected
to chromatographic purification on silica gel
(petroleum ether [50/70]–ethyl acetate 3:1) Yield:
1.10 g (85%).
3.3.44. 1,2-Di-O-[(2%R,4%R,6%R)-2%,4%,6%-trimethyl-
octano-yl]-3-O-(i-D-glucopyranosyl)-sn-glycerol
(67)
Compound 66 (1.60 g, 2.10 mmol) was dissolved
in a mixture of 30 ml dry methanol and 10 ml dry
dichloromethane. Hydrazine hydrate (0.82 ml, 16.8
mmol) (100%) were added to this solution and the
mixture was heated at the temperature of reflux for
8 h. The solution was cooled in an ice-bath,
neutralised with formic acid and the solvent re-
moved in vacuo. The residue was submitted to
chromatographic purification on silica gel (chloro-
form–methanol 30:1) and gel filtration on a column
of Serva LH-20 suspended in methanol. Yield: 0.61
g (49%).
3.3.48. 1,2-Di-O-[(4%R,6%R,8%R)-4%,6%,8%-trimethyl-
decanoyl]-3-O-(i-D-glucopyranosyl)-sn-glycerol
(71)
Compound 70 (0.91 g, 1.12 mmol) was
dissolved in a mixture of 17 ml dry methanol and
6 ml dry dichloromethane. Hydrazine hydrate
(0.43 ml, 8.89 mmol) (100%) were added to this
solution and the mixture was heated at the
temperature of reflux for 8 h. The solution was
cooled in an ice-bath, neutralised with formic acid
and the solvent removed in vacuo. The residue
was submitted to chromatographic purification on
silica gel (chloroform–methanol 20:1) and gel
filtration on a column of Serva LH-20 suspended
in methanol. Yield: 0.32 g (42%).
3.3.45. 1,2-Di-O-[(2%R,4%R,6%R,8%R)-2%,4%,6%,8%-te-
tramethyldecanoyl]-3-O-(2¦,3¦,4¦,6¦-tetra-O-acet-
yl-i-D-glucopyranosyl)-sn-glycerol (68)
Compound 3 (1.00 g, 2.37 mmol) was acylated
with (2R,4R,6R,8R)-tetramethyldecanoic acid us-
ing general procedure 4. The crude product was
subjected to chromatographic purification on silica
gel (petroleum ether [50/70]–ethyl acetate 3:1)
Yield: 1.55 g (76%).
Acknowledgements
We are grateful to the Deutsche Forschungsgem-
einschaft for financial support (SFB 470,
Graduiertenkolleg 464) and to the Studienstiftung
des Deutschen Volkes for a grant (MvM).
3.3.46. 1,2-Di-O-[(2%R,4%R,6%R,8%R)-2%,4%,6%,8%-te-
tramethyldecanoyl]-3-O-(i-D-glucopyranosyl)-sn-
glycerol (69)
Compound 68 (1.39 g, 1.65 mmol) was dissolved
in a mixture of 25 ml dry methanol and 8 ml dry
dichloromethane. Hydrazine hydrate (0.64 ml,
13.11 mmol) (100%) were added to this solution
and the mixture was heated at the temperature of
reflux for 8 h. The solution was cooled in an
ice-bath, neutralised with formic acid and the
solvent removed in vacuo. The residue was submit-
ted to chromatographic purification on silica gel
References
Bertolini, M., Glaudemans, C.P.J., 1970. The chloroacetyl
group in synthetic carbohydrate chemistry. Carbohyd. Res.
15, 263–270.
Chittenden, G.J.F., Regeling, H., 1987. An improved proce-
dure for the synthesis of sugar chloroacetates and some
substitution reactions thereof. Recl. Trav. Chim. Pays-Bas
106, 44–47.

H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
79
Chupin, V., Smirnova, S., de Kruijff, B., 1994. Synthesis
and polymorphism of deuterium labelled unsaturated
monogalactosyl diglyceride as studied by 2H NMR. Recl.
Trav. Chim. Pays-Bas 113, 237–240.
Classon, B., Garegg, P.J., Samuelsson, B., 1984. The p-
methoxybenzyl group as protective group of the
anomeric centre. Selective conversion of hydroxy groups
into bromo groups in p-methoxybenzyl 2-deoxy-2-phthal-
glycerols of different alkyl chain length. Chem. Phys.
Lipids 47, 245–260.
Lewis, R.N.A.H., Mannock, D., McElhaney, R.N., Wong,
P.T.T., Mantsch, H.H., 1990. Physical properties of gly-
cosyldiacylglycerols: an infrared spectroscopic study the
gel-phase polymorphism of 1,2-di-O-acyl-3-O-(b-D-glu-
copyranosyl)-sn-glycerols. Biochemistry 29, 8933–8943.
Mannock, D.A., Lewis, R.N.A.H., McElhaney, R.N., 1987.
An improved procedure for the preparation of 1,2-di-O-
acyl-3-O-(b-D-glucopyranosyl)-sn-glycerols. Chem. Phys.
Lipids 43, 113–127.
imido-b-D-glucopyranosides. Acta Chem. Scan.
419–422.
B 38,
Curatolo, W., 1987. The physical properties of glycolipids.
Biochim. Biophys. Acta 906, 111–136.
Fortkamp, J., 1994. PhD Thesis, Technische Universita¨t
Braunschweig.
Mannock, D.A., Lewis, R.N.A.H., McElhaney, R.N., 1990.
The chemical synthesis and physical characterisation of
1,2-di-O-acyl-3-O-(b-D-glucopyranosyl)-sn-glycerols,
an
Hassner, A., Alexanian, V., 1978. Direct room temperature
esterification of carboxylic acids. Tetrahedron Lett. 46,
4475–4478.
Heppke, G., Lo¨tzsch, D., Morr, M., Ernst, L., 1997. New
chiral side chains for ferro- and antiferro-electric liquid
crystals derived from the preen-gland wax of the domes-
tic goose. J. Mater. Chem. 7, 1993–1999.
important class of membrane glycolipids. Chem. Phys.
Lipids 55, 309–321.
Minden, v.H.M., Brandenburg, K., Seydel, U., Koch,
M.H.J., Garamus, V., Willumeit, R., Vill, V. 2000.
Chem. Phys. Lipids, 106, 157–179.
Morr, M., Wray, V., Fortkamp, J., Schmid, R.D., 1992.
(2R,4R,6R,8R)-2,4,6,8-Tetramethyldecan-
und
-unde-
Heinz, E., 1971. Semisynthetic galactolipids of plant origin.
Biochim. Biophys. Acta 231, 537–544.
Heinz, E., Siebertz, H.P., Linscheid, M., 1979. Synthesis and
enzymatic conversion of an ether analogue of mono-
galactosyl diacylglycerol. Chem. Phys. Lipids 24, 265–
276.
cansa¨ure aus den Bu¨rzeldru¨senwachs der Hausgans Anser
a. f. domesticus: isolierung, synthese einiger derivate
sowie der rac-2,4,6,8-tetramethyldecansa¨ure. Liebigs Ann.
Chem., 433–439.
Morr, M., Fortkamp, J., Ru¨he, S., 1997. Chirale
methylverzweigte tenside und phospholipide: synthese
und eigenschaften. Angew. Chem. 109, 2567–2569;
Angew. Chem. Int. Ed. Engl. 36, 2460–2462.
Helferich, B., Ost, W., 1962. Synthese einiger b-D-xylopyra-
noside. Chem. Ber. 95, 2612–2615.
Hinz, H.-J., Kuttenreich, H., Meyer, R., Renner, M., Fru¨nd,
R., Koynova, R., Boyanov, A.I., Tenchov, B.G., 1991.
Stereochemistry and size of sugar head groups determine
structure and phase behavior of glycolipid membranes:
densiometric, calorimetric and X-ray studies. Biochem-
istry 30, 5125–5138.
Nagatsu, A., Watanabe, M., Ikemoto, K., Hashimoto, M.,
Murakami, N., Sakakibara, J., Tokuda, H., Nishino, H.,
Iwashima, A., Yazawa, K., 1994. Synthesis and struc-
ture–anti-tumor-promoting activity relationship of mono-
galactosyl diacylglycerols. Bioorg. Med. Chem. Lett. 4,
1619–1622.
Hinz, H.-J., Tenchova, R, Tenchov, B., Quinn, P.J., 1996.
Lamellar-non-lamellar phase transitions in synthetic
glycoglycerolipids studied by time-resolved X-ray diffrac-
tion. Liq. Cryst. 20, 469–482.
Ishizuka, I., Yamakawa, T., 1985. Glycolipids. In: Wiegandt,
H. (Ed.), New Comprehensive Biochemistry, vol. 10. El-
sevier, pp. 101–197.
Oikawa, Y., Yoshioka, T., Yonemitsu, O., 1982. Specific re-
moval of methoxybenzyl protection by DDQ oxidation.
Tetrahedron Lett. 23, 885–888.
Pick, U., Weiss, M., Gounaris, K., Barber, J., 1987. The
role of different glycolipids in the function of reconsti-
tuted chloroplast ATP synthase. Biochim. Biophys. Acta
891, 28–39.
Johansson, R., Samuelsson, B., 1984. Regioselective reduc-
tive ring-opening of 4-methoxybenzylidene acetals of hex-
Quinn, P.J., Williams, W.P., 1983. The structural role of
lipids in photosynthetic membranes. Biochim. Biophys.
Acta 737, 223–266.
opyranosides. Access to
a
novel protecting group
strategy. Part 1. J. Chem. Soc. Perkin Trans. I, 2371–
2374.
Koynova, R., Caffrey, M., 1994. Phases and phase transi-
tions of the glycoglycerolipids. Chem. Phys. Lipids 69,
181–207.
Koynova, R.D., Tenchov, B.G., Kuttenreich, H., Hinz, H.-
J., 1993. Structure and phase behavior of a charged gly-
colipid (1,2-O-dialkyl-3-O-b-D-glucuronosyl-sn-glycerol).
Biochemistry 32, 12 437–12 445.
Kuttenreich, H., Hinz, H.-J., Inczedy-Marcsek, M.,
Koynova, R., Technov, B., Laggner, P., 1988. Polymor-
phism of synthetic 1,2-O-dialkyl-3-O-b-D-galactosyl-sn-
Six, L., Rueß, K.-P., Liefla¨nder, M., 1983. An efficient syn-
thesis of 1,2-O-dialkyl-3-O-b-D-glycosyl-sn-glycerols. Te-
trahedron Lett. 24, 1229–1232.
Van Boeckel, C.A.A., Beetz, T., 1983. Hydrazinedithiocar-
bonate (hdtc) as a new reagent for the improved removal
of chloroacetyl and bromoacetyl protective groups. Te-
trahedron Lett. 24, 3775–3778.
Van Boeckel, C.A.A., Visser, G.M., van Boom, J.H., 1985.
Synthesis of phosphatidyl-b-glucosyl glycerols containing
a dioleoyl diglyceride moiety: application of the tetraiso-
propyldisiloxane-1,3-diyl (TIPS) protecting group in
sugar chemistry. Part IV. Tetrahedron 41, 4557–4565.

80
H.M. 6on Minden et al. / Chemistry and Physics of Lipids 114 (2002) 55–80
Vill, V., Minden, v.H.M., Koch, M.H.J., Seydel, U., Branden-
burg, K., 2000. Thermotropic and lyotropic properties of
long-chain alkyl glycopyranosides. Part I: monosaccharide
headgroups. Chem. Phys. Lipids 104, 75–91.
Wehrli, H.P., Pomeranz, Y., 1969. Synthesis of galactosyl
glycerides and related lipids. Chem. Phys. Lipids 3, 357–370.
Wickberg, B., 1958. Synthesis of 1-glyceritol D-galactopyra-
nosides. Acta Chem. Scan. 12, 1187–1201.
Ziegler, T., 1990. Preparation of some fully chloroacetylated
glucopyranosyl bromides: useful intermediates for the syn-
thesis of base- and hydrogenolysis-sensitive glycosides.
Liebigs Ann. Chem., 1119–1124.