954
Published on the web September 1, 2012
Self-assembling Property of 6,6¤-Di-O-octyltrehalose under Aqueous Conditions
Manami Kanemaru, Kazuya Yamamoto, and Jun-ichi Kadokawa*
Graduate School of Science and Engineering, Kagoshima University, 1-21-40 Korimoto, Kagoshima 890-0065
(Received June 20, 2012; CL-120663; E-mail: kadokawa@eng.kagoshima-u.ac.jp)
In this study, we synthesized a new trehalose-based
analytical results indicated that the self-assembly of 6-O-
dodecyltrehalose was completely different from that of the
other derivatives. The former material primary formed spherical
micelles in water, which further assembled according to the face-
centered cubic organization by drying process from the aqueous
dispersion. On the other hand, the other derivatives formed
vesicle-type particles via the formation of lamellar-like planes,
which were further merged with each other probably by fusion
of the planes to construct larger aggregates.
In this letter, we report the synthesis and self-assembling
behavior of a new trehalose ether amphiphile, i.e., 6,6¤-di-O-
octyltrehalose (di-C8), which is composed of two 6-O-octyl-
glucose residues linked through an ¡,¡-1,1¤-glycosidic linkage,
and accordingly has a symmetric molecular structure. Conse-
quently, this material exhibited morphologically controlled self-
organization under aqueous conditions to form rod-shaped
aggregates. The morphology of the aggregates was completely
different from that obtained from the previously reported 6-O-
alkyltrehaloses under the same aqueous conditions.10
The synthesis of di-C8 was carried out from trehalose in
five steps according to Scheme 1, which were the successive
ditritylation at 6- and 6¤-positions, benzylation of other free
hydroxy groups, detritylation, dietherification at 6- and 6¤-
posititons, and debenzylation. The first three reactions were
already conducted to give the intermediate 3 for the synthesis of
6-O-alkyltrehaloses in our previous study.10 The following
dietherification using 1-bromooctane and debenzylation were
carried out according to the usual manner to give di-C8 in
19.1% overall yield from 3.11
amphiphile, 6,6¤-di-O-octyltrehalose, from trehalose by five
reaction steps. The SEM and TEM images of the sample
prepared by drying its aqueous dispersion showed the formation
of morphologically controlled hollow rod nanoaggregates.
Amphiphilic molecules, of which soap is a typical example,
possess antagonistic hydrophilic and hydrophobic moieties in
the same molecule. In aqueous media, such molecules self-
assemble into diverse aggregate morphologies, depending on
the molecular shape and solution conditions.1 Because natural
amphiphiles containing carbohydrates as a hydrophilic part such
as glycolipids exhibit important in vivo functions in living
systems,2 synthetic carbohydrate-based amphiphiles have been
studied extensively to exhibit a large variety of self-assembling
morphologies.1b,3 For example, the self-assembling properties
and applications, as surfactants, of fatty acid esters of di-
saccharides such as sucrose and trehalose have been studied.4,5
Moreover, the sucrose fatty acid esters are commercially used as
effective additives as emulsifiers in various food industries.6 We
have considered that carbohydrate ether amphiphiles, which
have the structures composed of a hydrophilic carbohydrate
residue with hydrophobic alkyl chains by ether linkages, exhibit
different self-assembly from such carbohydrate ester amphi-
philes, owing to the more simple structure and exclusion of
hydrogen bonding by the carbonyl group. On the basis of this
viewpoint, in the previous paper, we reported morphologically
controlled self-assembly of a mixture of 6-O- and 6¤-O-
hexadecylsucroses under aqueous conditions.7
Trehalose is a nonreducing disaccharide, in which two
glucose units are linked through an ¡,¡-1,1¤-glycosidic linkage.8
Because trehalose has been produced industrially from starch by
enzymatic catalyses and has become available at lower costs, it
is regarded as a new renewable resource comparable to sucrose.
Naturally occurring glycolipids containing a trehalose residue
(trehalolipids) are found in nature as an example of which is
trehalose 6,6¤-dimycolate. This is the most reported trehalolipid
and is a ¡-branched-chain mycolic acid in which the 6-position
of each glucose unit is esterified.9 Therefore, studies on
synthesis and self-assembling properties of new amphiphiles
consisting of a trehalose residue as the hydrophilic part
considerably contribute to the development of practical emulsi-
fiers and food additives. Although the preparation and proper-
ties, as surfactant, of synthetic trehalose ester amphiphiles were
reported so far,5 to the best of our knowledge, trehalose ether
amphiphiles had hardly been investigated. In the previous paper,
we reported a study on the self-assemblies in a series of new
trehalose monoalkyl ether amphiphiles under aqueous condi-
tions, which were 6-O-alkyltrehaloses having different lengths
of alkyl chains, i.e., 8, 10, 12, 14, and 16, connecting to a
trehalose residue at the 6-position by an ether linkage.10 The
The structure of the product was confirmed by the 1H NMR
and MALDI-TOF MS measurements. All the signals in the
1H NMR spectrum (CD3OD, Figure S1a11) were assignable to
the structure of di-C8 as follows; ¤ 0.81 (t, 6H, CH3, J =
6.6 Hz), 1.13-1.36 (m, 20H, -(CH2)5-CH3), 1.44-1.49 (m, 4H,
-O-CH2-CH2-), 3.21-3.25 (m, 4H, H-4,4¤,6a,6¤a), 3.33-3.46 (m,
6H, H-2,2¤, -O-CH2-CH2-), 3.50-3.59 (m, 2H, H-6b,6¤b), 3.67
(t, 2H, H-3,3¤, J = 9.4 Hz), 3.80-3.83 (m, 2H, H-5,5¤), 4.98 (d,
2H, H-1,1¤, J = 3.6 Hz). The dietherified structure was con-
firmed by the detection of a set of glucose signals and the
integrated ratio of the signal due to CH3 protons of the octyl
groups to the signal due to two anomeric protons of the glucose
residues, which was 3:1. The MALDI-TOF MS showed a
significant peak corresponding to the molecular mass of
[di-C8]Na+ (found; m/z 589.6440, calcd; m/z 589.3564). To
further confirm the structure, the product was acetylated with
acetic anhydride in the presence of pyridine. The 1H NMR
spectrum in CDCl3 (Figure S1b11) of the acetylated derivative
showed that the chemical shifts of the signals assignable to the
H-6 and H-6¤ protons were not different from those before
acetylation (Figure S1a11), whereas the signals due to other
positions (besides anomeric signals) were shifted to lower
magnetic field. This data indicated that both 6- and 6¤-positions
Chem. Lett. 2012, 41, 954-956
© 2012 The Chemical Society of Japan