Synthesis of chiral dopants based on carbohydrates

Article abstract of DOI:10.1016/j.carres.2014.04.007

Chiral dopants based on carbohydrates for nematic liquid crystals were synthesized from d-glucose, and their helical twisting power (HTP) values were evaluated. The chiral dopants induced helices in the host nematic liquid crystals. An acetyl derivative having an ether-type glycosidic linkage between carbohydrate and a mesogenic moiety showed the highest HTP value of 10.4 μm^-1, while an acetyl derivative having an anomeric ester-type linkage did not show any HTP. It was surprising that this molecule had no HTP despite the presence of chirality in the molecule. A relationship between HTP and specific rotation was not observed in this study.

Full text of DOI:10.1016/j.carres.2014.04.007

Accepted Manuscript
Synthesis of chiral dopants based on carbohydrates
Toru Tsuruta, Tetsuo Koyama, Mikio Yasutake, Ken Hatano, Koji Matsuoka
PII:
S0008-6215(14)00157-8
DOI:
http://dx.doi.org/10.1016/j.carres.2014.04.007
CAR 6724
Reference:
Carbohydrate Research
To appear in:
Received Date:
Revised Date:
Accepted Date:
8 January 2014
3 April 2014
7 April 2014
Please cite this article as: Tsuruta, T., Koyama, T., Yasutake, M., Hatano, K., Matsuoka, K., Synthesis of chiral
dopants based on carbohydrates, Carbohydrate Research (2014), doi: http://dx.doi.org/10.1016/j.carres.
2014.04.007
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Synthesis of chiral dopants based on carbohydrates
Toru Tsuruta, Tetsuo Koyama, Mikio Yasutake, Ken Hatano, and Koji Matsuoka*
Division of Material Science, Graduate School of Science and Engineering, Saitama University, Sakura,
Saitama 338-8570, Japan
Keywords: carbohydrate; chiral dopant; glucose; HTP; liquid crystal
*Corresponding author. Tel/Fax: +81-48-858-3099; E-mail: koji@fms.saitama-u.ac.jp
1

Abstract
Chiral dopants based on carbohydrates for nematic liquid crystals were synthesized from D-glucose,
and their helical twisting power (HTP) values were evaluated. The chiral dopants induced helices in the
host nematic liquid crystals. An acetyl derivative having an ether-type glycosidic linkage between
carbohydrate and a mesogenic moiety showed the highest HTP value of 10.4 µm–1, while an acetyl
derivative having an anomeric ester-type linkage did not show any HTP. It was surprising that this
molecule had no HTP despite the presence of chirality in the molecule. A relationship between HTP and
specific rotation was not observed in this study.
2

1. Introduction
Chiral dopants are known as liquid crystal materials. They are optically active substances including
asymmetric carbons1-3 or axial chirality4,5 in a molecule and induce helical structures to a host nematic liquid
crystal mixture. Addition of a chiral dopant into a nematic liquid crystal mixture is needed in order to
regulate the helical pitch to 10-20 µm, when the chiral dopants are applied for a display panel. Since
estimation of the helical pitch and intensity of inducing helical structures was objectively needed, helical
twisting power (HTP) was introduced. Various molecules were investigated in regard to the intensity of the
HTP or relations between HTP and molecular structure or specific rotation.6
Carbohydrate chains in glycoconjugates play important roles in a variety of biological systems7,8, and
we have carried out synthetic studies of glycopolymers9,10 and glycodendrimers11-13 in order to evaluate the
carbohydrate-protein interactions. A key point of these studies is specific interaction between the
carbohydrate and a protein via the highly regulated structure of the carbohydrates. There is, however,
another predisposition in the carbohydrates. It is the use of carbohydrates as chiral resources. V. Vill et al.
focused on the chirality of carbohydrates and evaluated the relationship of the HTP and specific rotation of
carbohydrates, and an allopyranoside derivative having a benzylidene frame showed strong HTP in their
study.14 Moreover, chiral dopants of benzylidene-associated carbohydrates were reported and the
D-glucose was bifunctionalized by introducing both a mesogenic unit and a long alkyl moiety.15 Although
various chiral dopants related to carbohydrates were reported, our attention was focused on the
investigations of chiral dopants based on carbohydrates and the influences of linkages between
carbohydrates and mesogenic units. Since slight modification of a structure of a chiral dopant gave
3

attractive change of the physical properties of the chiral dopant, we planned to synthesize new
carbohydrate-related chiral dopants. Chiral dopants were, therefore, synthesized from D-glucose as the
most popular carbohydrate and a series of mesogenic units consisting of alkyl, cyclohexane and benzene as
shown in Figure 1. A benzene moiety in the mesogenic unit influences the molecular orientation of host
nematic liquid crystals by pi-stacking between aromatic rings.4 Furthermore, there have been a couple of
reports that carbohydrate derivatives themselves show liquid crystal phases in a heating or cooling
process.16,17 Therefore, the synthesized compounds including a mesogenic moiety are expected to show
some mesophases. These compounds are shown in Figure 2 and have three different glycosidic bond
formations between a carbohydrate and the aglycon. One is a compound having a phenyl glycosidic
linkage (phenyl glucoside derivatives), another is a compound having a benzyl glycosidic linkage (benzyl
glucoside derivatives), and the third one is a compound having a benzoate linkage at the anomeric position
(benzoyl glucose derivatives). Because of easy access and convenient handling of fully protected
compounds, the hydroxyl groups were chemically modified by acetyl and methyl groups. HTP and specific
rotation of these synthesized compounds were measured, and the causal relationship between the results of
HTP analyses and the results of the specific rotation was also investigated. Further evaluation was also
performed by means of DSC in order to analyze calorimetric properties, and thermal phase transfer was
compared among the synthesized compounds.
Figure 1 & Figure 2
2. Results and discussion
4

2.1. Synthesis of a mesogenic unit
In order to construct chiral dopants consisting of a carbohydrate and a mesogenic unit, synthesis of a
mesogenic unit was initially performed and the scheme for the preparation of a mesogenic unit is shown in
Scheme 1. A known 4CPA 218 was converted into ethyl ester 4 by means of Fischer’s esterification with
EtOH in the presence of H2SO4 in 93% yield. This esterification was needed before successive LAH
reduction, since reduction of 4CPA 2 with LiAlH4 did not proceed at all. The ester 4 was completely
reduced with LiAlH4 in THF to give the corresponding benzyl alcohol 3 (4CPMOH) in good yield.
Scheme 1
2.2. Synthesis of phenyl glucoside derivatives
The synthetic scheme for phenyl glucoside derivatives is summarized in Scheme 2. The starting
β-acetate 5 underwent glycosidation with 4CPOH 119 in the presence of boron trifluoride diethyl ether
complex (BF3–OEt2) to give β-glycoside 6 in 63% yield, in which the anomeric proton showed J1,2 = 7.35
Hz. Removal of protection of 6 proceeded completely in methanolic sodium methoxide to yield the
corresponding alcohol 7 as crystals. In addition to the ester 6 and the alcohol 7, further transformation of 7
was performed. Thus, compound 7 was treated by means of Williamson ether synthesis with MeI to afford
methyl ether 8 in 98% yield.
Scheme 2
2.3. Synthesis of benzyl glucoside derivatives
5

Since synthetic assembly of a series of phenyl glucosides was accomplished, our attention turned
toward alternative glucosides having other aglycons. 4CPMOH 3 was selected as an alternative mesogen.
Glycosidation of β-acetate 5 with 3 by means of boron trifluoride diethyl ether complex (BF3–OEt2) as a
Lewis acid in CH2Cl2 gave only 3.6% yield. Koenigs-Knorr reaction as an alternative glycosyl reaction
was then conducted. Thus, glucose acetate 5 was converted into 1-bromo-2,3,4,6-tetra-O-acetylglucose,
which was treated with mesogenic alcohol 3 in the presence of silver trifluoromethanesulfonate in CH2Cl2 to
yield glycoside 11. In general, the Koenigs-Knorr reaction gives a higher yield than does the reaction
using BF3–OEt2 as a promoter; however, glycosidation with mesogenic unit yielded only 5.9%. Therefore,
the Schmidt reaction20, which is a reaction via trichloroacetimidate, was conducted and the synthetic route is
shown in Scheme 3. After the conversion of hemiacetal 9 into the corresponding imidate 10, glycosidation
reaction between imidate 10 and alcohol 3 was carried out in the presence of Lewis acid as a promoter to
give glycoside 11 (J1,2 = 7.90 Hz in anomeric position) with high anomeric β-selectivity and higher yield
(33%) than that of the other reactions. Conventional de-O-acetylation with Zemplén’s condition gave the
alcohol 12 in quantitative yield. Alcohol 12 was further manipulated with MeI by Williamson ether
synthesis to afford 13 in 59% yield.
Scheme 3
2.4. Synthesis of benzoyl glucose derivatives
Syntheses of a series of benzyl glucoside derivatives were accomplished, and the synthetic approach
to afford benzoyl glucose derivatives was then considered. The reaction route is shown in Schemes 4 & 5.
6

A known benzyl-protected monoalcohol 1421 was prepared from methyl α-D-glucopyranoside
through a few steps. Carboxylic acid 2 and monoalcohol 14 were treated in the presence of EDC and
DMAP in DMF. The reaction gave an inseparable α- and β-mixture of ester 15, which had very similar Rf
on the TLC. Therefore, this mixture could not be separated at this stage either by silica gel column
chromatography or by crystallization.
Before separation of this mixture, a hydrogenation was
accomplished in the presence of Pd/C to give the corresponding mixture 16. Subsequently, compound 16
was treated with Ac2O and pyridine to yield acetate 17, which was a separable mixture by silica gel column
chromatography with 2:1 (v/v) n-hexane–EtOAc. The yield of α-ester was 33%, which has a coupling
constant J1,2 = 3.65 Hz in an anomeric position, and that of β-ester 17 was 52%, which has a coupling
constant J1,2 = 8.10 Hz in an anomeric position.
Scheme 4
In order to obtain methyl-protected compound 19, a known hemiacetal 1822 was prepared from
methyl α-D-glucopyranoside through a few steps along with compound 14.
Methyl-protected
monoalcohol 18 was esterified with carboxylic acid 2 with EDC and DMAP in DMF to afford β-acetate 19
(J1,2 = 7.50 Hz in an anomeric position) in 78% yield. In comparison to the anomeric mixture 15, a similar
mixture 19 was easily separated into α- and β-compound by using silica gel chromatography with 4:1 (v/v)
n-hexane–EtOAc.
Scheme 5
2.5. Calorimetric analysis
7

Calorimetric analyses of the compounds were performed by DSC, and the results of analyses are
shown in Table 1. From the results of DSC measurement, the acetates 6, 11 and 17 did not show any
liquid crystal phase and had obvious melting points, respectively. In methyl ethers 8, 13 and 19, phenyl
glucoside derivative 8 only showed a melting point at 38 °C, and benzyl glucoside derivative 13 and
benzoyl glucose derivative 19 were syrup at room temperature. Thus, measurements of compounds 13 and
19 were carefully performed by DSC from 40 °C to −40 °C (gradient of 5 °C/min), but the profile of the
compounds by DSC indicated only broad signals. The results suggested that compounds 13 and 19 did not
show any crystallinity. A comparison of acetates and methyl ethers revealed that conversion from the
acetyl group to a methyl group caused the melting point depression.
Table 1
2.6. Evaluation of HTP for the synthesized compounds
Since DSC measurements were accomplished for our compounds, our attention was turned to the
helical twisting power of the compounds. Synthesized compounds derived from D-glucose as chiral
dopants were evaluated by Cano wedge cells23 to measure the helical pitch of the chiral nematic phase.
A
chiral nematic liquid crystalline mixture was prepared by adding the chiral dopant (1 wt. %) to the host
nematic liquid crystal (ZLI-1132, Merck). HTP [µm–1] values were calculated by eq. 1, where p is the
pitch of the chiral nematic phase in µm and c is the mass fraction of the chiral dopant. In order to describe
HTP per molecule, we used the value of molar helical twisting power (MHTP, [µm–1mol–1Kg]), as defined
in eq. 2, where Md is the molecular weight of the chiral dopant.
8

ꢀ
ꢃꢄꢅ
HTP = ꢁꢂ
(1)
MHTP = HTP × Md × 10ꢄꢆ
(2)
Compound 6 has the strongest HTP (10.4 µm–1) among the synthesized compounds as shown in Table
1. It is notable that only compound 17 has no HTP, though compound 17 has several chiral moieties and
an adequate optical rotation value. Having the property of optical rotation means that the molecule
includes optically active parts and is not a racemate. Thus, in this case, the optical activity has very little
association with induction of a chiral nematic phase in liquid crystal. In order to obtain evidence of this
phenomenon, specific rotations were investigated in all synthesized compounds. Compound 8, which has
the 3rd strongest value of HTP (3.6 µm–1), shows the highest value of specific rotation (−29.1 °), and
compound 6, which has the strongest value of HTP (10.4 µm–1), shows the lowest value (−12.3 °) among the
synthesized compound as chiral dopants. In addition, there is no association between helical twisting
power and specific rotation in the other compounds. These results suggest that there is no relation between
optical activity derived from the chirality and helical twisting power and that these are independent.
3. Conclusion
Chiral dopants based on carbohydrate were synthesized from D-glucose and a mesogenic unit, and
physical properties of the chiral dopants were analyzed. From DSC measurement, a comparison of melting
points between acetates and methyl ethers revealed that conversion from the acetyl group to a methyl group
caused melting point depression. HTP measurements were also performed and the results showed that
9

O-phenyl glycosyl acetate had the highest HTP value of 10.4 µm–1. In contrast, the anomeric ester having
methyl ether protection did not show any HTP. A relationship between HTP and specific rotation was not
observed in this study, and optical activity derived from the chirality and helical twisting power is thus
independent.
4. Experimental
4.1. General methods
Unless otherwise stated, all commercially available solvents and reagents were used without further
purification. Pyridine (Pyr.) and N,N-dimethylformamide (DMF) were stored over molecular sieves
(MS4Å), and methanol (MeOH) was stored over MS3Å before use. Dichloromethane was stored over
MS4Å after distillation. Tetrahydrofuran (THF) was dried over sodium benzophenone ketyl under an Ar
atmosphere and distilled prior to use. Powdered molecular sieves were dried in vacuo at ca. 180 °C for 2 h.
Melting points were measured with a Laboratory Devices MELTEMP II apparatus and were uncorrected.
Optical rotations were determined with a JASCO DIP-1000 digital polarimeter. IR spectra were measured
in a KBr disc for solid samples or a KRS-5 cell for liquid samples with a Shimadzu IR Prestige-21
spectrometer. Phase transition temperatures were determined with an SII EXSTAR DSC6200. NMR
spectra were recorded at 400 Mz for 1H and at 100 MHz for 13C with a Bruker AVANCE 400 spectrometer
or at 500 MHz for 1H and at 125 MHz for 13C with a Bruker AVANCE 500 in chloroform-d (CDCl3),
deuterium oxide (D2O) and dimethyl sulfoxide-d6 (DMSO-d6). H-D exchange experiments were
performed in CDCl3 or DMSO-d6 in the presence of one drop of D2O. Chemical shifts are expressed as
10

parts per million (ppm, δ), and tetramethylsilane (TMS), CHCl3 (7.26 ppm for 1H or 77.0 ppm for 13C) and
HDO (4.78 ppm for 1H) were used as internal standards. Ring-proton assignments in the NMR spectra
were made by first-order analysis of the spectra and are supported by the results of homonuclear decoupling
experiments and H-H or HMQC experiments. Elemental analyses were performed with a Fisons EA1108
on samples extensively dried at 50-60 °C over phosphorus pentoxide for 4-5 h. Reactions were monitored
by thin-layer chromatography (TLC) on a precoated plate of Silica Gel 60F254 (layer thickness, 0.25 mm; E.
Merck, Darmstadt, Germany). For detection of the intermediates, TLC sheets were dipped in (a) a solution
of 85:10:5 (v/v/v) MeOH–p-anisaldehyde–conc H2SO4 and heated for a few minutes (for carbohydrate) or
(b) an ethanolic solution of 5 wt. % phosphomolybdic acid and heated similarly (for organic compound) or
sprayed with (c) an aqueous solution of 0.04 wt. % bromocresol green and heated similarly (for the carboxyl
group) or (d) a solution of 1:1 (v/v) MeOH–2 M aq HCl of 0.2 wt. % DNPH and heated similarly (for the
ketone or aldehyde group). Column chromatography was performed on silica gel (Silica Gel 60; 63-200
µm, E. Merck). Flash column chromatography was performed on silica gel (Silica Gel 60, spherical
neutral; 40-100 µm, E. Merck). All extractions were concentrated below 45 °C under diminished pressure.
4.2. Synthesis
4.2.1. Ethyl 4-(trans-4-butylcyclohexyl)benzoate 4
To a solution of 4CPA 2 (20.0 g, 76.8 mmol) in EtOH (100 mL) was added conc H2SO4 (10 mL) and
MS4Å at 70 °C under a N2 atmosphere. After stirring for 16 h, NaHCO3 was added to the suspension, and
then the suspension was filtered and extracted with CHCl3. The organic solution was washed successively
11

with water, satd aq NaHCO3, and brine and then dried over anhyd MgSO4, filtered, and concentrated in
vacuo. Silica gel chromatography of the residue with 20:1 (v/v) n-hexane–EtOAc gave pure 4 (20.7 g,
93.4%) as a colorless liquid: Rf 0.62 [4:1 (v/v) n-hexane–EtOAc]; 1H NMR (500 MHz, CDCl3) δ 7.95 (d, 2
H, J = 8.10 Hz, Haroma.-2), 7.26 (d, 2 H, J = 7.80 Hz, Haroma.-3), 4.35 (q, 2 H, J = 7.07 Hz, CH3-CH2-),
2.54-2.49 (m, 1 H, Hcyclo.-1ax.), 1.88 (d, 4 H, J = 10.4 Hz, Hcyclo.-2eq., Hcyclo.-3eq.), 1.46 (ddd, 2 H, J = 2.30
Hz, J = 12.3 Hz, J = 25.0 Hz, Hcyclo.-2ax.), 1.38 (t, 3 H, J = 7.10 Hz, CH3-CH2-), 1.31-1.24 (m, 7 H,
Hcyclo.-4ax., CH3-CH2-CH2-CH2-), 1.08-1.02 (m, 2 H, Hcyclo.-3ax.), 0.90 (t, 3 H, J = 6.20 Hz,
CH3-CH2-CH2-CH2-); 13C NMR (125 MHz, CDCl3) δ 166.69 (Ph-C=O), 153.19 (Caroma.-4), 129.62
(Caroma.-2), 128.12 (Caroma.-1), 126.82 (Caroma.-3), 60.85 (CH3-CH2-), 44.91 (Ccyclo.-1), 37.39, 37.20, 34.22
(Ccyclo.-2), 33.61 (Ccyclo.-3), 29.36, 23.15, 14.51 (CH3-CH2-CH2-CH2-), 14.29 (CH3-CH2-).
4.2.2. 4-(trans-4-Butylcyclohexyl)phenylmethanol 3
To a suspension of LiAlH4 (2.98 g, 78.7 mmol) in THF (15 mL) was added an ethyl ester 4 (15.1 g,
52.4 mmol) in THF (20 mL) via a syringe at 0 °C, and the mixture was stirred for 30 min at 0 °C under an
Ar atmosphere. The reaction mixture was carefully quenched with water at 0 °C and extracted with EtOAc.
The organic solution was successively washed with 1 M aq H2SO4, water, satd aq NaHCO3, and brine and
then dried over anhyd MgSO4, filtered, and evaporated. Silica gel chromatography of the residue with 4:1
(v/v) n-hexane–EtOAc gave pure 3 (12.0 g, 92.9%) as white crystals: Rf 0.56 [2:1 (v/v) n-hexane–EtOAc];
IR (KBr) : 3292 (νO-H), 2918 (νC-H), 1900 (δC-H, aromatic), 1514 (νC=C, aromatic) cm–1; 1H NMR (500 MHz,
CDCl3 w/D2O) δ 7.29 (d, 2 H, J = 8.10 Hz, Haroma.-2), 7.21 (d, 2 H, J = 8.05 Hz, Haroma.-3), 4.65 (s, 2 H,
12

Ph-CH2-), 2.47 (ddd, 1 H, J = 3.10 Hz, J = 6.25 Hz, J = 15.3 Hz, Hcyclo.-1ax.), 1.89-1.85 (m, 4 H, Hcyclo.-2eq.,
Hcyclo.-3eq.), 1.44 (ddd, 2 H, J = 3.05 Hz, J = 12.6 Hz, J = 25.2 Hz, Hcyclo.-2ax.), 1.32-1.22 (m, 7 H,
Hcyclo.-4ax., CH3-CH2-CH2-CH2-), 1.04 (ddd, 2 H, J = 4.10 Hz, J = 13.9 Hz, J = 25.3 Hz, Hcyclo.-3ax.), 0.90 (t,
3 H, J = 6.90 Hz, CH3-CH2-CH2-CH2-).
Anal. Calcd for C17H26O1: C, 82.87; H, 10.64. Found: C, 82.94; H, 10.84.
4.2.3. 4-(trans-4-Butylcyclohexyl)phenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside 6
To a solution of 5 (3.00 g, 7.69 mmol) in CH2Cl2 (33 mL) was added 4CPOH 1 (5.36 g, 23.1 mmol)
under an Ar atmosphere, and the mixture was cooled to 0 °C. BF3–OEt2 (5.80 mL, 46.1 mmol) was
dropwise added to the solution. The reaction solution was stirred for 30 min at 0 °C and then stirred for 5 h
at room temperature. When TLC indicated the end of the reaction, the solution was poured into ice-cold
water and partitioned. The organic layer was washed with water, satd aq NaHCO3, brine, and dried over
anhyd MgSO4. The solution was filtered through a celite bed and concentrated. The residue was purified
by crystallization from EtOH to give glucoside 6 (2.70 g, 62.5%) as white needle crystals: mp 163 ºC; Rf
ꢇ ꢈꢊꢋ
0.45 [4:1 (v/v) toluene–EtOAc]; α
− 12.3 º (c 1.00, CHCl3); IR (KBr) : 2916 (νC-H), 1751 (νC=O, ester),
ꢉ
1510 (νC=C, aromatic) cm–1; 1H NMR (500 MHz, CDCl3) δ 7.12 (d, 2 H, J = 8.50 Hz, Haroma.-3), 6.91 (d, 2 H,
J = 8.50 Hz, Haroma.-2), 5.30-5.24 (m, 2 H, H-2, H-3), 5.16 (t, 1 H, J = 9.53 Hz, H-4), 5.05 (d, 1 H, J = 7.35
Hz, H-1), 4.28 (dd, 1 H, J5,6a = 5.30 Hz, J6a,6b = 12.3 Hz, H-6a), 4.17 (dd, 1 H, J5,6b = 1.85 Hz, J6a,6b = 12.3 Hz,
H-6b), 3.86-3.83 (m, 1 H, H-5), 2.42 (t, 1 H, J = 12.2 Hz, Hcyclo.-1ax.), 2.08-2.03 (s×4, 12 H, OAc×3),
1.85 (d, 4 H, J = 11.3 Hz, Hcyclo.-2eq., Hcyclo.-3eq.), 1.40 (dd, 2 H, J = 12.5 Hz, J = 23.0 Hz, Hcyclo.-2ax.),
13

1.30-1.23 (m, 7 H, Hcyclo.-4ax., CH3-CH2-CH2-CH2-), 1.03 (dd, 2 H, J = 11.3 Hz, J = 22.8 Hz, Hcyclo.-3ax.),
0.90 (t, 3 H, J = 6.60 Hz, CH3-CH2-CH2-CH2-); 13C NMR (125 MHz, CDCl3) δ 170.73 (C=O), 70.40 (C=O),
169.54 (C=O), 169.45 (C=O), 155.12 (Caroma.-1), 143.17 (Caroma.-4), 127.91 (Caroma.-3), 116.97 (Caroma.-2),
99.48 (C-1), 72.94, 72.09 (C-5), 71.36, 68.51 (C-4), 62.14 (C-6), 44.00 (Ccyclo.-1), 37.41, 37.22, 34.64
(Ccyclo.-2), 33.73 (Ccyclo.-3), 29.38, 23.14, 20.84 (CH3CO-), 20.80 (CH3CO-), 20.77 (CH3CO-), 20.73
(CH3CO-), 14.29 (CH3-CH2-CH2-CH2-).
Anal. Calcd for C30H42O10: C, 64.04; H, 7.52. Found: C, 64.11; H, 7.52.
4.2.4. 4-(trans-4-Butylcyclohexyl)phenyl β-D-glucopyranoside 7
To a solution of acetate 6 (1.50 g, 2.67 mmol) in MeOH (20 mL) was added NaOMe (0.058
g, 1.07 mmol), and the mixture was stirred for 0.5 h at room temperature. IR-120B (H+) resin
was added to the mixture, and the suspension was filtered and concentrated to furnish
compound 7 in quantitative yield as white crystals: mp 145 ºC; Rf 0.65 [65:25:4 (v/v/v)
ꢇ ꢈꢊꢋ
CHCl3–MeOH–H2O]; α
− 22.3 º (c 1.00, DMSO-d6); IR (KBr) : 3416 (νO-H), 2918 (νC-H), 1512 (νC=C
,
ꢉ
aromatic) cm–1; 1H NMR (500 MHz, DMSO-d6 w/D2O) δ 7.07 (d, 2 H, J = 8.40 Hz, Haroma.-3), 6.90 (d, 2 H,
J = 8.35 Hz, Haroma.-2), 4.76 (d, 1 H, J 1,2 = 7.60 Hz, H-1), 3.66 (d, 1 H, J5,6b = 11.5 Hz, H-6a), 3.45 (dd, 1 H,
J5,6a = 5.66 Hz, J6a,6b = 11.9 Hz, H-6b), 3.33-3.27 (m, 2 H, H-3, H-5), 3.22 (t, 1 H, J= 8.38 Hz, H-2), 3.15 (t,
1 H, J = 9.23 Hz, H-4), 2.34 (t, 1 H, J = 12.0 Hz, Hcyclo.-1ax.), 1.72 (t, 4 H, J = 14.6 Hz, Hcyclo.-2eq.,
Hcyclo.-3eq.), 1.31 (q, 2 H, J = 12.1 Hz, Hcyclo.-2ax.), 1.21-1.14 (m, 7 H, Hcyclo.-4ax., CH3-CH2-CH2-CH2-),
0.95 (dd, 2 H, J = 11.2 Hz, J = 23.2 Hz, Hcyclo.-3ax.), 0.82-0.78 (m, 3 H, CH3-CH2-CH2-CH2-); 13C NMR
14

(125 MHz, DMSO-d6 w/D2O) δ 156.59 (Caroma.-1), 141.72 (Caroma.-4), 128.34 (Caroma.-3), 117.08 (Caroma.-2),
101.61 (C-1), 78.00, 77.63, 74.23 (C-2), 70.74 (C-4), 61.73 (C-6), 44.03 (Ccyclo.-1), 39.99, 37.61, 35.06
(Ccyclo.-2), 34.13 (Ccyclo.-3), 29.66, 23.45, 15.00 (CH3-CH2-CH2-CH2-).
Anal. Calcd for C22H34O6· 0.3H2O: C, 66.07; H, 8.72. Found: C, 66.21; H, 8.69.
4.2.5. 4-(trans-4-Butylcyclohexyl)phenyl 2,3,4,6-tetra-O-methyl-β-D-glucopyranoside 8
To a suspension of NaH (50%, 72.8 mg, 1.52 mmol, washed with hexane) in DMF (1 mL) was
dropwise added a solution of 7 (100 mg, 0.25 mmol) in DMF (2 mL) at 0 °C, and the mixture was stirred for
20 min. MeI (0.0950 mL, 1.52 mmol) was dropwise added to the mixture at 0 °C, and the whole mixture
was stirred for 2.5 h at room temperature. To the mixture was added MeOH at 0 °C, and the mixture was
evaporated and poured into ice-cold water. The whole mixture was extracted with CHCl3, washed with
water, satd aq NaHCO3, and brine and then dried over anhyd MgSO4, filtered, and concentrated in vacuo.
The residual yellow syrup was chromatographed on silica gel with 6:1 (v/v) n-hexane–EtOAc to yield pure 8
ꢇ ꢈꢊꢋ
(112 mg, 98.1%) as white crystals: mp 38 ºC; Rf 0.39 [4:1 (v/v) n-hexane–EtOAc]; α
− 29.1 º (c 1.00,
ꢉ
CHCl3); IR (KBr) : 2914 (νC-H), 1512 (νC=C , aromatic) cm–1; 1H NMR (500 MHz, CDCl3) δ 7.11 (d, 2 H, J =
8.40 Hz, Haroma.-3), 6.94 (d, 2 H, J = 8.40 Hz, Haroma.-2), 4.79 (d, 1 H, J = 7.25 Hz, H-1), 3.65 (m, 7 H, Me×
2, H-6a), 3.59-3.55 (m, 4 H, Me, H-6b), 3.38 (m, 4 H, Me, H-5), 3.27-3.22 (m, 3 H, H-2, H-3, H-4), 2.41 (t,
1 H, J = 12.2 Hz, Hcyclo.-1ax.), 1.85 (d, 4 H, J = 10.8 Hz, Hcyclo.-2eq., Hcyclo.-3eq.), 1.40 (q, 2 H, J = 12.2 Hz,
Hcyclo.-2ax.), 1.30-1.22 (m, 7 H, Hcyclo.-4ax., CH3-CH2-CH2-CH2-), 1.03 (q, 2 H, J = 11.4 Hz, Hcyclo.-3ax.),
0.90 (t, 3 H, J = 6.55 Hz, CH3-CH2-CH2-CH2-); 13C NMR (125 MHz, CDCl3) δ 155.52 (Caroma.-1), 142.10
15

(Caroma.-4), 127.62 (Caroma.-3), 116.66 (Caroma.-2), 101.74 (C-1), 86.34 (C-2), 83.53 (C-3), 79.15 (C-4), 74.77
(C-5), 71.22 (C-6), 60.86 (OMe), 60.50 (OMe), 60.42 (OMe), 59.39 (OMe), 43.84 (Ccyclo.-1), 37.28, 37.10,
34.51 (Ccyclo.-2), 33.63 (Ccyclo.-3), 29.24, 23.01, 14.14 (CH3-CH2-CH2-CH2-).
Anal. Calcd for C26H42O6 : C, 69.30; H, 9.40. Found: C, 69.43; H, 9.51.
4.2.6. 4-(trans-4-Butylcyclohexyl)phenylmethyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside 11
Trichloroacetonitrile (1.73 mL, 17.2 mmol) and DBU (0.214 mL, 1.44 mmol) were added to a solution
of the hemiacetal 9 (1.00 g, 2.87 mmol) in CH2Cl2 (10 mL) at −10 ºC under an Ar atmosphere. After being
stirred for
5
h
at −5 ºC, the mixture was concentrated in vacuo to afford
2,3,4,6-tetra-O-acethyl-α-D-glucopyranosyl trichloroacetimidate 10 as a crude compound, which was used
for the next step without further purification.
A solution of 4CPMOH 3 (3.54 g, 14.4 mmol) and imidate 10 in CH2Cl2 (10 mL) was stirred in the
presence of MS4Å under an Ar atmosphere at −5 ºC. TMSOTf (1.04 mL, 5.74 mmol) was slowly added to
the suspension via a syringe and stirred for 9 h until TLC showed consumption of imidate 10. The
suspension was allowed to warm until room temperature and was then filtered over a pad of celite. The
filtrate was diluted with CHCl3, washed with water, satd aq NaHCO3, and brine, and dried over anhyd
MgSO4. The mixture was filtered through a celite bed and concentrated. The residue was
chromatographed on silica gel with 4:1 (v/v) n-hexane–EtOAc to yield pure 11 (0.538 g, 32.5%) as white
ꢇ ꢈꢊꢋ
needle crystals: mp 126 ºC; Rf 0.50 [2:1 (v/v) n-hexane–EtOAc]; α
− 27.7 º (c 1.00, CHCl3); IR
ꢉ
(KBr) : 2920 (νC-H), 1744 (νC=O, ester) cm–1; 1H NMR (500 MHz, CDCl3) δ 7.26 (br d, 2 H, Haroma.-2), 7.18
16

(br d, 2 H, Haroma.-3), 5.16 (ddd, 1 H, J = 1.48 Hz, J = 9.35 Hz, J = 18.8 Hz, H-3), 5.10 (ddd, 1 H, J = 1.18
Hz, J = 9.63 Hz, J = 19.1 Hz, H-4), 5.05 (br t, 1 H, H-2), 4.85 (d, 1 H, J = 12.2 Hz, -CH2-), 4.58 (d, 1 H, J =
12.1 Hz, -CH2-), 4.53 (d, 1 H, J = 7.90 Hz, H-1), 4.27 (dd, 1 H, J5,6a = 3.45 Hz, J6a,6b = 11.2 Hz, H-6a), 4.16
(br d, 1 H, J6a,6b = 12.3 Hz, H-6b), 3.68-3.65 (br m, 1 H, H-5), 2.46 (t, 1 H, J = 12.2 Hz, Hcyclo.-1ax.), 2.10 (s,
3 H, OAc), 2.01-1.99 (s×3, 9 H, OAc×3), 1.87 (d, 4 H, J = 9.60 Hz, Hcyclo.-2eq., Hcyclo.-3eq.), 1.44 (q, 2 H,
J = 12.1 Hz, Hcyclo.-2ax.), 1.30-1.23 (m, 7 H, Hcyclo.-4ax., CH3-CH2-CH2-CH2-), 1.07 (q, 2 H, J = 11.7 Hz,
Hcyclo.-3ax.), 0.90 (t, 3 H, J = 5.30 Hz, CH3-CH2-CH2-CH2-); 13C NMR (125 MHz, CDCl3) δ 170.86 (C=O),
170.45 (C=O), 169.55 (C=O), 169.47 (C=O), 148.06 (Caroma.-4), 134.08 (Caroma.-1), 128.08 (Caroma.-2), 127.11
(Caroma.-3), 99.28 (C-1), 73.03 (C-3), 71.95 (C-5), 71.46 (C-2), 70.81 (-CH2-), 68.60 (C-4), 62.12 (C-6),
44.54 (Ccyclo.-1), 37.44, 37.24, 34.48 (Ccyclo.-2), 33.73 (Ccyclo.-3), 29.38, 23.16, 20.91 (CH3CO-), 20.80
(CH3CO-), 20.76 (CH3CO-), 20.74 (CH3CO-), 14.30 (CH3-CH2-CH2-CH2-).
Anal. Calcd for C31H44O10: C, 64.57; H, 7.69. Found: C, 64.58; H, 7.68.
4.2.7. 4-(trans-4-Butylcyclohexyl)phenylmethyl β-D-glucopyranside 12
To a solution of acetate 11 (2.23 g, 3.87 mmol) in MeOH (20 mL) was added NaOMe (0.083 g, 1.55
mmol), and the mixture was stirred for 5 h at room temperature. IR-120B (H+) resin was added to the
mixture. The suspension was filtered and concentrated to furnish the corresponding compound 12 as white
ꢇ ꢈꢊꢋ
crystals in quantitative yield: Rf 0.66 [65:25:4 (v/v/v) CHCl3–MeOH–H2O]; α
− 15.3 º (c 1.00,
ꢉ
MeOH); IR (KBr) : 3346 (νO-H), 2918 (νC-H) cm–1; 1H NMR (500 MHz, CDCl3 w/D2O) δ 7.31 (d, 2 H, J =
7.70 Hz, Haroma.-2), 7.16 (d, 2 H, J = 7.65 Hz, Haroma.-3), 4.86 (d, 1 H, J = 11.6 Hz, -CH2-), 4.62 (d, 1 H, J =
17

12.6 Hz, -CH2-), 4.35 (d, 1 H, J = 7.65 Hz, H-1), 3.87 (br d, 1 H, J6a,6b = 11.5 Hz, H-6a), 3.68 (dd, 1 H, J5,6b
= 4.98 Hz, J6a,6b = 11.9 Hz, H-6b), 3.37-3.22 (m, 4 H, H-2, H-3, H-4, H-5), 2.43 (t, 1 H, J = 11.8 Hz,
Hcyclo.-1ax.), 1.83 (t, 4 H, J = 12.6 Hz, Hcyclo.-2eq., Hcyclo.-3eq.), 1.43 (q, 2 H, J = 12.4 Hz, Hcyclo.-2ax.),
1.30-1.22 (m, 7 H, Hcyclo.-4ax., CH3-CH2-CH2-CH2-), 1.04 (q, 2 H, J = 12.1 Hz, Hcyclo.-3ax.), 0.87 (br t, 3 H,
CH3-CH2-CH2-CH2-); 13C NMR (125 MHz, CDCl3 w/D2O) δ 148.72 (Caroma.-4), 136.12 (Caroma.-1), 129.53
(Caroma.-2), 127.77 (Caroma.-3), 102.94 (C-1), 77.81, 77.75, 74.95, 71.83 (-CH2-), 71.48, 62.58 (C-6), 45.71
(Ccyclo.-1), 38.52, 38.21, 35.52 (Ccyclo.-2), 34.71 (Ccyclo.-3), 30.28, 23.98, 14.50 (CH3-CH2-CH2-CH2-).
Anal. Calcd for C23H36O6: C, 67.62; H, 8.88. Found: C, 67.59; H, 8.91.
4.2.8. 4-(trans-4-Butylcyclohexyl)phenylmethyl 2,3,4,6-tetra-O-methyl-β-D-glucopyranoside 13
To a suspension of NaH (50%, 59 mg, 2.47 mmol, washed with hexane) in DMF (2 mL) was dropwise
added a solution of 12 (168 mg, 0.411 mmol) in DMF (5.00 mL) at 0 °C, and the mixture was stirred for 20
min. MeI (0.154 mL, 2.47 mmol) was dropwise added to the mixture at 0 °C, and the whole mixture was
stirred for 3.0 h at room temperature. To the mixture was added MeOH at 0 °C, and the mixture was
evaporated and poured into ice-cold water. The whole mixture was diluted with CHCl3, washed with water,
satd aq NaHCO3, and brine and then dried over anhyd MgSO4, filtered, and concentrated in vacuo. The
residual yellow syrup was chromatographed on silica gel with 4:1 (v/v) n-hexane–EtOAc to yield pure 13
ꢇ ꢈꢊꢋ
(112 mg, 58.9%) as a colorless syrup: Rf 0.52 [2:1 (v/v) n-hexane–EtOAc]; α
− 25.5 º (c 1.00,
ꢉ
CHCl3); IR (neat) : 2920 (νC-H) cm–1; 1H NMR (500 MHz, CDCl3) δ 7.27 (d, 2 H, J = 8.15 Hz, Haroma.-2),
7.17 (d, 2 H, J = 8.10 Hz, H aroma.-3), 4.88 (d, 1 H, J = 11.9 Hz, -CH2-), 4.59 (d, 1 H, J = 11.9 Hz, -CH2-),
18

4.33 (d, 1 H, J = 7.65 Hz, H-1), 3.66-3.56 (m, 8 H, H-6a, H-6b, OMe×2), 3.53 (s, 3 H, OMe), 3.42 (s, 3 H,
OMe), 3.16-3.14 (m, 1 H, H-5), 3.08-3.05 (m, 2 H, H-3, H-4), 2.48-2.42 (m, 1 H, H-2), 2.45 (tt, 1 H, J =
3.10 Hz, J = 12.1 Hz, Hcyclo.-1ax.), 1.88-1.85 (m, 4 H, Hcyclo.-2eq., Hcyclo.-3eq.), 1.43 (ddd, 2 H, J = 3.33 Hz,
J = 12.7 Hz, J = 25.2 Hz, Hcyclo.-2ax.), 1.32-1.22 (m, 7 H, Hcyclo.-4ax., CH3-CH2-CH2-CH2-), 1.04 (ddd, 2 H,
J = 3.00 Hz, J = 13.3 Hz, J = 24.7 Hz, Hcyclo.-3ax.), 0.90 (t, 3 H, J = 7.03 Hz, CH3-CH2-CH2-CH2-); 13C
NMR (125 MHz, CDCl3) δ 147.51 (Caroma.-4), 135.06 (Caroma.-1), 127.95 (Caroma.-2), 126.96 (Caroma.-3),
102.43 (C-1), 86.59, 86.95 (C-2), 79.58, 74.75 (C-5), 71.55 (C-6), 70.96 (-CH2-), 60.95 (OMe), 60.69
(OMe), 60.53 (OMe), 59.54 (OMe), 44.53 (Ccyclo.-1), 37.45, 37.26, 34.49 (Ccyclo.-2), 33.76 (Ccyclo.-3), 29.39,
23.16, 14.30 (CH3-CH2-CH2-CH2-).
Anal. Calcd for C27H44O6· 0.1H2O: C, 69.53; H, 9.55. Found: C, 69.27; H, 9.54.
4.2.9. 1-O-{4-(trans-4-Butylcyclohexyl)benzoyl}-2,3,4,6-tetra-O-benzyl-D-glucopyranose 15
4CPA 2 (193 mg, 0.74 mmol), EDC (213 mg, 1.11 mmol), DMAP (46 mg, 0.370 mmol) and
glucopyranose 14 (200 mg, 0.370 mmol) were stirred for 24 h in DMF (3.0 mL) at 110 °C under a N2
atmosphere. After confirmation of the reaction by TLC, the solution was azeotropically evaporated with
toluene. The residue was diluted with CHCl3 and washed with ice-cold water, satd aq NaHCO3 and brine,
and dried over anhyd MgSO4. The suspension was filtered through a celite bed and concentrated.
Purification of the residue on silica gel with 8:1 (v/v) n-hexane–EtOAc yielded the corresponding ester 15
(206 mg, 71.4%) as white amorphous powder. This compound was a mixture of α-glucoside and
β-glucoside. The ratio of α and β was 1:4.3 (α:β): Rf 0.55, 0.52 (2 spots) [4:1 (v/v) n-hexane–EtOAc];
19

1H NMR (500 MHz, CDCl3) δ 6.59 (d, 1 H, J = 3.50 Hz, Hα-1), 5.70 (d, 4.3 H, J = 7.80 Hz, Hβ-1).
4.2.10. 1-O-{4-(trans-4-Butylcyclohexyl)benzoyl}-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose 17
An anomeric mixture of 15 (200 mg, 0.255 mmol) and 5 wt. % Pd/C (200 mg) in MeOH (2.0 mL)
was stirred under H2 gas for 2.5 h at room temperature and then the reaction mixture was filtered and
evaporated in vacuo to afford the corresponding alcohol 16 (97 mg, 89.9%) as white amorphous powder.
The anomeric mixture 16 (531 mg, 1.26 mmol) was stirred for 12 h in Ac2O (5.0 mL) and pyridine
(5.0 mL) at room temperature. After confirmation of the reaction by TLC, the solution was azeotropically
evaporated with toluene. The residue was diluted with CHCl3 and washed with ice-cold water, 1 M aq
H2SO4, satd aq NaHCO3, and brine. The solution was dried over anhyd MgSO4, filtered through a celite
bed, and concentrated. Purification on silica gel with 3:1 (v/v) n-hexane–EtOAc yielded crystalline β-ester
17 (385 mg, 51.9%) and crystalline α-ester (247 mg, 33.3%) as white crystals. mp 154 ºC; Rf 0.47
ꢇ ꢈꢊꢋ
(α-glucoside), 0.40 (β-glucoside) [2:1 (v/v) n-hexane–EtOAc]; α
− 17.0 º (c 1.00, CHCl3); IR (KBr) :
ꢉ
2920 (νC-H), 1740 (νC-H, ester) cm–1; 1H NMR (500 MHz, CDCl3) δ 7.95 (d, 2 H, J = 8.30 Hz, Haroma.-2), 7.29
(d, 2 H, J = 8.35 Hz, H aroma.-3), 5.92 (d, 1 H, J = 8.10 Hz, H-1), 5.35-5.33 (m, 2 H, H-2, H-3), 5.21-5.17 (m,
1 H, H-4), 4.32 (dd, 1 H, J5,6a = 4.48 Hz, J6a,6b = 12.5 Hz, H-6a), 4.13 (dd, 1 H, J5,6b = 2.15 Hz, J6a,6b = 12.5
Hz, H-6b), 3.93 (ddd, 1 H, J5,6b = 2.21 Hz, J5,6a = 4.43 Hz, J4,5 = 10.1 Hz, H-5), 2.55-2.50 (m, 1 H,
Hcyclo.-1ax.), 2.07-1.99 (s×4, 12 H, OAc×3), 1.88 (d, 4 H, J = 11.7 Hz, Hcyclo.-2eq., Hcyclo.-3eq.), 1.45 (dd, 2
H, J = 12.6 Hz, J = 23.4 Hz, Hcyclo.-2ax.), 1.32-1.23 (m, 7 H, Hcyclo.-4ax., CH3-CH2-CH2-CH2-), 1.09-1.02 (m,
2 H, Hcyclo.-3ax.), 0.90 (t, 3 H, J = 6.95 Hz, CH3-CH2-CH2-CH2-); 13C NMR (125 MHz, CDCl3) δ 170.61
20

(C=O), 170.09 (C=O), 169.34 (C=O), 164.55 (C=O), 154.65 (Ph-C=O), 130.36(Caroma.-4), 130.31 (Caroma.-2),
127.16 (Caroma.-3), 125.96 (Caroma.-1), 92.17 (C-1), 72.73 (C-5), 72.74, 70.18, 67.97 (C-4), 61.52 (C-6), 44.84
(Ccyclo.-1), 37.21, 37.02, 34.00 (Ccyclo.-2), 33.97 (Ccyclo.-3), 29.20, 22.99, 20.68 (-O-CH3), 20.61 (-O-CH3),
20.59 (-O-CH3), 20.57 (-O-CH3), 14.14 (CH3-CH2-CH2-CH2-).
Anal. Calcd for C31H42O11 : C, 63.04; H, 7.17. Found: C, 63.11; H, 7.23.
4.2.11. 1-O-{4-(trans-4-Butylcyclohexyl)benzoyl}-2,3,4,6-tetra-O-methyl-β-D-glucopyranose 19
4CPA (880 mg, 3.38 mmol), EDC (972 mg, 5.07 mmol), DMAP (206 mg, 1.69 mmol) and
glucopyranose 18 (400 mg, 1.69 mmol) were stirred for 9.5 h in DMF (5 mL) at 110 ºC under an N2
atmosphere. After confirmation of the reaction by TLC, the solution was azeotropically evaporated with
toluene. The residue was diluted with CHCl3 and washed with ice-cold water, satd aq NaHCO3, and brine.
The solution was dried over anhyd MgSO4. The suspension was filtered through a celite bed and
concentrated. Purification on silica gel with 4:1 (v/v) n-hexane–EtOAc yielded crystalline β-ester 19 (629
mg, 77.8%) and crystalline α-ester (197 mg, 24.4%) as colorless syrup: Rf 0.55 (α-ester), 0.60 (β-ester)
− 13.9 º (c 1.00, CHCl3); IR (neat) : 2922 (νC-H), 1736 (νC-H, ester) cm–1;
ꢇ ꢈꢊꢋ
[2:1 (v/v) n-hexane–EtOAc]; α
ꢉ
1H NMR (500 MHz, CDCl3) δ 8.00 (d, 2 H, J = 8.30 Hz, Haroma.-2), 7.27 (d, 2 H, J = 8.85 Hz, Haroma.-3),
5.70 (d, 1 H, J = 7.50 Hz, H-1), 3.66 (s, 3 H, OMe), 3.66-3.58 (m, 2 H, H-6a, H-6b), 3.56 (s, 3 H, OMe),
3.56 (s, 3 H, OMe), 3.48-3.45 (m, 1 H, H-5), 3.37 (s, 3 H, OMe), 3.37-3.27 (m, 3 H, H-2, H-3, H-4),
2.55-2.50 (m, 1 H, Hcyclo.-1ax.), 1.88 (d, 4 H, J = 10.9 Hz, Hcyclo.-2eq., Hcyclo.-3eq.), 1.49-1.42 (m, 2 H,
Hcyclo.-2ax.), 1.32-1.23 (m, 7 H, Hcyclo.-4ax., CH3-CH2-CH2-CH2-), 1.09-1.01 (m, 2 H, Hcyclo.-3ax.), 0.90 (t, 3
21

H, J = 6.95 Hz, CH3-CH2-CH2-CH2-); 13C NMR (125 MHz, CDCl3) δ 164.91 (Ph-C=O), 154.03 (Caroma.-4),
130.15 (Caroma.-2), 126.98 (Caroma.-3), 126.95 (Caroma.-1), 94.60 (C-1), 86.58, 82.92, 78.84 (C-2), 75.40 (C-5),
70.64 (C-6), 61.08 (OMe), 60.81 (OMe), 60.55 (OMe), 59.37 (OMe), 44.93 (Ccyclo.-1), 37.36, 37.17, 34.11
(Ccyclo.-2), 33.55 (Ccyclo.-3), 29.33, 23.13, 14.27 (CH3-CH2-CH2-CH2-).
Anal. Calcd for C27H42O7· 0.5H2O: C, 66.50; H, 8.89. Found: C, 66.64; H, 8.74.
Acknowledgment
We are grateful to Dr. Yoshio Aoki of Saitama Plant, DIC Corporation for providing the 4CPOH and
4CPA used in this study and for valuable discussions.
References and notes
1. Tojo, K.; Aoki, Y.; Yasutake, M.; Hirose, T. J. Fluorine Chem. 2006, 127, 620-626.
2. Fukuda, K.; Suzuki, H.; Tokita, M.; Watanabe, J.; Kawauchi, S. J. Mol. Struct. (Theochem.) 2007, 821,
95-100.
3. Fukuda, K.; Suzuki, H.; Ni, J.; Tokita, M.; Watanabe, J. Jpn. J. Appl. Phys. 2007, 46, 5208-5212.
4. Piao, G.; Akagi, K.; Shirakawa, H.; Kyotani, M. Curr. Appl. Phys. 2001, 1, 121-123.
5. Tojo, K.; Arisawa, T.; Aoki, Y.; Terunuma, D. Bull. Chem. Soc. Jpn. 2009, 82, 519-527.
6. Aoki, Y.; Nohira, H. Ferroelectrics 1998, 212, 273-280.
7. Wehner, J. W.; Hartmann, M.; Lindhorst, T. K. Carbohydr. Res. 2013, 371, 22-31.
8. Sauer, J.; Hachem, M. A.; Svensson, B.; Jensen, K. J.; Thygesen, M. B. Carbohydr. Res. 2013, 375,
22

21-28.
9. Matsuoka, K.; Goshu, Y.; Takezawa, Y.; Mori, T.; Sakamoto, J.; Yamada, A.; Onaga, T.; Koyama, T.;
Hatano, K.; Snyder, P. W.; Toone, E. J.; Terunuma, D. Carbohydr. Polym. 2007, 69, 326-335.
10. Oka, H.; Koyama, T.; Hatano, K.; Matsuoka, K. Bioorg. Med. Chem. 2012, 20, 435-445.
11. Matsuoka, K.; Terabatake, M.; Umino, A.; Esumi, Y.; Hatano, K.; Terunuma, D.; Kuzuhara, H.
Biomacromolecules 2006, 7, 2274-2283.
12. Sakamoto, J.; Koyama, T.; Miyamoto, D.; Yingsakmongkon, S.; Hidari, Kazuya I. P. J.; Jampangern,
W.; Suzuki, T.; Suzuki, Y.; Esumi, Y.; Nakamura, T.; Hatano, K.; Terunuma, D.; Matsuoka, K. Bioorg.
Med. Chem. 2009, 17, 5451-5464.
13. Oka, H.; Onaga, T.; Koyama, T.; Guo, C.; Suzuki, Y.; Esumi, Y.; Hatano, K.; Terunuma, D.;
Matsuoka K. Bioorg. Med. Chem. 2009, 17, 5465-5475.
14. Vill, V.; Fischer, F.; Thiem, J. Z. Naturforsch. 1988, 43a, 1119-1125.
15. Smits, E. The sweet world of liquid crystal [dissertation]. : St. Groningen: Groningen Univ; 1998.
16. Ewing, D. F.; Glew, M.; Goodby, J. W.; Haley, J. A.; Kelly, S. M.; Komanschek, B. U.; Letellier, P.;
Mackenzie, G.; Mehl, G. H. J. Mater. Chem. 1998, 8(4), 871-880.
17. Cook, A. G.; Wardell, J. L.; Brooks, N. J.; Seddon, J. M.; Martínez-Felipe, A.; Imrie, C. T. Carbohydr.
Res. 2012, 360, 78-83.
18. Motoyama, H.; Mine, T.; Shirono, M. inventors; Mitsubishi Gas Chem Co. Inc., assignee. Optically
active compound and liquid crystal composition comprising the same. JP patent 2004-250341. 2004
September 9.
23

19. (a) Iwatani, K.; Yoshida, S.; Asano M.; Fujiwara, H.; Fukui, M. inventors; Chisso Co., assignee.
Method for rearranging cyclic compound. JP 1993-201881. 1993 August 10; (b) Ogiwara, T.; Asakura,
K.; Shimizu, T. inventors; Shin Etsu Chemical Co., assignee. Production of trans-cyclohexane
compound. JP patent 1997-110883. 1997 April 28; (c) Sasada, Y.; Shimada, T.; Ushioda, M.; Matsui, S.
Liq. Cryst. 2007, 34, 569-576.
20. (a) Mendoza, V. M.; Gallo-Rodriguez, C.; De Lederkremer, R. M. ARKIVOC 2003, part x, 82-94; (b)
Kashiwagi, G. A.; Mendoza, V. M.; De Lederkremer, R. M.; Gallo-Rodriguez, C. Org. Biomol. Chem.
2012, 10, 6322-6332.
21. (a) Schmidt, O. T.; Auer, T.; Schmadel, H. Chem. Ber. 1960, 93, 556-557; (b) Koto, S.; Morishima, N.;
Miyata, Y.; Zen, S. Bull. Chem. Soc. Jpn. 1976, 49, 2639-2640.
22. (a) Kuhn, R.; Löw, I.; Trischmann, H. Chem. Ber. 1955, 88, 1492-1507; (b) Sugihara, J. M.; Wolfrom,
M. L. J. Am. Chem. Soc. 1949, 71, 3357-3359.
23. Cano, R.; Bull. Soc. fr. Minéral. Cristallogr. 1968, 91, 20-27.
24

Table 1. Characteristic properties of the compounds
Compound
R
Phase Transfer*1
HTP*2
[ µm–1 ]
10.4
2.8
MHTP*3
[µm–1mol–1Kg]
5.85
[α]
No.
6
X
[°]
[°C]
-O-
Cr 163 Iso*4
Cr 126 Iso
Cr 153 Iso
Cr 38 Iso
N.D.*5
−12.3
−27.7
−17.0
−29.1
−25.5
−13.9
11
17
8
Ac
-O-CH2-
-O-CO-
-O-
1.61
0.0
0.00
3.6
1.62
13
19
Me
-O-CH2-
-O-CO-
6.4
2.97
N.D.
1.3
0.62
*1 Determined by the average of the 2nd and 3rd heatings in DSC at a heating rate of 5 °C min–1.
*2 Determined by Cano wedge cells.
*3 MHTP = HTP×Mw÷1000. Mw shows the molecular weight of a chiral dopant.
*4 Abbreviations: Cr means crystalline phase and Iso means isotropic phase.
*5 N.D. means not detectable because the sample has broad signals by DSC.
25

Legends to Figures and Schemes
Figure 1. Compounds as mesogenic units.
C H
4
OH
1 : 4CPOH
2 : 4CPA
9
C H
4
COOH
9
9
C H
4
3 : 4CPMOH
CH OH
2
26

Figure 2. Chiral dopants consisting of glucose and various mesogenic moieties.
OR
6
5
O
4
RO
X
C4H9
4
1
4
1
1
3
2
3
2
2
3
aroma.
cyclo.
RO
OR
Phenyl Glucoside Derivatives (X=-O-)
6
8
:
:
R = Ac
R = Me
Benzyl Glucoside Derivatives (X=-O-CH2-)
11
13
:
:
R = Ac
R = Me
Benzoyl Glucose Derivatives (X=-O-CO-)
17
19
:
:
R = Ac
R = Me
27

Scheme 1. Synthesis of a mesogenic unit. Reagents and conditions: (i) conc H2SO4, EtOH, 70 ºC, 16 h,
93%; (ii) LiAlH4, THF, 0 ºC, 30 min, 93%.
C H
4
COOH
9
2 : 4CPA
i )
C H
4
COOEt
9
4
ii )
C H
4
CH OH
2
9
3 : 4CPMOH
28

Scheme 2. Synthesis of phenyl glucoside derivatives. Reagents and conditions: (i) BF3–OEt2, 4CPOH,
CH2Cl2, 0 ºC to rt, 5.5 h, 63%; (ii) NaOMe, MeOH, rt, 0.5 h, quant.; (iii) NaH, MeI, DMF, 0 ºC to rt, 2.5 h,
98%.
OR
OAc
O
O
i )
RO
O
AcO
AcO
OAc
OAc
RO
OR
5
C H
4
9
6 : R = Ac
ii )
7 : R = H
iii )
8 : R = Me
29