Accepted Manuscript Synthesis of chiral dopants based on carbohydrates Toru Tsuruta, Tetsuo Koyama, Mikio Yasutake, Ken Hatano, Koji Matsuoka PII: DOI: Reference:

S0008-6215(14)00157-8 http://dx.doi.org/10.1016/j.carres.2014.04.007 CAR 6724

To appear in:

Carbohydrate Research

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: [email protected] 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. host nematic liquid crystals.

The chiral dopants induced helices in the

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. another predisposition in the carbohydrates.

There is, however,

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. was then conducted.

Koenigs-Knorr reaction as an alternative glycosyl reaction

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. alcohol 12 in quantitative yield.

Conventional de-O-acetylation with Zemplén’s condition gave the

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. DMAP in DMF. on the TLC.

Carboxylic acid 2 and monoalcohol 14 were treated in the presence of EDC and

The reaction gave an inseparable α- and β-mixture of ester 15, which had very similar Rf

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. show any crystallinity.

The results suggested that compounds 13 and 19 did not

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

(1)

HTP = ሺ‫ܿ݌‬ሻିଵ MHTP = HTP × Md × 10ିଷ

(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. methyl ether protection did not show any HTP.

In contrast, the anomeric ester having

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. MS4Å after distillation.

Dichloromethane was stored over

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. 10

Chemical shifts are expressed as

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 H2 SO4 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). µm, E. Merck).

Column chromatography was performed on silica gel (Silica Gel 60; 63-200

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. 11

The organic solution was washed successively

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 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. dropwise added to the solution.

BF3–OEt2 (5.80 mL, 46.1 mmol) was

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 0.45 [4:1 (v/v) toluene–EtOAc]; ሾαሿଶହ ୈ − 12.3 º (c 1.00, CHCl3); IR (KBr) : 2916 (νC-H), 1751 (νC=O, ester), 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) CHCl3–MeOH–H2O]; ሾαሿଶହ ୈ − 22.3 º (c 1.00, DMSO-d6); IR (KBr) : 3416 (νO-H), 2918 (νC-H), 1512 (νC=C, aromatic) cm–1; 1H NMR (500 MHz, DMSO-d 6 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-d 6 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 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 (112 mg, 98.1%) as white crystals: mp 38 ºC; Rf 0.39 [4:1 (v/v) n-hexane–EtOAc]; ሾαሿଶହ ୈ − 29.1 º (c 1.00, 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, H aroma.-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 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

to

for

5

h

at

−5

ºC,

the

mixture

was

concentrated

in

vacuo

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 needle crystals: mp 126 ºC; Rf 0.50 [2:1 (v/v) n-hexane–EtOAc]; ሾαሿଶହ ୈ − 27.7 º (c 1.00, CHCl3); IR (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. mixture.

IR-120B (H+) resin was added to the

The suspension was filtered and concentrated to furnish the corresponding compound 12 as white

crystals in quantitative yield: Rf 0.66 [65:25:4 (v/v/v) CHCl3–MeOH–H2O]; ሾαሿଶହ ୈ − 15.3 º (c 1.00, 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 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 (112 mg, 58.9%) as a colorless syrup: Rf 0.52 [2:1 (v/v) n-hexane–EtOAc]; ሾαሿଶହ ୈ − 25.5 º (c 1.00, 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. toluene.

After confirmation of the reaction by TLC, the solution was azeotropically evaporated with

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. β-glucoside.

This compound was a mixture of α-glucoside and

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

1

H 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 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. bed, and concentrated.

The solution was dried over anhyd MgSO4, filtered through a celite

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

(α-glucoside), 0.40 (β-glucoside) [2:1 (v/v) n-hexane–EtOAc]; ሾαሿଶହ ୈ − 17.0 º (c 1.00, CHCl3); IR (KBr) : 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-); 20

13

C NMR (125 MHz, CDCl3) δ 170.61

(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 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. toluene.

After confirmation of the reaction by TLC, the solution was azeotropically evaporated with

The residue was diluted with CHCl3 and washed with ice-cold water, satd aq NaHCO3, and brine.

The solution was dried over anhyd MgSO4. concentrated.

The suspension was filtered through a celite bed and

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) –1 [2:1 (v/v) n-hexane–EtOAc]; ሾαሿଶହ ୈ − 13.9 º (c 1.00, CHCl3); IR (neat) : 2922 (νC-H), 1736 (νC-H, ester) cm ; 1

H 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, H aroma.-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 Phase Transfer*1

Compound No.

R

X

HTP*2 [ µm ]

[µm mol Kg]

[α] [°]

10.4

5.85

−12.3

–1

[°C] *4

MHTP*3 –1

–1

-O-

Cr 163 Iso

-O-CH2-

Cr 126 Iso

2.8

1.61

−27.7

17

-O-CO-

Cr 153 Iso

0.0

0.00

−17.0

8

-O-

Cr 38 Iso

3.6

1.62

−29.1

6.4

2.97

−25.5

1.3

0.62

−13.9

6 11

13 19

Ac

Me

*5

-O-CH2-

N.D.

-O-CO-

N.D.

*1 Determined by the average of the 2nd and 3 rd 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.

C4H9

OH

1 : 4CPOH

C4H9

COOH

2 : 4CPA

C4H9

CH2OH

3 : 4CPMOH

26

Figure 2. Chiral dopants consisting of glucose and various mesogenic moieties. OR 6 5

RO

4 3

RO

O 1

X

1

4 2

2

OR

3

aroma.

4

1 2

C4H9

3 cyclo.

Phenyl Glucoside Derivatives (X=-O-) 6

:

R = Ac

8

:

R = Me

Benzyl Glucoside Derivatives (X=-O-CH2-) 11

:

R = Ac

13

:

R = Me

Benzoyl Glucose Derivatives (X=-O-CO-) 17

:

R = Ac

19

:

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%. C4H9

COOH 2 : 4CPA i)

C4H9

COOEt 4

ii )

C4H9

CH2OH

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 AcO

OAc

AcO

OAc

i)

O RO

O RO

OR

5 C4H9 6 : R = Ac ii )

7: R=H iii )

8 : R = Me

29

Scheme 3. Synthesis of benzyl glucoside derivatives.

Reagents and conditions: (i) CCl3CN, DBU, CH2Cl2,

−5 °C, 5 h, Crude; (ii) 4CPMOH, TMSOTf, CH2 Cl2, −5 °C, 9 h, 33%; (iii) NaOMe, MeOH, rt, 5 h, quant.; (iv) MeI, NaH, DMF, 0 °C to rt, 3 h, 59%. OAc

OAc NH

O AcO

OH

AcO

O

i)

CCl3

AcO

OAc

O

AcO

9

OAc 10

OR O

ii )

C4H9

RO

O RO

OR 11 : R = Ac iii )

12 : R = H iv )

13 : R = Me

30

Scheme 4. Synthesis of a benzoyl glucose derivative.

Reagents and conditions: (i) 4CPA, EDC, DMAP,

DMF, 110 °C, 24 h, 71%; (ii) Pd/C, H2, MeOH, rt, 2.5 h, 90%; (iii) Ac2O, Pyr., rt, 12 h, 52%. OBn

OR O

O BnO

O

i)

OH

BnO

C4 H9

RO

OBn

O RO

OR

14

15 : R = Bn ii )

16 : R = H

OAc O O

iii )

AcO AcO

C4 H9 O OAc

17

31

Scheme 5. Synthesis of a benzoyl glucose derivative.

Reagents and conditions: (i) 4CPA, EDC, DMAP,

DMF, 110 °C, 9.5 h, 78%.

OMe

OMe

O

O

O MeO

OH

MeO

OMe

i)

MeO

C4 H9 O

MeO

18

OMe

19

32

Graphical Abstract

Phenyl Glucoside Derivatives (X=-O-)

OR

6 : R = Ac O RO

X RO

OR

C4H9

8 : R = Me

Benzyl Glucoside Derivatives (X=-O-CH2-) 11 : R = Ac

13 : R = Me

Benzoyl Glucose Derivatives (X=-O-CO-) 17 : R = Ac

19 : R = Me

Highlights Saccharidic chiral dopants for nematic liquid crystals were synthesized from D-glucose. The helical twisting power (HTP) values were evaluated. The chiral dopants induced helices in the host nematic liquid crystals. No relationship between HTP and specific rotation on the chiral dopants was observed in this study.

33