Stereodivergent synthesis of both (2S)- and (2R)-1-monoricinolein derivatives by lipase-catalyzed hydrolysis or transesterification directed to new ferroelectric liquid crystals

Article abstract of DOI:10.1016/j.tetasy.2007.04.009

The preparation of both (2S)- and (2R)-1-monoricinolein derivatives has been developed to synthesize ferroelectric liquid crystals. Lipase-catalyzed hydrolysis of 2-protected-1,3-diricinoleins provided (2S)-1-monoricinolein derivatives with high diastereoselectivities, while transesterification of 2-protected glycerols with vinyl recinoleate gave (2R)-1-monoricinolein counterparts in good yields with high diastereoselectivities.

Full text of DOI:10.1016/j.tetasy.2007.04.009

Tetrahedron: Asymmetry 18 (2007) 915–918
Stereodivergent synthesis of both (2S)- and (2R)-1-monoricinolein
derivatives by lipase-catalyzed hydrolysis or transesterification
directed to new ferroelectric liquid crystals
Iwao Hachiya,a Yoshihumi Sugiura,a Hiromasa Araki,a Osamu Inaoka,a Makoto Shimizu,a,*
Masatsugu Akitab and Takashi Hamaguchib
aDepartment of Chemistry for Materials, Graduate School of Engineering, Mie University, Tsu, Mie 514-8507, Japan
bItoh Oil Chemicals Co., Ltd., Yokkaichi, Mie 510-0052, Japan
Received 5 March 2007; accepted 11 April 2007
Dedicated to the memory of Professor Yoshihiko Ito. Deceased on December 23, 2006
Abstract—The preparation of both (2S)- and (2R)-1-monoricinolein derivatives has been developed to synthesize ferroelectric liquid crys-
tals. Lipase-catalyzed hydrolysis of 2-protected-1,3-diricinoleins provided (2S)-1-monoricinolein derivatives with high diastereoselectiv-
ities, while transesterification of 2-protected glycerols with vinyl recinoleate gave (2R)-1-monoricinolein counterparts in good yields with
high diastereoselectivities.
Ó 2007 Elsevier Ltd. All rights reserved.
R
1. Introduction
H2n+1CnO
OC2mH2m+1
Ferroelectric liquid crystals, which have an asymmetric
structure and show a smectic phase, are possible to be uti-
lized as an indicator device possessing a high-speed switch-
ing character and a memory function. In general, the
characteristic structure contains an alkyl chain, a flexible
acyclic structure at both ends of a rigid skeletal structure
(core part). It is also necessary to have an asymmetric
structure for ferroelectricity, namely spontaneous polariza-
tion (Fig. 1).1
Core
part
Terminal
part
Chiral
part
Figure 1. Ferroelectric liquid crystal compounds.
hydrolysis of triricinolein to monoricinolein gave an unde-
sired regioisomer 2-monoricinolein. We next examined the
lipase-catalyzed hydrolysis of 1,3-diricinolein prepared
from glycerol with ricinoleic acid. Herein, we report a dia-
stereoselective preparation of 1-monoricinolein derivatives
by lipase-catalyzed hydrolysis of 1,3-diricinolein deriva-
tives and lipase-catalyzed transesterification of 2-protected
glycerols with vinyl ricinoleate as an acyl donor.
In order to prepare ferroelectric liquid crystals, we first
planned to prepare 1-monoricinolein as a chiral part
including asymmetric carbons using lipase-catalyzed
hydrolysis2 of triricinolein obtained by purification of cas-
tor oil, which is commercially available and consists of
approximately 90% ricinoleate (12-hydroxy-cis-octadece-
noic) acid esters with a hydroxy group and a double bond
as the dominant constitutive fatty acid. Castor oil is sapon-
ified in industry for the preparation of ricinoleic acid. The
core part with a rigid skeletal structure can be introduced
at the hydroxy group. However, the lipase-catalyzed
2. Results and discussion
We examined the lipase-catalyzed hydrolysis of 1,3-diricin-
olein 1a, which was prepared from glycerol with ricinoleic
acid, in THF–phosphate buffer at room temperature. Table
1 summarizes the results. When the lipase PS-catalyzed
hydrolysis was carried out for 20 min, the desired 1-mono-
ricinolein 2a was obtained in 26% yield with 28% de (entry
*
Corresponding author. Tel./fax: +81 59 231 9413; e-mail: mshimizu@
chem.mie-u.ac.jp
0957-4166/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.04.009

916
I. Hachiya et al. / Tetrahedron: Asymmetry 18 (2007) 915–918
tected glycerols4 with ricinoleic acid, were used as starting
Table 1. Lipase-catalyzed hydrolysis of 1
materials. When the lipase PS-catalyzed hydrolysis of 1b
was carried out, the des of 2b increased (entries 4–6). The
use of lipase AK, which has been found to be the most
effective lipase in the hydrolysis of triricinolein to
(2R)-2,3-diricinolein,5 gave 2b in low yield with moderate
de (entry 7). The highest 94% de was obtained, when the
hydrolysis of 1c was conducted for 25 min (entry 8).6
OCOR1
OH
OH
Lipase
OR2
OR2
+
OR2
THF-phosphate buffer, rt
1
OCOR1
OCOR
(2R)-2
1
OCOR
(2S)-2
2a: R2 =
H
1a: R2 =
H
2b: R2 = BOM
2c: R2 = MOM
1b: R2 = BOM (BnOCH 2
)
1c: R2 = MOM (MeOCH2)
OH
R1
=
We next examined the lipase-catalyzed transesterification
of 2-protected glycerol 3 with triricinolein 4 as an acyl
donor. Table 2 summarizes the results. Among the lipases
Entry Lipase R2
Time Yielda
(min) (%)
(2R)-2:(2S)-2b,c de
1
2
3
4
5
6
7
8
9
PS
PS
PS
PS
PS
PS
AK
PS
PS
H
H
H
20
30
40
10
20
30
30
26
36
55
24
40
35
14
36:64
22:78
47:53
12:88
5:95
5:95
15:85
3:97
28
56
6
76
90
90
70
94
88
Table 3. Lipase-catalyzed transesterification of 3c with vinyl ricinoleate 5a
OH
OH
OBn
OH
OBn
BOM
BOM
BOM
BOM
MOM 25
MOM 35
Lipase
+
+
OBn
OCOR
R =
MeCN, 50 °C, time
OH
OCOR
OCOR
32 (51)d
8
(2R)-2d
(2S)-2d
5
3c
OH
6:94
a Isolated yield.
b Diastereomeric excesses were determined by HPLC analysis using the
chiral stationary phase column, Chiralcel-OD after transformation of 2
into its di or tribenzoate ester.
Entry
Lipase
Time (h)
Yieldb (%)
(2R)-2d:(2S)-2dc
de
1
2
3
4
5
6
7
PPL
PS
3.5
3.5
3.5
15
29
49
58
64
65
38
80:20
88:12
88:12
96:4
98:2
96:4
60
76
76
92
96
92
62
c Configurations of product 2a and 2c were assigned by analogy.
d Yield in the parenthesis is based on the recovered 1,3-direcinolein
derivative 1c.
AK
AK
AK
AK
AK
6.0
12.0
18.0
24.0
1).3 When the hydrolysis was conducted for 30 min, a mod-
erate 56% de was obtained (entry 2). As the reaction times
increased, the de of 2a decreased presumably due to com-
peting acyl migration (entries 1–3). To prevent the acyl
migration of 1-monoricinolein 2a, 2-protected-1,3-diricino-
lein derivatives 1b and 1c, which were prepared from 2-pro-
81:19
a 5 (1.0 equiv) in entries 1–3. 5 (2.0 equiv) in entries 4–7.
b Isolated yield.
c Diastereomeric excesses were determined by the HPLC analysis using the
chiral stationary phase column, Chiralcel-OD after transformation of 2d
into its dibenzoate ester.
Table 2. Lipase-catalyzed transesterification of 2-protected glycerol derivatives 3 with triricinolein 4
OCOR1
OCOR1
OH
OH
OR2
OH
OR2
Lipase
OR2
+
+
solvent, rt, time
OH
OCOR1
OCOR1
OCOR1
(1.0 equiv)
4
(2R)-2
(2S)-2
3a: R2 = BOM
3b: R2 = MOM
3c: R2 = Bn
2b: R2 = BOM
2c: R2 = MOM
2d: R2 = Bn
OH
R1=
Entry
Lipase
R2
Solvent
Time (h)
Yield (%)a
(2R)-2:(2S)-2b
de
70
1
2
3
4
5
6
7
8
9
PPL
BOM
BOM
BOM
BOM
BOM
BOM
BOM
BOM
BOM
BOM
MOM
Bn
MeCN
MeCN
MeCN
MeCN
EtCN
EtCN
PrCN
MeCN:THF (2:1)
MeCN:tBuOMe (2:1)
MeCN:DME (2:1)
MeCN
3.5
3.5
19.0
3.5
6.5
3.5
3.5
3.5
3.5
3.5
3.5
3.5
22
Trace
Trace
43
3
13
3
3
31
4
32
10
85:15
ND
ND
AYS
CCL
Novozym 435
AK
PPL
PPL
PPL
PPL
PPL
PPL
50:50
80:20
67:33
86:14
87:13
80:20
82:18
85:15
85:15c
0
60
34
72
74
60
64
70
70
10
11
12
PPL
MeCN
a Isolated yield.
b Diastereomeric excesses were determined by the HPLC analysis using the chiral stationary phase column, Chiralcel-OD after transformation of 2 into its
dibenzoate ester.
c Product 2d configuration was assigned by analogy.

I. Hachiya et al. / Tetrahedron: Asymmetry 18 (2007) 915–918
917
OH
OH
OBz
Lipase PS
+
OH
OH
OBz
1,4-dioxane, rt, 187 h
46%
OH
(2R)-6
24
[α] D = +6.1
(c 0.66, MeOH)
OBz
OBz
R2CO2H, DCC, DMAP
BOMCl, Py
OH
OCOR2
OBOM
CH2Cl2, rt, 4 h
36%
CH2Cl2, rt, 14 h
OCOR2
61%
(2R)-7b
18% de
OH
OBz
BzCl, Py
OBOM
OCOR1
OBOM
CH2Cl2, rt, 13.5 h
74%
OCOR2
(2R)-7b
90% de
(2S)-2b
OH
OBz
R1 =
R2
=
Scheme 1. Determination of product 2b configuration.
OCOR2
OMOM
OH
DCC, DMAP
+
OMOM
OCOR1
(2S)-2C
R1
HO2C
O
CH2Cl2, 0 ºC to rt, 48 h
33%
OCOR1
10
9
OH
R2
=
=
O
Scheme 2. Preparation of 1,3-acyl glycerol derivative 9.
tested in transesterification of 3a4 with 4, lipase PPL was
found to be the most effective (entries 1–5). Regarding
the solvent, acetonitrile (MeCN) gave 2b in better yields
with good diastereomeric excesses (entries 1, 6–10). The
effect of a substituent on the 2-protected glycerols was
investigated.7 The desired products 2b, 2c, and 2d were
obtained with similar des (entries 1, 11 and 12). In an effort
to improve both the yield and de, vinyl ricinoleate 58 was
used as an acyl donor. Table 3 summarizes the results.
Among the lipases tested, lipase AK gave 2d in good yields
with good des (entries 1–3). The lipase AK-catalyzed
transesterifications were carried out for several reaction
times. The desired product 2d was obtained in high yields
with des 6.0, 12.0 and 18.0 h, respectively (entries 4–6).9
The 1,3-diacyl glycerol derivative 9 was synthesized using
the general condensation of the 1-monoricinolein deriva-
tive (2S)-2c (94% de) with 4-(4-hexyloxyphenyl)benzoic
acid 10 as a rigid skeletal structure as shown in Scheme
2.12 A preliminary result from differential scanning calo-
rimetry (DSC) of 1,3-diacyl glycerol derivative 9 showed
a liquid crystal phase from ꢀ20 to 75 °C.
3. Conclusion
In conclusion, we have demonstrated the preparation of
both (2S)- and (2R)-1-monoricinolein derivatives by
lipase-catalyzed hydrolysis of 2-protected-1,3-diricinolein
derivatives or transesterification of 2-protected glycerols
with vinyl ricinoleate as an acyl donor, respectively. 1,3-
Diacyl glycerol derivative 9 was prepared from 1-monori-
cinolein (2S)-2c and showed a liquid crystal phase.
The absolute configuration of 2b was determined by com-
paring the retention time of (2R)-7b, which was trans-
formed from 1-monobenzoyl glycerol (2R)-6,10 prepared
according to the literature method as shown in Scheme 1,
in the HPLC analysis. The result indicated that the major
diastereomer of 1-monoricinolein derivative 2b prepared
by lipase PS-catalyzed hydrolysis of 1b had an (S)-configu-
ration.11 On the other hand, the examination into the
retention time in HPLC indicated that the major diastereo-
mer of 2b prepared by lipase PPL-catalyzed transesterifica-
tion of 3a with 4 had an (R)-configuration.
References
1. (a) Nohira, H. J. Synth. Org. Chem. Jpn. 1991, 49, 467–474;
(b) Nohira, H. J. Synth. Org. Chem. Jpn. 1992, 50, 14–23.
2. For reviews, see (a) Santaniello, E.; Ferraboschi, P.; Grisenti,
P.; Manzocchi, A. Chem. Rev. 1992, 92, 1071–1140; (b)

918
I. Hachiya et al. / Tetrahedron: Asymmetry 18 (2007) 915–918
Nakamura, K.; Hirose, Y. J. Synth. Org. Chem. Jpn. 1995,
53, 668–677.
7. 2-Benzyloxypropane-1,3-diol 3c was prepared according to
the literature method Nali, M.; Rindone, B. Gazz. Chim. Ital.
1986, 116, 25–27.
3. The diastereomeric excess of 1-momoricinolein 2a was
determined by the HPLC analysis of its tribenzoate ester.
4. 2-Benzyloxymethoxypropane-1,3-diol (3a) and 2-methoxy-
methoxypropane-1,3-diol (3b) were prepared according to the
literature method and its modification, respectively. Chong, J.
M.; Sokoll, K. K. Tetrahedron Lett. 1992, 33, 879–882.
5. Hachiya, I.; Makino, A.; Shimizu, M.; Akita, M.; Hama-
guchi, T. Tetrahedron: Asymmetry 2004, 15, 2451–2454.
6. General procedure for the synthesis of 1-monoicinolein deriv-
atives 2. To a solution of 1,3-diricinolein derivative 1c
(1186.2 mg, 1.70 mol) in THF (8.0 mL) and phosphate buffer
(24.0 mL) was added lipase PS (101.6 mg) at room temper-
ature under an air. The mixture was stirred at room
temperature for 25 min and then filtered through a Celite
pad, which was washed with EtOAc. The filtrate was washed
with brine and dried over Na2SO4. The solvents were
evaporated in vacuo, and then the residue was purified by
silica gel column chromatography (hexane/EtOAc = 4/1) to
give 1-monoricinolein derivative 2c (224.4 mg, 32%, 51%
based on the recovered 1c) as a colorless oil and a mixture of
the recovered 1c and ricinoleic acid (942.2 mg, 48%, 39%,
respectively, by 1H NMR analysis). 1H NMR (500 MHz,
CDCl3): d 0.88 (t, J = 7.0 Hz, 3H), 1.24–1.40 (m, 16H), 1.40–
1.53 (m, 2H), 1.55–1.72 (m, 3H), 2.00–2.09 (m, 2H), 2.18–2.24
(m, 2H), 2.30–2.37 (m, 2H), 2.70 (s, 1H), 3.43 (s, 3H), 3.56–
3.73 (m, 3H), 3.78–3.88 (m, 1H), 4.17 (dd, J = 5.2, 11.6 Hz,
1H), 4.21 (dd, J = 5.6, 11.6 Hz, 1H), 4.74 (s, 2H), 5.35–5.46
(m, 1H), 5.52–5.60 (m, 1H). 13C NMR (67.8 MHz, CDCl3): d
13.9, 14.0, 22.5, 24.7, 25.6, 27.2, 28.9, 29.0, 29.2, 29.4, 31.7,
34.0, 35.2, 36.7, 55.5, 62.3, 63.2, 71.4, 76.5, 96.4, 125.2, 132.9,
173.6. IR (neat): 3418, 2927, 2855, 1737, 1459, 1156, 1113,
8. Waldinger, C.; Schneider, M. J. Am. Oil. Chem. Soc. 1996,
73, 1513–1519.
9. General procedure for the synthesis of (2R)-1-monoicinolein
derivatives 2 using lipase-catalyzed transesterification of the
2-protected glycerol 3 with vinyl ricinoleate 5. To vinyl
ricinoleate 5 (32.5 mg, 0.100 mol) was added a solution of
2-benzyloxypropane-1,3-diol (3c) in MeCN (1.5 mL) at room
temperature under an argon atmosphere and the mixture was
stirred at 50 °C for 5 min. Lipase AK (20.0 mg) was added to
the resulting mixture at 50 °C. The mixture was stirred at
50 °C for 12.0 h and then filtered through a Celite pad, which
was washed with EtOAc. The filtrate was washed with brine
and dried over Na2SO4. The solvents were evaporated in
vacuo, and then the residue was purified by silica gel column
chromatography (hexane/EtOAc = 1/2) to give 2d (29.7 mg,
1
64%) as a colorless oil. H NMR (500 MHz, CDCl3): d 0.88
(t, J = 6.7 Hz, 3H), 1.23–1.38 (m, 16H), 1.41–1.47 (m, 3H),
1.59–1.64 (m, 3H), 2.04 (t, J = 7.0 Hz, 2H), 2.20 (t,
J = 7.3 Hz, 2H), 2.32 (t, J = 7.3 Hz, 2H), 3.57–3.66 (m,
2H), 3.68–3.74 (m, 2H), 4.23–4.24 (m, 2H), 4.60 (d,
J = 11.6 Hz, 1H), 4.72 (d, J = 11.6 Hz, 1H), 5.37–5.42 (m,
1H), 5.52–5.58 (m, 1H), 7.30–7.36 (m, 5H). 13C NMR
(67.8 MHz, CDCl3): d 173.8, 137.8, 133.3, 128.5, 128.0,
127.8, 125.2, 77.2, 72.1, 71.5, 62.6, 62.0, 36.8, 35.3, 34.2, 31.8,
29.5, 29.3, 29.1, 29.0, 29.0, 27.3, 25.7, 24.9, 22.6, 14.1. 14.1,
22.6, 24.9, 25.7, 27.3, 29.0, 29.0, 29.1, 29.3, 29.5, 31.8, 34.2,
35.3, 36.8, 62.0, 62.6, 71.5, 72.1, 77.2, 125.2, 127.8, 128.0,
128.5, 133.3, 137.8, 173.8. IR (neat): 3418, 2927, 2857, 1736,
24
1457, 1178, 1117, 1060, 737, 699 cmꢀ1. ½aꢁD ¼ ꢀ8:5 (c 0.218,
CHCl3).
21
1034, 919, 725 cmꢀ1. ½aꢁD ¼ þ8:2 (c 0.093, CHCl3).
10. Kato, Y.; Fujiwara, I.; Asano, Y. J. Mol. Catal. B: Enzym.
2000, 9, 193–200.
The diastereomeric excesses of 1-momoricinolein derivatives
2b and 2c were determined by HPLC analysis of their
dibenzoates 7b and 7c. To a solution of 1-monoricinolein
derivative 2c (2.7 mg, 0.0065 mmol) in CH2Cl2 (1.5 mL) was
added pyridine (0.020 mL, 0.25 mmol) at 0 °C under an argon
atmosphere and the mixture was stirred at 0 °C for 5 min.
Benzoyl chloride (0.040 mL, 0.34 mmol) was added to the
resulting mixture at 0 °C. The mixture was warmed to room
temperature and then stirred for 14.0 h. HCl (2 M) was added
to quench the reaction. The mixture was extracted with
EtOAc. The combined extracts were washed with H2O,
saturated aqueous NaHCO3, and brine and dried over
Na2SO4. The solvents were evaporated in vacuo, and then
the residue was purified on preparative TLC (hexane/
EtOAc = 9/1) to give 7c along with a small amount of
impurities. Further purification on preparative TLC (hexane/
EtOAc = 1/1) gave pure 7c (10.9 mg, 99%) as a colorless oil.
The de of 7c was determined as 94% by HPLC analysis
(DAICEL CHIRALCEL OD, hexane/2-propanol = 50/1 (v/
v)), at a flow rate of 0.3 mL minꢀ1. The minor (2R)-7c was
eluted first (t2R = 32.5 min), followed by major (2S)-7c
(t2S = 37.0 min).1H NMR (270 MHz, CDCl3): d = 0.86 (t,
J = 6.6 Hz, 3H), 1.26–1.38 (m, 16H), 1.59–1.70 (m, 4H), 2.01–
2.05 (m, 2H), 2.33 (t, J = 7.6 Hz, 2H), 2.43 (dd, J = 5.9,
11.6 Hz, 2H), 3.39 (s, 3H), 4.15–4.51 (m, 5H), 4.76 (s, 2H),
5.11–5.16 (m, 1H), 5.38–5.47 (m, 2H), 7.40–7.47 (m, 4H),
7.52–7.57 (m, 2H), 8.00–8.06 (m, 4H). 13C NMR (67.8 MHz,
CDCl3): d = 14.0, 22.5, 24.8, 25.4, 27.3, 29.0, 29.1, 29.2, 29.5,
31.7, 32.0, 33.7, 34.1, 55.6, 63.4, 64.0, 72.7, 74.6, 77.2, 96.0,
124.1, 128.2, 128.4, 129.5, 129.6, 129.7, 130.7, 132.7, 133.2,
166.2, 173.5. IR (neat): 2928, 2856, 1721, 1602, 1453, 1273,
11. Configurations of product 2a and 2c were tentatively assigned
by analogy.
12. Procedure for the synthesis of 1,3-diacyl glycerol derivative 9.
To
55.5 mg,
a
mixture of 1-monoricinolein (2S)-2c (94.2% de,
0.133 mmol) and 4-dimethylaminopyridine
(DMAP) (37.4 mg, 0.306 mmol) was added a solution of
4-(4-hexyloxyphenyl)-benzoic acid (59.6 mg, 0.200 mmol) in
CH2Cl2 (2.0 mL) at room temperature under an argon
atmosphere and the mixture was stirred at 0 °C for 5 min. A
solution of N,N0-dicyclohexylcarbodiimide (DCC) (68.7 mg,
0.333 mmol) in CH2Cl2 (2.0 mL) was added to the resulting
mixture at 0 °C. The mixture was allowed to warm to room
temperature and then stirred for 48 h. The mixture was
filtered through a Celite pad, which was washed with
EtOAc. The filtrate was washed with 0.5 M HCl and dried
over Na2SO4. The solvents were evaporated in vacuo, and
then the residue was purified on preparative TLC (hexane/
EtOAc = 6/1) to give 1,3-diacyl glycerol derivative
9
(30.5 mg, 33%) as a colorless oil. 1H NMR (270 MHz,
CDCl3): d 0.80–0.90 (m, 6H), 1.20–1.40 (m, 20H), 1.40–1.53
(m, 4H), 1.52–1.72 (m, 3H), 1.76–1.86 (m, 2H), 1.98–2.12
(m, 2H), 2.18–2.23 (m, 2H), 2.35 (t, J = 7.4 Hz, 2H), 3.41 (s,
3H), 3.55–3.68 (m, 1H), 4.01 (t, J = 6.6 Hz, 2H), 4.11–4.58
(m, 5H), 4.77 (s, 2H), 5.37–5.44 (m, 1H), 5.50–5.59 (m, 1H),
6.95–7.00 (m, 2H), 7.48–7.64 (m, 4H), 8.04–8.09 (m, 2H).
13C NMR (67.8 MHz, CDCl3): d 14.0, 14.1, 22.6, 24.8, 25.7,
27.4, 29.0, 29.1, 29.2, 29.3, 29.5, 31.6, 31.8, 34.1, 35.4, 36.8,
55.6, 63.4, 63.9, 71.5, 72.7, 77.2, 96.0, 114.9, 125.2, 126.3,
126.5, 127.7, 128.0, 128.3, 130.2, 132.0, 133.3, 145.6, 159.5,
166.2, 173.5. IR (neat): 2929, 2857, 1721, 1605, 1497, 1466,
20
26
1172, 1111, 1070, 1031, 921, 712, 447, 418 cmꢀ1. ½aꢁD ¼ þ14:6
1274, 1186, 1111, 1035, 829, 757 cmꢀ1. ½aꢁD ¼ þ0:9 (c 0.29,
(c 0.091, CHCl3).
CHCl3).