Synthesis of structurally weil-defined triglyceryl di-, tri-, and tetra-fatty acid esters as new oil gelators

Article abstract of DOI:10.1055/s-0028-1083601

We are interested in developing chemically modified linear and cyclic polyglycerols and their esters that have a single polymerization degree and fine structure. Triglyceryl di-, tri-, and tetra-fatty acid esters were synthesized from common substrate as new prominent gelators. The triglyceryl esters were capable of gelling up cooking oils. A comparison of the gelation ability of structurally related compounds clarified that the introduction of alkyl chains of suitable length is required for effective gelation. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0028-1083601

PAPER
3663
Synthesis of Structurally Well-Defined Triglyceryl Di-, Tri-, and Tetra-Fatty
Acid Esters as New Oil Gelators
Synthesis of
T
riglycery
a
l
D
i-
,
T
ri-,
s
a
nd Tetra
a
-Fatty Acid
h
E
sters iro Hamada,*a,b Megumi Terayama,a Kei-ichi Kaneko,a Tohru Ooya,b Takao Kishimoto,a,b
Noriyuki Nakajima*a,b
a
Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, Imizu, Toyama 939-0398, Japan
Fax +81(766)562498; E-mail: nori@pu-toyama.ac.jp; E-mail: hamada@pu-toyama.ac.jp.
Biotechnology Research Center, Toyama Prefectural University, Imizu, Toyama 939-0398, Japan
b
Received 3 July 2008; revised 7 August 2008
and measurement of new gelators, triglycerol multi-fatty
Abstract: We are interested in developing chemically modified lin-
acid esters.
ear and cyclic polyglycerols and their esters that have a single poly-
merization degree and fine structure. Triglyceryl di-, tri-, and tetra-
fatty acid esters were synthesized from common substrate as new
prominent gelators. The triglyceryl esters were capable of gelling
up cooking oils. A comparison of the gelation ability of structurally
related compounds clarified that the introduction of alkyl chains of
suitable length is required for effective gelation.
We synthesized tetra-, tri-, di-stearates with control of
both the binding position and number of fatty acids.
Readily available bis-acetonide of triglycerol 1,18 which
was prepared from ( )-solketal and ( )-epichlorohydrin,10
was used as a common starting material in expectation of
macro-scale synthesis (Scheme 1).19 The hydroxy group
of 1 was protected with benzyl bromide to give benzyl
ether 2 in 98% yield. The acetonides were deprotected
with 80% aqueous acetic acid to afford 1,2,10,11-tetraol 3
quantitatively. The tetraol 3 was reacted with stearoyl
chloride in pyridine containing catalytic 4-(di-
methylamino)pyridine to give the corresponding tet-
raester 4 in 35% yield. The deprotection of 4 was carried
out by hydrogenolysis with palladium on carbon to give
the desired 6-hydroxy-1,2,10,11-tetrastearate 5 in 93%
yield.
Key words: triglycerol, fatty acid esters, gelation, aggregation,
mechanistic study
Polyglycerols are oligomers of glycerol (glycerin). Their
fatty acid esters are generally dispersible in water and sol-
uble in oil. As these compounds are readily available in
bulk quantities by industrial manufacturers, they are wide-
ly used as food additives, cosmetic materials and as phar-
maceuticals as surfactants.1 However, commercially
available polyglycerols are mixtures of structural isomers
with the same hydroxy value.2 There are a few represen-
tative, standard polyglycerols in the literature.3–8 Rollin
and co-workers reported the synthesis of linear, branched,
and cyclic polyglycerol standards.9 We have continuously
studied the synthesis of cyclic polyglycerols as authentic
standards.10 However, there are few reports on the synthe-
sis of linear polyglycerol fatty acid esters with highly pure
and well-defined structures.
On the other hand, selective silylation of tetraol 3 with
tert-butyldiphenylsilyl chloride (TBDPSCl) gave disilyl
ether 6 in 81% yield. Debenzylation and esterification of
6 afforded 2,6,10-triester 8, and then the desilylation by
tetrabutylammonium fluoride gave the desired 1,11-dihy-
droxytristearate 9 in moderate yield. Disilyl ether 6 could
also be treated with benzyl bromide, followed by desilyla-
tion to give 1,11-diol 11 in good yield. Diol 11 was treated
with stearoyl chloride in pyridine with catalytic 4-(di-
methylamino)pyridine at 40 °C to give the 1,11-distea-
rate 12a in 78% yield. Debenzylation of 12a was carried
out with palladium hydroxide on activated carbon in eth-
anol–tetrahydrofuran under a hydrogen atmosphere to
give the desired trihydroxy ester 13a in moderate yield.
Low-molecular-weight compounds capable of gelling up
oils have stimulated considerable interest, in not only ac-
ademic investigations, but also for technological applica-
tions. Various types of small-molecule-based gelators of
organic and aqueous solvents have been investigated to
determine their essential characteristics for gelation.11 Al-
though dozens of different categories of gelators have so
far been identified, limited compounds have been used to
date: 12-hydroxystearic acid,12 N-lauroyl-L-glutamic-a,g-
dibutylamide,13 1,3:2,4-dibenzylidene-D-sorbitol,14 N-oc-
tyl-D-gluconamide-6-benzoate,15 and TAISET®.16 Be-
sides the above gelators, Hanabusa17 and Shinkai18 group
reported several all-powerful gelators capable of gelling
up a wide variety of fluids. We report here the synthesis
All synthesized esters are white powder having melting
points less than 90 °C. These compounds are dissoluble in
chloroform and tetrahydrofuran and are insoluble in meth-
anol, ethanol, water, N,N-dimethylformamide, dimethyl
sulfoxide, hexane, benzene, toluene, acetone, and ethyl
acetate at room temperature. The etherate solvents and
dichloromethane are slightly dissoluble at room tempera-
ture. Triglycerol tetra-, tri- and distearates 5, 9, and 13a
transform cooking oils into gels. The gelation ability of
synthesized esters 5, 9, and 13a was assayed by the values
of minimum gel concentration (MGC, mg/mL). The re-
sults of gelation tests of are summarized in Table 1. In
comparison with those of tetrastearate 5 at 30 mg/mL and
SYNTHESIS 2008, No. 22, pp 3663–3669
x
x.
x
x
.
2
0
0
8
Advanced online publication: 30.10.2008
DOI: 10.1055/s-0028-1083601; Art ID: F15108SS
© Georg Thieme Verlag Stuttgart · New York

3664
M. Hamada et al.
PAPER
O
O
O
O
O
O
a
b
O
O
O
O
HO
O
O
O
OH
O
OH
O
O
OBn
O
98%
quant.
OH
c
OBn
OH
1
2
3
R
R
R
R
35%
d
O
O
O
O
O
O
OH
O
O
OBn
O
93%
e
81%
R
R
R
R
5: R = stearoyl
4: R = stearoyl
c
d
SiO
O
O
OSi
OH
SiO
O
O
OSi
30%
98%
OH
OH
OH
OBn
6: Si = TBDPS
OH
7: Si = TBDPS
f
83%
SiO
O
O
OSi
HO
O
O
OH
O
O
O
O
R
O
O
a
98%
R
R
R
R
R
8: R = stearoyl, Si = TBDPS
9: R = stearoyl
c
g
98%
HO
O
O
OH
SiO
O
O
OSi
78%
OBn
OBn
OBn
OBn
R
OBn
10: Si = TBDPS
OBn
11
R
R
R
h
O
O
O
O
O
O
O
O
55%
OBn
OBn
OBn
OH
OH
OH
12a: R = stearoyl
13a: R = stearoyl
Scheme 1 Reagents and conditions: (a) NaH, THF, 0 °C, 20–30 min; BnBr, r.t., 16–20 h; (b) 80% aq AcOH, r.t., 6 h; (c) RC(O)Cl, cat. DMAP,
py, r.t.; (d) H2, Pd/C (10%), EtOH or THF–EtOH (1:1), r.t.; (e) TBDPSCl, Et3N, DMAP, CH2Cl2, r.t.; (f) TBAF, AcOH, THF, r.t.; (g) TBAF,
THF, r.t.; (h) H2, Pd(OH)2/C, THF–EtOH, 40 °C.
R
R
a
Table 1 Gelation Test of the Esters with Rapeseed Oil
O
O
O
O
11
OBn
OBn
OBn
O
Entry
Ester
Minimum gel concentrationa
12b: R = myristoyl
12c: R = palmitoyl
12d: R = arachidoyl
1
2
3
4
5
6
5
30
40
R
R
b
9
O
O
O
OH
OH
OH
13a (stearate)
13b (myristate)
13c (palmitate)
13d (arachidate)
10
13b: R = myristoyl (45%)
13c: R = palmitoyl (48%)
13d: R = arachidoyl (34%)
40
30
Scheme 2 Reagents and conditions: (a) RC(O)Cl, cat. DMAP, py,
r.t.; (b) H2, Pd(OH)2/C, THF–EtOH, 40 °C.
>40
a The gel formation was judged by test tube titling method after stand-
ing at 25 °C for 2 h. Values mean minimum gel concentration, whose
unit is mg/mL.
tristearate 9 at 40 mg/mL, distearate 13a has an effective
gelation ability at 10 mg/mL. This ability showed the
same range of TAISET®.
interesting to note that 13d was found to have a slight ge-
lation ability.
Our next attention was focused on the length of the carbon
chain of the fatty acid moiety in the esters. The myristoyl
diesters 13b, palmitoyl diesters 13c, arachidoyl diesters
13d, which had different length carbon chains in the fatty
acid moiety, were prepared from 11 by a two-step se-
quence to give 13b, 13c, and 13d in 45%, 48%, and 34%
yields, respectively (Scheme 2).
The gelation ability of esters 13a–d was also assayed for
their minimum gel concentration values (mg/mL) com-
pared to TAISET® in various oils (Table 2). TAISET® and
13a have good oil gelation ability. Stearate 13a, in partic-
ular, transforms various oils into gels at concentrations of
less than 20 mg/mL. The carbon chain length is very im-
portant for oil gelation ability: arachidate (13d) did not
show oil gelation ability even at 40 mg/mL.
The gelation ability of esters 13b–d was also assayed for
their minimum gel concentration values (mg/mL) as
shown in Table 1. It has become apparent that the gelation
ability requires a suitable length carbon chain on the fatty
acid. The gelation ability rises as the carbon chain is
lengthened from C14 to C18 (Table 1, entries 3–5). It is
To quantitatively observe this aggregation, we measured
the transmittance at 500 nm from 85 °C to 20 °C contain-
ing various concentrations of gelator under variable tem-
Synthesis 2008, No. 22, 3663–3669 © Thieme Stuttgart · New York

PAPER
Synthesis of Triglyceryl Di-, Tri-, and Tetra-Fatty Acid Esters
3665
Figure 1 (a) Aggregation curves for esters 13a–d (10 mg); (b) aggregation curve (blue line) and dissociation curve (purple) for ester 13a
(10 mg).
Table 2 Gelation Test of the Diesters for Oils
Table 3 The Apparent Critical Aggregation Temperatures (°C)
Minimum gel concentrationa
Amount of ester 13a
13b
13c
13d
(mg)
stearate
myristate
palmitate arachidate
Oil
13a
10
10
10
20
13b
40
13c
30
13d
>40
>40
>40
>40
TAISET®
1
37.6
57.1
63.0
67.3
73.9
34.8
47.1
52.7
58.8
64.2
36.5
54.1
59.1
64.9
77.1
41.7
56.9
64.2
68.2
72.9
rapeseed
soybean
sunflower seed
sesame
10
15
10
35
5
30
>40
40
10
20
40
30
30
>40
a The gel formation was judged by test tube titling method after stand-
ing at 25 °C for 2 h. Values mean minimum gel concentration, whose
unit is mg/mL.
Melting points were measured with a Yanagimoto micro melting
point apparatus and are uncorrected. IR spectra were measured with
a Shimazu OR-800 spectrophotometer. ATR-IR spectra were mea-
sured with a Perkin-Elmer Spectrum 100 spectrometer equipped
with Universal ATR accessory. 1H and 13C NMR spectra were re-
corded on a Bruker Biospin Avance II 400 spectrometer or a Jeol
JNM LA-400 spectrometer using TMS or solvent peak as an inter-
nal standard. LR- and HRMS (FAB) spectra were recorded on a Jeol
JMS-AX500 spectrometer. LR-ESI or APCI-MS spectra were re-
corded on an Agilent Technology 1100 LC-MSD spectrometer
flowing a mixed soln of MeOH or MeCN and H2O or diluted
AcOH. HRMS (ESI) spectra were recorded on a Bruker Daltonics
micrOTOF focus spectrometer. The transmittance in Figure 1 was
measured on a Jasco V-550 UV-Vis spectrophotometer with non-
adding rapeseed oil as a blank. Analytical TLC was conducted on
precoated TLC plate (silica gel 60F254, Merck). Column chromatog-
raphy was performed using Kanto Chemical silica gel 60N (70–230
mesh). All reagents were used of commercial quality. THF and
CH2Cl2 were used of Kanto Chemical dehydrated grade without pu-
rification. All air- and moisture-sensitive reactions were carried out
under inert gas (N2 or argon).
peratures. The aggregation curves of rapeseed oil with 10
mg of each of esters 13a–d is showed in Figure 1(a). In all
cases, the transmittance value suddenly decreased after a
certain temperature. This temperature was read from each
spectrum and is regarded an apparent critical aggregation
temperature (CAT).
As shown in Table 3, the critical aggregation tempera-
tures increased when the amount of ester increased and
also the carbon chain lengthened. On the other hand, dis-
sociation curves were depicted by the measurement of
transmittance at 500 nm from 20 °C to 85 °C. In the all
samples, a hysteresis curve was observed. The apparent
critical dissociation temperatures were higher than the
critical aggregation temperatures and dissociation curves
were a gentler slope than the aggregation curves [see
Figure 1(b)].
In conclusion, we have developed new gelators, triglycer-
yl di-, tri-, tetra-fatty acid esters, with well-defined struc- Compound 1 was supplied from Riken Vitamin Co., Ltd. TAISET®
and rapeseed oil were supplied from Taiyo Chemical Co., Ltd.
ture. The triglyceryl ester gelators exhibit prominent
gelation ability and gel up a wide variety of oils. The mea-
surement of transmittance at 500 nm could be the apprais-
al standard for the aggregation level.
6-(Benzyloxy)-1,2;10,11-bis(isopropylidenedioxy)-4,8-dioxa-
undecane (2)
To a suspension of NaH (60% in oil, 449 mg, 18.7 mmol) in THF
(60 mL) was added a soln of 1,2;10,11-bis(isopropylidenedioxy)-
Synthesis 2008, No. 22, 3663–3669 © Thieme Stuttgart · New York

3666
M. Hamada et al.
PAPER
4,8-dioxaundecan-6-ol (1, 3.0 g, 9.36 mmol) in THF (30 mL) at 0
°C; the mixture was stirred at this temperature for 20 min. BnBr
(2.41 g, 14.1 mmol) was added to the mixture at 0 °C and then the
mixture was warmed to r.t. and stirred for 20 h. When the reaction
was complete (TLC), the mixture was treated with H2O and extract-
ed with EtOAc. The organic layer was washed with brine and dried
(Na2SO4). The solvent was removed under reduced pressure and the
residual oil was purified by column chromatography (silica gel,
hexane–EtOAc, 4:1) to give 2 (3.74 g, 98%) as a colorless oil;
Rf = 0.41 (hexane–EtOAc, 2:1).
13C NMR (100 MHz, CDCl3): d = 14.1, 14.2, 20.7, 20.9(8), 21.0,
22.7, 24.7, 24.8(8), 24.9, 29.1(0), 29.1(4), 29.2, 29.3, 29.3(5), 29.4,
29.5, 29.6(5), 29.7, 31.9, 33.7, 34.1, 34.3, 60.4, 62.5, 62.6, 62.9,
69.8, 69.8(5), 69.9, 70.3, 71.6, 72.4, 127.6, 127.7, 128.3, 138.4,
170.6, 171.1, 173.1, 173.4.
MS (ESI): m/z (%) = 1418 (100) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C88H162NaO11: 1418.2009;
found: 1418.2033.
1,2,10,11-Tetrakis(stearoyloxy)-4,8-dioxaundecan-6-ol (5)
A soln of 4 (1.02 g, 0.73 mmol) and Pd-C (10% containing Pd, 77
mg) in THF (10 mL) and EtOH (10 mL) was stirred at r.t. for 1 d
under a H2 atmosphere. When the reaction was complete, the mix-
ture was filtered and concentrated under reduced pressure. The re-
sidual solid was purified by column chromatography (silica gel,
CHCl3–MeOH, 100:1) to give 5 (886 mg, 93%) as a white solid; mp
57–58 °C (EtOAc); Rf = 0.40 (CHCl3–MeOH, 100:1).
IR (neat): 2986, 2936, 2874, 1497, 1456, 1379, 1372, 1256, 1213,
1144, 1055 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.34 (s, 6 H, CH3 of acetonide),
1.39 (s, 6 H, CH3 of acetonide), 3.46 (q, J = 5.4 Hz, 2 H, H2, H10),
3.51–3.63 (m, 6 H), 3.69–3.75 (m, 3 H), 4.01 (t, J = 7.2 Hz, 2 H),
4.24 (q, J = 5.8 Hz, 2 H), 4.65 (s, 2 H, benzylic), 7.24–7.34 (m, 5 H,
Ar-H).
13C NMR (100 MHz, CDCl3): d = 25.4, 26.7, 66.7(2), 66.7(4), 66.8,
71.6, 72.2(6), 72.3(3), 72.3(9), 72.4, 74.6, 127.6, 127.7, 127.7(1),
127.7(3), 128.3.
MS (FAB): m/z (%) = 411 (13) [M + H]+, 395 (14), 114 (28), 91
(100).
HRMS (FAB): m/z [M + H]+ calcd for C22H35O7: 411.2383; found:
411.2390.
IR (neat): 2910, 2850, 1730 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.88 (t, J = 6.6 Hz, 12 H, CH3),
1.25 (s, 112 H, CH2 of fatty acid), 1.60–1.61 (m, 8 H, CH2 of fatty
acid), 2.28–2.34 (m, 8 H, CH2 of fatty acid), 3.45–3.66 (m, 8 H),
3.90 (br s, 1 H, OH), 4.13–4.18 (m, 2 H), 4.30–4.35 (m, 2 H), 5.18–
5.23 (m, 2 H, H2, H10).
13C NMR (100 MHz, CDCl3): d = 14.1, 22.7, 24.8(9), 24.9, 29.1(0),
29.1(4), 29.3, 29.4, 29.5, 29.6(6), 29.7, 31.9, 34.1, 34.3, 62.5, 69.9,
173.4.
6-(Benzyloxy)-4,8-dioxaundecane-1,2,10,11-tetraol (3)
A soln of 2 (2.47 g, 6.0 mmol) in 80% aq AcOH (60 mL) was stirred
at r.t. for 6 h, followed by concentration under reduced pressure to
give tetraol 3 (1.98 g, quant.) as a colorless oil. This compound was
used in the next step without further purification.
MS (FAB): m/z (%) = 1329 (13) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C81H156NaO11: 1328.1540;
found: 1328.1539.
IR (neat): 3600–3200, 3090, 3063, 3032, 2876, 2244, 1717, 1500,
1455, 1395, 1352, 1256, 1115, 1049, 926, 866, 739, 700 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.47–3.75 (m, 13 H), 3.82–3.86
(m, 2 H, H2, H10), 4.63 (s, 2 H, benzylic), 7.26–7.37 (m, 5 H, Ar-
H).
13C NMR (100 MHz, CDCl3): d = 63.7, 70.5(9), 70.6(4), 70.7, 72.0,
72.8, 73.0, 76.4, 127.9, 128.5, 137.8.
MS (FAB): m/z (%) = 353 (66) [M + Na]+, 331 (61) [M + H]+, 131
(11), 92 (100).
6-(Benzyloxy)-1,11-bis(tert-butyldiphenylsiloxy)-4,8-dioxa-
undecane-2,10-diol (6)
To a soln of 3 (10.4 g, 31.5 mmol), Et3N (13.15 g, 0.13 mol), and
DMAP (1.93 g, 15.8 mmol) in CH2Cl2 (300 mL) was added
TBDPSCl (18.2 g, 66.2 mmol) at 0 °C. The mixture was stirred at
r.t. for 1 d. When the reaction was complete, the mixture was treated
with H2O and extracted with CH2Cl2. The organic layer was washed
with brine and dried (Na2SO4). The solvent was removed under re-
duced pressure and the residual oil was purified by column chroma-
tography (silica gel, hexane–EtOAc, 3:1) to give disilyl ether 6
(20.5 g, 81%) as a colorless oil; Rf = 0.27 (hexane–EtOAc, 3:2).
HRMS (FAB): m/z [M + H]+ calcd for C16H27O7: 331.1757; found:
331.1749.
IR (neat): 3600–3200, 3071, 3049, 2955, 2930, 2859, 2361, 1590,
1472, 1428, 1391, 1362, 1188, 1113, 1028, 999, 939, 824, 741, 702,
613, 505, 492, 419 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.08 [s, 18 H, C(CH3)3], 2.66–2.73
(br, 2 H, OH), 3.48–3.61 (m, 7 H), 3.70 (d, J = 4.8 Hz, 4 H), 3.89
(br, 2 H, CH), 4.63 (s, 2 H, benzylic), 7.22–7.31 (m, 5 H, Bn), 7.35–
7.45 (m, 12 H, Ph-H), 7.66–7.68 (m, 8 H, Ph-H).
13C NMR (100 MHz, CDCl3): d = 19.3, 21.1, 26.9, 60.4, 64.7(9),
64.8(2), 70.7(1), 70.7(4), 71.4(9), 71.5(5), 72.3, 72.5, 127.6, 127.8,
128.3, 129.8, 133.2, 135.5, 138.4.
6-(Benzyloxy)-1,2,10,11-tetrakis(stearoyloxy)-4,8-dioxaundec-
ane (4); Typical Procedure for the Esterification of Triglycerol
Derivatives
To a soln of alcohol 3 (2.17 g, 6.56 mmol) and DMAP (1.60 g, 13.1
mmol) in pyridine (40 mL) was added stearoyl chloride (7.54 g,
24.9 mmol) at r.t. and the mixture was stirred at r.t. for 18 h. When
the reaction was complete, the mixture was treated with MeOH (10
mL) and concentrated under reduced pressure. The residual mixture
was diluted with CHCl3, washed with brine, and dried (Na2SO4).
The solvent was removed under reduced pressure and the residue
was purified by column chromatography (silica gel, hexane–
EtOAc, 7:1) and by PTLC (silica gel 60F254, Merck, hexane–
EtOAc, 5:1) to give tetraester 4 (3.21 g, 35%) as a white solid; mp
45–47 °C (hexane–EtOAc); Rf = 0.80 (hexane–EtOAc, 3:1).
MS (FAB): m/z (%) = 830 (100) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C48H62NaO7Si2: 829.3926;
found: 829.3914.
1,11-Bis(tert-butyldiphenylsiloxy)-4,8-dioxaundecane-2,6,10-
triol (7)
A mixture of diol 6 (2.22 g, 3.10 mmol) and Pd-C (10% containing
Pd, 328 mg) in EtOH (40 mL) was stirred at r.t. for 1 d under a H2
atmosphere. When the reaction was complete, the mixture was fil-
tered and concentrated under reduced pressure to give pure 7 (2.17
g, 98%) as a colorless oil; Rf = 0.13 (hexane–EtOAc, 1:1).
IR (neat): 2910, 2845, 1743, 1738 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.88 (t, J = 6.6 Hz, 12 H, CH3),
1.25 (s, 112 H, CH2 of fatty acid), 1.56–1.61 (m, 8 H, CH2 of fatty
acid), 2.27–2.32 (m, 8 H, CH2 of fatty acid), 3.50–3.69 (m, 8 H),
3.83 (br s, 1 H, OH), 4.11–4.16 (m, 2 H), 4.31–4.33 (m, 2 H), 4.65–
4.66 (m, 2 H), 5.05–5.35 (br, 2 H, CH), 7.33–7.52 (m, 5 H, Ar-H).
Synthesis 2008, No. 22, 3663–3669 © Thieme Stuttgart · New York

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Synthesis of Triglyceryl Di-, Tri-, and Tetra-Fatty Acid Esters
3667
IR (ATR, neat): 3370, 3071, 3049, 2930, 2857, 1589, 1472, 1427,
1104, 1006, 998, 823, 739, 699 cm–1.
2,6,10-Tris(benzyloxy)-1,11-bis(tert-butyldiphenylsiloxy)-4,8-
dioxaundecane (10)
To a mixture of NaH (60% in oil, 12.7 g, 0.32 mol) in THF (250
mL) was added a soln of 6 (64.1 g, 79.3 mmol) in THF (250 mL) at
0 °C; the mixture was stirred at this temperature for 30 min. BnBr
(40.7 g, 0.24 mol) was added and the mixture was stirred at r.t. for
16 h. When the reaction was complete, the mixture was treated with
50% aq THF at 0 °C and the solvent was removed under reduced
pressure. The residual oil was diluted with H2O and EtOAc. The
mixed soln was extracted with EtOAc. The organic layer was
washed with H2O and brine and dried (Na2SO4). The solvent was re-
moved under reduced pressure and the residual oil was purified by
column chromatography (silica gel, hexane–EtOAc, 9:1) to give 10
(76.4 g, 98%) as a colorless oil; Rf = 0.67 (hexane–EtOAc, 3:2).
1H NMR (400 MHz, CDCl3): d = 1.05 [s, 18 H, C(CH3)3], 3.03 (br,
3 H, OH), 3.43–3.60 (m, 8 H), 3.66 (d, J = 5.6 Hz, 4 H, H1, H11),
3.86–3.93 (m, 3 H), 7.35–7.44 (m, 12 H, Ar-H), 7.63–7.65 (m, 8 H,
Ar-H).
13C NMR (100 MHz, CDCl3): d = 19.2, 26.8, 64.6(6), 64.6(8), 69.5,
70.7(8), 70.8(2), 72.4(8), 72.5(8), 72.6(6), 72.7(0), 77.2, 127.8,
129.8, 133.1, 135.5.
MS (ESI): m/z (%) = 739 (100) [M + Na]+, 561 (28), 483 (8).
HRMS (ESI): m/z [M + Na]+ calcd for C41H56NaO7Si2: 739.3457;
found: 739.3439.
IR (neat): 3071, 3033, 3000, 2957, 2930, 2859, 1590, 1497, 1472,
1428, 1391, 1113, 1028, 911, 824, 735, 700, 648, 613, 505 cm–1.
1,11-Bis(tert-butyldiphenylsiloxy)-2,6,10-tris(stearoyloxy)-4,8-
dioxaundecane (8)
1H NMR (400 MHz, CDCl3): d = 1.04 [s, 18 H, C(CH3)3], 3.53–3.75
(m, 15 H), 4.62 (s, 6 H, benzylic), 7.23–7.40 (m, 27 H, Ar-H), 7.66
(AB q, J = 7.8, 1.5 Hz, 8 H, Ph-H).
13C NMR (100 MHz, CDCl3): d = 19.3, 26.9, 63.9, 71.7, 71.8, 72.1,
72.3, 72.4, 77.2, 78.8(9), 78.9(1), 127.4(7), 127.5(5), 127.5(8),
127.6(9), 127.7(5), 128.1, 128.2(9), 128.3(2), 129.6(1), 129.6(9),
129.7(2), 133.4(9), 133.5(4), 134.9, 135.6(6), 135.6(9), 135.9(8),
135.9(9), 138.8(0), 138.9.
Following the typical procedure for 4, 8 (962 mg, 30%) was ob-
tained as an amorphous solid; Rf = 0.39 (hexane–EtOAc, 6:1).
IR (ATR, neat): 2923, 2854, 1739, 1591, 1465, 1429, 1113, 824,
740, 700 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.88 (t, J = 6.8 Hz, 9 H, CH3 of
fatty acid), 1.03 [s, 18 H, C(CH3)3], 1.25 (s, 84 H, CH2 of fatty acid),
1.55–1.60 (m, 6 H, CH2 of fatty acid), 2.21–2.28 (m, 6 H, CH2 of
fatty acid), 3.52–3.61 (m, 8 H), 3.76 (d, J = 4.9 Hz, 4 H, H1, H11),
5.04–5.07 (m, 3 H, CH), 7.37–7.41 (m, 12 H, Ar-H), 7.63–7.65 (m,
8 H, Ar-H).
13C NMR (100 MHz, CDCl3): d = 14.1, 19.2, 22.7, 24.9, 26.7, 29.1,
29.2, 29.3, 29.4, 29.5, 29.6(7), 29.7(2), 31.9, 34.4, 62.5, 69.7, 69.9,
72.5, 127.7, 129.7, 133.2, 133.3, 135.5, 135.6, 173.1.
MS (ESI): m/z (%) = 1009.5 (59) [M + Na]+, 919 (100), 829 (37).
HRMS (FAB): m/z [M + Na]+ calcd for C62H74NaO7Si2: 1009.4871;
found: 1009.4842.
2,6,10-Tris(benzyloxy)-4,8-dioxaundecane-1,11-diol (11)
To a soln of 10 (12.2 g, 12.3 mmol) in THF (63 mL) was added 1.0
M TBAF in THF (37.0 mL, 37.0 mmol) at 0 °C; the mixture was
stirred at r.t. for 6 h. When the reaction was complete, the solvent
was removed under reduced pressure and the residual oil was puri-
fied by column chromatography (silica gel, hexane–EtOAc, 1:1 to
1:4) to give 11 (6.17 g, 98%) as a colorless oil; Rf = 0.20 (CHCl3–
MeOH, 9:1).
MS (ESI): m/z (%) = 1542 (10), 1541 (29), 1540 (69), 1539 (100),
1538 (95) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C95H158NaO10Si2: 1538.1286;
found: 1538.1279.
2,6,10-Tris(stearoyloxy)-4,8-dioxaundecane-1,11-diol (9)
To a soln of 8 (937 mg, 0.62 mmol) in THF (15 mL) was added
AcOH (445 mg, 7.41 mmol) and 1.0 M TBAF in THF (3.71 mL,
3.71 mmol); the mixture was stirred at r.t. for 20 h. When the reac-
tion was complete, the mixture was treated with sat. aq NH4Cl and
extracted with CHCl3. The organic layer was washed with brine and
dried (Na2SO4). The solvent was removed under reduced pressure
and the residue was purified by column chromatography (silica gel,
CHCl3–MeOH, 10:1) to give 9 (532 mg, 83%) as a white solid; mp
59–61 °C (EtOAc); Rf = 0.29 (hexane–EtOAc, 3:2).
IR (neat): 3434, 3088, 3063, 3031, 2872, 1497, 1455, 1208, 911,
737, 698 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.25 (br, 2 H, OH), 3.56–3.72 (m,
15 H), 4.54–4.70 (m, 6 H, benzylic), 7.25–7.38 (m, 15 H, Ar-H).
13C NMR (100 MHz, CDCl3): d = 62.4(6), 62.4(9), 62.5(8), 62.6(1),
71.3, 71.3(8), 71.4(0), 71.4(5), 71.5(1), 71.5(4), 71.6, 72.1, 72.2,
72.3, 76.9, 77.9, 127.7, 127.7(8), 127.8(1), 128.3, 128.4, 128.5,
138.3, 138.4.
MS (FAB): m/z (%) = 511 (100) [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C30H38NaO7: 533.2510;
IR (ATR, neat): 3440, 2916, 2850, 1734, 1468, 1195, 1178, 1105,
721 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.88 (t, J = 6.8 Hz, 9 H, CH3 of
fatty acid), 1.25 (s, 84 H, CH2 of fatty acid), 1.59–1.62 (m, 6 H, CH2
of fatty acid), 2.31–2.36 (m, 6 H, CH2 of fatty acid), 3.48–3.78 (m,
10 H), 3.99–4.18 (m, 2 H), 4.97–4.99 (m, 2 H, CH), 5.11–5.14 (m,
1 H, CH).
13C NMR (100 MHz, CDCl3): d = 14.1, 22.7, 24.9, 25.0, 29.1, 29.2,
29.3, 29.4, 29.5, 29.6, 29.6(7), 29.7(1), 31.9, 34.2, 34.3, 65.2, 68.8,
69.9, 72.5, 77.2, 173.6, 174.0.
MS (FAB): m/z (%) = 1062 (41) [M + Na]+, 681 (22), 341 (98), 176
(49), 97 (34), 91 (40), 84 (49), 82 (48), 72 (54), 70 (64), 58 (100),
56 (88).
HRMS (ESI): m/z [M + Na]+ calcd for C63H122NaO10: 1061.8930;
found: 1061.8930.
found: 533.2520.
2,6,10-Tris(benzyloxy)-1,11-bis(stearoyloxy)-4,8-dioxaundec-
ane (12a)
Following the typical procedure for 4 using stearoyl chloride gave
12a (78% yield) as a colorless amorphous; Rf = 0.60 (hexane–
EtOAc, 3:1).
IR (neat): 3032, 2924, 2853, 1740, 1497, 1115, 735, 696 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.81 (t, J = 6.6 Hz, 6 H, CH3 of
fatty acid), 1.18 (s, 56 H, CH2 of fatty acid), 1.49–1.57 (m, 4 H, CH2
of fatty acid), 2.22 (t, J = 7.6 Hz, 4 H, CH2 of fatty acid), 3.57–3.70
(m, 8 H), 3.75–3.80 (m, 3 H), 4.06 (dd, J = 11.7, 5.8 Hz, 2 H, H1 or
H11), 4.19–4.23 (m, 2 H, H1 or H11), 4.58 (s, 4 H, benzylic), 4.59
(s, 2 H, benzylic), 7.19–7.26 (m, 15 H, Ar-H).
13C NMR (100 MHz, CDCl3): d = 14.1, 22.7, 25.0, 29.1, 29.2, 29.3,
29.3(6), 29.4(3), 29.5, 29.6, 29.6(6), 29.7(0), 31.9, 34.1(5), 34.2(3),
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M. Hamada et al.
PAPER
63.4, 63.6, 71.1(7), 71.2(2), 71.7, 71.8, 72.2, 72.4, 72.7, 75.8, 126.8,
127.0, 127.6, 127.6(7), 127.7(0), 127.7(3), 127.9(8), 128.1,
128.3(2), 128.3(5), 128.3(9), 128.4(2), 129.0, 129.8, 130.1, 133.1,
134.5, 138.2, 138.5, 173.5, 173.7.
of fatty acid), 2.27 (t, J = 7.3 Hz, 4 H, CH2 of fatty acid), 3.50–3.58
(m, 8 H), 3.69–3.77 (m, 3 H, CH), 4.10 (dd, J = 7.1, 5.1 Hz, 2 H, H1
or H11), 4.25 (dt, J = 11.7, 3.9 Hz, 2 H, H1 or H11), 4.63 (s, 4 H,
benzylic), 4.64 (s, 2 H, benzylic), 7.22–7.31 (m, 15 H, Ar-H).
MS (APCI): m/z (%) = 1066 (5) [M + Na]+, 1026 (13), 950 (24), 936
(66), 846 (41), 738 (89), 431 (100), 341 (69).
HRMS (ESI): m/z [M + Na]+ calcd for C66H106NaO9: 1065.7729;
found: 1065.7757.
13C NMR (100 MHz, CDCl3): d = 14.1, 14.2, 22.7, 24.9, 29.1,
29.2(7), 29.3(3), 29.5, 29.6(0), 29.6(3), 29.7, 31.9, 34.2, 63.6, 71.1,
71.7, 71.8, 72.2, 72.3, 75.7(8), 75.8(0), 127.5, 127.6, 127.6(5),
127.6(8), 128.2(9), 128.3(1), 138.2, 138.5, 173.6.
MS (ESI): m/z (%) = 1122 (100) [M + Na]+.
2,6,10-Tris(benzyloxy)-1,11-bis(myristoyloxy)-4,8-dioxaundec-
ane (12b)
Following the typical procedure for 4 using myristoyl chloride gave
12b (100% yield) as a colorless amorphous; Rf = 0.80 (hexane–
EtOAc, 2:1).
HRMS (ESI): m/z [M + Na]+ calcd for C70H114NaO9: 1121.8361;
found: 1121.8377.
Debenzylation of Triglyceryl Di-Fatty Acid Esters; General
Procedure
IR (neat): 2924, 2855, 1740, 1497, 1466, 1455, 1113, 911, 735, 696
cm–1.
A mixture of diester 12a–d (2.00 mmol) and Pd(OH)2-C (20% con-
taining Pd, 400 mg) in THF (30 mL) and EtOH (15 mL) was stirred
at 40 °C under a H2 atmosphere. After stirring overnight, the mix-
ture was filtered and concentrated under reduced pressure. The res-
idue was purified by recrystallization (EtOAc) to give the desired
ester as a white solid.
1H NMR (400 MHz, CDCl3): d = 0.86 (t, J = 6.8 Hz, 6 H, CH3 of
fatty acid), 1.23 (s, 40 H, CH2 of fatty acid), 1.56–1.61 (m, 4 H, CH2
of fatty acid), 2.22–2.36 (m, 4 H, CH2 of fatty acid), 3.52–3.57 (m,
8 H), 3.70–3.75 (m, 3 H, CH), 4.10 (dd, J = 6.8, 5.4 Hz, 2 H, H1 or
H11), 4.25 (dt, J = 11.7, 3.9 Hz, 2 H, H1 or H11), 4.59–4.68 (m, 6
H, benzylic), 7.24–7.34 (m, 15 H, Ar-H).
13C NMR (100 MHz, CDCl3): d = 14.1, 22.7, 25.0, 29.1, 29.2, 29.3,
29.4, 29.5, 29.6, 29.6(7), 29.7(0), 31.9, 34.2, 63.6, 71.2, 71.3, 71.7,
71.8, 72.1(9), 72.2(0), 72.4, 75.8, 75.9, 127.6, 127.6(7), 127.7(1),
127.7(4), 128.2, 128.3, 128.4, 138.3, 138.6, 173.6.
MS (FAB): m/z (%) = 954 (1), [M + Na]+, 375 (5), 285 (9), 181 (18),
91 (100).
HRMS (ESI): m/z [M + Na]+ calcd for C58H90NaO9: 953.6477;
found: 953.6459.
1,11-Bis(stearoyloxy)-4,8-dioxaundecane-2,6,10-triol (13a)
Yield: 55%; mp 82–83 °C (EtOAc); Rf = 0.10 (CHCl3–EtOAc, 1:1).
IR (ATR, neat): 3367, 2956, 2917, 2850, 1732, 1471, 1122, 1033,
1011, 887, 719 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.86 (t, J = 6.6 Hz, 6 H, CH3 of
fatty acid), 1.23 (s, 56 H, CH2 of fatty acid), 1.55–1.65 (m, 4 H, CH2
of fatty acid), 2.31 (t, J = 7.6 Hz, 4 H, CH2 of fatty acid), 3.47–3.58
(m, 8 H), 3.96–4.01 (m, 3 H, CH), 4.13 (qd, J = 10.5, 5.8 Hz, 4 H,
H1, H11).
13C NMR (100 MHz, CDCl3): d = 14.1, 22.7, 24.9, 29.1, 29.3, 29.4,
29.5, 29.6, 29.6(5), 29.6(8), 31.9, 34.2, 65.2, 69.0, 72.5, 72.7, 174.0.
2,6,10-Tris(benzyloxy)-1,11-bis(palmitoyloxy)-4,8-dioxaundec-
ane (12c)
MS (FAB): m/z (%) = 796 (100) [M + Na]+, 341 (15), 176 (15).
Following the typical procedure for 4 using palmitoyl chloride gave
12c (88% yield) as a colorless amorphous solid; Rf = 0.50 (hexane–
EtOAc, 3:1).
HRMS (FAB): m/z [M + Na]+ calcd for C45H88NaO9: 795.6308;
found: 795.6308.
IR (neat): 2923, 2853, 1740, 1497, 1466, 1455, 1113, 911, 735, 696
cm–1.
1,11-Bis(myristoyloxy)-4,8-dioxaundecane-2,6,10-triol (13b)
Yield: 45%; mp 94–96 °C (EtOAc); Rf = 0.10 (CHCl3–EtOAc, 1:1).
1H NMR (400 MHz, CDCl3): d = 0.86 (t, J = 6.8 Hz, 6 H, CH3 of
fatty acid), 1.23 (s, 48 H, CH2 of fatty acid), 1.55 (s, 4 H, CH2 of
fatty acid), 2.30 (dt, J = 22.9, 7.8 Hz, 4 H, CH2 of fatty acid), 3.52–
3.57 (m, 8 H), 3.70–3.75 (m, 3 H, CH), 4.15 (dd, J = 6.5, 5.6 Hz, 2
H, H1 or H11), 4.30 (dt, J = 11.5, 3.6 Hz, 2 H, H1 or H11), 4.66 (s,
4 H, benzylic), 4.68 (s, 2 H, benzylic), 7.24–7.31 (m, 15 H, Ar-H).
13C NMR (100 MHz, CDCl3): d = 14.1, 22.7, 24.7, 29.1, 29.2, 29.3,
29.4, 29.5, 29.6, 29.6(6), 29.7(0), 31.9, 34.2, 63.6, 71.1(8), 71.2(4),
71.7, 71.8, 72.2, 72.4, 75.8(2), 75.8(4), 127.6, 127.6(7), 127.6(9),
127.7, 128.3, 128.4, 138.2, 138.6, 173.7.
IR (ATR, neat): 3528, 3431, 2917, 2850, 1727, 1472, 1118, 1033,
1012, 888, 716 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.88 (t, J = 6.6 Hz, 6 H, CH3 of
fatty acid), 1.23 (s, 40 H, CH2 of fatty acid), 1.53–1.60 (m, 4 H, CH2
of fatty acid), 2.32 (t, J = 7.6 Hz, 4 H, CH2 of fatty acid), 3.51–3.59
(m, 8 H), 3.93–4.02 (m, 3 H, CH), 4.29 (qd, J = 7.1, 5.8 Hz, 4 H,
H1, H11).
13C NMR (100 MHz, CDCl3): d = 14.1, 22.7, 24.9, 29.1, 29.3, 29.4,
29.5, 29.6(0), 29.6(3), 29.7, 31.9, 34.2, 65.2, 69.0, 72.5, 72.7, 174.0.
MS (ESI): m/z (%) = 684 (100) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C37H72NaO9: 683.5074;
MS (APCI): m/z (%) = 1010 (10) [M + Na]+, 970 (37), 880 (100),
790 (67).
HRMS (ESI): m/z [M + Na]+ calcd for C62H98NaO9: 1009.7103;
found: 683.5068.
found: 1009.7118.
1,11-Bis(palmitoyloxy)-4,8-dioxaundecane-2,6,10-triol (13c)
Yield: 55%; mp 79–80 °C (EtOAc); Rf = 0.10 (CHCl3–EtOAc, 1:1).
1,11-Bis(arachidoyloxy)-2,6,10-tris(benzyloxy)-4,8-dioxa-
undecane (12d)
Following the typical procedure for 4 using arachidoyl chloride
(prepared from arachidic acid and SOCl2) gave 12d (100% yield) as
a colorless amorphous solid; Rf = 0.80 (hexane–EtOAc, 2:1).
IR (ATR, neat): 3369, 2917, 2850, 1735, 1467, 1124, 1029, 886,
720 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.85 (t, J = 6.3 Hz, 6 H, CH3 of
fatty acid), 1.23 (s, 48 H, CH2 of fatty acid), 1.55 (s, 4 H, CH2 of
fatty acid), 2.32 (t, J = 7.3 Hz, 4 H, CH2 of fatty acid), 3.52–3.59 (m,
8 H), 3.91–4.02 (m, 3 H, CH), 4.08 (qd, J = 13.9, 4.6 Hz, 4 H, H1,
H11).
IR (neat): 2919, 2851, 1736, 1497, 1464, 1456, 1115, 909, 733, 698,
648 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.86 (t, J = 6.6 Hz, 6 H, CH3 of
fatty acid), 1.23 (s, 64 H, CH2 of fatty acid), 1.56–1.59 (m, 4 H, CH2
Synthesis 2008, No. 22, 3663–3669 © Thieme Stuttgart · New York

PAPER
Synthesis of Triglyceryl Di-, Tri-, and Tetra-Fatty Acid Esters
3669
13C NMR (100 MHz, CDCl3): d = 14.1, 22.7, 24.9, 29.1, 29.3, 29.4,
29.5, 29.6(0), 29.6(5), 29.6(8), 31.9, 34.2, 65.2, 69.0, 72.5, 72.7,
174.0.
MS (FAB): m/z (%) = 740 (8) [M + Na]+, 575 (12), 483 (25), 391
(56), 369 (60).
HRMS (ESI): m/z [M + Na]+ calcd for C41H80NaO9: 739.5695;
found: 739.5712.
(8) Serbrryakov, E. P.; Abylgaziev, R. I. Bull. Acad. Sci. USSR,
Div. Chem. Sci. (Engl. Transl.) 1986, 34, 1916.
(9) Cassel, S.; Debaig, C.; Benvegnu, T.; Chaimbault, P.;
Lafosse, M.; Plusquellec, D.; Rollin, P. Eur. J. Org. Chem.
2001, 875.
(10) Kawagishi, T.; Yoshikawa, K.; Ubukata, M.; Hamada, M.;
Nakajima, N. Heterocycles 2007, 69, 107.
(11) (a) Terech, P.; Weiss, R. G. Chem. Rev. 1997, 97, 3133.
(b) Van Esch, L. A.; Feringa, B. L. Angew. Chem. Int. Ed.
2000, 39, 2263. (c) Estroff, L. A.; Hamilton, A. D. Chem.
Rev. 2004, 104, 1201.
1,11-Bis(arachidoyloxy)-4,8-dioxaundecane-2,6,10-triol (13d)
Yield: 34%; mp 86–87 °C (EtOAc); Rf = 0.10 (CHCl3–EtOAc, 1:1).
(12) Tachibana, T.; Mori, T.; Hori, K. Bull. Chem. Soc. Jpn.
1980, 53, 1714.
(13) Honma, M. Gendai Kagaku 1987, 54.
(14) Yamamoto, S. Kogyo Kagaku Zasshi 1943, 46, 279; Chem.
Abstr. 1952, 46, 7047i.
IR (ATR, neat): 3363, 2917, 2850, 1735, 1468, 1177, 1108, 885,
720 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.86 (t, J = 6.6 Hz, 6 H, CH3 of
fatty acid), 1.23 (s, 64 H, CH2 of fatty acid), 1.60 (t, J = 7.1 Hz, 4 H,
CH2 of fatty acid), 2.32 (t, J = 7.3 Hz, 4 H, CH2 of fatty acid), 3.42–
3.59 (m, 8 H), 3.95–4.00 (m, 3 H, CH), 4.13 (qd, J = 13.9, 4.4 Hz,
4 H, H1, H11).
13C NMR (100 MHz, CDCl3): d = 14.1, 22.7, 24.9, 29.1, 29.3, 29.4,
29.5, 29.6, 29.7, 31.9, 34.2, 65.2, 72.3, 172.5.
(15) Hafkamp, R. J. H.; Kokke, B. P. A.; Danke, I. M.; Geurts, H.
P. M.; Rowan, A. E.; Feiters, M. C.; Nolte, R. J. M. Chem.
Commun. 1997, 545.
(16) TAISET® is the 1:1 mixture of the triglyceryl pentastearate
and monoglyceryl monobehenate, which is commercially
available from Taiyo Kagaku Co., Ltd
MS (APCI): m/z (%) = 852 (13) [M + Na]+, 794 (100), 639 (27), 549
(36), 517 (77).
(http://www.taiyokagaku.com/).
(17) (a) Hanabusa, K.; Tange, J.; Taguchi, Y.; Koyama, T.;
Shirai, Y. Chem. Commun. 1993, 390. (b) Hanabusa, K.;
Miki, T.; Taguchi, Y.; Koyama, T.; Shirai, H. Chem.
Commun. 1993, 1382. (c) Hanabusa, K.; Kawakami, A.;
Kimura, M.; Shirai, H. Chem. Lett. 1997, 191.
(d) Hanabusa, K.; Matsumoto, M.; Kimura, M.; Kakehi, A.;
Shirai, H. J. Colloid Interface Sci. 2000, 224, 231.
(e) Hanabusa, K.; Nakayama, H.; Kimura, M.; Shirai, H.
Chem. Lett. 2000, 1070. (f) Sakamoto, A.; Ogata, D.;
Shikata, T.; Hanabusa, K. Macromolecules 2005, 38, 8983.
(g) Hanabusa, K.; Fukui, H.; Suzuki, M.; Shirai, Y.
Langmuir 2005, 21, 10383.
(18) (a) Yoza, K.; Ono, Y.; Yoshihata, K.; Akao, T.; Shinmori,
H.; Takeuchi, M.; Shinkai, S.; Reinhoudt, D. N. Chem.
Commun. 1998, 907. (b) Inoue, K.; Ono, Y.; Kanekiyo, Y.;
Kiyanaka, S.; Hamachi, I.; Shinkai, S. Chem. Lett. 1999,
225. (c) Inoue, K.; Ono, Y.; Kanekiyo, Y.; Hanabusa, K.;
Shinkai, S. Chem. Lett. 1999, 429.
HRMS (ESI): m/z [M + Na]+ calcd for C49H96NaO9: 851.6947;
found: 851.6946.
Acknowledgment
We gratefully acknowledge the financial support from the Scholar-
ship Foundation of First bank of Toyama.
References and Notes
(1) Kaufman, V. R. J. Am. Oil Chem. Soc. 1982, 59, 471.
(2) McIntyre, R. T. J. Am. Oil Chem. Soc. 1979, 56, 835.
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(19) All synthesized compounds were mixture of diastereomers.
However, their spectral data appeared as the single structure.
For example, the benzylic protons of compound 12a were
observed at d = 4.58 (4 H) and 4.59 (2 H), both as singlets
(see the experimental section).
Synthesis 2008, No. 22, 3663–3669 © Thieme Stuttgart · New York