Synthesis and characterization of a series of novel phenol- and polyphenol-based glycerolipids

Article abstract of DOI:10.1139/V06-102

A building block approach was used to design a modular synthetic route for the preparation of novel glycerolipids with phenolic and polyphenolic headgroups. Based on this scheme, it is possible to vary the substitution pattern of the headgroup, the stereo

Full text of DOI:10.1139/V06-102

1411
Synthesis and characterization of a series of novel
phenol- and polyphenol-based glycerolipids1
Rolf Schmidt, Joseph G. Carrigan, and Christine E. DeWolf
Abstract: A building block approach was used to design a modular synthetic route for the preparation of novel
glycerolipids with phenolic and polyphenolic headgroups. Based on this scheme, it is possible to vary the substitution
pattern of the headgroup, the stereochemistry of the backbone, and the length of the sidechains. Five glycerolipids with
different headgroups and identical backbone stereochemistry and chain length have been prepared.
Key words: glycerolipid, polyphenol, hydrogen bonding, lipid-protein interaction, self-adhering.
Résumé : On a développé une méthode modulaire de synthèse de nouveaux glycérolipides comportant des têtes phéno-
liques et polyphénoliques. En se basant sur ce schéma, il est possible de faire varier la nature du groupe de tête, la sté-
réochimie du squelette et la longueur des chaînes latérales. On a préparé cinq glycérolipides dont la stéréochimie du
squelette et la longueur de la chaîne sont les mêmes, mais qui diffèrent par la nature de leur groupe de tête.
Mots clés : glycérolipide, polyphénol, liaison hydrogène, interaction lipide-protéine, autoadhérente.
[Traduit par la Rédaction] Schmidt et al. 1415
Introduction
cerebrosides, DPGG provides an ideal template for a library
of analogous lipids. We have employed a building block ap-
proach to design a modular synthetic route for the prepara-
tion of this library of novel glycerolipids with phenolic and
polyphenolic headgroups. We report here the preparation of
DPGG analogues with headgroups varying in number and
position of hydroxyl groups (Fig. 1).
It is well-known that polyphenols bind and precipitate
proteins and (or) peptides and can act as antioxidants
(Handique and Baruah (1) provide a comprehensive review
of natural and synthetic polyphenols). Furthermore,
poly(phenol) films have been used as protective coatings for
proteins immobilized onto electrodes (2). A novel synthetic
lipid, 1,2-dipalmitoylgalloylglycerol (DPGG), has been pre-
pared (3) that incorporates a polyphenol as the headgroup.
The authors suggest that this lipid has the potential to
exhibit comparable protein-binding properties (4) so that
Langmuir–Blodgett films of such lipids could prove useful
as biocompatible coatings. Pollastri et al. (3) demonstrated
the self-adhesive nature of DPGG bilayers and proposed both
strong inter- and intra-bilayer hydrogen bonding between
gallic acid headgroups. We have recently shown that DPGG
monolayers exhibit strong lateral cohesion and high rigidity,
which can also be attributed to lateral hydrogen bonding (5).
The influence of hydrogen bonding on monolayer and
bilayer phase behaviour has been previously documented for
lipids such as phosphatidylethanolamines and cerebrosides
(3, 6, 7). To probe and understand the lateral cohesion in
monolayers due to a hydrogen bonding network requires
systematic chemical modification with respect to hydrogen
bonding sites. In contrast to phosphatidylethanolamines and
Results and discussion
The preparation of DPGG in two steps from tri-O-
benzylgalloyl chloride and dipalmitoylglycerol has been
described in the literature (3). The key features of this syn-
thesis are the use of the benzyl protecting group and the in-
troduction of a side chain bearing glycerol moiety. We report
a more modular synthetic route to DPGG and some of its an-
alogues, which allows for easy variation not only of the
headgroup (number and position of hydroxyl groups) but
also the stereochemistry of the backbone (R or S) and the
chemical character of the side chains (chain length, units of
unsaturation, functionalization, etc.) (Scheme 1). All of
these parameters are known to influence monolayer phase
behaviour and more generally, lipid self-assembly proper-
ties.
Compounds 3a, 3c, and 3e are commercially available in
gram quantities. Compounds 3b and 3d were prepared by
well-known methods from 3-hydroxybenzoic acid methyl es-
ter and 3,4-dihydroxybenzoic acid, respectively. Therefore, it
is easy to alter the headgroup structure of the title com-
pounds by varying the substitution pattern of the starting
material. In the first step of the synthesis of the title com-
pounds, phenol-bearing benzoic acids 3 are reacted with a
racemic mixture of 2,2-dimethyl-1,3-dioxolane-4-methanol
(solketal, a protected glycerol) to give compounds 4. Impor-
tantly, the same procedure could be used to prepare the
enantiomerically pure analogues starting from commercially
Received 14 November 2005. Accepted 21 December 2005.
Published on the NRC Research Press Web site at
http://canjchem.nrc.ca on 11 October 2006.
R. Schmidt, J.G. Carrigan, and C.E. DeWolf.2 Department
of Chemistry and Biochemistry, Concordia University, 7141
Sherbrooke St. West, Montréal, QC H4B 1R6, Canada.
1This article is part of a Special Issue dedicated to Dr. Alfred
Bader.
2Corresponding author (e-mail: cdewolf@alcor.concordia.ca).
Can. J. Chem. 84: 1411–1415 (2006)
doi:10.1139/V06-102
© 2006 NRC Canada

1412
Can. J. Chem. Vol. 84, 2006
Fig. 1. Chemical structure of DPGG (7e) and prepared analogues.
R
R
R
R
R
HO
O
HO
OH
HO
HO
OH
OH
7e
OH
7a
OH
7c
7b
7d
O
O
O
R:
O
O
Scheme 1. Reagents: (a) BnBr, K2CO3, CH2Cl2–MeOH, (b) KOH, THF–H2O, (c) solketal, 1-methylimidazole, p-TsCl, MeCN,
(d) Amberlyst® 15, MeOH–H2O, (e) hexadecanoic acid, DMAP, EDCI, CH2Cl2, ( f ) H2, 10% Pd–C.
O
O
O
O
R3
R2
R3
R2
R3
R2
R3
R2
O
O
O
O
OH
c
a
b
d
O
R1
R1
R1
R1
1
2
3
4
O
O
O
O
O
R3
R2
R3
R2
R3
R2
O
O
R
R
O
OH
O
O
R
R
e
f
O
OH
O
R1
O
R1
R1
O
5
6
7
R1
H
OH
OH
OH OH
R2
OH
H
R3
H
H
OH
H
R1
H
OBn
OBn
OBn OBn
OBn OBn OBn
R2
OBn
H
R3
H
H
OBn
H
1, 7
2–6
a
b
c
d
a
b
c
d
e
H
H
OH OH OH
e
available (R)-(-)- or (S)-(+)-2,2-dimethyl-1,3-dioxolane-4-
methanol instead of the racemic mixture, provided that the
pH is held between 7 to 8 to retain optical purity (8). The
isopropylidene and benzyl protecting groups were chosen
from orthogonal sets to provide selective deprotection of the
isopropylidene in step d (Fig. 1). The protected benzoates 4
were not isolated, but the glycerol moiety was deprotected
by treatment with wet Amberlyst® 15, a strongly acidic resin
that allows for easy removal from the reaction mixture by
gravity filtration. The advantage of Amberlyst® 15, aside
from easy removal, is the fact that the sulfonic residues
bound to the resin beads provide significant steric hindrance
to prevent ester cleavage (9). Cleavage of the isopropylidene
protecting group with I2 in methanol (10) or under acidic
conditions using aqueous acetic acid (11) was not success-
ful. It has to be noted that a similar approach has previously
been employed by Schmidt and Blank (12) for the prepara-
tion of compounds 4e and 5e. However, reaction times are
generally much shorter and workup much simpler for our
synthetic scheme with similar yields. In the next step, the
palmitoyl side chains were introduced by coupling 5 with
palmitic acid in the presence of N-(3-dimethylaminopropyl)-
N-ethylcarbodiimide hydrochloride (EDCI) and 4-dimethyl-
aminopyridine (DMAP) (13, 14). This acylation method was
shown to be superior to the coupling of acid chlorides or
anhydrides with the corresponding aliphatic acids (15). Fur-
thermore, excess EDCI and the 1-(3-dimethylamino-propyl)-
3-ethyl-urea formed during the reaction can easily be
removed from the reaction mixture by liquid–liquid extrac-
tion because of their good solubility in water. The reaction
has also been successfully carried out with the correspond-
ing myristoyl and stearoyl side chains (data not shown). In
addition, it is possible to selectively introduce two dissimilar
side chains (e.g., palmitoyl and stearoyl) by successive cou-
pling with the respective acids (15, 16).
Diacetylation in the first step as well as 1,2-acyl migration
in the second step can be avoided by maintaining the reac-
tion temperature between 0 and 20 °C (15). The benzyl pro-
tecting group is removed by catalytic hydrogenation under
moderate pressure in the final step. The reaction time in-
© 2006 NRC Canada

Schmidt et al.
1413
creases with the number of benzyl groups to be removed.
DPGG and its benzyl-protected precursor were also prepared
by this method with comparable yields to the literature (3).
were combined, dried over Na2SO4, and the solvent removed
under reduced pressure to yield 0.67 g of a white solid in
95% yield.
3,4-Bis-benzyloxy-benzoic acid (3d)
Conclusion
Compound 3d was prepared in a manner analogous to 3b
with a reaction time of 48 h. The reaction gave 0.67 g of a
white solid in 70% yield.
We have prepared a library of phenolic and polyphenolic
glycerolipids according to a relatively simple modular reac-
tion scheme. Moreover, the same scheme can be used to pre-
pare glycerolipids that are enantiomerically pure and (or)
have dissimilar side chains.
Synthesis of the benzyloxybenzoic acid 2,3-dihydroxy-
propyl esters (5a–5d)
Typical procedure
Experimental
Compound 3a (1.0 g, 4.38 mmol), 1-methyl-imidazole
(1.08 g, 13.14 mmol, 3 equiv.), and p-toluenesulfonyl chlo-
ride (1.17 g, 6.13 mmol, 1.4 equiv.) were dissolved in 45 mL
of CH3CN and stirred for 30 min. After the addition of
racemic 2,2-dimethyl-1,3-dioxolane-4-methanol (0.58 g,
4.38 mmol, 1 equiv.), the solution was stirred under inert at-
mosphere for 3 h. The volume of the solution was reduced to
approximately 4 mL under reduced pressure and the solution
filtered through Al2O3 with 40 mL of CH2Cl2. The solvent
was removed under reduced pressure to give 1.0 g of a white
solid which was used without further purification. Com-
pound 4a (0.15 g, 0.438 mmol) was suspended in 40 mL of
EtOH–H2O (95:5). Wet Amberlyst® 15 (0.180 g, 1 equiv.)
was added to the suspension and the suspension was
refluxed for 24 h. The solution was allowed to cool to room
temperature and 40 mL of CH2Cl2 and 300 mL of brine
were added. The mixture was extracted with CH2Cl2 (2 ×
20 mL). The organic layers were combined, dried over
Na2SO4, and the solvent removed under reduced pressure.
The crude was purified by flash chromatography on SiO2
(ethyl acetate – hexanes, 70:30) to give 0.105 g of a white
solid in 80% yield.
All chemicals were purchased from commercial suppliers
and used without further purification. 4-Benzyloxybenzoic
acid, 3,5-di-benzyloxybenzoic acid, and 3,4,5-tris-benzyl-
oxybenzoic acid were obtained from Tokyo Chemical Indus-
1
try Co., Ltd. (TCI, Tokyo, Japan). H spectra were obtained
at 300 MHz and 13C NMR spectra were obtained at 75 MHz
in CDCl3 unless otherwise noted using the NMR solvent as
an internal reference. Abbreviations used in the descriptions
of NMR spectra are singlet (s), doublet (d), triplet (t),
multiplet (m), broad signal (br). The coupling constants (J)
are given in Hertz. Mass spectrometry measurements were
carried out on a MALDI mass spectrometer using dithranol
as a matrix. IR measurements were carried out using a liquid
cell equipped with KBr windows and in CDCl3 unless other-
wise noted. All melting points are uncorrected. Silica gel for
flash chromatography was acquired from Life Force Inc.
(Flushing, New York).
3,4-Dihydroxybenzoic acid methyl ester (1d)
3,4-Dihydroxybenzoic acid (1 g, 6.49 mmol) was dis-
solved in 40 mL of MeOH. After the addition of 2 drops of
concd. H2SO4, the solution was refluxed for 7 days. The re-
action was stopped by the addition of 300 mL of distilled
H2O. The mixture was extracted with ethyl acetate – hexanes
(60:40). The organic layers were combined, dried over
Na2SO4, and the solvent removed under reduced pressure to
give 0.8 g of a light-brown solid in 73% yield.
Data for 5a
Melting point 77–79 °C. IR (cm–1) ν: 3614, 3036, 2952,
1
2886, 1713, 1606. H NMR δ: 8.01 (m, 2H), 7.40 (m, 5H),
7.01 (m, 2H), 5.13 (s, 2H, ArCH2), 4.42 (m, 2H), 4.00 (m,
1H), 3.71 (m, 2H). 13C NMR δ: 166.7, 162.8, 136.1, 131.8,
128.7, 128.2, 127.5, 122.1, 114.6, 70.45, 70.13, 65.5, 63.4.
MS m/z: 325.3 [M + Na]+
3-Benzyloxybenzoic acid methyl ester (2b)
Compound 2b was prepared according to the literature
(17) with a reaction time of 6 h. The product was purified by
flash chromatography on SiO2 (hexanes – ethyl acetate,
80:20) to give 0.98 g of a white solid in 61% yield.
Data for 5b
Yield 80%, mp 76–78 °C. IR (cm–1) ν: 3618, 3036, 2952,
1
2884, 1719, 1586. H NMR δ: 7.68 (m, 2H), 7.40 (m, 6H),
7.19 (m, 1H), 5.11 (s, 2H, ArCH2), 4.42 (m, 2H), 4.06 (m,
1H), 3.72 (m, 2H). 13C NMR δ: 166.8, 158.7, 136.4, 130.9,
129.6, 128.6, 128.1, 127.5, 122.4, 120.5, 115.4, 70.3, 70.2,
65.8, 63.4. MS m/z: 325.3 [M + Na]+.
3,4-Bis-benzyloxybenzoic acid methyl ester (2d)
Compound 2d was prepared in a manner analogous to 2b.
However, 2.3 equiv. of benzyl bromide were used and gave
1.19 g of a white solid in 77% yield.
Data for 5c
3-Benzyloxybenzoic acid (3b)
Yield 85%, mp 94 to 95 °C. IR (cm–1) ν: 3618, 3035,
1
Compound 2b (0.75 g, 3.1 mmol) was dissolved in 35 mL
of THF. A solution of KOH (1.04 g, 18.6 mmol, 6 equiv.) in
50 mL of distilled H2O was added and the reaction was
stirred for 24 h. The reaction mixture was added to 250 mL
of distilled H2O and acidified to pH 5 with 2N HCl. The
mixture was extracted with diethylether. The organic layers
2952, 2884, 1717, 1596. H NMR δ: 7.38 (m,10H), 7.28 (d,
2H, J = 2.33 Hz), 6.82 (t, 1H, J = 2.34 Hz), 5.07 (s, 4H,
ArCH2), 4.52 (m, 2H), 4.05 (m, 1H), 3.71 (m, 2H). 13C
NMR δ: 166.6, 159.8, 136.4, 131.4, 128.6, 128.2, 127.6,
108.6, 107.4, 70.4, 70.3, 65.9, 63.4. MS m/z: 431.4 [M +
Na]+.
© 2006 NRC Canada

1414
Can. J. Chem. Vol. 84, 2006
29.6, 29.5, 29.4, 29.3, 29.2, 29.1, 24.9, 24.8, 22.7, 14.1. MS
Data for 5d
Yield 83%, mp 80 to 81 °C. IR (cm–1) ν: 3613, 3034,
m/z: 908.3 [M + Na]+.
1
2951, 2885, 1712, 1601. H NMR δ: 7.63 (m, 2H), 7.39 (m,
Data for 6d
10H), 6.93 (m, 1H), 5.23 (s, 2H, ArCH2), 5.20 (s, 2H,
ArCH2), 4.37 (m, 2H), 4.02 (m, 1H), 3.68 (m, 2H). 13C
NMR δ: 166.7, 153.3, 148.3, 136.7, 136.4, 128.6, 128.5,
128.0, 127.9, 127.4, 127.1, 124.3, 122.3, 115.7, 113.2, 71.3,
70.8, 70.4, 65.6, 63.3. MS m/z: 431.4 [M + Na]+.
Reaction time 12 h, yield 63%, mp 45–47 °C. IR (cm–1) ν:
1
2927, 2855, 1736, 1601. H NMR δ: 7.62 (m, 1H), 7.58 (d,
1H, J = 2.1 Hz), 7.42 (m, 10H), 6.93 (d, 1H, J = 8.5 Hz),
5.41 (m, 1H), 5.23 (s, 2H, ArCH2), 5.20 (s, 2H, ArCH2),
4.40 (m, 3H), 4.17 (m, 1H), 2.33 (t, 4H, J = 7.5 Hz,
CH2COO), 1.61 (m, 4H, CH2CH2COO), 1.27 (m, 48H), 0.88
(t, 6H, J = 6.7 Hz, CH3). 13C NMR δ: 173.3, 172.9, 165.6,
153.2, 148.4, 136.8, 136.5, 128.6, 128.5, 128.0, 127.9,
127.4, 127.1, 124.1, 122.3, 115.5, 113.2, 71.6, 70.8, 68.9,
62.7, 62.2, 34.3, 34.1, 31.9, 29.7, 29.6, 29.5, 29.4, 29.3,
29.2, 29.1, 24.9, 24.8, 22.7, 14.1. MS m/z: 908.3 [M + Na]+.
Data for 5e
Yield 57%.
Synthesis of benzyloxybenzoic acid 2,3-bis-hexadec-
anoyloxypropyl esters (6a–6e)
Typical procedure
Compound 5a (0.38 g, 1.25 mmol) and hexadecanoic acid
(0.73 g, 2.825 mmol, 2.26 equiv.) were dissolved in 20 mL
of CH2Cl2. A suspension of DMAP (0.35 g, 2.825 mmol,
2.26 equiv.) and EDCI (0.58 g, 3 mmol, 2.4 equiv.) in 10 mL
of CH2Cl2 was added to the reaction mixture and the mix-
ture was stirred for 4 h. Brine (300 mL) was added and the
reaction mixture was extracted with CH2Cl2 (2 × 20 mL).
The organic layers were combined, dried over Na2SO4, and
the solvent removed under reduced pressure. The product
was purified by flash chromatography on SiO2 (hexanes –
ethyl acetate, 80:20) to give 0.80 g of a white solid in 82%
yield.
Data for 6e
Reaction time 15 h, yield 70%.
Synthesis of hydroxybenzoic acid 2,3-bis-hexadecanoyl-
oxypropyl esters (7a–7e)
Typical procedure
Compound 6a (0.2 g, 0.257 mmol) was dissolved in
20 mL of dry THF. 10% Pd–C (0.07 g, 30 wt%) was added
and the reaction mixture was placed in a pressure reactor
and stirred under 3.5 atm (1 atm = 101.325 kPa) of hydrogen
gas for 4 h. The mixture was filtered through Celite 545 and
the solvent removed under reduced pressure to give 0.14 g of
a white solid in 80% yield.
Data for 6a
Melting point 64–66 °C. IR (cm–1) ν: 2927, 2855, 1736,
1
Data for 7a
1606. H NMR δ: 7.98 (m, 2H), 7.39 (m, 5H), 7.01 (m, 2H),
Melting point 69–71 °C. IR (cm–1) ν: 3587, 2927, 2855,
5.41 (m, 1H), 5.12 (s, 2H, ArCH2), 4.41 (m, 3H), 4.24 (m,
1H), 2.33 (t, 2H, J = 7.5 Hz, CH2COO), 2.32 (t, 2H, J =
7.6 Hz, CH2COO), 1.61 (m, 4H, CH2CH2COO), 1.27 (m,
48H), 0.88 (t, 6H, J = 6.70 Hz, CH3). 13C NMR δ: 173.3,
172.9, 165.7, 162.8, 136.2, 131.8, 128.7, 128.2, 127.4,
122.1, 114.6, 70.1, 68.9, 62.6, 62.3, 34.3, 34.1, 31.9, 29.7,
29.6, 29.5, 29.4, 29.3, 29.2, 29.1, 24.9, 24.8, 22.7, 14.1. MS
m/z: 802.1 [M + Na]+.
1
1736, 1610. H NMR δ: 7.94 (m, 2H), 6.86 (m, 2H), 5.42
(m, 1H), 5.33 (br, 1H, OH), 4.44 (m, 3H), 4.24 (m, 1H),
2.33 (t, 2H, J = 7.5 Hz, CH2COO), 2.32 (t, 2H, J = 7.5 Hz,
CH2COO), 1.61 (m, 4H, CH2CH2COO), 1.27 (m, 48H), 0.88
(t, 6H, J = 6.7 Hz, CH3). 13C NMR δ: 173.5, 173.1, 165.7,
160.0, 132.1, 122.1, 115.3, 69.0, 62.7, 62.3, 34.3, 34.1, 31.9,
29.7, 29.6, 29.5, 29.4, 29.3, 29.2, 29.1, 24.9, 24.8, 22.7,
14.1. MS m/z: 712.0 [M + Na]+.
Data for 6b
Reaction time 6 h, yield 44%, mp 51 to 52 °C. IR (cm–1)
Data for 7b
Reaction time 6 h, 61% yield, mp 64 to 65 °C. IR (cm–1)
1
ν: 2927, 2855, 1735, 1586. H NMR δ: 7.64 (m, 2H), 7.39
1
ν: 3594, 2927, 2855, 1734, 1593. H NMR δ: 7.61 (m, 1H),
(m, 6H), 7.18 (m, 1H), 5.42 (m, 1H), 5.11 (s, 2H, ArCH2),
4.43 (m, 3H), 4.24 (m, 1H), 2.33 (t, 2H, J = 7.5 Hz,
CH2COO), 2.32 (t, 2H, J = 7.6 Hz, CH2COO), 1.61 (m, 4H,
CH2CH2COO), 1.27 (m, 48H), 0.88 (t, 6H, J = 6.7 Hz,
CH3). 13C NMR δ: 173.3, 172.9, 165.8, 158.8, 136.5, 130.8,
129.5, 128.6, 128.1, 127.5, 122.3, 120.5, 115.3, 70.2, 68.9,
63.0, 62.2, 34.3, 34.1, 31.9, 29.8, 29.7, 29.5, 29.4, 29.3,
29.2, 29.1, 24.9, 24.8, 22.7, 14.1. MS m/z: 802.1 [M + Na]+.
7.48 (m, 1H), 7.32 (m, 1H), 7.06 (m, 1H), 5.43 (m, 1H),
5.20 (br, 1H, OH), 4.43 (m, 3H), 4.24 (m, 1H), 2.33 (t, 2H,
J = 7.4 Hz, CH2COO), 2.32 (t, 2H, J = 7.5 Hz, CH2COO),
1.61 (m, 4H, CH2CH2COO), 1.27 (m, 48H), 0.88 (t, 6H, J =
6.7 Hz, CH3). 13C NMR δ: 173.4, 173.1, 165.7, 155.8, 130.1,
129.8, 122.1, 120.5, 116.3, 68.9, 63.0, 62.2, 34.3, 34.1, 31.9,
29.7, 29.6, 29.5, 29.4, 29.3, 29.2, 29.1, 24.9, 24.8, 22.7,
14.1. MS m/z: 712.0 [M + Na]+.
Data for 6c
Reaction time 12 h, yield 94%, mp 66–68 °C. IR (cm–1) ν:
Data for 7c
2927, 2855, 1736, 1596. H NMR δ 7.38 (m, 10H), 7.26 (d,
Reaction time 7 h, 53% yield, mp 78 to 79 °C. IR (cm–1)
1
1
2H, J = 2.3 Hz), 6.81 (t, 1H, J = 2.3 Hz), 5.41 (m, 1H), 5.07
(s, 4H, ArCH2), 4.45 (m, 3H), 4.22 (m, 1H), 2.33 (t, 4H, J =
7.5 Hz, CH2COO), 1.61 (m, 4H, CH2CH2COO), 1.27 (m,
48H), 0.88 (t, 6H, J = 6.7 Hz, CH3). 13C NMR δ 173.3,
172.9, 165.7, 159.8, 136.4, 131.4, 128.6, 128.1, 127.6,
108.5, 107.5, 70.3, 68.8, 63.0, 62.1, 34.3, 34.1, 31.9, 29.7,
ν: 3594, 2927, 2855, 1733, 1605. H NMR δ: 7.07 (d, 2H,
J = 2.2 Hz), 6.59 (t, 1H, J = 2.3 Hz), 5.45 (m, 3H), 4.41 (m,
3H), 4.24 (m, 1H), 2.33 (t, 6H, J = 7.6 Hz, CH2COO), 1.61
(m, 4H, CH2CH2COO), 1.27 (m, 48H), 0.88 (t, 6H, J =
6.7 Hz, CH3). 13C NMR δ: 173.6, 173.3, 165.4, 157.1, 131.6,
109.2, 107.8, 68.5, 63.1, 62.2, 34.3, 34.1, 31.9, 29.7, 29.6,
© 2006 NRC Canada

Schmidt et al.
1415
29.5, 29.4, 29.3, 29.2, 29.1, 24.9, 24.8, 22.7, 14.1. MS m/z:
References
728.0 [M + Na]+.
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(2002).
2. D.W.M. Arrigan and P.N. Bartlett. Biosens. Bioelectron. 13,
293 (1998).
Data for 7d
Reaction time 7 h, 50% yield, mp 92 to 93 °C. IR (cm–1)
1
ν: 3566, 2927, 2855, 1734, 1616. H NMR δ: 7.07 (d, 2H,
3. M.P. Pollastri, N.A. Porter, T.J. McIntosh, and S.A. Simon.
J = 2.2 Hz), 6.59 (t, 1H, J = 2.3 Hz), 5.45 (m, 3H), 4.41 (m,
3H), 4.24 (m, 1H), 2.33 (t, 6H, J = 7.6 Hz, CH2COO), 1.61
(m, 4H, CH2CH2COO), 1.27 (m, 48H), 0.88 (t, 6H, J =
6.7 Hz, CH3). 13C NMR δ: 173.7, 173.4, 166.3, 149.8, 146.8,
123.1, 120.9, 115.9, 114.6, 68.9, 62.5, 62.2, 34.3, 34.1, 31.9,
29.7, 29.6, 29.5, 29.4, 29.3, 29.2, 29.1, 24.9, 24.8, 22.7,
14.1. MS m/z: 728.0 [M + Na]+.
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Data for 7e
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ica in the presence of 1 mL of acetic acid and purified by
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Acknowledgements
The authors acknowledge the Natural Science and Engi-
neering Research Council (NSERC) of Canada and the
Canada Foundation for Innovation for financial support.
Dr. Heidi Muchall and Dr. Louis Cuccia are acknowledged
for their contribution to discussions and provision of addi-
tional facilities.
© 2006 NRC Canada