Synthesis and characterisation of new types of side chain cholesteryl polymers

Article abstract of DOI:10.1016/j.steroids.2010.10.011

A series of cholesterol derivatives have been synthesised via the alkylation reaction of the 3-hydroxyl group with the aliphatic bromide compounds with different chain lengths, namely 3β-alkyloxy-cholesterol. The double bond between the C5 and C6 positions in these cholesterol derivatives was oxidised into epoxy, followed by an epoxy-ring-opening reaction with the treatment with acrylic acid, resulting in a series of 3β-alkyloxy-5α- hydroxy-6β-acryloyloxycholesterol, C_nOCh (n = 1, 2, 4, 6, 8, 10, 12), The acrylate group is connected to the C6 position, which is confirmed by the single crystal structure analysis. The corresponding polymers, PC _nOCh, were prepared via free radical polymerisation. The structure of monomers and the resulting polymers were characterised with nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR) and gel permeation chromatography (GPC). The thermal properties of PC_nOCh were studied using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). To determine the secondary structure of polymers, circular dichroism (CD) spectra were performed. It was found that not all monomers produce high-molecular-weight polymers because of steric hindrance. However, all polymers have a helical structure, which can be enhanced by increasing the alkoxy chain length. In addition, increasing the alkoxy chain length decreases the glass transition temperature and increases the decomposition temperature of the polymers.

Full text of DOI:10.1016/j.steroids.2010.10.011

Steroids 76 (2011) 204–209
Contents lists available at ScienceDirect
Steroids
journal homepage: www.elsevier.com/locate/steroids
Synthesis and characterisation of new types of side chain cholesteryl polymers
∗
Bin Wang, Haiyan Du, Junhua Zhang
State Key Laboratory of Polymer Materials Engineering of China, Sichuan University, Chengdu, Sichuan Province 610065, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 July 2010
Received in revised form 25 October 2010
Accepted 30 October 2010
Available online 9 November 2010
A series of cholesterol derivatives have been synthesised via the alkylation reaction of the 3-hydroxyl
group with the aliphatic bromide compounds with different chain lengths, namely 3␤-alkyloxy-
cholesterol. The double bond between the C5 and C6 positions in these cholesterol derivatives was
oxidised into epoxy, followed by an epoxy-ring-opening reaction with the treatment with acrylic acid,
resulting in a series of 3␤-alkyloxy-5␣-hydroxy-6␤-acryloyloxycholesterol, CnOCh (n = 1, 2, 4, 6, 8, 10,
1
2), The acrylate group is connected to the C6 position, which is confirmed by the single crystal struc-
Keywords:
Cholesterol
Circular dichroism
Secondary structure
Helical structure
ture analysis. The corresponding polymers, PCnOCh, were prepared via free radical polymerisation. The
structure of monomers and the resulting polymers were characterised with nuclear magnetic resonance
(NMR), Fourier transform infrared spectroscopy (FT-IR) and gel permeation chromatography (GPC). The
thermal properties of PCnOCh were studied using differential scanning calorimetry (DSC) and thermo-
gravimetric analysis (TGA). To determine the secondary structure of polymers, circular dichroism (CD)
spectra were performed. It was found that not all monomers produce high-molecular-weight polymers
because of steric hindrance. However, all polymers have a helical structure, which can be enhanced by
increasing the alkoxy chain length. In addition, increasing the alkoxy chain length decreases the glass
transition temperature and increases the decomposition temperature of the polymers.
©
2010 Elsevier Inc. All rights reserved.
Cholesteryl derivatives and some polymers bearing cholesterol
have attracted considerable interest for their unique optical prop-
erties, including selective reflection of light, thermochromism and
circular dichromism [1–5]. Cholesterol has the nature of a mesogen,
which usually makes polymers have liquid crystalline properties
3␤-alkylxoy-5␣-hydroxy-6␤-acryloyloxycholesterol, CnOCh (n = 1,
2, 4, 6, 8, 10, 12).
Because the polymerisable groups are connected on the lat-
eral side of the cholesterol structure, the steric hindrance is quite
large; thus, these monomers are quite like the mesogen-jacketed
monomers in which the polymerisable groups are connected to the
mesogenic units at their lateral parts with or without short flexible
spacers, as reported by Zhou et al. [12–15]. If the cholesteryl skele-
ton has enough rigidity, it can be regarded as a mesogen and the
corresponding polymers may have mesogen-jacketed properties;
if not, the polymers, at least, have a helical structure because of the
large side groups bearing on the main chain.
[
6–11].
Almost all of those cholesteryl polymers were prepared using
the hydroxyl group at C3 position of cholesterol with or with-
out suitable flexible spacers. However, in the cholesterol skeleton,
except for the hydroxyl group on C3, there still exists a double bond
between C5 and C6. A suitable method can be used to functionalise
the C6 position; for example, one can introduce a hydroxyl group
on the C6 position, and then a suitable polymerisable group can
be introduced to yield a series of new monomers and their corre-
sponding polymers. To the best of our knowledge, there is no such
reported research.
To produce the above-mentioned new derivatives starting from
the C6 position, the hydroxyl group at C3 is first protected by differ-
ent lengths of alkoxy groups by the etherification method, and then
the double bond is epoxided. Next, acrylic acid to open it and a series
of new acrylate derivatives of steroid molecules is obtained, namely
1. Experimental
1.1. Materials
Cholesterol, sodium hydrogen, idomethane (MeI), bro-
moethane, n-butyl bromide, bromohexane, 1-bromooctane,
-bromodecane, 1-bromododecane, potassium iodide, benzoyl
1
peroxide, chlorobenzene, acrylic acid, potassium iodide, tetrahy-
drofuran (THF), dichloromethane and 3-chloroperoxybenzoic
acid (mCPBA) were purchased from Guanghua Chemical Co. of
China. THF (analytical reagent; Guanghua Chemical Reagents) was
purified by refluxing over sodium and was freshly distilled before
use. Benzoyl peroxide (BPO) was purified by recrystallisation from
∗ Corresponding author. Tel.: +86 28 85460890; fax: +86 28 85402465.
E-mail addresses: zhangjh@scu.edu.cn, zhangjunhua100@hotmail.com
(
J. Zhang).
0
039-128X/$ – see front matter © 2010 Elsevier Inc. All rights reserved.
doi:10.1016/j.steroids.2010.10.011

B. Wang et al. / Steroids 76 (2011) 204–209
205
Scheme 1. Synthetic routes for monomers and polymers.
methanol and dichloromethane. Chlorobenzene was washed with
H SO , NaHCO and distilled water separately, refluxed over CaH2
1.3.1. Cholesteryl 3ˇ-alkyloxy
A
typical synthesis method is shown as follows: 5.00 g
2
4
3
and distilled before use. Other solvents were used as received.
(12.95 mmol) of cholesterol was dissolved in 40 ml of freshly dis-
tilled THF, 0.47 g (19.42 mmol) NaH and 1.33 g (14.09 mmol) of MeI
were added. The reaction mixture was kept at 60 C for 24 h; then
the reaction mixture was quenched with 40 ml of distilled water
and extracted with 10 ml petroleum ether. The organic layer was
◦
1.2. Measurements
Nuclear magnetic resonance (NMR) spectra were recorded at
washed with H O, dried (anhydrous MgSO ) and evaporated to
2
4
room temperature on BrukerAMx-400 operating at 400 MHz for
give a residue. The product was obtained by recrystallisation from
1
H in deuterochloroform. Elemental analyses were determined
petroleum ether.
on a Carlo ERBA 1106 instrument. Differential scanning calorime-
try (DSC) was carried out on a thermal analysis (TA) DSC-Q30 in
1
Cholesteryl 3ˇ-methoxy: yield: 96.80%. H NMR (400 MHz, CDCl ,
3
ppm) ı = 0.68 (s, 3H), 0.85–2.37 (m, 43H), 3.02–3.06 (m, 1H,
◦
−1
nitrogen at a heating rate of 10 C min . Thermogravimetric anal-
C3–H), 3.35 (s, 3H, –OCH ), 5.34–5.36 (t, 1H, C6–H). FTIR (KBr)
◦
3
ysis (TGA) was performed from 30 to 500 C at a heating rate
−
1
−1
ꢀ
–
= 2934.09 cm (stretching of –CH ), 2866.50 cm (stretching of
◦
−1
3
of 10 C min
on a TA TGA-DSC Q600 thermogravimetric anal-
− −1
CH –), 1636.94 cm (stretching of CH–), 1190.59 cm (stretch-
2
1
yser under nitrogen atmosphere. The number-average molecular
weight (Mn), weight-average molecular weight (Mw) and the poly-
dispersity (Mw/Mn) of polymers was estimated by gel permeation
chromatography (GPC) equipped with a Waters 515 HPLC pump.
ing of –O–CH ).
3
Cholesteryl 3ˇ-ethoxy: yield: 54.30%. 1H NMR (400 MHz, CDCl3,
ppm) ı = 0.68 (s, 3H), 0.85–2.40 (m, 43H), 3.15–3.19 (m, 1H, C3–H),
3
ꢀ
–
.50–3.55 (m, 2H, –O–CH –), 5.33–5.35 (t, 1H, C6–H). FTIR (KBr)
−
1
◦
2
THF was used as the eluent at a flow rate of 1.0 ml min at 25 C.
The calibrating curve was obtained against a series of polystyrene
standards. Circular dichroism (CD) spectra were recorded on JASCO
J-810. The sample solution was thermostatted at the desired tem-
perature with a Julabo F25-Me controller. The light path length of
−
1
−1
= 2931.84 cm (stretching of –CH ), 2855.19 cm (stretching of
3
−
1
−1
CH –), 1658.20 cm (stretching of CH–), 1108.93 cm (stretch-
2
ing of –O–CH ).
3
Cholesteryl 3ˇ-butoxy: yield: 42.80%. 1H NMR (400 MHz, CDCl3,
ppm) ı = 0.68 (s, 3H), 0.87–2.40 (m, 47H), 3.09–3.16 (m, 1H, C3–H),
−
1
the quartz cell used was 10 mm. The concentration was 2 g l
.
3
ꢀ
.44–3.48 (m, 2H, –O–CH –), 5.33–5.35 (t, 1H, C6–H). FTIR (KBr)
2
− −1
= 2931.66 cm (stretching of –CH ), 2852.66 cm (stretching of
3
1
−
1
1.3. Monomer synthesis
–CH2–), 1108.32 cm (stretching of –O–CH3).
Cholesteryl 3ˇ-hexyloxy: yield: 60.20%. 1H NMR (400 MHz,
CDCl3, ppm) ı = 0.67 (s, 3H), 0.85–2.41 (m, 51H), 3.00–3.20 (m, 1H,
C3–H), 3.42–3.46 (m, 2H, –O–CH2), 5.33–5.34 (t, 1H, C6–H). FTIR
The synthetic route for the preparation of the monomers is
shown in Scheme 1.

2
06
B. Wang et al. / Steroids 76 (2011) 204–209
−1
(
KBr) ꢀ = 2934.11 cm−1 (stretching of –CH ), 2846.05 cm (stretch-
anhydrous MgSO4, and concentrated under reduced pressure. The
residue was purified by preparative column chromatography (silica
gel, eluent: ethyl acetate/petroleum ether = 1:4), and cholesteryl
3␤-alkyloxy-5␣-hydroxy-6␤-acryloyloxy was obtained.
3
−1
ing of –CH –), 1107.02 cm (stretching of –O–CH ).
2
3
1
Cholesteryl 3ˇ-octyloxy: yield: 66.90%. H NMR (400 MHz, CDCl ,
3
ppm) ı = 0.68 (s, 3H), 0.85–2.40 (m, 59H), 3.00–3.15 (m, 1H, C3–H),
3
ꢀ
–
.42–3.46 (m, 2H, –O–CH –), 5.33–5.34 (t, 1H, C6–H). FTIR (KBr)
Cholesteryl 3ˇ-methoxy-5˛-hydroxy-6ˇ-acryloyloxy C1OCh:
yield: 63.2%. 1H NMR (400 MHz, CDCl3, ppm) ı = 0.67 (s, 3H),
0.84–1.98 (m, 42H), 3.31 (s, 3H, –OCH3), 3.55–3.62 (m, 1H, C3–H),
4.79 (s, 1H, C6–H), 5.82–5.86 (m, 1H, CH–), 6.05–6.14 (q, 1H, CH),
2
−1
−1
= 2929.75 cm (stretching of –CH ), 2852.25 cm (stretching of
3
−1
CH –), 1106.25 cm (stretching of –O–CH ).
Cholesteryl 3ˇ-decyloxy: yield: 64.50%. H NMR (400 MHz, CDCl ,
2
3
1
3
−
1
ppm) ı = 0.68 (s, 3H), 0.85–2.40 (m, 63H), 3.00–3.20 (m, 1H, C3–OH),
6.34–6.40 (q, 1H, CH). FTIR (KBr) ꢀ = 3454.26 cm (stretching of
−
1
−
1
3
ꢀ
–
.42–3.46 (m, 2H, –O–CH –), 5.33–5.35 (t, 1H, C6–OH). FTIR (KBr)
C6–OH), 2943.31 cm (stretching of –CH3), 2866.79 cm (stretch-
2
−1
−1
−1
−1
= 2931.15 cm (stretching of –CH ), 2852.12 cm (stretching of
ing of –CH2–), 1712.51 cm
(stretching of –CO–), 1613.94 cm
3
−1
−1
CH –), 1108.82 cm (stretching of –O–CH ).
(stretching of –CH CH2), 1100.36 cm (stretching of –O–).
2
3
Cholesteryl 3ˇ-dodecyloxy: yield: 29.00%. 1H NMR (400 MHz,
Cholesteryl 3ˇ-ethoxy-5˛-hydroxy-6ˇ-acryloyloxy C2OCh: yield:
62.8%. 1H NMR (400 MHz, CDCl3, ppm): ı = 0.67 (s, 3H), 0.85–2.10
(m, 44H), 3.45–3.54 (m, 2H, –OCH2–), 3.66–3.71 (m, 1H, C3–H),
4.78 (s, 1H, C6–H), 5.83–5.85 (d, 1H, CH–), 6.10–6.13 (d, 1H, CH),
CDCl , ppm) ı = 0.68 (s, 3H), 0.85–2.40 (m, 67H), 3.00–3.20 (m, 1H,
C3–H), 3.42–3.46 (m, 2H, –O–CH –), 5.33–5.35 (t, 1H, C6–H). FTIR
3
2
−1
−1
(
KBr) ꢀ = 2930.71 cm (stretching of –CH ), 2851.942852.12 cm
3
−1
−1
(
stretching of –CH –), 1108.92 cm (stretching of –O–CH ).
6.35-6.40 (d, 1H, CH). FTIR (KBr) ꢀ = 3489.87 cm (stretching of
2
3
−
1
−1
C6–OH), 2943.55 cm (stretching of –CH ), 2867.67 cm (stretch-
3
−
1
−1
ing of –CH –), 1710.53 cm
(stretching of –CO–), 1613.26 cm
2
1.3.2. Cholesteryl 3ˇ-alkyloxy-5,6-epoxy
−
stretching of –CH CH ), 1106.60 cm (stretching of –O–).
2
1
(
Cholesteryl 3ˇ-alkyloxy-5,6-epoxy was synthesised by epoxiding
Cholesteryl 3ˇ-butoxy-5˛-hydroxy-6ˇ-acryloyloxy C OCh: yield:
4
the double bond of cholestryl 3␤-alkyloxy using mCPBA as reported
in the literature [12].
6
3.5%. 1H NMR (400 MHz, CDCl , ppm) ı = 0.67 (s, 3H), 0.85–2.02
3
(
m, 53H), 3.41–3.45 (m, 2H, –OCH –), 4.77 (s, 1H, C6–H),
Cholesteryl 3ˇ-methoxy-5˛,6˛-epoxy: yield: 86.2%. 1H NMR
2
5
1
2
–
.83–5.85 (d, 1H, CH–), 6.06–6.13 (d, 1H, CH), 6.35–6.40 (d,
(
400 MHz, CDCl , ppm) ı = 0.60 (s, 3H), 0.84–2.40 (m, 41H),
3
−1
H, CH). FTIR (KBr) ꢀ = 3501.77 cm
(stretching of C6–OH),
2
1
2
–
.88–2.90 (m, 1H, C6–H), 3.32 (s, 3H, –OCH ), 3.38–3.43 (m,
3
−1
−1
942.97 cm
(stretching of –CH ), 2868.28 cm
(stretching of
−1
3
H, C3–H). FTIR (KBr) ꢀ = 2948.25 cm
(stretching of –CH ),
3
−1
−1
CH –), 1712.23 cm (stretching of –CO–), 1626.01 cm (stretch-
−1
−1
2
866.68 cm (stretching of –CH –), 1104.72 cm (stretching of
O–CH ).
2
−1
ing of –CH CH ), 1103.94 cm (stretching of –O–).
2
3
Cholesteryl 3ˇ-hexyloxy-5˛-hydroxy-6ˇ-acryloyloxy C6OCh:
Cholesteryl 3ˇ-ethoxy-5˛,6˛-epoxy: yield 87.8%. 1H NMR
yield: 55.0%. 1H NMR (400 MHz, CDCl , ppm): ı = 0.67 (s, 3H),
3
(
400 MHz, CDCl , ppm) ı = 0.60 (s, 3H), 0.63–2.10 (m, 43H),
3
0
.85–2.20 (m, 48H), 3.40–3.44 (m, 1H, C3–H and –OCH –), 4.78
2
2
(
.88–2.90 (m, 1H, C6–H), 3.48–3.51 (m, 3H, –OCH – and C3–H). FTIR
2
(
6
s, 1H, C6–H), 5.82–5.86 (m, 1H, CH–), 6.05–6.14 (q, 1H, CH),
− −1
KBr) ꢀ = 2946.17 cm (stretching of –CH ), 2868.68 cm (stretch-
3
1
−1
.34–6.40 (q, 1H, CH). FTIR (KBr) ꢀ = 3475.11 cm (stretching of
−
1
ing of –CH –), 1112.43 cm (stretching of –O–CH ).
2
3
−1
−1
C6–OH), 2936.83 cm (stretching of –CH ), 2867.91 cm (stretch-
ing of –CH –), 1706.27 cm
Cholesteryl 3ˇ-butoxy-5˛,6˛-epoxy: yield: 66.1%. 1H NMR
3
−
1
−1
(stretching of –CO–), 1614.00 cm
2
(
400 MHz, CDCl , ppm) ı = 0.61 (s, 3H), 0.85–2.10 (m, 47H),
3
−1
(stretching of –CH CH ), 1102.93 cm (stretching of –O–).
2
2
(
.88–2.90 (m, 1H, C6–H), 3.38–3.53 (m, 3H, –OCH – and C3–H). IR
2
Cholesteryl 3ˇ-octyloxy-5˛-hydroxy-6ˇ-acryloyloxy
C8OCh:
− −1
KBr) ꢀ = 2934.42 cm (stretching of –CH ), 2867.54 cm (stretch-
3
1
yield: 69.3%. 1H NMR (400 MHz, CDCl , ppm): ı = 0.60 (s, 3H),
−
1
3
ing of –CH –), 1104.18 cm (stretching of –O–CH ).
2
3
0
.85–2.10 (m, 55H), 3.45–3.53 (m, 3H, C3–H and –OCH –), 4.75
2
Cholesteryl 3ˇ-hexyloxy-5˛,6˛-epoxy: yield: 78.7%. 1H NMR
(
6
s, 1H, C6–H), 5.81–5.86 (m, 1H, CH–), 6.05–6.12 (q, 1H, CH),
(
400 MHz, CDCl , ppm) ı = 0.61 (s, 3H), 0.86–2.04 (m, 51H),
3
−1
.31–6.40 (d, 1H, CH). FTIR (KBr) ꢀ = 3462.18 cm (stretching of
2
(
.88–2.89 (m, 1H, C6–H), 3.41–3.46 (m, 3H, –CH –O–, C3–H). FTIR
2
−1
−1
C6–OH), 2932.28 cm (stretching of –CH ), 2867.33 cm (stretch-
ing of –CH –), 1711.49 cm
− −1
KBr) ꢀ = 2933.24 cm (stretching of –CH ), 2866.95 cm (stretch-
3
1
3
−1
−1
(stretching of –CO–), 1622.89 cm
−1
2
ing of –CH –), 1109.42 cm (stretching of –O–).
2
−1
(stretching of –CH CH ), 1115.24 cm (stretching of –O–).
Cholesteryl 3ˇ-octyloxy-5˛,6˛-epoxy: yield: 80.6%. 1H NMR
2
Cholesteryl 3ˇ-decyloxy-5˛-hydroxy-6ˇ-acryloyloxy C10OCh:
(
400 MHz, CDCl , ppm) ı = 0.60 (s, 3H), 0.85–2.10 (m, 55H),
3
yield: 58.13. 1H NMR (400 MHz, CDCl , ppm) ı = 0.61 (s, 3H),
3
2
.88–2.89 (m, 1H, C6–H), 3.39–3.51 (m, 3H, –CH –O– and C3–H).
2
0
3
6
ꢀ
.85–2.10 (m, 59H), 3.37–3.53 (m, 3H, C3–H and –OCH –),
−1
−1
(stretching of –CH ), 2867.32 cm
3
2
FTIR (KBr) ꢀ = 2931.34 cm
.38–3.57 (m, 3H), 4.74 (s, 1H, C6–H), 5.84–5.86 (m, 1H, CH–),
.05–6.13 (q, 1H, CH), 6.35–6.40 (d, 1H, CH). FTIR (KBr)
−
stretching of –CH –), 1115.42 cm (stretching of –O–).
2
1
(
Cholesteryl 3ˇ-decyloxy-5˛,6˛-epoxy: yield: 82.5%. 1H NMR
400 MHz, CDCl , ppm) ı = 0.61 (s, 3H), 0.85–2.10 (m, 59H),
−
1
−1
= 3456.54 cm (stretching of C6–OH), 2928.41 cm (stretching
(
3
−1
−1
of –CH ), 2852.74 cm
(stretching of –CH –), 1709.49 cm
3
2
2
.88–2.89 (m, 1H, C6–H), 3.37–3.53 (m, 3H, –O–CH – and C3–H).
2
−1
(stretching of –CO–), 1624.60 cm
(stretching of –CH CH ),
−1
−1
(stretching of –CH ), 2852.50 cm
3
2
FTIR (KBr) ꢀ = 2929.35 cm
−1
1
113.46 cm (stretching of –O–).
Cholesteryl 3ˇ-dodecyloxy-5˛-hydroxy-6ˇ-acryloyloxy C12OCh:
yield: 82.1%. 1H NMR (400 MHz, CDCl , ppm) ı = 0.67 (s, 3H),
−
stretching of –CH –), 1466.64, 1376.14, 1113.64 cm (stretching
2
1
(
of –O–).
Cholesteryl 3ˇ-dodecyloxy-5˛,6˛-epoxy: yield: 64.3%. 1H NMR
3
0
.85–2.20 (m, 57H), 3.38–3.66 (m, 3H, C3–H and –OCH –), 4.77
2
(
400 MHz, CDCl , ppm) ı = 0.60 (s, 3H), 0.85–2.10 (m, 63H),
3
(
6
s, 1H, C6–H), 5.83–5.86 (d, 1H, CH–), 6.06–6.13 (q, 1H, CH),
2
.88–2.89 (m, 1H, C6–H), 3.41–3.45 (m, 3H, –O–CH – and C3–H).
2
−1
.36–6.40 (d, 1H, CH). FTIR (KBr) ꢀ = 3522.95 cm (stretching of
−1
−1
(stretching of –CH ), 2852.63 cm
FTIR (KBr) ꢀ = 2928.32 cm
3
−1
−1
C6–OH), 2925.37 cm (stretching of –CH ), 2851.75 cm (stretch-
−1
3
(
stretching of –CH –), 1110.62 cm (stretching of –O–).
2
−1
−1
ing of –CH –), 1712.48 cm
(stretching of –CO–), 1630.01 cm
2
−
stretching of –CH CH ), 1105.97 cm (stretching of –O–).
2
1
(
1.3.3. Cholesteryl 3ˇ-alkyloxy-5˛-hydroxy-6ˇ-acryloyloxy
A total of 1.20 mmol of epoxy compound was dissolved in 10 ml
acrylic acid. After vigorous stirring at 60 C for 48 h, the mixture
1.4. Polymer synthesis
◦
was quenched with saturated NaHCO , and the resulting solution
was extracted with ethyl acetate. The organic layer was dried over
All the corresponding polymers were prepared by free radical
polymerisation in chlorobenzene. A representative procedure is as
3

B. Wang et al. / Steroids 76 (2011) 204–209
207
Fig. 1. The crystal structure of 3␤-alkoxy-5␣-hydroxy-6␤-acrylatecholestane.
follows: C OCh (0.20 g, 0.41 mmol), BPO (5.00 mg, 0.020 mmol) and
crystal size: 0.48 mm × 0.46 mm × 0.44 mm; reflection collected:
1
chlorobenzene (0.8 g) were added to a reaction tube. After three
freeze–pump–thaw cycles, the tube was sealed under vacuum and
3600.
◦
placed in an oil bath thermostatted at 90 C for 48 h. After being
2.3. Polymerisation
cooled to room temperature, the tube was opened and the solution
was dropped into cold methanol (10 ml). White solids precipitated
and were filtered and then dried under vacuum for 24 h.
The free radical polymerisations of monomers were carried out
in chlorobenzene at 90 C using BPO as the initiator. The poly-
◦
meriszation results are summarised in Table 1. All the monomers
can be polymerised to give the corresponding polymers, but the
molecular weights are not high, corresponding to 8–12 repeat units.
This may be due to the fact that the large lateral structure exhibits
steric hindrance, decreasing the accessibility of the double bond
for polymerisation. The polymers obtained are white solids that
have good solubility in many common organic solvents, such as
THF, chloroform, dichloromethane, toluene, dimethylsulphoxide
2
. Results and discussion
2.1. Synthesis
The cholesteryl monomers, cholesteryl 3␤-alkyloxy-5␣-
hydroxy-6␤-acryloyloxy, were prepared though
a three-step
synthetic route as shown in Scheme 1. The cholesterol was
etherised by alkyl halides with different chain lengths. To intro-
duce a polymerisable group on position C6, the double bond was
converted to two-diol on position C5 and position C6 by oxidation
using HCOOH and H O . The hydroxyl group at position C6 can be
connected to a polymerisable group by esterification under DCC
and DMAP as catalysts [16]. It was found that the reactivity of the
hydroxyl group on C6 is quite low resulting in low yield. As a result
of larger steric hindrance at the C5 position, the reactivity of the
hydroxyl group on C5 is lower than that on C6.
To improve the reactivity of C5 and C6 of cholesterol, the epox-
idation method was adopted and then the epoxide was opened
using suitable reagents with carboxyl groups, such as acrylic acid.
Cholesteryl 3␤-alkyloxy-5,6-epoxy was obtained in the presence
of 3-chloroperoxybenzoic acid in dry CH Cl under nitrogen atmo-
(DMSO) and ethyl acetate.
The chemical structures of CnOCh and PCnOCh were confirmed
by a combination of analytical techniques, for example, infrared
1
(
IR), H NMR and elemental analysis. Fig. 2 shows the 1H NMR
2
2
spectra of C OCh and PC OCh in CDCl . The characteristic three
1
1
3
1
peaks at 5.8–6.4 ppm of vinyl groups in the H NMR spectrum of
monomer disappeared after being polymerised and those of the
–
CH–CH –, polymer backbone were observed instead, indicating
2
the formation of the polymers. The results of polymerisation are
summarised in Table 1. The sharp characteristic signals of C OCh
1
became broad after polymerisation (Fig. 2(b)) due to the limited
mobility of protons.
2.4. Thermal properties
2
2
sphere. The target monomers were prepared by opening the epoxy
◦
ring by an excess amount of acrylic acid at 60 C without any cat-
DSC results clearly show that the structure of PCnOCh is amor-
phous rather than crystalline. As Fig. 3 shows, no crystal peak can
be observed, only glass transition temperature presents at the tem-
1
alyst. H NMR, and elemental analysis confirmed the expected
structures. The synthetic route developed in the present work is
quite efficient, and therefore is more convenient for exploring new
cholesterol derivatives.
Table 1
Polymerisation results and cholesteryl monomers.
2
.2. The space structure of C OCh
Polymersa
Mnb (×l0−3
Mw (×l0−3
PDIb
◦
Tdc ( C)
◦
1
Yield (%)
)
)
Tg ( C)
PC1OCh
PC2OCh
90
84
79
63
84
77
80
5.19
4.71
4.69
4.32
4.05
4.41
4.85
10.00
6.83
6.74
6.87
6.27
6.57
7.15
1.93
1.11
1.44
1.59
1.55
1.49
1.48
179.7
173.3
152.2
119.2
112.2
101.2
96.7
334.5
339.5
343.6
352.1
345.2
353.6
355.8
The double bond in the cholesterol structure provides rigid-
ity, but little is known about the space structure without a
double bond..To determine this, cholesteryl 3␤-dodecyloxy-5␣-
hydroxy-6␤-acryloyoxy was cultivated to a single crystal, and the
structure was confirmed by X-ray diffraction (XRD) (seen in Fig. 1).
It was found that C5–OH and C6–O–CO– are axial bonds, but
the direction is opposite, and the C3–O–R is in the same direc-
PC OCh
4
PC6OCh
PC8OCh
PC10OCh
PC12OCh
a
PCnOCh are products obtained by polymerising the corresponding monomer
CnOCh, and n represents the number of C in alky chain.
tion with C6–O–CO–. The detail data is: space group: 21; unit
b
PDI: polydisperity index, expressed as Mw/Mn, where Mn is the number average
space cell: a = 5.791 A˚ , b = 9.336 A˚ , c = 21.524 A˚ ; density (calculated)
weight, and Mw is weight average molecular weight.
−3
−1
c
1
.072 mg m ; absorption coefficient: 0.069 mm ; F(0 0 0) = 540;
Td: the degradation temperature.

2
08
B. Wang et al. / Steroids 76 (2011) 204–209
Fig. 4. TGA thermograms of PCnOCh.
bring about more free volume, which promotes the flexibility of
lateral structure, leading to the relatively low Tg.
TGA was performed to study the thermal stability property of
the synthesised polymers. Fig. 4 shows that all polymers have high
thermal stability, and the main mass loss occurs at a temperature
◦
region from approximately 300–400 C, although they do not have
high molecular weight. In addition, generally speaking, the degra-
dation temperature, as listed in Table 1, increases with increasing
carbon number. When the carbon number increases, the symmetry
of the side group increases and the steric hindrance also increases.
These characteristics are helpful to improve the thermal stability
of polymers.
2.5. CD spectra
CD spectroscopy was used to characterise the chiroptical prop-
erties of monomers CnOCh and polymers PCnOCh. Figs. 5 and 6
show the CD spectra of CnOCh and PCnOCh in THF, respectively. The
Fig. 2. 1H NMR spectra of C1OCh in CDCl3 (a) and PC1Ch in CDCl3 (b), respectively.
CD spectra of C OCh and C OCh exhibit similar negative and pos-
1
6
◦
itive Cotton effects at 196 and 203 nm, C OCh and C10OCh exhibit
perature region from 20 to 250 C and the number of carbon atoms
2
resemble positive Cotton effects at 198 nm, C OCh possess a strong
in alky chains on C3 position has an obvious effect on Tg. When the
carbon number (n) increases from 1 to 12, Tg decreases from about
79.7 to 96.7 C (Table 1). This is because the longer alky chains
4
negative Cotton effect at 202 nm and C OCh and C12OCh repre-
8
◦
sent negative and positive absorbents, respectively. From the above
results, the C3 alkyl chain has an obvious relationship with the CD
spectroscopy of CnOCh.
1
◦
Fig. 5. Comparison of the CD spectra of model monomers CnOCh (recorded at 20 C
in THF), [ꢁ] = molar ellipticity with repeating unit: deg cm dmol .
Fig. 3. DSC thermograms of PCnOCh observed from the second scanning.
2
−1

B. Wang et al. / Steroids 76 (2011) 204–209
209
ature increases with the length of the alkyl chain. The helical
conformations of the polymers are determined through CD spec-
tra, and this effect is pronounced when the alkyl chain lengths are
longer.
Acknowledgement
This work described in this article was supported by the National
Nature Science of China (Grant No. 20804026).
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. Conclusion
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