F. A. Jaipuri et al. / Tetrahedron: Asymmetry 14 (2003) 3249–3252
3251
using porcine pancreatic lipase (PPL) as previously
relative to polystyrene, were measured using a Waters
gel permeation chromatography (GPC) system consist-
ing of a Waters 510 pump, a Waters 717plus autosam-
pler, and a Water 410 refractive index detector. The
measurements were taken at 40°C with THF as mobile
phase on four columns (Polymer labs Plgel 100, 500,
1
1
reported. This chiral butyrolactone was polymerized
using the above mentioned procedure to produce
poly(b-hydroxybutyrate). The stereochemical configura-
tion of the repeating units in the polymer was deter-
mined by degradation of the polymer to its
corresponding ethyl b-hydroxybutyrate units with
4
5
1×10 , 1×10 angstrom).
4
a
ethanolic sulfuric acid. Interestingly, triflic acid could
also be used for this degradation reaction starting from
the commercially available polymer to synthesize the
acid instead of the ester.
4.1. Polymerization of b-butyrolactone
An oven dried round bottom flask equipped with a stir
bar and sealed with a septum was purged with nitrogen.
b-Butyrolactone (500 mg, 5.81 mmol), triflic acid (8.67
ml, 0.098 mmol, for DP=30), and methanol (7.88 ml,
0.195 mmol) were added to the round bottom flask
containing toluene (5 mL) and the mixture was stirred
at 35°C. The mixture was poured into water and
extracted with chloroform (3×20 mL). The organic
layer was washed with sodium bicarbonate, water and
brine and then dried over magnesium sulfate. The
solvent was removed under reduced pressure and the
polymer was isolated as a colorless gel. Characteriza-
The reaction mixture was analyzed on a chiral gas
chromatography column to separate the two enan-
12
tiomers as previously described
and ethyl-(R)-3-
hydroxybutyrate was found to be the predominant
enantiomer possessing enantiomeric excess in the same
ratio as the starting lactone. This evidence indicated
that the reaction proceeds with the retention of configu-
ration of the repeating units in the polymer. This
polymerization method, therefore, complements the
polymerization of (S)-b-butyrolactone initiated with
sodium salt of (R)-3-hydroxybutyric acid in the pres-
ence of crown ether, which proceeds by inversion of
configuration and yields polymers of comparable
13
tion data matched previously reported data.
4.2. Depolymerization of poly(hydroxybutyrate)
1
3
molecular weights. In contrast, the triflic acid cata-
lyzed polymerization of b-butyrolactone proceeds
through the cleavage of the bond between the carbonyl
carbon and oxygen (acyl cleavage) as shown by path a.
A mixture of poly(b-hydroxybutyrate) (1.48 g) and
dichloroethane (15 mL) was heated at reflux until the
poly(hydroxybutyrate) completely dissolved. The solu-
tion was cooled to 40°C and acetonitrile (15 mL) was
added followed by triflic acid (0.47 mL) and water (2
mL). The solution was refluxed for 70 h. The reaction
was quenched with brine/water (1:1, 15 mL) and the
organic layer was removed. The aqueous layer was
extracted with chloroform (3×50 mL) and the combined
organic layers were washed with brine (10 mL) and
dried over magnesium sulfate. The solvent was removed
under reduced pressure and the resulting crude mixture
was purified by flash column chromatography (silica
gel, 30% ethyl acetate/hexane) to yield (R)-3-hydroxy-
butyric acid (1.3 g, 88% conversion) as yellow oil.
Characterization data matched previously reported
3. Conclusion
In summary, a novel method for the synthesis of
biomimetic polymers analogous to natural PHB
polyester produced by enzymes in living organisms is
presented. The polymerization proceeds with the reten-
tion of configuration and can be accomplished using
triflic acid as a catalyst without a metal species present
and with methanol as an initiator in an aprotic solvent.
Triflic acid in acetonitrile with water could also serve to
depolymerize this polymer to produce chiral b-hydroxy-
alkanoic acid building blocks. In addition to serving as
a soluble substrate to study the enzymes involved in
degrading this class of polymers, this synthetic PHB
could be used for medical applications, for example
4
a,d
20
4d
RT
data.
[h] =−22.5 (c 6.0, water). [lit. [h]D =−24.7
D
1
(c 5.0, water).] H NMR (300 MHz, CDCl , l ppm):
3
1.28 (d, J=6.9 Hz, 3H), 2.42–2.52 (m, 2H), 4.18–4.25
13
(m, 1H), 7.79 (br s, 1H). C NMR (75 MHz, CDCl , l
3
14
drug delivery systems, or solid-surface coatings.
ppm): 22.6, 42.8, 64.6, 177.9.
4
.3. Polymerization of L-lactide
4. Experimental
To an oven dried round bottom flask equipped with a
stir bar was added -lactide (444 mg, 3.08 mmol); the
All reagents were bought from Aldrich (Milwaukee,
L
WI) and used as received except as noted below. b-
flask was sealed with a septum and was purged with
nitrogen. Triflic acid (4.60 mL, 0.052 mmol, for DP=
30), methanol (4.00 mL, 0.103 mmol), and toluene (5
ml) were added to the lactide and the mixture was
stirred at 50°C for 14 h. The solvent was removed
under reduced pressure and the resulting solid was
suspended in methanol (10 ml) for 30 min to dissolve
triflic acid and any oligomers present. The white solid
was then filtered and washed with methanol (2×5 mL).
15a
Butyrolactone was purified as previously described.
Methanol was distilled over calcium hydride. Other
1
5b
solvents were purified by standard procedures. Purifi-
cation by flash chromatography was performed on
Selecto Scientific silica gel (32–63). The commercial
natural poly(b-hydroxybutyrate) for hydrolysis was
1
13
purchased from Aldrich. H and C NMR on a Varian
VXR-300 using TMS as an internal standard. Optical
rotations were measured using sodium D line on a
Jasco DIP-370 digital polarimeter. Molecular weights,
Poly(
L-lactide) was obtained as a white powder. When
a 30:1 monomer to initiator ratio was used, DP=30