M. Bueno et al. / Carbohydrate Research 344 (2009) 2100–2104
2103
computerised data station. Three Waters styragel HR columns
were placed in series, and the analysis was performed in chloro-
form at a flow rate of 1 mL min . Calibration was performed using
65.32 (CH
2
glyc), 64.72 (C-4), 25.19, 24.86 (C(CH
3
)
2
). Anal. Calcd
for C H O : C, 50.00; H, 5.59. Found: C, 49.74; H, 5.40.
9
12 6
ꢀ1
1
2 polystyrene samples of narrow molecular-weight distribution.
1.3.3. 2-O-(2-Bromopropanoyl)-3,4-O-isopropylidene-L-
threonic acid (6)
1
.2. Materials
2
Treatment of a solution of 4 in dry Et O with (±)-2-bromoprop-
anoyl chloride as described for 5 gave, after concentration under
reduced pressure, 6 as an oil (mixture of stereoisomers, 75%). IR:
D,L-Lactide was obtained from Aldrich and sublimed before
ꢀ3
ꢀ1 1
polymerisation (45 °C, 10 mmHg). 5,6-O-Isopropylidene-
L-ascor-
m
1749 (CO) cm
(m, 1H, H-2), 4.61 (m, 1H, H-3), 4.55–4.4 (m, 1H, CHBr), 4.11 (m,
1H, H-4a), 3.97 (m, 1H, H-4b), 1.90–1.82 (m, 3H, CH ), 1.44, 1.35
): d 171.38, 171.17, 169.82,
), 74.36, 74.19 (C-3), 73.04,
2.68 (C-2), 65.50, 65.38 (C-4), 39.58, 39.13 (CHBr), 26.10, 26.06,
25.44, 25.35 (C(CH ), 21.68, 21.55(CH ). HRMS: m/z 334.992881
3
; H NMR (CDCl ): d 8.77 (br s, 1H COOH), 5.10
bic acid (2) and calcium 3,4-O-isopropylidene- -threonate (3) were
L
prepared as described by Wei15 and Voeffray, respectively. 5,6-O-
16
3
1
3
Isopropylidene- -isoascorbic acid (7) was prepared as described by
D
(2s, 6H, 2CH
169.50 (CO), 110.57, 110.53 (C(CH )
7
3
);
C NMR (CDCl
3
1
7
Emons.
3 2
1
.3. 3,4-O-Isopropylidene-
L
-threonic acid (4)
3
)
2
3
+
and 332.995306 (calcd for [M+Na] : 334.992923 and 332.994969).
To a suspension of calcium 3,4-O-isopropylidene-
3) (1 g, 2.56 mmol) in water (15 mL), cooled in an ice-water bath,
L
-threonate16
(
1.3.4. IPTP monomer
HCl (2 M) was added up to pH 3–4. Immediately, the solution was
extracted with EtOAc (9 ꢁ 25 mL). The pH of the aqueous solution
was checked from time to time in order to keep it at about 3. The
organic phase was dried over sodium sulfate and concentrated un-
der reduced pressure to give 4 as an oil that crystallised on stand-
Treatment of a solution of 6 in dimethylformamide as described
for IPTA gave, after concentration under reduced pressure, IPTP
2
(mixture of stereoisomers) as an oil, which crystallised from Et O
ꢀ1
1
(1.3 g, 30%). IR:
5.08 (2q, 1H, JH,CH3 = 7.0 Hz, CH propanoyl), 4.91 and 4.89 (2d, 1H,
2,3 = 1.34 Hz and J2,3 = 3.50 Hz, H-2), 4.63–4.56 (m, 1H, H-3), 4.22
3
m 1756 (CO) cm ; H NMR (CDCl ): d 5.27 and
ꢀ
1
1
ing (0.65 g, 73%); mp 71–73 °C; IR (KBr):
NMR (CDCl ): d 4.45 (ddd, 1H, J2,3 = 2.9, J3,4a = J3,4b = 6.65 Hz, H-3),
.18 (d, 1H, H-2), 4.13 (dd, 1H, J4a,4b = 8.45 Hz, H-4a), 4.03 (dd,
H, H-4b), 1.44, 1.36 (2s, 6H, 2CH ): d 175.63
); 13C NMR (CDCl
), 76.00 (C-3), 70.11(C-2), 65.65 (C-4), 26.00,
). Anal. Calcd for C : C, 47.72; H, 6.87. Found:
m
1737 cm (CO);
H
J
3
and 4.16 (2 dd, 1H, J4a,3 = 6.9 and 7.0 Hz, J4a,4b = 8.8 and 8.6 Hz, H-
4a), 4.03 and 4.00 (2 dd, 1H, J4b,3 = 6.7 and 7.2 Hz, H-4b), 1.72 and
4
1
3
3
1.65 (2d, 3H, CH
3
propanoyl), 1.40, 1.35 and 1.33 (3s, 6H, CH
pylidene); C NMR (CDCl ): d 166.55, 165.66, 165.08, 163.85 (2CO),
111.41, 111.11 (C(CH ), 76.19, 75.88, 75.62, 74.67, 73.06, 72.56 (C-
2,3 and CH propanoyl), 65.37, 64.79 (C-4), 25.85, 25.30, 25.11 (CH
isopropylidene), 18.15, 17.64 (CH propanoyl). Anal. Calcd for
: C, 52.17; H, 6.13. Found: C, 52.18; H, 6.11.
3
isopro-
1
3
(
CO), 110.31(C(CH
3
)
2
3
2
5.13 (C(CH
3
)
2
H
7 12
O
5
3 2
)
C, 47.49; H, 6.86.
3
3
1
.3.1. 2-O-(2-Bromoacetyl)-3,4-O-isopropylidene-
acid (5)
To a solution of 4 (1.0 g, 5.67 mmol) in dry Et
L
-threonic
10 14 6
C H O
2
O (24.0 mL),
1.3.5. Calcium 3,4-O-isopropylidene-
D-erythronate (8)
bromoacetyl chloride (0.6 mL, 7.24 mmol) was added at 0 °C under
argon. To this solution, stirred vigorously in an ice/salt bath, trieth-
To a suspension of calcium carbonate (16.0 g, 0.16 mol) in water
1
7
(200 mL), 5,6-O-isopropylidene-D-isoascorbic acid
(7, 17.3 g,
ylamine (1.32 mL) dissolved in dry Et
wise over a period of 1 h. After this time, the mixture was stirred at
°C for a further 30 min, diluted with more Et O (10 mL), washed
2
O (6.0 mL) was added drop-
0.08 mol) was added. The resulting mixture was cooled in an ice bath,
and 30% aqueous hydrogen peroxide (33.0 mL) was added dropwise.
Once the addition was complete, the mixture was warmed to room
temperature, stirred for 1 h more and then heated at 40 °C for
30 min. After that, charcoal (4.3 g) was added, and the mixture was
heated at 80 °C for 1 h. Then, the suspension was filtered over Celite
and the filtrate was concentrated under vacuum to half volume; addi-
tion of acetone (200 mL) gave 8 as a solid (10.7 g, 70%); mp>250 °C; IR
0
2
with water (2 ꢁ 2 mL) and dried over sodium sulfate. Concentra-
tion of the organic solution under vacuum gave a pale yellow vis-
ꢀ
1
cous liquid (1.4 g, 83%). IR:
m
1749 cm (CO); 1H NMR (CDCl
3
): d
8
1
4
.72 (br s, 1H COOH), 5.15 (d, 1H, J2,3 = 4.2 Hz, H-2), 4.61 (ddd,
H, J3,4a = 5.7, J3,4b = 6.6 Hz, H-3), 4.13 (dd, 1H, J4a,4b = 8.9 Hz, H-
ꢀ1
1
a), 3.97 (dd, 1H, H-4b), 3.96 and 3.95 (m, 2H, glyc), 1.45, 1.36
(KBr):
2,3 = 1.8, J3,4a = J3,4b = 4.4 Hz, H-3), 4.27 (d, 1H, H-2), 4.00 (dd, 1H,
4a,4b = 8.3 Hz, H-4a), 3.92 (dd, 1H, H-4b), 1.43, 1.36 (2s, 6H, 2CH );
), 76.93 (C-3), 71.49
). Anal. Calcd for
O: C, 42.10; H, 5.80. Found: C, 41.80; H, 5.81.
2
m 3410 (OH), 1602 cm (CO); H NMR (D O): d 4.49 (ddd, 1H,
1
3
(
(
(
(
2s, 6H, 2CH
C(CH
C(CH
3
); C NMR (CDCl
), 73.89, 72.73 (C-2,3), 65.00 (C-4), 26.00, 25.26
), 24.96 (CH Br). HRMS: m/z 320.977313 and 318.979444
3
): d 169.91, 166.78 (2 CO), 110.50
J
3
)
)
2
J
3
1
3
3
2
2
C NMR (D
(C-2), 63.59 (C-4), 25.11, 23.95 (C(CH
101/2H
2 3 2
O): d 177.30 (CO), 109.96 (C(CH )
+
calcd for [M+Na] : 320.977273 and 318.979319).
3 2
)
C
14
22
H O
2
1
.3.2. IPTA monomer
A solution of 5 (0.614 mg, 2.07 mmol) in dimethylformamide
1.3.6. 3,4-O-Isopropylidene-D-erythronic acid (9)
(
(
5.2 mL) was added to a vigorously stirred suspension of NaHCO
0.295 g, 3.5 mmol) in dimethylformamide (73 mL) at 40 °C over
3
Treatment of a suspension of 8 in water as described for 4 gave,
after concentration under reduced pressure, 9 as an oil which crys-
ꢀ
1
4
h. After the addition, the solution was stirred for 3 h more, and
concentrated under reduced pressure to give a residue that was ex-
tracted with Et
tallised on standing (72%); mp 58–60 °C; IR (KBr):
m
1736 cm
4.28 (m, 1H, H-3), 4.20 (d, 1H,
2,3 = 5.6 Hz, H-2), 4.09–3.98 (m, 2H, H-4a,b), 1.14, 1.32 (2s, 6H,
1
(CO);
3
H NMR (CDCl ): d
2
O (10 ꢁ 10 mL). The organic phase was washed
J
1
3
with water (1 ꢁ 2 mL) and dried over sodium sulfate. Concentra-
tion of the organic solution under reduced pressure gave IPTA as
a crystalline solid (0.251 g, 56%); mp 133–135 °C (recrystallised
2CH
3
); C NMR (CDCl
3
): d 174.84 (CO), 110.54 (C(CH
). Anal. Calcd
2
O: C, 46.53; H, 6.97. Found: C, 46.35; H, 6.69.
3 2
) ), 76.24
(C-3), 70.54 (C-2), 65.27 (C-4), 26.25, 24.93 (C(CH
for C 1/4H
HRMS: m/z 199.058831 (calcd for [M+Na] : 199.058243).
3 2
)
7
H
12
O
5
ꢀ
1
1
+
from EtOAc); [
NMR (CDCl ): d 5.11 (d, 1H, J = 16.5 Hz, CH
2,3 =1.5 Hz, H-2), 4.85 (d, 1H, CH glyc), 4.61 (ddd, 1H, H-3), 4.17
dd, 1H, 3,4a = 7.1 Hz, 4a,4b = 8.6 Hz, H-4a), 4.03 (dd, 1H,
3,4b = 7.0 Hz, H-4b), 1.38, 1.34 (2s, 6H, 2CH
63.92, 163.29 (2 CO), 111.48 (C(CH ), 76.16 (C-3), 75.06 (C-2),
a]
D
3
ꢀ94 (c 1.1, CHCl ); IR:
m
1746 cm (CO);
H
3
2
glyc), 4.91 (d, 1H,
J
(
J
1
2
1.3.7. 2-O-(2-Bromoacetyl)-3,4-O-isopropylidene-D-erythronic
acid (10)
J
J
13
3
); C NMR (CDCl
3
): d
Treatment of a solution of 9 in dry Et
10 as a pale yellow viscous liquid (63%). IR: m 1747 cm (CO); H
2
O as described for 5 gave
ꢀ1
1
3
)
2