Vol. 25, No. 2 (2013)
A Facile Route for Synthesis of (±)-Dinoprost, (±)-Carboprost and Its Analogs 917
(
300 MHz) (CDCl
CH ), 0.87 (t, 3H, J = 7.5 Hz, CH
H, J = 6.3 Hz, HC-(CH ), 1.20-1.25 (m, 4H, 2CH
.56 (m, 4H, 2CH ), 1.87-2.02 (m, 6H, 3CH ), 2.06 (t, 2H, J =
.2 Hz, CH ), 2.29 (t, 2H, J = 6.9 Hz, CH ), 2.69-2.74 (m, 1H,
3
) δ (ppm): 0.79 (t, 3H, J = 7.2 Hz, CH
-CH -C-OH), 1.19 (d,
), 1.51-
3
-
1.27 (s, 3H, CH
(m, 3H, CH , CH), 2.09-2.18 (m, 3H, CH
J = 7.2 Hz, CH -(CH -CH -C-OH), 3.66 (s, 3H, O-CH
3
3
-C-OH), 1.48-1.52 (m, 4H, 2CH
, CH), 2.32 (t, 2H,
), 3.93-
2
), 1.63-1.82
(
2
)
4
3
2
2
2
6
1
7
3
)
2
2
3
)
2 3
2
2
2
3.98 (m, 1H, HO-CH), 4.19 (t, 1H, J = 4.2 Hz, HO-CH), 5.35-
2
2
5.51 (m, 3H, HC=CH(cis), HC=CH(trans)), 5.62 (d, 1H, J =
1
3
CH), 2.86-2.89 (m, 1H, CH), 4.07 (q, 2H, J = 7.2 Hz, CH
CH -C-OH), 4.91-4.99 (m, 1H, HC-(CH ), 5.20-5.50 (m, 4H,
HC=CH(cis), (OBz-CH) ), 5.62 (d, 2H, J = 3.9 Hz,
HC=CH(trans)), 7.33 (t, 2H, J = 7.5 Hz, HAr), 7.47 (t, 2H, J =
.5 Hz, HAr), 7.50 (t, 1H, J = 7.2 Hz, HAr), 7.58 (t, 1H, J = 7.5
Hz, HAr), 7.93 (dd, 2H, J = 8.1, 1.5 Hz, HAr), 8.07 (dd, 2H, J =
3
-
3
15.3 Hz, HC=CH(trans)). C NMR (75 MHz) (CDCl ) δ
2
3
)
2
(ppm): 13.91, 22.50, 23.63, 24.68, 25.58, 26.48, 28.17, 32.13,
33.26, 42.65, 42.80, 50.90, 51.50, 56.04, 72.69, 73.19, 78.45,
128.40, 129.06, 129.53, 138.91, 174.19. MS (ES): m/z 405
2
+
+
7
[M+Na ]. HRMS (ESI): Calcd. for C22
H
38
O
5
Na [M+Na]
405.2794; found 405.2785.
(Z±)Methyl 7)(2)((E±)3)ethyl)3)hydroxyoct)1)enyl±)3,5)
dihydroxycycloꢀentyl±heꢀt)5)enoate (16±: IR (KBr, νmax
+
8
.1, 1.5 Hz, HAr). MS (ES): m/z 655 [M+Na ].
)((E±)3)Hydroxy)3)isoꢀroꢀyloct)1)enyl±)5)((Z±)7)iso)
roꢀoxy)7)oxoheꢀt)2)enyl±cycloꢀentane)1,3)diyl diꢁenzoate
4
,
cm ): 3401, 2956, 2932, 2860, 1726, 1458, 1438, 1376, 1275,
-1
ꢀ
-1
1
(
15c±: IR (KBr, νmax, cm ): 3525, 3063, 2957, 2930, 1721,
1170, 1075. H NMR (300 MHz) (CDCl
(t, 3H, J = 7.2 Hz, CH -(CH ), 0.87 (t, 3H, J = 7.5 Hz,
CH -CH -C-OH), 1.21-1.31 (m, 8H, 4CH ), 1.49-1.71 (m,
8H, 4CH ), 2.09-2.13 (m, 3H, CH , CH), 2.29 (m, 1H, CH),
2.32 (t, 2H, J = 7.2 Hz, CH -CH -C-OH), 3.67 (s, 3H, O-CH ),
3.95-3.97 (m, 1H, HO-CH), 4.20-4.23 (m, 1H, HO-CH),
3
) δ (ppm): 0.86
1
1
452, 1374, 1271, 1176, 1111, 1070. H NMR (300 MHz)
CDCl ) δ (ppm): 0.85 (t, 3H, J = 7.2 Hz, CH -(CH ), 0.90
d, 6H, J = 6.3 Hz, HC-(CH ), 1.19 (d, 6H, J = 6.3 Hz,
), 1.20-1.31 (m, 8H, 4CH ), 1.45-1.72 (m, 3H,
, CH), 1.89-2.01 (m, 3H, CH , CH), 2.06 (t, 2H, J = 7.5
Hz, CH ), 2.29 (t, 2H, J = 7.2 Hz, CH ), 2.70-2.78 (m, 1H,
CH), 2.87-2.91 (m, 1H, CH), 4.91-4.99 (m, 1H, HC-(CH ),
), 5.29-5.46 (m, 4H,
), 5.60-5.63 (m, 2H, HC=CH(trans)),
3
2 4
)
(
(
3
3
2
)
4
3
2
2
3
)
2
2
2
O-CH-(CH
3
)
2
2
3
2
3
CH
2
2
13
2
2
5.39-5.49 (m, 4H, HC=CH(cis), HC=CH(trans)). C NMR
(75 MHz) (CDCl ) δ (ppm): 7.79, 13.90, 22.50, 23.12,
3
)
2
3
5
.22-5.26 (m, 1H, O-CH-(CH
3
)
2
24.68, 25.54, 26.45, 28.12, 32.20, 33.35, 40.53, 42.73,
50.70, 51.44, 55.91, 72.95, 75.03, 78.33, 128.67, 129.34,
+
130.74, 137.32, 174.21. MS (ES): m/z 419 [M+Na ]. HRMS
HC=CH(cis), (OBz-CH)
2
7
.30-7.36 (m, 2H, HAr), 7.43 (t, 2H, J = 8.1 Hz, HAr), 7.48 (t,
H, J = 7.5 Hz, HAr), 7.59 (t, 1H, J = 7.5 Hz, HAr), 7.92-7.95
+
Na [M+Na] 419.2781; found
1
(ESI): Calcd. for C23
419.2773.
H
40
O
5
(
[
m, 2H, HAr), 8.06-8.09 (m, 2H, HAr). MS (ES): m/z 669
+
M+Na ].
(Z±)Methyl 7)(3,5)dihydroxy)2)((E±)3)hydroxy)3)iso)
ꢀroꢀyloct)1)enyl±cycloꢀentyl±heꢀt)5)enoate (17±: IR (KBr,
4
)((E±)3)Hydroxy)3)ꢀhenyloct)1)enyl±)5)((Z±)7)iso)
-1
ꢀ
roꢀoxy)7)oxoheꢀt)2)enyl±cycloꢀentane)1,3)diyl)diꢁenzoate
νmax, cm ): 3403, 3005, 2956, 2934, 2872, 1725, 1457, 1438,
-1
1
(
15d±: IR (KBr, νmax, cm ): 3502, 3061, 2935, 2870, 1721,
1
602, 1492, 1451, 1374, 1273, 1111, 1027. H NMR (300
1316, 1218, 1171, 1027. H NMR (300 MHz) (CDCl
0.87 (t, 3H, J = 7.2 Hz, CH -(CH ), 0.88 (d, 6H, J = 6.3 Hz,
HC-(CH ), 1.23-1.29 (m, 8H, 3CH , CHa, CH), 1.50-1.72
(m, 4H, 2CH ), 2.04-2.16 (m, 6H, 2CH , CHb, CH), 2.31
(t, 2H, J = 7.2 Hz, CH ), 2.41 (m, 1H, CH), 3.66 (s, 3H,
O-CH ), 3.95-3.97 (m, 1H, HO-CH), 4.20 (t, 1H, J = 3.9 Hz,
HO-CH), 5.39-5.49 (m, 4H, HC=CH(cis), HC=CH(trans)). C
NMR (75 MHz) (CDCl ) δ (ppm): 13.92, 16.49, 17.53, 22.53,
3
) δ (ppm):
1
3
2 4
)
MHz) (CDCl
3
) δ (ppm): 0.82 (t, 3H, J = 7.5 Hz, CH
.10-1.19 (m, 4H, 2CH ), 1.21 (d, 6H, J = 6.3 Hz, CH-(CH
.22-1.25 (m, 4H, 2CH ), 1.56-1.67 (m, 2H, CH
), 2.16-2.27 (m, 6H, 3CH ), 2.62-2.79 (m, 2H,
CH), 4.92-5.03 (m, 1H, CH-(CH ), 5.12-5.15 (m, 1H, OBz-
3 2
-(CH )
4
),
3
)
2
2
1
1
2
3
)
2
),
2
2
2
2
), 1.76-1.84
2
(m, 2H, CH
2
2
3
13
2
3 2
)
CH), 5.17 (t, 1H, J = 4.5 Hz, OBz-CH), 5.31-5.39 (m, 2H,
HC=CH(cis)), 5.66 (ddd, 1H, J = 15.6, 9.0, 4.2 Hz, HC=CH-
C-OH(trans)), 5.98 (dd, 1H, J = 15.6, 4.2 Hz, HC=CH(trans)),
3
22.94, 24.68, 25.66, 26.47, 32.26, 33.27, 38.47, 38.66, 42.76,
50.77, 51.45, 56.12, 73.09, 77.14, 78.52, 129.10, 129.38,
+
129.92, 135.61, 174.19. MS (ES): m/z 433 [M+Na ]. HRMS
7
.18-7.24 (m, 4H, HAr), 7.36-7.45 (m, 5H, HAr), 7.55-7.56 (m,
+
H, HAr), 7.95-8.02 (m, 4H, HAr). MS (ES): m/z 703 [M+Na ].
+
Na [M+Na] 433.2936; found
2
(ESI): Calcd. for C24
433.2930.
H
42
O
5
Preꢀaration of (Z±)methyl 7)(3, 5)dihydroxy)2)((E±)3)
hydroxy)3)methyloct)1)enyl±cycloꢀentyl±heꢀt)5)enoate (2±:
(Z±)Methyl)7)(3,5)dihydroxy)2)((E±)3)hydroxy)3)ꢀhenyl)
-1
Compound 15 (0.4 g, 0.647 mmol), potassium carbonate
(
oct)1)enyl±cycloꢀentyl±heꢀt)5)enoate (18±: IR (KBr, νmax, cm ):
3395, 3058, 2952, 2933, 1737, 1493, 1446, 1374, 1172, 1117,
0.316 g, 2.29 mmol) and (4 mL) of MeOH were stirred at
1
ambient temperature for 20 h. The progress of the reaction
was monitored by TLC. After complete conversion of the
reaction, (4 mL) of water was added and pH adjusted to 2
with 10 % citric acid (4 mL) and aqueous layer was extracted
with EtOAc (3 × 10 mL). Combined ethyl acetate layers were
1026. H NMR (300 MHz) (CDCl
3
) δ (ppm): 0.83 (t, 3H, J =
), 1.20-1.26 (m, 8H, 4CH ), 1.50-1.91 (m,
), 2.01-2.37 (m, 8H, 4CH ), 3.64 (s, 1.8H, O-CH ),
3.67 (s, 1.2H, O-CH ), 3.95-3.98 (m, 1H, HO-CH), 4.18 (br,
7.2 Hz, CH
3 2
-(CH )
4
2
4H, 2CH
2
2
3
3
1H, HO-CH), 5.30-5.59 (m, 3H, HC=CH(cis), HC=CH(trans)),
5.93 (dd, 1H, J = 15.3, 3.0 Hz, HC=CH (trans)), 7.22 (t, 1H,
J = 7.2 Hz, HAr), 7.32 (t, 2H, J = 7.2 Hz, HAr), 7.42 (d, 2H, J =
2 4
dried over anhydrous Na SO and concentrated under reduced
pressure at 40 ºC to obtain crude product which was purified
by flash column chromatography using eluent as ethyl acetate/
hexane. The pure fractions were combined and concentrated
under vacuum at 40 ºC to give compound 2. Yield 0.12 g (50
13
3
7.2Hz, HAr). C NMR (75 MHz) (CDCl ) δ (ppm): 14.28,
22.80, 23.51, 24.99, 25.03, 25.79, 26.72, 32.42, 33.59, 33.63,
42.74, 43.12, 50.81, 51.83, 56.01, 72.99, 76.84, 78.10, 125.96,
126.75, 129.60, 130.73, 138.94, 146.54, 174.63. MS (ES):
-1
%
). IR (KBr, νmax, cm ): 3395, 2958, 2928, 2858, 1720, 1454,
1
372, 1278, 1178, 1072. H NMR (300 MHz) (CDCl
+
+
1
3
) δ (ppm):
m/z 467 and 483 [M+Na ] and [M+K ]. HRMS (ESI): Calcd.
+
0
.86 (t, 3H, J = 7.2 Hz, CH -(CH ), 1.26-1.28 (m, 8H, 4CH
3
2
)
4
2
),
40 5
for C27H O Na [M+Na] 467.2788; found 467.2773.