Synthesis of optically active methyl 12-oxo-9,10-epoxyoctadecanoate

Article abstract of DOI:10.1023/A:1013198614115

The procedure for synthesizing optically active methyl 12-oxo-9,10-epoxyoctadecanoate (enantiomeric purity ～90%) was developed, starting from ricinolic acid methyl ester.

Full text of DOI:10.1023/A:1013198614115

Russian Journal of Organic Chemistry, Vol. 37, No. 9, 2001, pp. 1220 1222. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 9, 2001,
pp. 1287 1289.
Original Russian Text Copyright
2001 by Davletbakova, Baibulatova, Dokichev, Muslukhov, Yunusova, Yunusov.
Synthesis of Optically Active
Methyl 12-Oxo-9,10-epoxyoctadecanoate
*
A. M. Davletbakova, N. Z. Baibulatova, V. A. Dokichev, R. R. Muslukhov,
S. G. Yunusova, and M. S. Yunusov
Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
e-mail: chemorg@anrb.ru
Received September 1, 2000
Abstract The procedure for synthesizing optically active methyl 12-oxo-9,10-epoxyoctadecanoate (enantio-
meric purity 90%) was developed, starting from ricinolic acid methyl ester.
Derivatives of ricinolic [(9Z,12R)-12-hydroxy-
-octadecenoic] acid are known to exhibit a wide
spectrum of biological activity [1 3]. One of the key
compounds in the chemistry of ricinolic acid is methyl
2-oxo-9,10-epoxyoctadecanoate (I). Due to its high
reactivity compound I can be used for preparation of
a number of practically important substances [1, 4, 5].
Up to now, there were no published data on the syn-
thesis of optically active ketoepoxy ester I.
latter was taken in a 1.5 2-fold excess. The reaction
afforded 95% of methyl 12-hydroxy-9,10-epoxyocta-
decanoate which was formed as a mixture of two dia-
stereoisomers, (9S,10R,12R) (IIIa) and (9R,10S,12R)
(IIIb) at a ratio of 62:38; enantiomeric excess (ee)
9
1
2
0
24%; [ ]
3.25 . Taking into account that neither
D
1
13
H nor C NMR spectra of compounds IIIa and IIIb
were reported, they were identified by epoxidation of
hydroxy ester II with tert-butyl hydroperoxide in the
The goal of the present study was to synthesize
optically active compound I through intramolecular
asymmetric induction of the chiral (R)-center at C12
in the molecule of methyl (9S,12R)-12-hydroxy-9-
octadecenoate (II). The procedure was based on the
epoxidation of the double C C bond in ester II,
followed by oxidation of the 12-hydroxy group to
carbonyl (Scheme 1).
presence of VO(acac) [6], which leads to formation
2
of (9S,10R,12R)-isomer IIIa as the major product
(ee 90%). The configurations of IIIa and IIIb were
1
13
thus determined by comparing the H and C NMR
spectral parameters of the products obtained by the
above two methods.
The reaction of methyl (9Z,12R)-12-acetoxy-9-octa-
decenoate (IV) with monoperoxyphthalic acid in
diethyl ether showed that replacement of the hydroxy
group by acetoxy did not change the stereoselectivity
In the first stage compound II was treated with
monoperoxyphthalic acid as epoxidating agent. The
Scheme 1.
II, III, R = H; IV, V, R = Ac.
_
*
___________
This study was financially supported by the Russian Founda-
tion for Basic Research (project no. 00-15-97325).
1
070-4280/01/3709-1220$25.00 2001 MAIK Nauka/Interperiodica

SYNTHESIS OF OPTICALLY ACTIVE METHYL 12-OXO-9,10-. . .
1221
Scheme 2.
of the process to an appreciable extent. Methyl
9S,10R,12R)- and (9R,10S,12R)-12-acetoxy-9,10-
eluent petroleum ether containing 1 to 100% of di-
2
0
(
ethyl ether) we isolated 7.8 g of ester II, [ ] +4.98 .
D
epoxyoctadecanoates Va and Vb were identified by
acetylation of a 95:5 mixture of hydroxy derivatives
IIIa and IIIb and subsequent comparison of the
H and C NMR spectra. It should be noted that
the reaction of IV with tert-butyl hydroperoxide in
Methyl (9Z,12R)-12-acetoxy-9-octadecenoate
IV) was synthesized by acetylation of ester II with
(
AcCl in benzene in the presence of pyridine, follow-
1
13
20
D
ing the procedure reported in [3], [ ] +21.05 .
Epoxidation of ester II with monoperoxy-
phthalic acid. To a solution of 1.0 g (3.2 mmol) of
ester II in 20 ml of diethyl ether we added dropwise
with stirring at 0 C a solution of 0.9 g (4.8 mmol) of
peroxyphthalic acid in 7 ml of diethyl ether. The
mixture was kept for 3 h at 0 C and was left over-
night at room temperature. It was then filtered,
washed with saturated solutions of Na SO (3 5 ml)
the presence of VO(acac) [6] gave no epoxidation
2
products. Optically active ketoepoxy derivative I
was obtained by oxidation of a mixture of compounds
IIIa and IIIb according to Collins (CrO pyridine).
3
The reaction afforded a mixture of methyl (9S,10R)-
and (9R,10S)-12-oxo-9,10-epoxyoctadecanoates Ia
and Ib in 52 56% yield. From diastereoisomeric mix-
ture IIIa/IIIb enriched in IIIa (95:5) we obtained
compound I with a high enantiomeric purity (ee 90%).
In addition, methyl (10E)-9-hydroxy-12-oxo-10-octa-
decenoate (VI) was isolated as by-product; its yield
did not exceed 4%.
2
3
and Na CO (3 5 ml), dried over MgSO , and
2
3
4
evaporated. By column chromatography on silica gel
L 100/250 m, eluent petroleum ether ethyl acetate,
5:1) we isolated 1 g (95%) of a mixture containing
diastereoisomeric hydroxyepoxides IIIa and IIIb at
(
1
1
3
a ratio of 62:38 (ee 24%, according to the C NMR
EXPERIMENTAL
2
0
data), [ ]
3.25 (c = 11.25, CHCl ). IR spectrum,
D
3
1
13
1
The H and C NMR spectra were recorded on
, cm : 752 (C O C, epoxy group); 1172, 1740
(CO ); 3448 (OH). H NMR spectrum, , ppm (J, Hz):
0.84 t (3H, C H , 7.0), 1.2 1.66 m (22H, CH ),
.67 1.73 m (2H, C H , IIIb), 1.77 t (1H, C H,
IIIa, 4.0), 1.82 t (1H, C H, IIIa, 4.0), 2.28 t (2H,
CH CO , 7.5), 2.87 2.98 m (1H, C H), 3.08 3.17 m
1
1
a Bruker AM-300 spectrometer (300.13 MHz for H
and 75.47 MHz for C) using CDCl as solvent
2
1
3
18
3
3
2
1
1
11
which contained TMS as internal reference. The IR
spectra were measured on a Specord M-80 instrument;
samples were examined as thin films. The UV spec-
trum was obtained on a Specord M-400 spectrophoto-
meter. The mass spectra were run on an MKh-1300
spectrometer. Samples were introduced through
an inlet batch heated to 100 C; energy of ionizing
electrons 12 and 70 eV. The optical rotations were
measured on a Perkin Elmer 241MS polarimeter.
1
2
11
9
2
2
1
0
(
1H, C H), 3.65 s (3H, CO CH ), 3.80 3.93 m (1H,
2 3
1
2
13
C H). C NMR spectrum of IIIa, , ppm: 13.98
C
1
8
17
3
14
(
(
C ), 22.51 (C ), 24.76 (C ), 25.43 (C ), 26.28
7
8
4
5
15
C ), 27.77 (C ), 28.89 (C ), 29.04 (C ), 29.16 (C ),
6
16
2
11
29.20 (C ), 31.72 (C ), 33.90 (C ), 34.73 (C ),
1
3
10
Methyl (9Z,12R)-12-hydroxy-9-octadecenoate
37.30 (C ), 51.34 (CO CH ), 55.18 (C ), 56.27
2 3
9
12
1
13
(
II). To a 0.5% solution of sodium methoxide in
toluene (100 ml) we added dropwise a solution of
0 g of castor oil in 20 ml of toluene. The mixture
(C ), 70.53 (C ), 174.18 (C ). C NMR spectrum of
1
8
17
3
IIIb, , ppm: 13.98 (C ), 22.51 (C ), 24.76 (C ),
C
1
14
7
8
14
2
2
3
5
5.51 (C ), 26.30 (C ), 27.89 (C ), 28.89 (C ),
was stirred for 10 min at 50 C, evaporated by half,
and neutralized with acetic acid. Water, 70 ml, was
added, the mixture was extracted with petroleum
ether, and the extract was washed with water, dried
over Na SO , and evaporated to obtain 9.6 g of
5
15
6
16
9.04 (C ), 29.16 (C ), 29.20 (C ), 31.72 (C ),
2
11
13
3.90 (C ), 35.14 (C ), 37.70 (C ), 51.34 (CO CH ),
2
3
1
0
9
12
1
4.48 (C ), 57.11 (C ), 69.71 (C ), 174.18 (C ).
+
Mass spectrum, m/z: 328 [M] .
2
4
methyl esters derived from fatty acids of castor oil. By
column chromatography on silica gel (L 100/160 m,
Epoxidation of ester II with tert-butyl hydro-
peroxide in the presence of VO(acac) was carried
2
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 9 2001

1
222
DAVLETBAKOVA et al.
out according to the known procedure [6]. From 0.5 g
1.6 mmol) of ester II we obtained 0.51 g (98%) of
a mixture of hydroxyepoxides IIIa and IIIb at a ratio
we added 0.88 g (2.68 mmol) of a mixture of
hydroxyepoxides IIIa and IIIb (ratio 62:38) in
3 ml of CH Cl , and the mixture was stirred for
(
2
2
1
3
of 95:5 (ee 90%, according to the C NMR data),
30 min at 20 C. It was then passed through a layer
of Al O , the sorbent was washed with CHCl , the
2
8
0
0
[
]
8.75 (c = 1.16, CHCl3).
2
3
3
solvent was evaporated, and pyridine was removed
under reduced pressure on heating to 50 C. The
residue, 0.55 g, was subjected to column chromatog-
raphy on silica gel (L 40/100 m; eluent petroleum
ether ethyl acetate, 10:1) to isolate 0.29 g (52%) of
a mixture of ketoepoxides Ia and Ib and 0.02 g (4%)
Epoxidation of ester IV with monoperoxy-
phthalic acid. Following the above procedure, from
a solution of 1 g (2.8 mmol) of ester IV in 20 ml of
diethyl ether and 1 g (5.6 mmol) of monoperoxy-
phthalic acid in 5.4 ml of diethyl ether we obtained
.93 g (90%) of a mixture containing acetoxyepoxides
Va and Vb at a ratio of 54:46 (ee 8%, according to
0
2
0
of ester VI. Mixture Ia/Ib, [ ] +2.12 (c = 1.00,
D
1
13
the 13C NMR data), [ ] +13.88 (c = 11.00, CHCl ).
20
CHCl ). The IR, H and C NMR, and mass spectra
3
D
3
1
of compound I were consistent with those reported
previously [4].
IR spectrum, , cm : 760 (C O C, epoxy group);
240, 1736 (CO ). H NMR spectrum, , ppm (J, Hz):
1
1
0
1
2
1
8
Ester VI. UV spectrum (ethanol), max, nm (log ):
.77 t (3H, C H , 6.6), 1.20 1.67 m (22H, CH ),
3 2
1
1
1
11
223.4 (3.70). IR spectrum, , cm : 976 (trans-C C);
.68 1.75 m (2H, C H , Vb), 1.80 t (1H, C H,
2
1
1
1072, 1472 (OH); 1176, 1732 (CO2); 1376, 1676
Va, 4.6), 1.83 t (1H, C H, Va, 4.5), 1.95 s (3H,
CH CO ), 2.19 t (2H, C H , 7.6), 2.71 2.91 m (2H,
C H, C H), 3.55 s (3H, CO CH ), 4.92 5.10 m
1H, C H). C NMR spectrum of Va, C, ppm:
4.02 (C ), 21.20 (CH CO ), 22.56 (C ), 24.86
C ), 25.20 (C ), 26.47 (C ), 27.94 (C ), 29.01 (C ),
9.06 (C , C ), 29.15 (C ), 31.69 (C ), 32.76 (C ),
1
2
(C O). H NMR spectrum, , ppm (J, Hz): 0.77 t
18
3
2
2
(
(
(
6
1
(
3H, C H , 6.7), 1.12 1.63 m (20H, CH ), 2.21 t
9
10
3
2
2
13
2
3
2H, C H , 7.5), 2.47 t (2H, C H , 7.4), 2.90 br.s
1
2
13
2 2
(
1
(
9
1H, OH), 3.57 s (3H, CO CH ), 4.21 q (1H, C H,
.7), 6.21 d (1H, C H, 15.9), 6.71 d.d (1H, C H,
5.9 and 4.9). C NMR spectrum, , ppm: 13.67
C ), 22.16 (C ), 23.85 (C ), 24.53 t (C ), 24.86
(C ), 28.63 t (C ), 28.69 (C ), 28.78 (C ), 28.95
C ), 31.27 (C ), 33.70 (C ), 36.40 (C ), 40.33 (C ),
1.08 (CO CH ), 70.72 (C ), 127.70 (C ), 148.02
(C ), 173.98 (C ), 200.72 (C ). Mass spectrum,
1
8
17
2 3
11
10
3
2
3
14
8
15
4
13
5
6
7
16
13
C
2
3
5
18
17
3
7
2
11
10
4.06 (C ), 34.33 (C ), 51.41 (OCH ), 53.65 (C ),
14
15
6
4
3
9
12
1
6.10 (C ), 72.39 (C ), 170.60 (CO), 174.19 (C ).
5
16
2
8
13
(
5
1
3
18
C NMR spectrum,
, ppm: 14.02 (C ), 21.20
9
11
C
1
7
3
14
2 3
(
CH CO ), 22.68 (C ), 24.86 (C ), 25.34 (C ),
10
1
12
3
2
8
15
4
5
6
+
2
2
3
6.47 (C ), 27.94 (C ), 29.01 (C ), 29.06 (C , C ),
m/z: 326 [M] .
7
16
13
2
9.15 (C ), 31.69 (C ), 32.62 (C ), 34.06 (C ),
From a mixture of hydroxyepoxides IIIa and IIIb
(0.34 g, 1.04 mmol; ratio IIIa:IIIb 95:5) oxidized
with Collins’ reagent by a similar procedure we ob-
tained 0.34 g of a nonvolatile residue. By column
chromatography we isolated 0.19 g (56%) of Ia/Ib,
1
1
10
4.33 (C ), 51.41 (CO CH ), 53.86 (C ), 56.76
C ), 72.39 (C ), 170.77 (CO), 174.19 (C ). Mass
spectrum, m/z: 370 [M] .
2
3
9
12
1
(
+
Acetylation of hydroxyperoxides IIIa and IIIb.
A solution of hydroxyepoxides IIIa and IIIb (0.5 g,
2
0
[
]
+10.60 (c = 1.0, CHCl3).
D
1
.53 mmol) at a ratio of 95:5, freshly distilled acetic
anhydride (0.16 g, 1.53 mmol), and pyridine (0.15 g,
.84 mmol) in benzene (5 ml) was refluxed for 3 h.
The mixture was cooled and poured into ice water
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1
1
2
.
.
Zabolotskii, D.A. and Myagkova, G.I., Bioorg. Khim.,
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977, vol. 25, no. 7, pp. 1717 1724.
1
(
10 ml), and the products were extracted into Et O
2
(2 1 ml). The extract was washed with 5% hydro-
chloric acid (2 2 ml) and water (2 2 ml), dried over
MgSO , and evaporated to obtain 0.54 g (97%) of
a mixture of acetoxyepoxides Va and Vb at a ratio
of 95:5 (ee 90%, according to the C NMR data),
1
4
3. Jacobson, M. and Jones, W.A., J. Org. Chem., 1962,
vol. 27, no. 7, pp. 2523 2525.
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1
3
2
0
[
]
+11.24 (c = 10.0, CHCl3).
D
no. 6, pp. 467 468.
Oxidation of hydroxyepoxides IIIa/IIIb with
Collins’ reagent. To a mixture of 2.75 g (34.7 mmol)
5. Foglia, T.A., Sonnet, R.E., Nunez, A., and
Dudley, D.L., J. Am. Oil Chem. Soc., 1998, vol. 75,
no. 5, pp. 601 607.
of pyridine and 18 ml of CH Cl we added on cooling
2
2
to 0 C 1.6 g (16 mmol) of CrO in small portions, and
3
the mixture was stirred for 2 h until its color changed
from yellow to red. To the resulting Collins’ reagent
6. Mihelich, E.D., Daniels, K., and Eickhoff, D.J., J. Am.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 9 2001