A concise approach to both enantiomers of phytoprostane B1 type II

Article abstract of DOI:10.1016/j.tetasy.2011.10.005

The synthesis of enantiomeric phytoprostane B₁ type II methyl esters has been accomplished in approximately 30% overall yield via two basic transformations starting from 3-[(dimethoxyphosphoryl)methyl]cyclopentenone as a key reagent. They include ethylation of the ring C(2) carbon and a Horner olefination reaction using the phosphonate moiety at C(3). The novel components of the Horner reaction, the enantiomeric methyl 9-formyl-9-hydroxynanoates, were easily prepared from racemic methyl 9-hydroxy-10-undecenoate via asymmetric Sharpless epoxidation (kinetic resolution) followed by ozonolysis.

Full text of DOI:10.1016/j.tetasy.2011.10.005

Tetrahedron: Asymmetry 22 (2011) 1767–1771
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Tetrahedron: Asymmetry
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A concise approach to both enantiomers of phytoprostane B type II
1
⇑
Wiesława Perlikowska, Marian Mikołajczyk
Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of Heteroorganic Chemistry, Sienkiewicza 112, 90-363 Łód ´z , Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of enantiomeric phytoprostane B1 type II methyl esters has been accomplished in approx-
imately 30% overall yield via two basic transformations starting from 3-[(dimethoxyphospho-
ryl)methyl]cyclopentenone as a key reagent. They include ethylation of the ring C(2) carbon and a
Horner olefination reaction using the phosphonate moiety at C(3). The novel components of the Horner
reaction, the enantiomeric methyl 9-formyl-9-hydroxynanoates, were easily prepared from racemic
methyl 9-hydroxy-10-undecenoate via asymmetric Sharpless epoxidation (kinetic resolution) followed
by ozonolysis.
Received 13 September 2011
Accepted 14 October 2011
Available online 15 November 2011
Ó 2011 Elsevier Ltd. All rights reserved.
1
. Introduction
Phytoprostanes are botanical analogues of prostaglandins.1,2 The
first evidence for their formation in plants was reported by
Parchmann and Mueller in 1998. Phytoprostanes are formed from
CO H
2
3
a
-linolenic acid by a free-radical-catalyzed nonenzymatic mecha-
7
14
11
nism and their levels increase under conditions of enhanced free-
radicalgeneration. Asimplifiedbiosyntheticroutetophytoprostanes
-H
-H
4
B
1
(PPB
1
) 1 and 2 from
a
-linolenic acid is shown in Scheme 1.
CO H
2
Both phytoprostanes PPB
1
type I and II exhibit a wide range of
5
biological activities including the activation of mitogen-activated
protein kinase and the induction of glutathione-S-transferase, de-
fense genes and phytoalexins. They are regarded to be useful as
markers of oxidative degradation of plant-derived food.
Interest in the bioactivity of phytoprostanes has stimulated
much research on the total synthesis of enantiomerically pure com-
pounds belonging to this family.2 With regard to phytoprostane
7
7
CO H
2
O2
O2
1 1
methyl esters 1 (PPB type I) and 2 (PPB type II), the first synthesis
O
O
O
O
7
of their single enantiomers was reported by Durand and
CO H
2
6
co-workers in 2005, who started from 2-(8-carboxyoctyl)furan
7
CO H
2
and 2-propylfuran. In 2009, Riera and co-workers developed a new
OOH
OOH
approach to 1 and 2 using an intermolecular Pauson–Khand reaction
7
of internal alkynes. Our interest in phytoprostanes stemmed from
red.
2
red.
our general strategy toward the synthesis of biologically active
cyclopentenones and cyclopentanones using 3-(phosphorylmeth-
-
H O
H O
2
8
yl)cyclopentenone 3 as a building block. The latter is easily avail-
O
O
9
able and especially useful for the synthesis of 2,3-disubstituted
cyclopentenones because the mesomeric anion generated from 3
CO2H
7
undergoes alkylation mainly at the
carbonyl electrophiles react at the
terms of the Horner olefination reaction (see Scheme 2).
a
-carbonyl carbon atom and
a
-phosphonate carbon atom in
7
CO H
OH
PPB type I, 1
OH
2
1
PPB type II, 2
1
⇑
Corresponding author.
E-mail address: marmikol@cbmm.lodz.pl (M. Mikołajczyk).
1
Scheme 1. Phytoprostanes B biosynthetic pathway.
0
957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.10.005

1
768
W. Perlikowska, M. Mikołajczyk / Tetrahedron: Asymmetry 22 (2011) 1767–1771
vinylmagnesium bromide to afford the desired racemic alcohol
X-Ac
O
R–X
O
16
7.
The spectroscopic properties of (±)-7, in addition to the inter-
O
mediate products, were in accordance with those reported in the
literature.
Base
O
1
4–16
P(OMe)2
P(OMe)2
3
OH
OH
HO
MeOH/H+
95%
HO
O
7
7
6
CO H
2
6
CO2Me
OH
OH
8% NaIO4
Scheme 2. Reactivity of the anion from 3.
7
CH2=CHMgBr
63%
Using cyclopentenone 3 as a key substrate, the synthesis of
enantiomeric prostaglandin B
methyl esters 410 and racemic
rosaprostol 5 was accomplished. Recently, we turned our atten-
7 CO Me
OHC
CO Me
2
2
1
OH
±)-7
7
1
1
(
tion to phytoprostanes and successfully applied our strategy to
1
the synthesis of both enantiomers of phytoprostane 1 (PPB type
I).
1
2
Scheme 4. Synthesis of racemic alcohol 7.
The details of the synthesis of both enantiomeric aldehydes 6
from (±)-7 are outlined in Scheme 5.
OH
O
(
CH ) CO Me
2
6
2
(
CH ) CO H
D-DIPT, TBHP
L-DIPT, TBHP
2
5
2
i
i
Ti(OPr) , MS 4Å
Ti(OPr) , MS 4Å
4
4
(
CH ) Me
(CH ) Me
(±)-7
2
4
2 4
33%
38%
OH
+)- and (-)-4
(
(±)-5
(CH ) CO Me
2 7 2
(CH2)7CO2Me
OH
+)-(S)-7
OH
(-)-(R)-7
(
Continuing our interest in this field, we herein report a straight-
forward and efficient approach to the enantiopure forms of phyto-
prostane B methyl ester 2 starting from 3.
2
0
20
[
α]D = +5.75 (CHCl3)
[α]D = -5.8 (CHCl3)
1
t
BuMe SiCl
Imd., DMF
83%
2
85%
2
. Result and discussion
According to our strategy, cyclopentenone 3 would be elabo-
(CH2)7CO2Me
(CH ) CO Me
2
7
2
rated into 2 via ethylation of the anion of 3 and a subsequent
Horner olefination reaction with the enantiomeric O-tert-butyldi-
methylsilyl protected hydroxyaldehydes 6 as shown in Scheme 3.
t
t
OSiMe Bu
2
OSiMe Bu
2
(
+)-(S)-8
(
[α]
-)-(R)-8
2
0
[
α]
= +6.1 (CHCl3)
20
D
= -6.15 (CHCl3)
D
O
EtI
85%
O , MeOH
81%
3
t
OSiMe Bu
2
HCCH(CH ) CO Me
2
7
2
(
MeO) PO
O
O
2
O
3
(+)- and (-)-6
HC
(CH ) CO Me
2 7 2
HC
(CH2)7CO2Me
Scheme 3. Synthetic plan for 2 (PPB
1
type II).
t
t
OSiMe Bu
2
OSiMe Bu
2
(
-)-(S)-6
D
(+)-(R)-6
D
A literature search revealed that the required enantiomers of 6
have not been previously prepared or described. However, we
found that a potential precursor of 6, methyl (S)-9-hydroxy-10-
20
20
[
α]
= -20.6 (CHCl3)
[α]
= +21.0 (CHCl3)
Scheme 5. Synthesis of enantiomeric aldehydes 6.
1
3
undecenoate 7, has been obtained by Miura and Kuwahara by
subjecting racemic alcohol (±)-7 to the Sharpless kinetic resolution
conditions. As a result we decided to prepare both enantiomeric
alcohols 7, which after protection of the hydroxy group and ozon-
olysis of the double bond, should afford enantiomeric aldehydes 6
as components of the Horner reaction.
Thesynthesisstartedwiththe enantioselectiveSharplessepoxida-
tionof(±)-7performedunderkineticresolutionconditions. According
1
3
totheproceduredescribedbyMiuraandKuwahara, theasymmetric
epoxidation of(±)-7 with tert-butylhydroperoxide(TBHP)inthe pres-
ence of (ꢀ)-
D-diisopropyl tartrate (DIPT) and tetraisopropoxytitani-
2
.1. Synthesis of aldehydes (ꢀ)-(S)-6 and (+)-(R)-6
um gave a mixture of the unoxidized alcohol (+)-(S)-7 and the
correspondingepoxide. The isolated (+)-(S)-7 exhibited the samespe-
2
D
0
Herein compound (±)-7 was prepared by a three-step reaction
cific rotation, ½
aꢁ
3
¼ þ5:75 (CHCl ), as that reported by the earlier
sequence from commercially available aleuritic acid (Scheme 4).
Its acid-catalyzed methanolysis gave the corresponding methyl es-
ter, which was subjected to oxidative cleavage with sodium
authors. The enantiomeric excess of this alcohol (determined by the
Mosher method) was found by the authors to be >98%. When we used
1
4
(+)-L-diisopropyl tartrate (DIPT), the epoxidation reaction afforded
1
5
20
D
metaperiodate. The aldehydoester isolated was treated with
the unreacted alcohol (ꢀ)-(R)-7 with ½
aꢁ
3
¼ ꢀ5:8 (CHCl ). The same

W. Perlikowska, M. Mikołajczyk / Tetrahedron: Asymmetry 22 (2011) 1767–1771
1769
2
D
0
enantiomer of 7 with ½
aꢁ
¼ ꢀ3:41 (CHCl
3
) was earlier obtained from
3
racemic 7 by lipase-catalyzed enantioselective acetylation by Yokok-
awa et al. The ee value of this sample (as determined by the Mosher
method) was reported to be 99%. To clear this discrepancy, we
1
. NaH, DMSO
4
6%
1
7
2. EtI
O
1
checked up the enantiomeric purity of alcohol 7 by the H NMR meth-
(+)-(R)-6
(-)-(S)-6
O
od using (ꢀ)-(S)-tert-butylphenylphosphinothioic acid (t-BuPhPSOH)
as a chiral solvating agent.18
P(OMe)2
It was found that magnetic non-equivalence of the diastereo-
meric solvates of (±)-7 formed with this chiral thiophosphinic acid
9
DBU
83%
8
5%
DBU
LiClO
LiClO
4
4
is clearly visible for the terminal vinylic protons, which appear in
1
the H NMR spectrum as two well separated (
D
d = 6.7 Hz) double
O
O
doublets as shown in Figure 1a. As the solvate with alcohol (+)-
1
3
(
S)-7 obtained by Miura and Kuwahara and by us herein showed
1
only one double doublet in the H NMR spectrum (see Fig. 1c), the
enantiomeric excess (ee) of this alcohol should be above 96%.
7
7
CO Me
2
CO Me
2
OSiMe2But
t
OSiMe Bu
2
E-(+)-(R)-10
E-(-)-(S)-10
D
2
0
[α]D20 = +2.2 (CH Cl )
[
α]
= -2.1 (CH Cl )
2
2
2
2
Bu NF
4
Bu NF
80%
4
83%
THF
THF
O
O
7
7
CO Me
CO2Me
2
OH
OH
E-(+)-(S)-2
E-(-)-(R)-2
2
0
20
[
α]D = +24.0 (MeOH)
[α]D = -24.1 (MeOH)
1
Scheme 6. Synthesis of enantiomeric phytoprostane B type II methyl esters 2.
of 2,3-disubstituted cyclopentanones. This is shown in Scheme 6
and is also briefly discussed below.
Thus, the anion generated from 3 under the standard conditions
(
NaH, DMSO) was treated with ethyl iodide to give cyclopentenone
in 46% yield. The Horner reaction of the latter with aldehydes
ꢀ)-(S)-6 and (+)-(R)-6 afforded the corresponding olefination
products E-(ꢀ)-(S)-10 and E-(+)-(R)-10, respectively, in good yields
>80%). As in the case of the synthesis of phytoprostane B1 methyl
ester 1, the olefination reaction was performed using DBU–LiClO
9
(
(
4
as a mildly basic system to avoid racemization of the enantiomeric
aldehydes 6. Finally, desilylation of both enantiomers of 10 with
tetrabutylammonium fluoride in THF at room temperature gave
the desired targets (+)-(S)-2 and (ꢀ)-(R)-2. Their CD spectra show
a typical mirror image relationship with Cotton effects that are
negative at 220 nm and positive at 275 nm for the enantiomer
(
+)-(S)-2 (see Fig. 2).
Figure 1. 1H NMR spectra of the vinylic CH
tert-BuPhPSOH with (a) racemic alcohol 7; (b) alcohol 7 enriched with the (+)-(S)-
protons of a mixture (1.3:1) of (ꢀ)-(S)-
2
2
D
0
enantiomer; (c) alcohol (+)-(S)-7, ½
aꢁ
¼ þ5:75 (CHCl
3
).
Having obtained the practically enantiopure alcohols (+)-(S)-
and (ꢀ)-(R)-7, we were able to convert them into the required
aldehydes 6 in two steps; the protection of the hydroxy group by
tert-butyldimethylsilyl chloride and ozonolysis of the carbon–car-
bon double bond in both silylated alcohols 8.
2
.2. Synthesis of phytoprostane B
1
methyl esters (+)-(S)-2 and
(ꢀ)-(R)-2
With both enantiomerically pure aldehydes 6 in hand, we were
able to carry out the synthesis of enantiomeric phytoprostanes B
methyl esters 2 according to our general strategy for the synthesis
1
1
Figure 2. CD spectra of enantiomeric phytoprostane B methyl esters 2.

1
770
W. Perlikowska, M. Mikołajczyk / Tetrahedron: Asymmetry 22 (2011) 1767–1771
3
. Conclusion
4.4. Methyl 9-(tert-butyldimethylsilyloxy)-9-formyl-
nonanoates (ꢀ)-(S)-6 and (+)-(R)-6
In conclusion, a new efficient synthesis of both enantiomers of
methyl ester of phytoprostane B1 type II has been accomplished.
The synthesis involves the two-step functionalization of 3-
To a cooled solution of (+)-8 (0.83 g, 2.53 mmol) in dry metha-
nol, ozone was passed at ꢀ60 °C. When the stirred reaction solu-
tion turned blue, the reaction was quenched with dimethyl
sulfite (1 mL). After evaporation of the solvent and purification
by column chromatography on silica gel (PE–acetone, 100:5), alde-
hyde (ꢀ)-(S)-6 was obtained as a colorless liquid (0.70 g, 85%).
[
(dimethoxyphosphoryl)methyl]cyclopent-2-enone 3 [alkylation at
C(2) and Horner olefination]. The synthesis compares favorably in
terms of the use of simple reagents and transformations with the
previously reported syntheses. Moreover, our synthesis is modular
and can provide easy access to a variety of phytoprostane analogues.
2
D
0
1
½
aꢁ
¼ ꢀ20:6 (c 2.57, CH
2 2 3
Cl ). H NMR (200 MHz, CDCl ): d 0.06
(
s, 3H), 0.07 (s, 3H), 0.91 (s, 9H), 1.02–1.61 (m, 12H), 2.29 (t,
J = 7.5 Hz, 2H), 3.66 (s, 3H), 3.94 (dt, J = 6.4, 1.5 Hz, 1H), 9.58 (d,
4
4
. Experimental
1
3
J = 1.5 Hz, 1H). C NMR (50 MHz, CDCl
3
): d ꢀ4.9, ꢀ4.6, 18.2, 24.5,
2
4.9, 25.7, 29.0, 29.2, 32.6, 34.0, 51.4, 174.2, 204.3. HRMS (EI):
.1. General
+
Calcd for C16
H
33
O
3
Si (M ꢀCHO) 301.2195. Found: 301.2199.
According to the procedure described above, (ꢀ)-8 (0.94 g,
Melting points and boiling points are uncorrected. THF was dis-
2
.87 mmol) afforded the aldehyde (+)-(R)-6 (0.77 g, 81%)
tilled over K/benzophenone, and benzene was distilled over Na
wire, both immediately before use. CH Cl was distilled over
and stored over anhydrous Na CO . All reactions under anhy-
2
0
½
aꢁ
2 2
¼ þ21:0 (c 2.32, CH Cl ).
D
2
2
P
2
O
5
2
3
drous conditions were carried out under a dry argon atmosphere.
Column chromatography was performed using Merck silica gel
4.5. 2-Ethyl-3-[(dimethoxyphosphoryl)methyl]cyclopent-2-
enone 9
(
70–230 mesh). Reaction mixtures were analyzed by TLC using
Merck 60 F254 TLC plates. NMR spectra were recorded on a Bruker
AC 200 instrument at 200 MHz for H, 81 MHz for P, and 50 MHz
To a stirred solution of cyclopentenone 3 (3.7 g, 18.3 mmol)
and ethyl iodide (2.86 g, 18.3 mmol) in DMSO (35 mL) was added
NaH (50% in oil, 0.97 g, 20.1 mmol) at 0 °C. The reaction mixture
was stirred for 3 h at room temperature after which a saturated
1
31
1
3
1
for C with CDCl
3
as the solvent, unless noted otherwise. H and
1
3
C chemical shifts are reported relative to TMS as the external
3
1
standard. P NMR downfield chemical shifts are expressed with
a positive sign relative to an external standard of 85% H PO . HRMS
were recorded on a Finnigan MAT 95 apparatus. IR spectra were re-
corded with IR-FT apparatus. Optical rotations were measured at
aqueous solution of NH
tion was extracted with CHCl
was dried over MgSO and evaporated in vacuo (60 °C,
4
Cl (25 mL) was added. The resulting solu-
3
(3 ꢂ 25 mL) and the organic layer
3
4
4
0.01 mm Hg). The residue was purified by column chromatogra-
2
0 °C using a Perkin-Elmer MC 241 photopolarimeter. CD spectra
phy (PE–acetone, 2:1) to give the pure product 9 (1.95 g, 46%) as
31
were recorded on CD 6 dichrograph (Jobin-Yvon) in CH
tions using cells with 0.1 mm pathlength.
2
Cl
2
solu-
a colorless liquid. IR(film):
NMR (81 MHz, CDCl ): d 26.16: H NMR (200 MHz, CDCl
.95 (t, J = 7.6 Hz, 3H, CH CH ), 2.16 (q, J = 7.6 Hz, 2H, CH CH
2.31–2.40 (m, 2H, ring CH ), 2.52–2.64 (m, 2H, ring CH ), 2.93
), 3.71 (d, J = 11.1 Hz, 6H, POCH
): d 12.4, 16.5, 27.6, 28.9 (d, J = 133 Hz),
m
1695, 1644, 1254, 1052, 1032;
P
1
3
3
): d
),
0
2
3
2
3
4
.2. Methyl 9-hydroxy-10-undecenonates (+)-(S)-7 and (ꢀ)-(R)-7
Prepared by the procedure described by Miura and Kuwahara.13
2
2
13
(
d, J = 24.1 Hz, 2H, PCH
2
3
).
C
NMR (50 MHz, CDCl
3
Starting from racemic alcohol 7 (2.7 g, 12.7 mmol), (+)-(S)-7 was
obtained (0.877 g, 33% of the theoretical amount) as a pale yellow
oil by column chromatography on silica gel (PE–acetone, 15:1).
30.3, 34.3, 52.8 (d, J = 6.4 Hz), 144.6 (d, J = 10.8 Hz), 161.0 (d,
J = 11 Hz), 208.6. HRMS(EI): Calcd for C10H17PO 232.0864. Found:
4
232.0864.
20
1
½
a
ꢁ
¼ þ5:75 (c 1.2, CHCl
3 3
). H NMR (200 MHz, CDCl ): d 1.29–
D
1.49 (m, 8H), 152–160 (m, 4H), 1.80 (br s, 1H), 2.28 (t, J = 7.4 Hz,
2H), 3.64 (s, 3H), 4.04 (q, J = 6.3 Hz, 1H), 5.07 (d, J = 10.4 Hz, 1H),
5.20 (d, J = 17.2 Hz, 1H), 5.85 (ddd, J = 6.3 Hz, 10.4, 17.2 Hz, 1H).
From (±)-7 (2.6 g, 12.1 mmol), (ꢀ)-(R)-7 was isolated (1 g, 38%
4.6. 10E-Methyl 11-(2-ethyl-3-oxo-cyclopent-1-enyl)-9-tert-
butyldimethylsilyloxy-undec-10-enoates (ꢀ)-(S)-10 and (+)-(R)-
10
of the theoretical amount) as a pale yellow oil after column chro-
matography ½
4
To cyclopentenone 9 (0.288 g, 1.24 mmol) and LiClO (0.132 g,
2
0
a
ꢁ
¼ ꢀ5:8 (c 1.1, CHCl
3
).
1.24 mmol) was added THF (1 mL) with a syringe. To this stirred
mixture, DBU (0.185 mL, 1.24 mmol) was added and then a solu-
tion of aldehyde (ꢀ)-(S)-6 (0.549 g, 166 mmol) in THF (0.5 mL).
The mixture was stirred for 3 h at room temperature and the crude
product was purified by column chromatography on silica gel (PE–
acetone, 8:1) to afford the pure E-(ꢀ)-(S)-10 as an oil (0.46 g, 85%).
D
4
.3. Methyl 9-(tert-butyldimethylsilyloxy)-10-undecenoates (+)-
(S)-8 and (ꢀ)-(R)-8
Silylation of both enantiomeric alcohols 7 was carried out as de-
2
D
0
1
3
scribed in the literature. Purification of products 8 was carried
out by column chromatography on silica gel (PE–acetone, 100:1)
From (+)-(S)-7 (0.87 g, 4.06 mmol), the TBDMS-protected dex-
trorotatory alcohol (+)-(S)-8 was obtained (1.1 g, 83%) as a pale yel-
½
aꢁ
¼ ꢀ2:1 (c 1.86, CH
2
Cl
2
). IR (film):
m 2931, 1740, 1694, 1643,
1
1601, 777. H NMR (200 MHz, CDCl
3
): 0.01 (s, 3H), 0.04 (s, 3H),
0.89 (s, 9H), 0.97 (t, J = 7.4 Hz, 3H), 1.22–1.41 (m, 8H), 1.46–1.61
(m, 4H), 2.13–2.36 (m, 4H), 2.38–2.42 (m, 2H), 2.56–2.60 (m,
2H), 3.62 (s, 3H), 4.27 (q, J = 5.4 Hz, 1H), 6.20 (dd, J = 5.4,
2
D
0
19 1
low oil. ½
a
ꢁ
¼ þ6:1 (c 2.97 CHCl
3
).
3
H NMR (200 MHz, CDCl ): d
1
3
0
.02 (s, 3H), 0.04 (s, 3H), 0.89 (s, 9H), 1.28–140 (m, 8H), 1.42–1.52
3
15.6 Hz), 6.74 (d, J = 15.6 Hz, 1H). C NMR (50 MHz, CDCl ): d
(
(
5
m, 2H), 1.54–1.64 (m, 2H), 2.29 (t, J = 7.4 Hz, 2H), 3.66 (s, 3H), 4.02
q, J = 5.9 Hz, 1H), 5.00 (d, J = 10.5 Hz, 1H), 5.12 (d, J = 17.2 Hz, 1H),
ꢀ4.8, ꢀ4.5, 13.5, 16.2, 18.4, 24.8, 24.9, 25.0, 25.6, 25.7, 25.8, 29.0,
29.1, 29.4, 33.8, 34.0, 37.9, 51.4, 72.7, 122.9, 141.1, 142.2, 163.1,
.78 (ddd, J = 6.0, 10.3, 17.1 Hz, 1H). 13C NMR (50 MHz, CDCl
3
): d
174.2, 209.4. HRMS(EI): Calcd for C25
436.3009.
4
H44SiO 436.3007. Found:
ꢀ
4.8, ꢀ4.4, 18.3, 25.0, 25.1, 25.9, 29.1, 29.2, 29.4, 34.1, 38.0, 51.4,
7
3.8, 113.4, 141.9, 174.3.
According to the procedure described above (+)-(R)-6 (0.78 g,
Silylation of (ꢀ)-(R)-7 (1.0 g, 4.67 mmol) gave (ꢀ)-(R)-8 (1.3 g,
2.37 mmol) was converted into E-(+)-(R)-10 (0.66 g, 83%).
2
D
0
20
D
8
5%) as a yellow oil. ½
aꢁ
¼ ꢀ6:15 (c 2.77, CHCl
3
).
½
aꢁ
2 2
¼ þ2:2 (c 1.73, CH Cl ).

W. Perlikowska, M. Mikołajczyk / Tetrahedron: Asymmetry 22 (2011) 1767–1771
1771
4
.7. Phytoprostanes B
1
type II. 10-E-Methyl 11-(2-ethyl-3-oxo-
3. Parchmann, S.; Mueller, M. J. J. Biol. Chem. 1998, 273, 32650–32655.
4.
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Krischke, M.; Loeffler, C.; Mueller, M. J. Phytochemistry 2003, 62, 351–358; (c)
Thoma, I.; Krischke, M.; Loeffler, C.; Mueller, M. J. Chem. Phys. Lipids 2004, 128,
cyclopent-1-enyl)-9-hydroxyundec-10-enoates (+)-(S)-2 and
(ꢀ)-(R)-2
135–148.
5
.
(a) Imbusch, R.; Mueller, M. J. Plant Physiol. 2000, 124, 1293–1304; (b) Thoma,
I.; Loeffler, C.; Sinha, A. K.; Gupta, M.; Krischke, M.; Steffan, B.; Rotisch, T.;
Mueller, M. J. Plant J. 2003, 34, 363–375; (c) Traidl-Hoffmann, C.; Mariani, V.;
Hochrein, H.; Karg, K.; Wagner, H.; Ring, J.; Mueller, M. J.; Jakob, T.; Behrendt, H.
J. Exp. Med. 2005, 201, 627–636; (d) Loeffler, C.; Berger, S.; Guy, A.; Durand, T.;
Birngmann, G.; Dreyer, M.; Von Rad, U.; Durner, J.; Mueller, M. J. Plant Physiol.
To a 1 M solution of Bu
4
NF in THF (4.4 mL, 4.4 mmol) was added
+)-10 (0.63 g, 1.45 mmol) in THF (2 mL). Stirring was continued
(
for 1.5 h at room temperature. Then, the reaction solution was fil-
tered through silica gel (10 g) and washed with THF (20 mL). The
solvent was removed in vacuo and the crude product was purified
by column chromatography (PE–acetone, 3:1) to give E-(ꢀ)-(R)-2
6
2
005, 137, 328–340.
6. El Fangour, S.; Guy, A.; Vidal, J.-P.; Rossi, J.-C.; Durand, T. J. Org. Chem. 2005, 70,
89–997.
2
D
0
9
as a yellow oil. (0.39 g, 83%). ½
a
ꢁ
¼ ꢀ24:1 (c 2.07, MeOH) {Lit.
2
D
0
1
7. Vázquez-Romero, A.; Cárdenas, L.; Blasi, E.; Verdaguer, X.; Riera, A. Org. Lett.
½
aꢁ
¼ ꢀ24 (c 1.0, MeOH)}. H NMR (200 MHz, CDCl
3
): d 0.96 (t,
2009, 11, 3104–3107.
J = 7.4 Hz, 3H), 1.28–1.50 (m, 8H), 1.55–1.65 (m, 4H), 2.14–2.30
8. (a) Mikołajczyk, M.; Mikina, M.; Z_ urawi n´ ski, R. Pure Appl. Chem. 1999, 71, 473–
480; (b) Mikołajczyk, M.; Bałczewski, P. Top. Curr. Chem. 2002, 223, 161–214.
(
(
m, 4H), 2.35–2.42 (m, 2H), 2.55–2.63 (m, 2H), 3.62 (s, 3H), 4.27
9
.
For the synthesis of 3 see: (a) Oehler, E.; Zbiral, E. Synthesis 1991, 357–361; (b)
Mikołajczyk, M.; Mikina, M. J. Org. Chem. 1994, 59, 6760–6765; (c) Mphahlele,
M. J.; Modro, T. A. J. Org. Chem. 1995, 60, 8235–8240; (d) Mikołajczyk, M.;
Perlikowska, W. Synthesis 2007, 1225–1229.
dt, J = 5.8, 11.9 Hz, 1H), 6.22 (dd, J = 5.8, 15.7 Hz, 1H), 6.74 (d,
1
3
J = 15.7 Hz, 1H). C NMR (50 Hz, CDCl
3
): d 13.4, 16.2, 24.7, 25.2,
2
1
5.5, 28.9, 29.0, 29.2, 33.8, 33.9, 37.1, 51.4, 72.1, 123.5, 140.5,
42.5, 163.1, 174.3, 209.8.
In a similar manner, enantiomer E-(+)-(S)-2 was obtained (0.19 g,
1
1
0. Mikołajczyk, M.; Mikina, M.; Jankowiak, A. J. Org. Chem. 2000, 65, 5127–5130.
1. Mikołajczyk, M.; Mikina, M.; Jankowiak, A.; Mphahlele, M. J. Synthesis 2000,
1075–1077.
2
D
0
8
{
0%) from (ꢀ)-10 (0.32 g, 0.73 mmol) ½
a
ꢁ
¼ þ24:0 (c 2.30, MeOH)
12. Perlikowska, W.; Mikołajczyk, M. Synthesis 2009, 65, 3364–3368.
13. Miura, A.; Kuwahara, S. Tetrahedron 2009, 65, 3364–3368.
6
20
D
Lit. ½
a
ꢁ
¼ þ24 (c, 1.0, MeOH)}.
1
1
4. Malkar, N. B.; Kumar, V. G. Synth. Commun. 1998, 28, 977–993.
5. Pawar, A. S.; Sankaranarayanan, S.; Chattopadhyay, S. Tetrahedron: Asymmetry
1995, 6, 2219–2226.
Acknowledgment
16. Kai, J. K.; Takeuchi, J.; Kataoka, T.; Yokoyama, M.; Watanabe, N. Tetrahedron
2
008, 64, 6760–6769.
Financial support by the Ministry of Science and Higher
Education (Grant No. PBZ-KBN-126/T09/2004) is gratefully
acknowledged.
1
7. Yokokawa, Y.; Kobayashi, K.; Yokoyama, M.; Yamamura, S. Chem. Lett. 2003, 32,
844–845.
8. Omela n´ czuk, J.; Mikołajczyk, M. Tetrahedron: Asymmetry 1996, 7, 2687–2694.
9. In our hands, the silylation of (+)-(S)-7 produced (+)-(S)-8. The opposite sign of
rotation of the latter reported by Miura and Kuwahara13 is most probably due
to a typographical error.
1
1
References
1
2
.
.
Mueller, M. J. Curr. Opin. Plant Biol. 2004, 7, 441–448.
For a recent review on phytoprostanes see: Durand, T.; Bultel-Poncé, V.; Guy,
A.; Berger, S.; Mueller, M. J.; Galano, J. M. Lipids 2009, 44, 875–888.