Synthesis and biological activity of α,β,γ,δ-unsaturated aldehydes from diatoms

Article abstract of DOI:10.1016/S0040-4020(03)00382-X

α,β,γ,δ-Unsaturated aldehydes have gained increasing attention since 2,4-decadienal and 2,4,7-decatrienal were isolated from the diatom Thalassiosira rotula and characterized as cell antiproliferative metabolites. Structurally related α,β,γ,δ-unsaturated aldehydes were found in this alga as well as in other diatom species. We present a short and universal synthesis of this compound class along with a structure-activity study of the potential to inhibit sea urchin egg cleavage. Pd⁰- or Co^II-mediated cross coupling of 5-iodo-penta-2,4-dienal with organo-zincates allows the fast and flexible synthesis of numerous aldehydes from this universal precursor. The stereochemistry of the double bond system of the precursor was preserved during the coupling. Bioassays showed that the polarity of the side chain is important for antiproliferative activity with 2,4-decadienal as the most active compound tested compared to the shorter-chain aliphatic homologues and to ω-oxo acids with conjugated double systems. In contrast, the double bond geometry has no influence on biological activity. The α,β-unsaturated 2E-decenal was also highly active, while activity diminished in the case of saturated aldehydes of similar chain length. 1-Decanol, 2-decanone and decanoic acid were not active.

Full text of DOI:10.1016/S0040-4020(03)00382-X

Tetrahedron 59 (2003) 3003–3008
Synthesis and biological activity of a,b,g,d-unsaturated aldehydes
from diatoms
a
Sven Adolph, Serge A. Poulet and Georg Pohnert
b
a,*
a
¨
Max-Planck-Institut f u¨ r chemische Okologie, Winzerlaer Str. 10, D-07745 Jena, Germany
b
Station Biologique, CNRS, INSU, UPM, BP 74, F-29682 Roscoff, France
Received 16 January 2003; revised 10 March 2003; accepted 13 March 2003
Abstract—a,b,g,d-Unsaturated aldehydes have gained increasing attention since 2,4-decadienal and 2,4,7-decatrienal were isolated from
the diatom Thalassiosira rotula and characterized as cell antiproliferative metabolites. Structurally related a,b,g,d-unsaturated aldehydes
were found in this alga as well as in other diatom species. We present a short and universal synthesis of this compound class along with a
0
II
structure–activity study of the potential to inhibit sea urchin egg cleavage. Pd - or Co -mediated cross coupling of 5-iodo-penta-2,4-dienal
with organo-zincates allows the fast and flexible synthesis of numerous aldehydes from this universal precursor. The stereochemistry of the
double bond system of the precursor was preserved during the coupling. Bioassays showed that the polarity of the side chain is important for
antiproliferative activity with 2,4-decadienal as the most active compound tested compared to the shorter-chain aliphatic homologues and to
v-oxo acids with conjugated double systems. In contrast, the double bond geometry has no influence on biological activity. The a,b-
unsaturated 2E-decenal was also highly active, while activity diminished in the case of saturated aldehydes of similar chain length.
1
-Decanol, 2-decanone and decanoic acid were not active. q 2003 Elsevier Science Ltd. All rights reserved.
1 1
similar thresholds of ca. 1 mg L2 . Previous studies with
1. Introduction
sea urchin eggs found comparable effects and threshold
5
concentrations. It was concluded that these aldehydes in
Diatoms are among the most abundant algae in phyto-
plankton and contribute significantly to global carbon
fixation. These unicellular algae are also an important
basis of the marine food chain. Despite their significance,
little is known about their chemical defence. Recently, it
was reported that 2E,4E/Z-decadienal (1ab), and 2E,4E/Z,
the copepod maternal diet reduce the viability of the
offspring, thus acting as a wound-activated chemical
defence. Besides 2E,4E/Z-decadienal (1ab), and 2E,4E/
Z,7Z-decatrienal (4ab), other a,b,g,d-unsaturated aldehydes
have been identified after cell disruption of diatoms
2
–8
7
rotula act antiproliferatively against herbivorous
Z-decatrienal (4ab) from the marine diatom Thalassiosira
(Scheme 1).
1
copepods. These aldehydes are derived from the lipoxy-
genase/hydroperoxid lyase dependent degradation of
arachidonic or eicosapentaenoic acid that takes place
T. rotula releases in addition the shorter-chain unsaturated
aldehydes 2E,4E/Z-heptadienal (3ab), 2E,4E/Z-octadienal
(2ab) and 2E,4E,7-octatrienal (5) as well as elevated
2
–4
5,7
within seconds after wounding of the diatom cells.
If
amounts of saturated aldehydes. Skeletonema costatum
and S. pseudocostatum release predominantly 2E,4E/
administered to copepod eggs 2E,4E/Z-decadienal (1ab),
and 2E,4E/Z,7Z-decatrienal (4ab) inhibit cell cleavage with
5
,8
Z-heptadienal (3ab) and 2E,4E/Z-octadienal (2ab),
Scheme 1. a,b,g,d-Unsaturated alehydes from diatoms.
Keywords: aldehydes; 2,4-dienals; synthesis; cell division; diatoms; Michael-acceptor; bioassays.
*
Corresponding author. Tel.: þ49-3641-571258; fax: þ49-3641-571256; e-mail: pohnert@ice.mpg.de
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00382-X

3004
S. Adolph et al. / Tetrahedron 59 (2003) 3003–3008
while the fresh-water diatoms Gomphonema parvulum and
Asterionella formosa produce 9-oxo-nona-5Z,7E-dienoic
acid (7b) and 12-oxo-dodeca-5Z,8Z,10E-trienoic acid (6a),
completing the aliphatic or carboxylic chains of the target
molecules. Using 5-iodo-penta-2E,4E-dienal (9a) or 5-iodo-
penta-2E,4Z-dienal (9b) as key-intermediates, we could
exploit the pre-formed a,b,g,d-unsaturated aldehyde for
coupling reactions and finish the aldehydes with both
isomers of the g,d-double bond in one reaction step. The
coupling protocols proved to be tolerant to aliphatic esters,
allowing build-up of unsaturated v-oxo-acids from the same
precursors in two steps. 5-Iodo-penta-2E,4E/Z-dienal (9ab)
thus serves as an universal key-intermediate that allows the
flexible generation of a,b,g,d-unsaturated aldehydes.
2
,3
respectively. Despite the potential role of these aldehydes
in the chemical defence of diatoms, no detailed structure-
activity investigation has been reported and the few
1
,5,8
bioassays
mercially available mixtures of 2E,4E-decadienal (1a) and
E,4Z-decadienal (1b).
rely on purified material or crude com-
2
Here we present a short synthesis of isomerically pure
a,b,g,d-unsaturated aldehydes, a compound class also
known as inhibitors of embryonic development of marine
The iodide 9ab could be generated on a multigram scale in
two steps following known procedures as a 55:45 mixture of
9
invertebrates, as cytotoxic agents against human erythro-
1
0
11
16,17
cytes, as DNA-alkylating agents, and, fused to phos-
2
pholipids, as potential signalling molecules in mammals.
2E,4E- and 2E,4Z-isomers.
This mixture was purified
1
by flash chromatography on florisil using a binary solvent of
petrol-ether: THF (99:1) as mobile phase. Both isomers can
be separated and stored for several months at 2208C in a
benzene matrix. The coupling reactions of 9a with
organozincates or dialkyl zinc reagents proceeded
smoothly, retaining the configuration of the double bonds
using Pd(PPh ) as a catalyst (Scheme 2, Table 1). In
The biological activity of the aldehydes found in diatoms
was characterized by their potential to inhibit cell division in
sea urchin eggs, and the activity was compared with other
short chain fatty acids, ketones, and aldehydes.
3
4
2
. Results and discussion
contrast, application of this protocol to the coupling of 9b
yielded primarily the more stable undesired 4E-isomers.
The isomerization during the coupling reaction can be
exploited to generate 2E,4E-dienals from isomeric mixture
of the iodide 9ab without prior separation. In contrast to
2
.1. Synthesis of a,b,g,d-unsaturated aldehydes
The importance of a,b,g,d-unsaturated aldehydes as
biologically active molecules as well as building blocks
for polyenes resulted in numerous synthesis of these
compounds. These often rely on deprotection and oxidation
of alcohols in the final reaction steps, generate the
unsaturated aldehydes by electrocyclic ring opening of
0
previously reported stereoselective cross couplings with Pd
1
8
and vinylic iodides that rely on a kinetic discrimination of
the educts, here the entire pool of 4E- and 4Z-isomers of the
iodide are transformed predominantly to 2E,4E-dienals.
2
1
3
cyclobutenes or use Wittig-procedures in multistep-
2
Using cobalt-catalyzed alkenylation of zinc organo-
19
1
approaches. Other sequences do not provide access to
1
both isomers of the double bond at C4-position or allow
metallics, this isomerization could be prevented and the
isomeric purity of 9b was conserved during the coupling
(Scheme 2, Table 1).
4
1
5
only the generation of the 2Z-isomers. Our aim was to
synthesize the set of a,b,g,d-unsaturated aldehydes found in
diatoms with a minimum number of manipulations after
This Co(acac) -mediated coupling could also be applied to
2
Scheme 2. Transition-metal mediated coupling of vinylic iodides.
Table 1. Transition metal-mediated preparation of a,b,g,d-unsaturated aldehydes
Metal species
Catalyst
Reaction time (min)
T (8C)
Yield
a
C
C
C
C
5
5
3
2
H
H
H
H
11ZnBr
11ZnBr
Pd(PPh
3
)
4
2
2
2
2
2
20
15
30
30
30
30
278
1a 79% (4E/Z.95/5)
1b 81% (4E/Z,5/95)
b
Co(acac)
Co(acac)
Co(acac)
Co(acac)
Co(acac)
230–0
230–0
230–0
230–0
230–0
c
c
c
c
7
5
ZnBr
ZnBr
2a,b 47% (4E/Z¼55/45)
3a,b 49% (4E/Z¼55/45)
7a,b 49% (5E/Z¼55/45)
8a,b 53% (9E/Z¼55/45)
(
(
EtOOCC
MeOOCC
3
H
6
)
2
Zn
Zn
7
H
14
)
2
a
b
c
From pure 2E,4E-iodide 9a.
From pure 2E,4Z-iodide 9b.
From the 2E,4E/Z-mixture of 9ab.

S. Adolph et al. / Tetrahedron 59 (2003) 3003–3008
3005
2
E,4E/Z-mixtures of the vinylic iodide 9ab without loss of
for the inhibition of cell cleavage. To exclude the possible
influence of isomerization or degradation during the assay
period, we checked the stability of 2E,4Z-decadienal (1b) in
seawater. If added as DMSO solution to filtered seawater in
comparable concentrations to those used in the assay,
2E,4Z-decadienal (1b) (4E/Z.95/5) is stable over the 2–3 h
assay period. Only slow isomerization to the thermo-
dynamically more stable 2E,4E-decadienal (1a) is observed
at 228C with an isomeric composition of 1b to 1a (85/15)
after 24 h. Thus the similar activity of the respective isomers
in the bioassay is not due to their fast interconversion. In this
context it is noteworthy, that T. rotula releases isomeric
the configuration of the double bonds giving access to
mixtures of 4E and 4Z isomers. Since the isomers of
a,b,g,d-unsaturated aldehydes are easily separable by
column chromatography on SiO , we simplified the
2
preparation of a multitude of isomeric dienals by reacting
the mixture of 2E,4E/Z-vinylic iodides 9ab with the
respective alkylzincates and separating the resulting
aliphatic aldehydes.
To generate the v-oxo-acids 7ab and 8ab, we used 4-iodo-
butanoic acid ethyl ester or 8-iodo-octanoic acid methyl
ester which had been transformed to the di-alkanoic acid
ester-zinc-compounds using diethylzinc. These were
coupled with the iodide 9ab using Co(acac)2 and the
purified products were saponified with porcine liver esterase
7
mixtures of 2E,4E/Z-decadienal 1ab. This seems to be the
result of the biosynthesis and not of an abiotic isomeriza-
tion, since both isomers are stable during the short time
2
0
2
2
required for extraction and analysis.
2
1
(PLE). After extraction the free acids could be directly
used for biological testing.
To evaluate if the observed biological activity is a general
phenomenon with a,b,g,d-unsaturated dienals, we syn-
thesized and tested both the 9-oxo-nona-5E/Z,7E-dienoic
acid (7a,b) and the 12-oxo-dodeca-5Z,8Z,10E-trienoic acid
2
.2. Biological activity
2
,3
To test for activity of the 2,4-dienals, as well as of other
aldehydes from diatoms, we monitored the inhibition of cell
division in synchronized sea urchin eggs (Sphaerechinus
granularis) incubated with test compounds added to
seawater. As a control, the threshold concentrations and
IC50 for the inhibition of the first cell cleavage by a
commercially available mixture of 2,4-decadienal isomers
and by taxol were compared with those from previous
(6b) previously identified from diatoms. The trienoic acid
6b reached an intermediate level of activity compared to
2,4-decadienal (1ab) and the unsaturated short-chain
aldehydes (Fig. 2).
5
experiments and proved to be highly reproducible.
To test for the influence of the isomeric composition and of
the length of the aliphatic chains, the activity of the alkyl-
substituted 2,4-dienals 1a,b, 2a,b, and 3a,b was tested
(
Fig. 1).
Figure 2. Inhibition of the first cell cleavage in sea urchin eggs by 13-oxo-
trideca-9Z,11E-dienoic acid (8b) (A), 12-oxo-dodeca-5Z,8Z,10E-trienoic
acid (6b) (W), 9-oxo-nona-5E,7E-dienoic acid (7a) (L), and 9-oxo-nona-
5
5Z,7E-dienoic acid (7b) (K).
Surprisingly, both isomers of the shorter-chain homologue
-oxo-nona-5E/Z,7E-dienoic acid (7ab) were not active,
9
even at elevated concentrations. To verify if this lack of
activity is a general feature of dienoic acids, we synthesized
and tested the higher homologue 13-oxo-trideca-9Z,11E-
dienoic acid (8b), not found in diatoms. The activity of this
acid resembled that of the 12-oxo-dodeca-5Z,8Z,10E-
trienoic acid (6b). The lack of activity of the 9-oxo-acid
Figure 1. Inhibition of the first cell cleavage in sea urchin eggs by 2E,4E-
decadienal (1a) (W), 2E,4Z-decadienal (1b) (A), 2E,4E-octadienal (2a) (S),
and 2E,4Z-octadienal (2b) (þ), 2E,4E-heptadienal (3a) (K), 2E,4Z-
heptadienal (3b) (L).
7ab is thus not a general feature of v-oxo-dienoic acids but
most likely attributable to an intramolecular interaction of
the acidic group with the dienal terminus via a cyclic ring
transition state, as suggested previously. An interaction of
the acidic group with the double bond system is also
supported by the observation that 9-oxo-nona-5Z,7E-
dienoic acid (7b) isomerised rapidly in seawater into the
more stable 7a. The half life of 2 h at 228C is significantly
shorter than that of 2E,4Z-decadienal (1b), a molecule
which does not permit such an intramolecular interaction.
Both isomers of 2,4-decadienal (1ab) were more active than
their shorter-chain homologues, indicating the significance
of chain length. The reduced activity of 2,4-octadienal (2ab)
3
8
was also observed with purified material from S. costatum.
In all cases, the geometry at the C4-position of the double
bond system of the a,b,g,d-unsaturated aldehydes had no
influence on biological activity (Fig. 1) since the isomers
were comparable in their threshold concentrations and IC50

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S. Adolph et al. / Tetrahedron 59 (2003) 3003–3008
In diatoms aldehydes lacking the a,b,g,d-unsaturation are
7
4. Experimental
4.1. General remarks
Reactions were performed under Ar. Solvents and were
also found. Among those are mono-unsaturated aldehydes
5
and high abundances of saturated aldehydes. The influence
of the Michael-acceptor of the a,b,g,d-unsaturated
aldehydes for the inhibitory activity was evaluated using
different C10-derivatives (Fig. 3).
1
13
dried according to standard methods. H and C NMR:
Bruker Avance DRX 500 or AV 400 spectrometer.
1
13
Chemical shifts of H and C NMR are given in ppm (d)
downfield relative to TMS. GCMS: Finnigan Trace MS
equipped with an Alltech EC5 column, Helium as carrier.
HR-MS: Micromass MasSpec (Micromass, Manchester,
UK). HPLC: HP1100, equipped with a ChromSil ODS3
column. Preparative column chromatography was per-
˚
formed on Florisil (Sigma), or SiO (ICN) 32-63, 60 A.
2
Reagents and solvents were purchased from Aldrich, Merck
and Fluka.
4.2. Preparation of alkylzincates
2
3
3.1 mmol of the respective alkyl Grignard-compound in
0 mL THF were treated with 25.4 mmol ZnBr in 40 mL
2
THF at room temperature. After stirring for 30 min, the
formed precipitate was allowed to settle and 48 mL of the
supernatant were used for the coupling-reaction.
Figure 3. Inhibition of the first cell cleavage in sea urchin eggs by 2E-
decenal (A), 4Z-decenal (W), decanal (K), and 2-decanone (L).
4.3. Co(II)-mediated coupling
Decanal, which lacks this Michael-acceptor structural
element was active only at elevated concentrations. The
same is true for 4Z-decenal, although the introduction of
the additional double bond increases activity. In contrast,
the Michael-acceptor 2E-decenal was among the most
active molecules tested.
0.77 mmol cobalt-(II)-acetylacetonate and 4.6 mmol LiBr
were suspended in 20 mL THF before addition of 11.2 mL
1-methyl-2-pyrrolidone and 3.85 mmol 5-iodo-penta-2,4-
dienal (9b or 9ab) at room temperature. The reaction
mixture was cooled to 2308C and 15.9 mmol alkylzicate or
7.95 mmol di-alkanoic acid ester-zinc-compound were
added. After 30 min the reaction mixture was warmed to
08C in an ice-bath and hydrolysed with 200 mL of a
2
0
The overall importance of an aldehyde for biological
activity is supported by the finding that 2-decanone is not
active even at elevated concentrations. This was also the
case for decanoic acid and 1-decanol. Other saturated
saturated NaHCO
solution. The aqueous layer was
3
extracted three times with diethylether and the combined
organic phases were washed with brine and dried over
MgSO . The solvent was removed under reduced pressure
4
5
aldehydes (C8 and C13 ) exhibited lower activity compared
to decanal.
and the products were purified by column chromatography.
0
4
.4. Pd -mediated coupling
3
. Conclusion
4.4.1. 2E,4E-Decadienal (1a). 0.04 mmol tetrakis(tri-
phenylphosphine)palladium(0) and 0.7 mmol 5-iodo-
penta-2,4-dienal (9a or 9ab) were dissolved in 20 mL
THF at 2788C and 2.9 mmol pentyl-zinc-bromide, dis-
solved in 30 mL THF were added. After 20 min at 2788C
the reaction mixture was hydrolysed with 200 mL of
saturated NaHCO solution and the aqueous layer was
3
extracted three times with diethylether. The combined
organic phases were washed with brine and dried over
The new synthesis of a,b,g,d-unsaturated aldehydes
allowed to perform a detailed study of the structural
elements contributing to their biological activity to inhibit
sea urchin egg cleavage. Screening a series of diatom-
derived oxylipins showed that the activity is related to the
presence of a Michael-acceptor and not a specific feature of
2E,4E/Z-decadienal (1ab). Whether this activity is due to a
covalent addition of nucleophiles, as suggested after model
MgSO
and the product purified by column chromatography on
SiO (petrol ether/ether 95/5) to give 84 mg (0.55 mmol,
. The solvent was removed under reduced pressure
4
2
3
studies with 1a and a deoxyadenosine derivative has yet to
be established. The minimum structural element required
for activity is one double bond conjugated to the aldehyde
functionality as in 2E-decenal. The geometry or even
absence of the g,d-double bond is not determining for
such activity. In contrast, the shorter chain length 2,4-
dienals 2ab and 3ab had reduced activity as it was also the
case for the acidic 7ab and 8ab. Polarity of the aldehydes
thus seems to be an important feature influencing the
biological activity.
2
79%) of 1a.
4.5. Enzymatic saponification
0.53 mmol of the ester 7a,b or 8b were suspended in
100 mL 0.02 mol L2 phosphate buffer (pH 7.2) by
vigorous stirring at room temperature. After addition of
164 units of porcine liver esterase (PLE, Sigma) the
1

S. Adolph et al. / Tetrahedron 59 (2003) 3003–3008
3007
suspension was stirred for 1 h, washed with 10 mL petrol
ether and pH 3 was adjusted with 10% sulphuric acid. The
reaction mixture was extracted three times with diethylether
and the combined organic phases were dried with Na SO .
4.8.3. 13-Oxo-trideca-9Z,11E-dienoic acid methyl ester.
1
H NMR (d -THF, 400 MHz) d: 1.24 (m, 6H, C4, C5, C6),
8
1.36 (m, 2H, C3), 1.48 (m, 2H, C7), 2.15 (t, J¼7.4 Hz, 2H,
C2), 2.26 (m, 2H, C8), 3.47 (s, 3H, O–CH ), 5.86 (dt,
3
2
4
The solvent was removed under reduced pressure to give the
pure (NMR, RP-HPLC) product.
J¼10.7, 7.9 Hz, 1H, C9), 5.97 (dd, J¼15.2, 7.9 Hz, 1H,
C12), 6.17 (m, 1H, C10), 7.45 (ddd, J¼15.2, 11.5, 0.9 Hz,
1
3
1
H, C11), 9.53 (d, J¼7.8 Hz, 1H, C13). C NMR (d -THF,
8
4
.6. Kinetic investigations of the isomerization
100 MHz) d: 29.3 (C3), 30.3–30.4 (C4–C8), 34.6 (C2),
51.5 (O–CH ), 128.2 (C10), 133.5 (C12), 143.7 (C9), 146.7
3
1
0 mL of a solution of 1b or 7b in DMSO (10 mg/mL) were
(C11), 174.0 (C1), 193.4 (C13). EI-MS (70 eV) m/z: 55 (30),
67 (31), 79 (18), 81 (100), 95 (31), 109 (17), 121 (9), 149
(14), 178 (6), 238 (3). HR-MS: m/z calcd for C H O :
added to 1 mL of filtered seawater. Decadienal 1a,b was
extracted by solid phase microextraction (SPME) on
polydimethylsiloxane and the rearrangement was
14 22 3
238.15747, found: 238.15690.
2
1
monitored by GC-MS (408C for 2 min, 38C min
2
to
to 2808C, hold for 2 min). The
1
1
1108C, 158C min
rearrangement of 9-oxo-5Z,7E-nonadionic acid 7b was
4.8.4. 13-Oxo-trideca-9Z,11E-dienoic acid (8a). H NMR
(d -THF, 400 MHz) d: 1.24 (m, 6H, C4, C5, C6), 1.36 (m,
8
examined using HPLC-DAD (RP18 25% CH CN, 75%
3
2H, C3), 1.47 (m, 2H, C7), 2.10 (t, J¼7.4 Hz, 2H, C2), 2.26
(m, 2H, C8), 5.86 (dt, J¼10.6, 7.9 Hz, 1H, C9), 5.96 (dd,
J¼15.2, 7.8 Hz, 1H, C12), 6.17 (m, 1H, C10), 7.41 (ddd,
J¼15.2, 11.5, 0.9 Hz, 1H, C11), 9.48 (d, J¼7.8 Hz, 1H,
H O, 0.5% HOAc, 20 min to 100% CH CN, 5 min CH CN,
3
2
3
2
80 nm).
1
3
4
.7. Bioassays
C13). C NMR (d -THF, 100 MHz) d: 29.3 (C3), 30.3 (C4-
8
C7), 30.5 (C8), 34.5 (C2), 128.1 (C10), 133.5 (C12), 143.7
(C9), 146.7 (C11), 174.7 (C1), 193.5 (C13). EI-MS (70 eV)
m/z: 55 (29), 67 (30), 79 (17), 81 (100), 83 (40), 95 (33), 109
(17), 149 (29), 167 (14), 178 (13), 196 (8), 206 (12), 224
(17). HR-MS: m/z calcd for C H O : 224.141245, found:
All non-synthesized compounds used in the assays were
purchased at Sigma, (Deisenhofen, Germany) and purified
by SiO chromatography prior to use. 6b was synthesized as
2
2
described elsewhere. The bioassays were performed
1
4 22 3
according to a previously described procedure using
solutions of the test compounds in DMSO that were added
to seawater, the co-solvent DMSO had no influence on the
224.141438.
1
4.8.5. 2E,4Z-Octadienal (2b). H NMR (CDCl , 400 MHz)
3
5
assay.
d: 0.96 (t, J¼7.4 Hz, 3H, C8), 1.50 (m, 2H, C7), 2.33 (ddt,
J¼8.8, 7.6, 1.4 Hz, 2H, C6), 6.01 (dt, J¼11.8, 7.9 Hz, 1H,
C5), 6.15 (dd, J¼15.2, 7.9 Hz, 1H, C2), 6.29 (m, 1H, C4),
4
.8. Spectroscopic data
7
.45 (ddd, J¼15.3, 11.5, 1.0 Hz, 1H, C3), 9.61 (d,
1
3
The spectroscopic data for the aliphatic aldehydes 1ab, 2a,
1
J¼8.1 Hz, 1H, C1). C NMR (CDCl , 100 MHz) d: 13.4
3
3,24
3
3ab,
literature.
and the ester of 7b match those from the
(C8), 22.2 (C7), 30.1 (C6), 126.6 (C4), 131.4 (C2), 143.5
(C5), 146.5 (C3), 193.7 (C1). EI-MS (70 eV) m/z: 53 (13),
67 (16), 81 (100), 95 (10), 124 (17). HR-MS: m/z calcd for
C H O: 124.088815, found: 124.088796.
1
4
.8.1. 9-Oxo-nona-5E,7E-dienoic acid ethyl ester.
H
8
12
NMR (d -benzene, 400 MHz) d (ppm): 1.09 (t, J¼7.1 Hz,
6
3
H, –CH ), 1.62 (m, 2H, C3), 1.89 (dt, J¼7.6, 7.4 Hz, 2H,
3
C4), 2.12 (t, J¼7.4 Hz, 2H, C2), 4.07 (q, J¼7.1 Hz, 2H,
Acknowledgements
–
O–CH –), 5.66 (dt, J¼14.9, 7.2 Hz, 1H, C5), 5.86 (ddd,
2
J¼15.3, 11.0, 0.6 Hz, 1H, C6), 5.99 (dd, J¼15.4, 7.7 Hz,
We thank Professor W. Boland for the helpful discussion
during the preparation of this work. We are grateful to the
divers at the Roscoff Marine Station for providing the sea
urchin samples. This work was supported by the Max-
Planck Gesellschaft, CNRS and the PROCOPE-EGIDE
program.
1
H, C8), 6.53 (dd, J¼15.4, 10.6 Hz, 1H, C7), 9.53 (d,
13
J¼7.8 Hz, 1H, C9). C NMR (d -Benzene, 100 MHz) d:
6
1
CH –), 129.5 (C6), 130.9 (C8), 144.2 (C5), 150.8 (C7),
4.2 (–CH ), 24.0 (C3), 32.3 (C4), 33.4 (C2), 60.1 (–O–
3
2
1
(
1
72.4 (C1), 192.3 (C9). EI-MS (70 eV) m/z: 66 (18), 67
22), 77 (21), 79 (61), 81 (100), 104 (31), 107 (29), 108 (23),
22 (29), 150 (18), 196 (2). HR-MS: m/z calcd for
C H O : 196.10995, found: 196.11062.
1
1 16 3
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1
4
(
.8.2. 9-Oxo-nona-5E,7E-dienoic acid (7a). H NMR
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3
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