Identification and total synthesis of novel fatty acids from the siphonarid limpet Siphonaria denticulata

Article abstract of DOI:10.1021/np010307r

The novel fatty acids 17-methyl-6(Z)-octadecenoic acid and 17-methyl-7(Z)-octadecenoic acid were identified for the first time in nature in the mollusk Siphonaria denticulata from Queensland, Australia. The principal fatty acids in the limpet were hexadecanoic acid, octadecanoic acid, and (Z)-9-octadecenoic acid, while the most interesting series of monounsaturated fatty acids was a family of five nonadecenoic acids with double bonds at either Δ⁷, Δ⁹, Δ¹², or Δ¹³. The novel compounds were characterized using a combination of GC-MS and chemical transformations, such as dimethyl disulfide derivatization. The first total syntheses for the two novel methyl-branched nonadecenoic acids are also described, and these were accomplished in four to five steps and in high yields.

Full text of DOI:10.1021/np010307r

1426
J . Nat. Prod. 2001, 64, 1426-1429
Id en tifica tion a n d Tota l Syn th esis of Novel F a tty Acid s fr om th e Sip h on a r id
Lim p et Siph on a r ia d en ticu la ta
Ne´stor M. Carballeira,*,† Heidyleen Cruz,† Craig A. Hill,‡ J ames J . De Voss,‡ and Mary Garson‡
Department of Chemistry, University of Puerto Rico, Rio Piedras, Puerto Rico 00931, and Department of Chemistry,
The University of Queensland, Brisbane QLD 4072, Australia
Received J une 15, 2001
The novel fatty acids 17-methyl-6(Z)-octadecenoic acid and 17-methyl-7(Z)-octadecenoic acid were identified
for the first time in nature in the mollusk Siphonaria denticulata from Queensland, Australia. The
principal fatty acids in the limpet were hexadecanoic acid, octadecanoic acid, and (Z)-9-octadecenoic acid,
while the most interesting series of monounsaturated fatty acids was a family of five nonadecenoic acids
with double bonds at either ∆7, ∆9, ∆11, ∆12, or ∆13. The novel compounds were characterized using a
combination of GC-MS and chemical transformations, such as dimethyl disulfide derivatization. The
first total syntheses for the two novel methyl-branched nonadecenoic acids are also described, and these
were accomplished in four to five steps and in high yields.
Siphonariid limpets have previously been shown to
contain branched-chain polypropionate metabolites of con-
siderable biosynthetic interest.1 For example, the air-
breathing gastropod Siphonaria diemenensis contains the
diemenensins A and B, compounds that display anti-
microbial properties.2 On the other hand, the pulmonate
Siphonaria denticulata Quoy and Gaimard biosynthesizes
the denticulatins A and B, polypropionate compounds that
have attracted considerable attention from both synthetic
and bioorganic chemists.3-5 In addition, Siphonaria ze-
landica produces the siphonarins A and B, which have also
been the subject of considerable biosynthetic efforts.1
Despite all of these isolation and biosynthetic efforts, the
fatty acid composition of S. denticulata (class Gastropoda,
order Pulmonata, family Siphonariidae) has not been
explored. Earlier work with the related S. diemenensis
revealed the presence of high amounts of 16:0, 18:1n-9,
and 20:1n-9 fatty acids, as well as the non-methylene
interrupted fatty acids 20:2(∆5,11 and ∆5,13) and 22:2(∆7,13
and ∆7,15).6 Unexpectedly, in S. diemenensis the fatty acid
18:1n-7 was not identified, which translated into a 18:
1n-9/18:1n-7 ratio greater than 10.0.6 In addition, the
isoprenoid fatty acid 4,8,12-trimethyltridecanoic acid was
also identified in the limpet. Therefore, on the basis of
earlier findings, we examined the fatty acid composition
of the pulmonate S. denticulata from Queensland, Austra-
lia, so as to compare its fatty acid composition with that of
other mollusks such as S. diemenensis. During this work
we uncovered the presence of two novel nonadecenoic acids,
namely, the acids 17-methyl-6(Z)-octadecenoic acid and 17-
methyl-7(Z)-octadecenoic acid, which we report herein
together with their total synthesis. We also describe the
total fatty acid composition of S. denticulata at a detection
limit of 0.01%.
comparison with authentic standards, and dimethyl dis-
ulfide derivatization. Fatty acid chain lengths ranged
between 14 and 24 carbons, mainly consisting of saturated
and monounsaturated fatty acids. Normal-chain saturated
fatty acids, such as hexadecanoic acid, were particularly
abundant in this pulmonate; they made up 51.4% of the
total fatty acid composition. On the other hand, iso-anteiso
odd-chain fatty acids made up 10% of the fatty acid
composition, while monounsaturated fatty acids between
C16 and C22 accounted for almost 30% of the total composi-
tion. Among the monounsaturated fatty acids the (Z)-9-
octadecenoic acid (18:1n-9) and the (Z)-11-octadecenoic
acid (18:1n-7) were among the most prominent. In fact,
the 18:1n-9/18:1n-7 ratio was close to 2, in contrast to
what was previously reported from other mollusks from
the Siphonariidae in Australian waters, such as Siphonaria
diemenensis, where a ratio of 10 was reported.6 In fact, for
S. diemenensis no 18:1n-7 fatty acid was reported. Another
interesting finding in S. denticulata was the identification
of the 4,8,12-trimethyltridecanoic acid, a common fatty acid
in mollusks, which is most likely arising from a dietary
intake of phytol (as chlorophyll).6 The typical series of non-
methylene-interrupted diunsaturated fatty acids with chain
lengths between 20 and 22 carbons, characteristic for this
type of mollusk, was also found in S. denticulata.
In addition to the aforementioned fatty acids, a set of
unusual nonadecenoic acids was also identified in S.
denticulata in which the ∆7, ∆9, ∆11, ∆12, and ∆13 monoun-
saturations were identified by dimethyl disulfide deriva-
tization. Moreover, two rather unusual methyl-branched
nonadecenoic acids with ∆6 and ∆7 monounsaturations
were also detected. The methyl ester of the ∆6 isomer
presented an equivalent chain-length (ECL) value of 18.37,
while the ECL value for the methyl ester of the ∆7 isomer
was 18.33, practically unresolvable peaks in nonpolar
capillary gas chromatography. The low fractional chain-
length (FCL) values of 0.33-0.37 compared favorably with
that of other iso-methyl-branched methyl esters, thus
supporting a possible iso-methyl branching in addition to
one unsaturation for both unknown methyl nonade-
cenoates.
Resu lts a n d Discu ssion
The limpet S. denticulata presented a rather complex
fatty acid composition of around 59 identifiable fatty acids,
as shown in Table 1. These fatty acids were identified on
the basis of their GC retention times, mass spectral data,
* To whom correspondence should be addressed. Tel: (787)-764-0000,
ext. 4791. Fax: (787)-756-8242. E-mail: ncarball@upracd.upr.clu.edu.
† University of Puerto Rico.
Mass spectrometry was the spectrometric technique of
choice used to initially identify structures 1 and 2 because
of their low abundance in the mollusk and almost identical
‡ The University of Queensland.
10.1021/np010307r CCC: $20.00
© 2001 American Chemical Society and American Society of Pharmacognosy
Published on Web 11/02/2001

Novel Fatty Acids from Siphonaria
J ournal of Natural Products, 2001, Vol. 64, No. 11 1427
Sch em e 1
Ta ble 1. Identified Fatty Acids from S. denticulata
fatty acid
tetradecanoic (14:0)
4,8,12-trimethyltridecanoic (16:0)
13-methyltetradecanoic (i-15:0)
12-methyltetradecanoic (ai-15:0)
pentadecanoic (15:0)
14-methylpentadecanoic (i-16:0)
13-methylpentadecanoic (ai-16:0)
(Z)-9-hexadecenoic (16:1)
(Z)-11-hexadecenoic (16:1)
hexadecanoic (16:0)
methylhexadecanoic (br-17:0)
methylhexadecanoic (br-17:0)
(6Z)-15-methyl-6-hexadecenoic (i-17:1)
(8Z)-15-methyl-8-hexadecenoic (i-17:1)
(9Z)-15-methyl-9-hexadecenoic (i-17:1)
(10Z)-15-methyl-10-hexadecenoic (i-17:1)
15-methylhexadecanoic (i-17:0)
14-methylhexadecanoic (ai-17:0)
(Z)-9-heptadecenoic (17:1)
(Z)-10-heptadecenoic (17:1)
(Z)-11-heptadecenoic (17:1)
(Z)-12-heptadecenoic (17:1)
heptadecanoic (17:0)
(9Z,12Z)-9,12-octadecadienoic (18:2)
(Z)-5-octadecenoic (18:1)
(Z)-9-octadecenoic (18:1)
(Z)-11-octadecenoic (18:1)
(Z)-13-octadecenoic (18:1)
octadecanoic (18:0)
(E)-11-methyl-12-octadecenoic (19:1)
methyloctadecanoic (br-19:0)
(6Z)-17-methyl-6-octadecenoic (19:1)a
(7Z)-17-methyl-7-octadecenoic (19:1)a
17-methyloctadecanoic (i-19:0)
16-methyloctadecanoic (ai-19:0)
(Z)-7-nonadecenoic (19:1)
(Z)-9-nonadecenoic (19:1)
(Z)-11-nonadecenoic (19:1)
(Z)-12-nonadecenoic (19:1)
(Z)-13-nonadecenoic (19:1)
nonadecanoic (19:0)
abundance (wt %)
2.2
2.1
0.2
0.1
1.1
0.6
0.1
1.1
0.1
26.5
0.2
0.2
0.1
0.1
0.1
0.1
2.0
5.8
0.4
0.1
0.1
0.1
4.4
1.6
0.3
9.5
5.1
0.1
15.7
0.4
0.1
0.1
0.1
0.5
0.2
0.3
0.2
0.2
0.2
0.1
0.2
0.3
0.4
0.2
1.3
4.7
4.4
2.1
0.9
0.2
0.1
1.0
0.6
0.3
0.1
0.1
0.1
0.3
0.1
determine the presence of the ∆6 and ∆7 isomers in a single
GC peak. For example, one of the unknowns yielded methyl
17-methyl-6,7-bis(methylthio)octadecanoate upon reaction
with CH3SSCH3/I2. In the mass spectrum of the latter [M+
) 404] the principal cleavage occurred between the carbons
that originally constituted the double bonds (C-6 and C-7),
yielding two substantial fragment ions (one containing the
terminal methyl group of the molecule at m/z 229 and a
second at m/z 175 containing the ester group). A third
prominent peak was observed at m/z 143 due to the loss of
methanol from the m/z 175 ion. Therefore, one of the
unknown methyl nonadecenoates is methyl 17-methyl-6(Z)-
octadecenaote (1), which to the best of our knowledge has
no literature precedence.
5,8,11,14-eicosatetraenoic (20:4)
eicosadienoic (20:2)b
eicosadienoic (20:2)b
eicosadienoic (20:2)
(Z)-7-eicosenoic (20:1)
(Z)-11-eicosenoic (20:1)
(Z)-13-eicosenoic (20:1)
eicosanoic (20:0)
(Z)-7-heneicosenoic (21:1)
heneicosanoic (21:0)
docosadienoic (22:2)c
docosadienoic (22:2)c
The second unknown methyl nonadecenoate, upon DMDS
derivatization, yielded 17-methyl-7,8-bis(methylthio)octa-
decanoate. In this case, the DMDS adduct also presented
a mass spectrum with a molecular ion peak at m/z 404 and
key fragment ions at m/z 215 (methyl end) and m/z 189
(carboxy end), with the latter ion losing methanol to afford
a third prominent ion at m/z 157. Therefore, the mass
spectral data indicate that the second methyl nonade-
cenoate could only be methyl 17-methyl-7(Z)-octadecenoate
(2), which also does not have literature precedence.
Final structural confirmation of 1 and 2, including the
double bond stereochemistry, was achieved by total syn-
thesis (Scheme 1). The synthesis of methyl 17-methyl-6(Z)-
octadecenoate (1) was based on Wittig coupling to generate
the ∆6 double bond and commercially available methyl 11-
methyldodecanoate (Sigma) to introduce the iso branching.
Therefore, the synthesis started with the lithium alumi-
num hydride reduction of methyl 11-methyldodecanoate to
11-methyl-1-dodecanol. Then, the alcohol was transformed
into 11-methyldodecanal, required for the Wittig coupling,
upon reaction with pyridinium chlorochromate in dichloro-
(Z)-7-docosenoic (22:1)
(Z)-9-docosenoic (22:1)
(Z)-13-docosenoic (22:1)
(Z)-15-docosenoic (22:1)
docosanoic (22:0)
tetracosanoic (24:0)
a
b
Unprecedented as natural compounds. Most likely ∆5,11 and/
c Most likely ∆7,13 and/or ∆7,15
or ∆5,13
.
.
GC retention times. Both methyl esters 1 and 2 displayed
a molecular ion peak [M+] at m/z 310 and typical fragmen-
tations of a monounsaturated methyl ester at m/z 278 [M+
- 32, loss of methanol], m/z 255 [M+ - 55], m/z 236 [M+
-
74, loss of the McLafferty ion], m/z 194 [M+ - 116], and
m/z 74 [McLafferty rearrangement ion]. However, there
were no ions that permitted the unequivocal location of the
monounsaturation due to double-bond migration during
ionization. For this purpose, dimethyl disulfide (DMDS)
adducts were used to “fix” the double bonds and permit
their location by mass spectrometry.7 In fact, it was
through the DMDS adducts that it was possible to initially

1428 J ournal of Natural Products, 2001, Vol. 64, No. 11
Carballeira et al.
Sch em e 2
transport back to Brisbane, and stored at -18 °C until needed.
A voucher of the animals (Voucher No. sd-1) is held at the
Department of Chemistry, the University of Queensland.
Isola tion a n d Id en tifica tion of F a tty Acid s. Approxi-
mately 150 animals were shelled and extracted with 3 × 200
mL of CH2Cl2/MeOH (1:1). The extract was filtered through
Celite, concentrated in vacuo, and then partitioned between
EtOAc (3 × 100 mL) and water (50 mL) to give a crude extract
(0.73 g) after concentration. An aliquot (30 mg) of crude extract
was dissolved in methanolic HCl (1.5 M; 7 mL) and refluxed
for 2 h. The soluble products were concentrated, then resus-
pended in toluene (0.5 mL) and passed through a pipet column
(Celite, 0.25 g Celite) eluting with 3 mL of toluene. A second
purification step involved silica column chromatography using
hexane (10 mL) as eluant, giving the fatty acid methyl ester
extract (2.9 mg).
11-Meth yl-1-d od eca n ol. To a stirred solution of lithium
aluminum hydride in ethyl ether (10 mL) at 0 °C was added
dropwise methyl 11-methyldodecanoate (0.050 g, 0.22 mmol)
in ether (1 mL). The resulting gray mixture was stirred for 2
h and then quenched carefully with a saturated aqueous
ammonium chloride solution. The product was extracted with
diethyl ether, and the organic layer was dried over MgSO4.
The solvent was filtered and concentrated in vacuo, affording
0.042 g (98% yield) of 11-methyl-1-dodecanol with spectral data
identical to that reported in the literature.9
methane, resulting in an almost quantitative yield of the
aldehyde. Final Wittig coupling of 11-methyldodecanal with
(5-carboxypentyl)triphenylphosphonium bromide (prepared
from 6-bromohexanoic acid as described in the Experimen-
tal Section) resulted in a 7:2 mixture (as determined by
capillary GC of the methyl esters) of 17-methyl-6(Z)-
octadecenoic acid and 17-methyl-6(E)-octadecenoic acid,
which together accounted for an 88% isolated yield (86%
overall yield from methyl 11-dodecanoate). These acids
were then transformed into the corresponding methyl
esters by reaction with acidic MeOH. A capillary GC
coelution of 1Z (ECL ) 18.37) and 1E (ECL ) 18.43) with
the original methyl esters from S. denticulata established
the Z double bond sterochemistry for 1 and confirmed the
structure.
Following a similar strategy methyl 17-methyl-7(Z)-
octadecenoate (2) was synthesized as outlined in Scheme
1. In this case the synthesis started with the lithium
aluminum hydride reduction of methyl 10-methylunde-
canoate to 10-methyl-1-undecanol, which was then trans-
formed into 10-methylundecanal upon reaction with pyri-
dinium chlorochromate in dichloromethane, resulting in an
almost quantitative yield of the aldehyde. The Wittig
coupling of 10-methylundecanal with (6-carboxyhexyl)-
triphenylphosphonium bromide (prepared from ethyl 7-bro-
moheptanoate after saponification with LiOH and further
reaction with triphenylphosphine in toluene) resulted in a
9:1 mixture (88% overall yield from methyl 10-methylun-
decanoate) of 17-methyl-7(Z)-octadecenoic acid and 17-
methyl-7(E)-octadecenoic acid. The acids were then trans-
formed into the methyl esters (HCl/MeOH) for capillary GC
comparisons. In this case capillary GC coelution of 2Z (ECL
) 18.33) and 2E (ECL ) 18.43) with the methyl esters from
S. denticulata also confirmed the Z double bond stereo-
chemistry for 2 in the original methyl nonadecenoate.
On the basis of these results some unprecedented bio-
synthetic pathways for iso odd-chain fatty acids in nature
can be postulated (Scheme 2). Our new iso-C19:1 fatty acids
could have very well originated from i-15:0. For example,
chain elongation of i-15:0 to i-17:0 and desaturation at C-5
is a likely pathway for the known i-17:1∆5, a reported fatty
acid.8 A subsequent two-carbon elongation of i-17:1∆5 can
then result in the novel i-19:1∆7. The other new acid, i-19:
1∆6, could very well have originated from a four-carbon
elongation of i-15:0 to i-19:0 followed by ∆6 desaturation
to i-19:1∆6.
11-Meth yld od eca n a l. To a stirred solution of pyridinium
chlorochromate (0.16 g, 0.75 mmol) in 15 mL of CH2Cl2 was
added dropwise 11-methyl-1-dodecanol (0.043 g, 0.21 mmol)
in 1 mL of CH2Cl2 at room temperature. After 24 h the reaction
mixture was filtered through Florisil and washed with diethyl
ether (50 mL). Evaporation of the solvent afforded 11-meth-
yldodecanal in a 100% GC yield with spectral data identical
to that reported in the literature.10
(5-Car boxypen tyl)tr iph en ylph osph on iu m Br om ide. Into
a 50 mL round-bottomed flask were placed 6-bromohexanoic
acid (5.0 g, 23.9 mmol) and triphenylphosphine (6.3 g, 23.9
mmol) in 20 mL of toluene. The mixture was refluxed for 24
h, after which it was cooled to room temperature and the
toluene was removed in vacuo. The product was washed
several times with diethyl ether, affording (5-carboxypentyl)-
triphenylphosphonium bromide (2.2 g, 98% yield) as a white
solid with spectral data identical to that reported in the
literature.11
Meth yl 17-Meth yl-6(Z)-octa d ecen oa te. To 20 mL of a
THF stirred solution of previously dried (5-carboxypentyl)-
triphenylphosphonium bromide (0.66 g, 0.33 mmol) was added
dropwise n-BuLi (2.5 M, 2.2 mmol) at 0 °C. The resulting
mixture was stirred for 30 min at room temperature. Then,
11-methyldodecanal (0.025 g, 0.13 mmol) in 1 mL of THF was
slowly added. After 2 h, the mixture was poured into ice and
the solution was acidified with 1 M HCl. The acidic solution
was extracted with diethyl ether (2 × 20 mL), and the organic
layer was washed with H2O (2 × 10 mL), dried over MgSO4,
and filtered. After rotoevaporation of the solvent the acid was
obtained as a yellow oil (0.034 g) for an 88% yield of a 7:2 Z/E
mixture, which were characterized as the methyl esters after
refluxing the acids in 1 M HCl (MeOH) for 4 h. The spectral
data for the Z isomer follows: 1H NMR (CDCl3, 300 MHz) δ
5.34 (2H, m, H-6, H-7), 3.66 (3H, s, -OCH3), 2.30 (2H, t, J )
7.6 Hz, H-2), 2.01 (4H, m, H-5, H-8), 1.65 (2H, m, H-3), 1.53
(1H, m, H-17), 1.35-1.25 (16H, m, -CH2), 1.15 (2H, m, H-16),
0.86 (6H, d, J ) 6.6 Hz, H-18, Me-17); 13C NMR (CDCl3, 75.5
MHz) δ 174.3 (s, C-1), 130.5 (d, C-7), 129.0 (d, C-6), 51.5 (q,
-OCH3), 39.0 (t, C-16), 34.0 (t, C-2), 29.9 (t), 29.7 (t), 29.6 (t),
29.5 (t), 29.3 (t), 29.2 (t), 27.9 (d, C-17), 27.4 (t), 27.2 (t), 26.9
(t), 26.8 (t), 24.6 (t), 22.6 (q, C-18, Me-19); ECL ) 18.37, GC-
MS (70 eV) m/z 310 [M]+ (3), 279 (8), 278 (18), 260 (1), 255 (6),
249 (2), 236 (10), 221 (1), 208 (1), 194 (10), 180 (4), 166 (3),
152 (6), 141 (8), 138 (6), 137 (8), 128 (5), 123 (17), 111 (19),
110 (23), 101 (8), 97 (45), 96 (54), 95 (34), 87 (38), 84 (63), 81
(49), 79 (18), 74 (78), 69 (53), 67 (51), 57 (44), 55 (100); HREIMS
m/z 310.2880 (calcd for C20H38O2, 310.2872).
Exp er im en ta l Section
Gen er a l Exp er im en ta l P r oced u r es. Fatty acid methyl
esters were analyzed by GC-MS at 70 eV using a Hewlett-
Packard 5972A MS ChemStation equipped with a 30 m × 0.25
mm special performance capillary column (HP-5MS) of poly-
methylsiloxane cross-linked with 5% phenyl methylpolysilox-
ane. The temperature program was as follows: 130 °C for 1
min, then increased at a rate of 3 °C/min to 270 °C, and
maintained for 30 min at 270 °C.
Mollu sk Collection . Specimens (40 g) of S. denticulata
Quoy and Gaimard (class Gastropoda, order Pulmonata, family
Siphonariidae) were collected from the rock platform at
Caloundra, SE Queensland, in May 1999, placed onto ice for
Met h yl 17-m et h yl-6,7-bis(m et h ylt h io)oct a d eca n oa t e:
GC-MS (70 eV) m/z 404 [M]+ (11), 355 (1), 325 (1), 309 (1),

Novel Fatty Acids from Siphonaria
J ournal of Natural Products, 2001, Vol. 64, No. 11 1429
277 (2), 230 (14), 229 (85), 213 (3), 193 (1), 187 (1), 175 (59),
174 (25), 157 (1), 144 (8), 143 (100), 127 (25), 126 (7), 121 (3),
115 (12), 111 (6), 101 (6), 97 (18), 95 (22), 87 (19), 85 (22), 83
(25), 81 (27), 79 (13), 74 (13), 69 (38), 67 (52), 61 (57), 59 (15),
57 (26), 55 (61).
7-Br om oh ep ta n oic Acid . Into a 50 mL round-bottomed
flask was placed LiOH (1 g, 4.8 mmol) in 30 mL of MeOH/
H2O/THF (1:1:3) together with ethyl 7-bromoheptanoate (10.95
g, 46.2 mmol). The reaction mixture was refluxed for 4 h, and
then it was cooled to room temperature and neutralized to pH
7. The organic solvents were removed under vacuum, and the
remaining water solution was acidified to pH 2. The product
was extracted with dichloromethane (2 × 15 mL), and the
organic layer was dried over MgSO4. Dichloromethane was
removed under vacuum, affording 6.4 g of the known 7-bro-
moheptanoic acid for a 66% yield.12,13
10-Meth yl-1-u n d eca n ol. To a stirred solution of lithium
aluminum hydride in ethyl ether (10 mL) at 0 °C was added
dropwise methyl 10-methylundecanoate (0.050 g, 0.23 mmol)
in ether (1 mL). The resulting gray mixture was stirred for
2.5 h and then carefully quenched with a saturated aqueous
ammonium chloride solution. The product was extracted with
diethyl ether, and the organic layer was dried over MgSO4.
The solvent was filtered and concentrated in vacuo, affording
0.043 g (100% yield) of 10-methyl-1-undecanol, whose spectral
data were identical to that previously reported.14
10-Meth ylu n d eca n a l. To a stirred solution of pyridinium
chlorochromate (0.14 g, 0.64 mmol) in 15 mL of dichloro-
methane was added dropwise 10-methylundecanol (0.040 g,
0.22 mmol) in 1 mL of dichloromethane at room temperature.
After 24 h the reaction mixture was filtered through Florisil
and washed with diethyl ether (50 mL). Evaporation of the
solvent afforded 0.040 g of the previously reported 10-methyl-
undecanal for a 100% GC yield.15
(6-Car boxyh exyl)tr iph en ylph osph on iu m Br om ide. Into
a 50 mL round-bottomed flask were placed 7-bromoheptanoic
acid (1.0 g, 4.8 mmol) and triphenylphosphine (1.0 g, 3.8 mmol)
in 20 mL of toluene. The mixture was refluxed for 24 h, after
which it was cooled to room temperature and the toluene was
removed in vacuo. The product was washed several times with
diethyl ether, affording (6-carboxyhexyl)triphenylphosphonium
bromide (1.9 g, 86% yield) as a white solid.
Meth yl 17-Meth yl-7(Z)-octa d ecen oa te. To 20 mL of a
THF/DMSO (2:1) stirred solution of previously dried (6-
carboxyhexyl)triphenylphosphonium bromide (0.05 g, 0.11
mmol) was added dropwise n-BuLi (2.5 M, 3.4 mmol) at 0 °C.
The resulting mixture was stirred for 30 min at room tem-
perature. Then, 10-methylundecanal (0.020 g, 0.11 mmol) in
1 mL of THF was added dropwise. After 2 h, the mixture was
poured into ice and the solution was acidified with 1 M HCl.
The acidic solution was extracted with diethyl ether (2 × 20
mL), and the organic layer was washed with H2O (2 × 20 mL),
dried over MgSO4, and filtered. After rotoevaporation of the
solvent 0.030 g of a yellow oil (88% yield) was obtained as a
9:1 Z/E mixture, which were characterized as the methyl esters
after refluxing the acids in 1 M HCl (MeOH) for 4 h. The
spectral data for the Z isomer follows: 1H NMR (CDCl3, 300
MHz) δ 5.34 (2H, m, H-7, H-8), 3.66 (3H, s, -OCH3), 2.30 (2H,
t, J ) 7.6 Hz, H-2), 2.01 (4H, m, H-6, H-9), 1.65 (2H, m, H-3),
1.53 (1H, m, H-17), 1.35-1.25 (16H, m, -CH2), 1.15 (2H, m,
H-16), 0.86 (6H, d, J ) 6.6 Hz, H-18, Me-17); 13C NMR (CDCl3,
75.5 MHz) δ 174.3 (s, C-1), 130.2 (d, C-8), 129.5 (d, C-7), 51.4
(q, -OCH3), 39.0 (t, C-16), 34.0 (t, C-2), 29.9 (t), 29.74 (t), 29.68
(t), 29.5 (t), 29.35 (t), 29.32 (t), 28.8 (t), 27.4 (t), 27.2 (t), 27.0
(t), 27.9 (d, C-17), 24.8 (t), 22.6 (q, C-18, Me-19); ECL ) 18.33,
GC-MS (70 eV) m/z 310 [M]+ (3), 279 (7), 278 (14), 260 (1),
255 (5), 249 (1), 236 (7), 221 (1), 208 (1), 194 (4), 180 (2), 166
(2), 152 (4), 141 (6), 138 (5), 137 (7), 128 (3), 123 (12), 111 (15),
110 (15), 101 (6), 97 (33), 96 (35), 95 (27), 87 (33), 84 (41), 81
(32), 79 (12), 74 (56), 69 (58), 67 (44), 57 (43), 55 (100); HREIMS
m/z 310.2869 (calcd for C20H38O2, 310.2872).
Met h yl 17-m et h yl-7,8-bis(m et h ylt h io)oct a d eca n oa t e:
GC-MS (70 eV) m/z 404 [M]+ (11), 216 (10), 215 (79), 207 (16),
190 (8), 189 (62), 158 (10), 157 (93), 140 (30), 121 (3), 115 (4),
111 (9), 101 (3), 97 (24), 95 (26), 87 (27), 85 (12), 83 (32), 81
(72), 79 (19), 74 (22), 69 (56), 67 (49), 61 (84), 59 (23), 57 (35),
55 (100).
Ack n ow led gm en t. This work was supported in part by a
grant from the National Institutes of Health (Grant No.
SO6GM08102 to N.M.C.). H.C. was supported by a doctoral
fellowship from the NIH-RISE program. M.J .G. and J .J .D.V.
acknowledge funding from the Australia Research Council. We
thank Sharna Graham for technical assistance.
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