(S)-3,7-Dimethyl-2-oxo-6-octene-1,3-diol: An aggregation pheromone of the Colorado potato beetle, Leptinotarsa decemlineata (Say)

Article abstract of DOI:10.1016/S0040-4039(02)00349-0

(S)-3,7-Dimethyl-2-oxo-6-octene-1,3-diol has been identified as a male-produced pheromone from the Colorado potato beetle. Its gross structure was deduced from its mass and NMR spectra plus synthesis from geraniol. The absolute configuration was determined to be (S) by syntheses of both enantiomers from (R)- and (S)-linalool, respectively.

Full text of DOI:10.1016/S0040-4039(02)00349-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 2641–2643
(S)-3,7-Dimethyl-2-oxo-6-octene-1,3-diol: an aggregation
pheromone of the Colorado potato beetle,
Leptinotarsa decemlineata (Say)
James E. Oliver,a,* Joseph C. Dickensa and Thomas E. Glassb
aUS Department of Agriculture, Agricultural Research Service, Plant Sciences Institute, Chemicals Affecting Insect Behavior
Laboratory, Beltsville, MD 20705-2350, USA
bDepartment of Chemistry, Virginia Tech, Blacksburg, VA 24061-0212, USA
Received 23 January 2002; accepted 6 February 2002
Abstract—(S)-3,7-Dimethyl-2-oxo-6-octene-1,3-diol has been identified as a male-produced pheromone from the Colorado potato
beetle. Its gross structure was deduced from its mass and NMR spectra plus synthesis from geraniol. The absolute configuration
was determined to be (S) by syntheses of both enantiomers from (R)- and (S)-linalool, respectively. Published by Elsevier Science
Ltd.
The use of pheromone(s) by the Colorado potato beetle
(CPB, Leptinotarsa decemlineata (Say)) has been the
subject of controversy for many years, as has been
discussed by Dickens, et al.1 In that paper we reported
the discovery, by gas chromatography with electroan-
tennogram detection, of a volatile pheromone produced
by male CPB but recognized by both sexes, and also
described behavioral responses of both sexes to syn-
thetic pheromone. We here describe in detail the iden-
tification and synthesis of the novel pheromone as the
terpenoid ketodiol 1.
peak for 1 seemed to invariably contain a peak repre-
senting 6-methyl-5-heptene-2-one (2), but that the ratios
of the two weren’t necessarily constant. A possible
explanation was that 2 was being formed thermally
from 1, and some similar features in the electron ioniza-
tion (EI) mass spectra of 1 and 2 seemed to support a
possible relationship between the two compounds. The
EI spectrum of 12 did not contain a molecular ion, but
its chemical ionization (CI) spectrum (ammonia as
reagent gas) displayed an adduct ion at m/z 204, indi-
cating a probable molecular weight of 186. Signifi-
cantly, the CI spectrum also contained strong ions at
m/z 144 and 127 just as did the CI spectrum of 2
(M+NH+4 and M+H+, respectively). The CI spectrum of
1 with deuteroammonia as reagent gas displayed an
ammonium adduct with m/z 210, consistent with a
compound with mw 186 containing two exchangeable
Compound 1 was initially encountered as a minor peak
in
a complex gas chromatogram produced from
volatiles collected above adult male CPB feeding on
potato leaves. A majority of the components were
sesquiterpenes produced by the potato plants, but 1
could occasionally be observed as a barely detectable
peak in gas chromatograms of samples derived from
males, but never in female-derived samples. The
discovery1 that production of 1 could be enhanced by
both topical application of juvenile hormone III and by
antennectomy facilitated its study by gas chromatogra-
phy–mass spectrometry (GC–MS), and eventually per-
mitted isolation of enough material by preparative gas
chromatography to acquire NMR spectra.2
OH
OH
O
O
1a racemic
1b 3-(S)
1c 3-(R)
2
A pivotal observation was that gas chromatograms
(obtained from any of several columns) containing a
* Corresponding author. E-mail: oliverj@ba.ars.usda.gov
Figure 1.
0040-4039/02/$ - see front matter. Published by Elsevier Science Ltd.
PII: S0040-4039(02)00349-0

2642
J. E. Oli6er et al. / Tetrahedron Letters 43 (2002) 2641–2643
hydrogens. The deuteroammonia spectrum also con-
tained fragment ions indicative of 2. These observations
collectively suggested an empirical formula of C10H18O3
with two of the oxygens being OH’s and eight of the
carbons configured such as to allow facile fragmenta-
tion to 2. Of the few possible structures meeting these
requirements, the most probable appeared to the rather
highly oxygenated terpene 1 (Fig. 1).
tion proceeded smoothly to give 7a.6 Desilylation with
TBAF provided the desired 1a whose gas chromato-
graphic and mass spectral properties2 matched those of
the natural product.
Racemic 1a was readily resolved on a chiral GC
column;8 comparison with the natural product estab-
lished that the latter was a single enantiomer (the
later-eluting of the two). Linalool (8, absolute configu-
ration not described) has been converted to monoepox-
3,7-Dimethyl-2-oxo-oct-6-ene-1,3-diol 1 appears in the
literature once, having been proposed as a geraniol
metabolite produced by the soil pseudomonad, Pseu-
domonas incognita.3 No attempts to synthesize the com-
pound or establish its absolute configuration were
reported. To confirm the gross structure, we first syn-
thesized racemic 1 from geraniol (3) (Scheme 1).
ide
9
with t-BuOOH/VO(acac)2,9 similar to the
conversion of 3 to 4 (Scheme 1). We repeated the
epoxidation with commercially available (Fluka) (R)-
linalool 8b, and hydrolyzed the product 9b as described
above to give 5c.6 Repeating the remainder of the
sequence just described gave 1b, which, on chiral GC,
proved to be the earlier-eluting enantiomer (about 96:4,
reflecting the composition of the starting linalool), indi-
cating that the absolute configuration of the natural
product must be (S).
Regioselective epoxidation of
3 was achieved as
described by Mori, et al.4 After acetylation (Ac2O, Py),
epoxyacetate 4 was hydrolyzed (HClO4/DMF followed
by K2CO3/MeOH saponification)5 to triol 5a.6 Reaction
of 5a with one equivalent of t-butylchlorodiphenyl-
silane provided the mono silyl ether 6a.6 Oxidation of
6a with pyridinium chlorochromate afforded primarily
t-butyldiphenylsilanol and ketone 2, but Swern7 oxida-
In contrast to the (R)-enantiomer, (S)-linalool 8a is not
readily available. We developed a procedure for isola-
tion and purification of (S)-linalool from oil of corian-
der,10 and repeated the above sequence. The product,
O
OH
OAc
a,
b
4
3
c,d
e
OH
O
OH
OH
O
OH
OH
OTBDPS
OTBDPS
OH
g
OH
OH
f
6a racemic
6b 3-(S)
6c 3-(R)
7a racemic
7b 3-(S)
7c 3-(R)
5a racemic
5b 3-(S)
5c 3-(R)
1a racemic
1b 3-(S)
1c 3-(R)
c,d
OH
OH
a
O
9a 3-(S)
9b 3-(R)
8a 3-(S)
8b 3-(R)
Scheme 1. (a) t-BuOOH, VO(acac)2; (b) Ac2O, Py; (c) HClO4, DMF; (d) K2CO3, MeOH; (e) TBDPS-Cl, imidazole; (f) Swern
oxidation; (g) TBAF

J. E. Oli6er et al. / Tetrahedron Letters 43 (2002) 2641–2643
2643
1b, of essentially 100% chiral purity, was identical to
(1H, m, H-5b); 1.79 (1H, ddd, J=14.1, 9.7, 6.0 Hz,
H-4a); 1.71 (1H, ddd, J=14.1, 9.7, 6.0 Hz, H-4b); 1.66
(3H, m, H-8); 1.58 (3H, broad s, H-9); 1.37 (3H, s, H-10).
13C NMR l 214.15 (C-2); 133.32 (C-7); 122.95 (C-6);
78.47 (C-3); 64.65 (C-1); 39.92 (C-4); 26.13 (C-10); 25.63
(C-9); 22.16 (C-5); 17.66 (C-8). Mass spectrum (m/z, %)
127 (6), 109 (37), 104 (10), 86 (7), 83 (7), 71 (11), 70 (5),
69 (88), 67 (9), 58 (5), 55 (10), 53 (6), 43 (100), 41 (72).
[h]D25 0.73 (CHCl3).
the natural product in all respects, including 1H and 13
C
NMR spectra.2 Synthetic 1b stimulates a response when
applied to antennae1 of beetles of either sex, and
attracts walking beetles of both sexes in a Y-tube
olfactometer.1 The (R)-enantiomer 1c was inactive
(indistinguishable from controls) in both tests.
Acknowledgements
3. Devi, J. R.; Bhattacharyya, J. P. Indian J. Biochem.
Biophys. 1977, 14, 288–291.
4. Mori, K.; Ebata, T.; Takechi, S. Tetrahedron 1984, 40,
1761–1766.
Dr. J. A. Klun performed preparative gas chromatogra-
phy, Mr. E. David DeVilbiss conducted mass spectro-
metric experiments, and Drs. John Davis and Ben
Hollister collected insect volatiles and performed insect
behavioral experiments. We thank Dr. Ashot Khrimian
for assistance with chiral gas chromatography. Mention
of a proprietary product or company does not imply
endorsement.
5. Hanson, R. M. Tetrahedron Lett. 1984, 25, 3783–3786.
6. Triols 5a–5c occur as mixtures of diastereomers and have
been characterized as such;9 we made no effort to sepa-
rate the isomers or to characterize them beyond their
mass spectra (essentially identical to each other): m/z (%)
170 (2), 152 (4), 110 (14), 109 (46), 71 (14), 69 (74), 67
(20), 55 (20), 44 (11), 43 (100), 41 (67). The DPTB ethers
6a–6c and 7a–7c were purified by flash chromatography
on silica gel; 6a–6c (mixture of diastereomers) eluted with
20% ethyl acetate in hexanes, mass spectrum (probe
introduction) m/z (%) 351 (18), 200 (17), 199 (70), 197
(11), 183 (12), 181 (12), 162 (16), 139 (28), 136 (14), 135
(100), 127 (11), 109 (40), 107 (28), 93 (35), 91 (11), 78
(10), 77 (16), 71 (10), 69 (72), 67 (10), 57 (14), 55 (27), 43
(28), 41 (58). Ketones 7a–7c eluted from silica gel with
10% ethyl acetate in hexanes, mass spectrum (probe
introduction) m/z (%) 349 (8), 310 (10), 309 (39), 289
(12), 231 (12), 200 (10), 199 (54), 197 (14), 181 (17), 163
(15), 143 (13), 139 (25), 135 (39), 133 (15), 123 (10), 109
(39), 107 (12), 105 (18), 93 (11), 91 (13), 77 (16), 71 (14),
69 (100), 59 (10), 57 (12), 55 (21), 43 (77), 41 (64).
7. Omura, K.; Swern, D. Tetrahedron 1978, 34, 1651–1660.
8. 30 m×0.25 mm ChiraldexTM (Advanced Separation Tech-
nologies, Inc) B-DM, H2 carrier, 100°C 2 min then
programmed at 5°C/min to 150°C and held at that tem-
perature.
References
1. Dickens, J. C.; Oliver, J. E.; Hollister, B.; Davis, J. C.;
Klun, J. A. J. Exp. Biol. 2002 (submitted).
2. The initial NMR spectra were recorded in deuteroben-
zene because of concern about possible instability of the
natural product to chloroform. Spectra of the synthetic
material have been recorded in both benzene and chloro-
1
form: Compound 1b: H NMR (d6-benzene, 500 MHz): l
4.95 (1H, tm, J=7.2, 1.4 Hz, H-6); 4.24 (1H, dd, J=19.7,
4.5, H-1a); 4.14 (1H, dd, J=19.7, 4.5, H-1b); 2.93 (1H, t,
J=4.5 Hz, OH); 2.27 (1H, s, OH); 1.96 (1H, m, H-5a);
1.81 (1H, m H-5b); 1.59 (3H, m, H-8); 1.44 (3H, broad s,
H-9); 1.46 (1H, ddd, J=14.0, 10.4, 5.4 Hz, H-4a); 1.33
(1H, ddd, J=14.0, 10.4, 5.4 Hz, H-4b); 0.88 (3H, s,
H-10). 13C NMR l 214.44 (C-2); 132.50 (C-7); 123.83
(C-6); 78.13 (C-3); 64.79 (C-1); 40.12 (C-4); 25.82 (C-10);
1
25.66 (C-8); 22.42 (C-5); 17.52 (C-9). H NMR (CDCl3,
6
9. Bongini, A.; Giuliana, C.; Orena, M.; Porzi, G.; Sandri,
S. J. Org. Chem. 1982, 47, 4626–4633.
10. Oliver, J. E.; J. Essent. Oil Res., in press.
500 MHz): l 5.04 (1H, tm, J=7.2, 1.4 Hz, H-6); 4.51
(1H, d, J=19.7 Hz, H-1a); 4.47 (1H, d, J=19.7 Hz,
H-1b); 2.94 (2H, broad s, OH); 2.08 (1H, m, H-5a); 1.89