Iridodials: Enantiospecific synthesis and stereochemical assignment of the pheromone for the golden-eyed lacewing, Chrysopa oculata

Article abstract of DOI:10.1016/j.tetlet.2004.03.034

1R,2S,5R,8R; 1R,2S,5R,8S; 1S,2S,5R,8R; and 1S,2S,5R,8S-Iridodials have been prepared in five steps from 4aS,7S,7aR and 4aS,7S,7aS-nepetalactones, major components of catnip oil. 1R,2S,5R,8R-Iridodial has been identified as a male-produced male-aggregation pheromone for Chrysopa oculata, the first pheromone of any kind identified for lacewings.

Full text of DOI:10.1016/j.tetlet.2004.03.034

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 3339–3340
Iridodials: enantiospecific synthesis and stereochemical assignment
of the pheromone for the golden-eyed lacewing, Chrysopa oculata
Kamlesh R. Chauhan,a,* Qing-He Zhanga,b and Jeffrey R. Aldricha
aUSDA-ARS Chemicals Affecting Insect Behavior Laboratory, B-007, BARC-West, Beltsville, MD 20705, USA
bDepartment of Entomology, University of Maryland, College Park, MD 20742, USA
Received 2 February 2004; revised 3 March 2004; accepted 8 March 2004
Abstract—1R,2S,5R,8R; 1R,2S,5R,8S; 1S,2S,5R,8R; and 1S,2S,5R,8S-Iridodials have been prepared in five steps from 4aS,7S,7aR
and 4aS,7S,7aS-nepetalactones, major components of catnip oil. 1R,2S,5R,8R-Iridodial has been identified as a male-produced
male-aggregation pheromone for Chrysopa oculata, the first pheromone of any kind identified for lacewings.
Ó 2004 Published by Elsevier Ltd.
Lacewings, especially green lacewings (Chrysopidae),
are some of the most common predators of aphids and
other soft-bodied insects.1 Furthermore, because of their
commercial availability and resistance to insecticides,
chrysopids are among the most commonly released
predators for augmentative biological control,2 albeit
with differing degrees of success. While green lacewings
are increasingly being released for biocontrol, methods
are still needed to retain the predators near augmenta-
tion sites and/or to attract wild predators to target
areas.3 Intra-specific chemical signals, namely phero-
mones, may have practical potential for managing
lacewings, and would be of great economic importance.
In our efforts4 to search for pheromones of Co. oculata
(Co. ¼ Chrysopa), one of the most common lacewings in
the eastern United States, a single isomer of iridodial
was discovered to be the key pheromone component.
The initial identification of iridodial occurred during gas
chromatography-electroantennogram detection (GC-
EAD) and GC–mass spectrometry (GC–MS)5;6 analyses
of nepetalactol 3, which contained iridodials 1a and 1b
as impurities (5–8%). Subsequent analyses of extracts
from the 1st to 8th abdominal segments of Co. oculata
males revealed the presence of iridodial 1a.
these cases, iridodials serve as defensive compounds.
Citronellal has been explored as a starting material for
the synthesis of iridodial and iridomyrmecin,9 however
to date synthesis of enantiomerically pure iridodial
diastereomers with four asymmetric centers has not been
reported. To establish absolute configuration, and to
prepare sufficient quantities of isomerically pure irido-
dial 1a, a convenient synthesis was developed (Fig. 2).
Availability of 4aS,7S,7aR(Z,E) 2a and 4aS,7S,7aS(E,Z)
2b nepetalactone [major components of catnip oil (Nepeta
7
7
6
6
CHO
CHO
2
4
2
4
1
5
1
5
3
3
CHO
CHO
8
8
R
R
R
R
1
2
1
2
1c:
R
=
1
CH , R
=
H
1a:
R
=
=
CH , R = H
3 2
1
3
2
1
1d:R
=
H, R
=
CH
1b:R
H, R = CH
2
3
1
2
3
OH
1
O
1
O
1
7
5
7
5
O
7
5
O
7a
4a
2
3
O
7a
4a
2
7a
4a
2
3
6
6
6
Iridodials have been identified from many other natural
sources such as ants, especially the Iridomyrmex spp.,7
as well as from rove beetles and a stick insect.8 In all
3
4
4
4
3
2b
2a
Figure 1. Monoterpene-iridoids: 1a: 1R,2S,5R,8R-iridodial; 1b:
1R,2S,5R,8S-iridodial; 1c: 1S,2S,5R,8R-iridodial; 1d: 1S,2S,5R,8S-
iridodial; 2a: 4aS,7S,7aR(Z,E)-nepetalactone; 2b: 4aS,7S,7aS(E,Z)-
nepetalactone; 3: 4aS,7S,7aR(Z,E)-nepetalactol.
Keywords: Iridodials; Nepetalactone; Lacewing.
* Corresponding author. Tel.: +1-3015045166; fax: +1-3015046580;
e-mail: chauhank@ba.ars.usda.gov
0040-4039/$ - see front matter Ó 2004 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2004.03.034

3340
K. R. Chauhan et al. / Tetrahedron Letters 45 (2004) 3339–3340
their timely help in NMR spectroscopy and stereo-
COOCH3
O
COOCH3
chemical assignments. We are grateful to Mr. Victor
Levi (USDA-ARS-CAIBL) for chromatography, and
Mr. Ajay Vellore (University of Maryland, College
Park) for logistical and laboratory support.
b
a
2a
CHO
O
4
R1
R2
c,d
5a:R1
5b:R1
=
=
CH3, R2
H, R2
= H
CH3
7
=
6
CHO
2
4
O
1
5
11
References and notes
3
e
12
9
1a, 1b
8
1. New, T. R. Trans. R. Entomol. Soc. London 1975, 127,
115–140; Tauber, M. J.; Tauber, C. A.; Daane, K. M.;
Hagen, K. S. Am. Entomol. 2000, 46, 26–38.
2. Ridgway, R. L.; Murphy, W. L. Biological Control in the
Field. In Biology of Chrysopidae; Canard, M., Semeria, Y.,
New, T. R., Eds.; Dr. W. Junk Publishers: The Hague,
1984; pp 220–228.
O
10
10
R2
R1
6a:R1
6b:R1
=
=
CH3, R2
= H
H, R2 CH3
=
Figure 2. Synthesis of iridodial 1a/1b. Reagents and conditions: (a)
NaHCO3 (5%), MeOH/H2O (95:5), rt; (b) ethane-1,2-diol, toluene, cat.
TsOH, azeotropic dehydration; (c) DIBAL, toluene, )78 to 0 °C; (d)
PDC, dry DCM, rt; (e) THF, 2 N HCl, rt.
3. Baker, T. C.; Obrycki, J. J.; Zhu, J. W. U.S. Patent
6,562,332, 2003.
4. Zhang, Q. H.; Chauhan, K. R.; Aldrich, J. R. J. Chem.
Ecol. 2003, submitted for publication.
cataria), quantitatively isolated by chemical separation]10
was the key to this synthetic approach. Methanolysis of
2a at room temperature in 5% methanolic NaHCO3
solution (95:5 methanol/water) gave an isomeric mixture
of methyl ester–aldehyde 4, which was quantitatively
protected to the cyclic acetals 5a and 5b by azeotropic
dehydration with ethane-1,2-diol in 94% yield over the
two steps. Cyclic acetals 5a and 5b were separated by flash
column chromatography.11 DIBAL reduction followed
by PDC oxidation of 5a and 5b individually afforded
mono-protected dialdehydes 6a and 6b in 78% yield over
two steps. At this stage, the absolute configuration at the
C-8 asymmetric center of each isomer was established by
NMR spectroscopy (1H, 13C-APT, and COSEY)12;13 of
mono-protected iridodials to avoid interference of lactol
formation in free iridodials. Deprotection of the cyclic
acetal was carried out under mild acidic hydrolysis at
room temperature to conclude the synthesis of iridodials
1a in 65% and 1b in 48% overall yields.
5. Cavill, G. W. K.; Houghton, E.; McDonald, F. J.;
Williams, P. J. Insect Biochem. 1976, 6, 483–490.
6. Hooper, A. M.; Donato, B.; Woodcock, C. M.; Park,
J. H.; Paul, R. L.; Boo, K. S.; Hardie, J.; Pickett, J. A.
J. Chem. Ecol. 2002, 28, 849–864.
7. Meinwald, J.; Jones, T. H.; Eisner, T.; Hicks, K. Proc.
Natl. Acad. Sci. 1977, 74(6), 2189–2193.
8. Weibel, D. B.; Oldham, N. J.; Feld, B.; Glombitza, G.;
Dettner, K.; Boland, W. Insect Biochem. Mol. Biol. 2001,
31, 583–591.
9. Clark, K. J.; Fray, G. I.; Jaeger, R. H.; Robinson, R.
Tetrahedron 1959, 6, 217–224.
10. Chauhan, K. R.; Zhang, A. Unpublished data; Birkett,
M. A.; Pickett, J. A. Phytochemistry 2003, 62, 651–
656.
11. Ethyl acetate (5%) in hexane as mobile phase and 230–
400 mesh silica gel as stationary phase.
12. Mono-protected iridodial 6a: 1H NMR (CDCl3,
300 MHz): d 9.75 (1H, d, J ¼ 3:8, H6), 4.71 (1H, d,
J ¼ 3:7 Hz, H9), 3.85 (4H, m, H11, H12), 2.54 (1H, ddd,
J ¼ 3:8, 3.0, 12.9 Hz, H1), 2.2 (2H, m, H2, H8), 1.92 (2H,
m, H5, H3), 1.41 (1H, m, H3), 1.15 (2H, m, H4), 1.01 (3H,
d, J ¼ 7:19 Hz, H7), and 0.91 (3H, d, J ¼ 6:81 Hz, H10)
ppm; J ¼ 13:2 Hz at H5–H8, indicating threo or trans
configuration.13 13C NMR (CDCl3, 75 MHz) d 204.5 (C6),
106.8 (C9), 64.9 (C11), 64.7 (C12), 60.41 (C1), 44.0 (C8),
36.9 (C2), 35.3 (C5), 32.9 (C3), 30.6 (C4), 21.4 (C7), and
13.7 (C10) ppm.
Repetition of the foregoing sequence using 4aS,7S,7aS-
nepetalactone 2b proceeded analogously and with com-
parable yields to give 1c and 1d (Fig. 1). When injected as
a mixture for GC analyses, only synthetic iridodial 1a co-
eluted with the natural iridodial extracted from the 1st to
8th abdominal segments of Co. oculata, and 1a was
identical to the natural product by GC–MS.
6b: (CDCl3, 300 MHz): d 9.69 (1H, d, J ¼ 4:5, H6), 4.82
(1H, d, J ¼ 3:0Hz, H9), 3.85 (4H, m, H11, H12), 2.43
(1H, ddd, J ¼ 4:1, 3.7, 12.6 Hz, H1), 2.0(4H, m, H2, H3,
H5, H8), 1.47 (1H, m, H3), 1.24 (2H, m, H4), 1.01 (3H, d,
J ¼ 6:81 Hz, H7), and 0.91 (3H, d, J ¼ 6:71 Hz, H10)
ppm; J ¼ 11:3 Hz at H5–H8, confirming erythreo or cis
configuration.13 13C NMR (CDCl3, 75 MHz) d 203.8 (C6),
105.9 (C9), 65.1 (C11), 65.0 (C12), 60.6 (C1), 45.8 (C8),
37.4 (C2), 33.9 (C5), 33.8 (C3), 30.6 (C4), 21.4 (C7), and
12.2 (C10) ppm.
In conclusion, 1R,2S,5R,8R-iridodial 1a, along with
three isomeric iridodials,14;15 have been conveniently
prepared in five steps from readily available starting
materials. Iridodial 1a attracts conspecific males and
possibly females in the field. The availability of synthetic
1R,2S,5R,8R-iridodial will facilitate further efforts to
semiochemically promote biocontrol involving this and
other lacewing species.
13. Meinwald, J.; Jones, T. H. J. Am. Chem. Soc. 1978, 100(6),
1883–1886.
14. Since iridodial isomers were derived from nepetalactone 2a
and 2b, the absolute configuration remain intact for 7a, 7,
and 4a positions of origin (which was established earlier by
Dawson et al.).
Acknowledgements
We thank Dr. Walter Schmidt and Ms. Ute Klingebiel,
NMR Facility, USDA-ARS, Beltsville, Maryland, for
15. Dawson, G. W.; Pickett, J. A.; Smiley, W. M. Bioorg.
Med. Chem. 1996, 4, 351–361.