(4 S,5 S)-2,2,4-Triethyl-5-methyl-1,3-dioxolane: A new volatile released by a triatomine bug

Article abstract of DOI:10.1021/ol102165q

Adults of the triatomine bug Triatoma brasiliensis release 2,2,4-triethyl-5-methyl-1,3-dioxolane (1) as a mixture of the (4S,5S)- and (4R,5R)-enantiomers in a ratio of 4:1. Among the volatile acetals identified from insects so far, this is the first example resulting from an intermolecular condensation of a carbonyl moiety and a diol substructure.

Full text of DOI:10.1021/ol102165q

ORGANIC
LETTERS
2010
Vol. 12, No. 24
5601-5603
(4S,5S)-2,2,4-Triethyl-5-methyl-1,3-dioxolane:
A New Volatile Released by a
Triatomine Bug
C. R. Unelius,*,†,| B. Bohman,†,⊥ M. G. Lorenzo,‡ A. Tro¨ger,§ S. Franke,§ and
W. Francke§
School of Natural Sciences, Linnaeus UniVersity, SE-391 82 Kalmar, Sweden,
Laborato´rio de Triatom´ıneos e Epidemiologia da Doenc¸a de Chagas, Centro de
Pesquisas Rene´ Rachou/FIOCRUZ, 30.190-002, Belo Horizonte, Minas Gerais, Brazil,
and UniVersity of Hamburg, Organic Chemistry, Martin-Luther-King-Platz 6,
D-20146 Hamburg, Germany
rikard.unelius@lnu.se
Received September 10, 2010
ABSTRACT
Adults of the triatomine bug Triatoma brasiliensis release 2,2,4-triethyl-5-methyl-1,3-dioxolane (1) as a mixture of the (4S,5S)- and (4R,5R)-
enantiomers in a ratio of 4:1. Among the volatile acetals identified from insects so far, this is the first example resulting from an intermolecular
condensation of a carbonyl moiety and a diol substructure.
Blood-sucking bugs of the Triatominae subfamily transmit
American trypanosomiasis, known as Chagas disease, in
Latin America.1 Results of investigations on the chemical
ecology of triatomine bugs have been reviewed by Cruz
Lo´pez et al.2 In Triatoma infestans (Klug 1834), analyses
of volatiles of the so-called Brindley’s glands, paired organs
situated on the dorsolateral metathorax, or of head space
volatiles collected over adult insects revealed the presence
of carboxylic acids and corresponding alcohols, as well as
their esters, as major components.2-5 The complete mixture,
and isobutyric acid in particular, was reported to exhibit
repellent effects. Volatiles from another source, the paired
metasternal glands that open to the ventral side of the
metathorax, have been proposed to play a role in the mating
behavior of triatomine bugs.6 The composition of the released
blend differed considerably from that of Brindley’s glands,
showing 3-pentanone and 3-pentanol as main products.5
Another major component among the volatiles of the
metasternal glands of Triatoma infestans remained un-
known.7 During our recent investigations on another tri-
atomine bug, T. brasiliensis (Neiva 1911), we encountered
the same unknown compound.7 Its structure elucidation and
synthesis are the subject of the present paper. Unfortunately,
available amounts of the target compound were too small to
obtain NMR spectra, and therefore, the structure assignment
† Linnaeus University.
‡ Centro de Pesquisas Rene´ Rachou/FIOCRUZ.
§ University of Hamburg.
| Present address: The Plant & Food Research Institute of New Zealand,
P.O.51 Lincoln, New Zealand.
⊥ Present address: Research School of Chemistry and Research School
of Biology, The Australian National University, Canberra ACT 0200,
Australia.
(4) Guerenstein, P. G.; Guerin, P. M. Entomol. Exp. Appl. 2004, 111,
151.
(5) Manrique, G.; Vitta, A. C. R.; Ferreira, R. A.; Zani, C. L.; Unelius,
C. R.; Lazzari, C. R.; Diotaiuti, L.; Lorenzo, M. G. J. Chem. Ecol. 2006,
32, 2035.
(1) Dias, J.C P.; Silveira, A. C.; Schofield, C. J. Mem. Inst. Oswaldo
Cruz 2002, 97, 603.
(2) Cruz Lo´pez, L.; Malo, E. A.; Rojas, J. C.; Morgan, E. D. Med. Vet.
Entomol. 2001, 15, 351.
(6) Pontes, G. B.; Bohman, B.; Unelius, C. R.; Lorenzo, M. G. J. Chem.
Ecol 2008, 34, 450.
(3) Fonta´n, A.; Audino, P. G.; Martinez, A.; Alzogaray, R. A.; Zerba,
(7) Vitta, A. C. R.; Bohman, B.; Unelius, C. R.; Lorenzo, M. G. J. Chem.
Ecol. 2009, 35, 1212.
E. N.; Camps, F.; Cork, A. J. Med. Entomol. 2002, 39, 191
.
10.1021/ol102165q  2010 American Chemical Society
Published on Web 11/18/2010

had to be based on mass spectrometry (coupled with gas
chromatography), microreactions, and independent synthesis.
The 70 eV-EI mass spectrum of the target compound is
depicted in Figure 1.
parent carbonyl compound involved in the formation of the
target compound was regarded to be 3-pentanone. Conse-
quently, 2,2-diethyl-1,3-dioxanes or 2,2-diethyl-1,3-diox-
olanes, carrying the remaining carbons as alkyl substituents,
were considered to be suitable candidates. Finally, two less
abundant signals in the mass spectrum, detected at m/z 128
(C8H16O upon HR-MS) and m/z 114 (C7H14O upon HR-MS)
(Figure 1), proved to represent key fragments decisive for
structure elucidation. Earlier it had been shown that upon
electron impact 4,5-dialkyl-1,3-dioxolanes extrude carbonyl
fragments consisting of an alkyl substituent, the correspond-
ing ring-carbon, and the adjacent oxygen.11 In the present
case, this was suggested to be acetaldehyde giving rise to
M+-44 ) m/z 128 and acetone or propanal producing M+-
58 ) m/z 114. Consequently, the target compound was
considered to be either 2,2-diethyl-4,4,5-trimethyl-1,3-diox-
olane or 2,2,4-triethyl-5-methyl-1,3-dioxolane.
The former compound, prepared upon boron trifluoride
catalyzed reaction12 of 3-pentanone and 2,2,3-trimethylox-
irane, yielded a mass spectrum similar to that of the natural
product (see Supporting Information); however, the gas
chromatographic retention time did not match. We, therefore,
synthesized both racemic cis-2,2,4-triethyl-5-methyl-1,3-
dioxolane (cis-1) and its trans-isomer. Boron trifluoride
catalyzed reaction of 3-pentanone with either trans-2-ethyl-
3-methyloxirane (trans-2) (obtained from (E)-2-pentene upon
epoxidation with m-chloroperbenzoic acid) or cis-2-ethyl-
3-methyloxirane (cis-2) (from (Z)-2-pentene) produced the
desired dioxolanes in good yields (Figure 2). NMR data of
Figure 1. Mass spectrum (70 eV-EI) of (4S,5S)-2,2,4-triethyl-5-
methyl-1,3-dioxolane (trans-1).
The fragment with the highest mass recorded was repre-
sented by a signal at m/z 143. High resolution mass
spectrometry (GC/HR-MS) of the corresponding ion showed
an atomic composition of m/z 143 ) C8H15O2. Chemical
ionization analysis (GC/CI-MS) revealed the molecular mass
of the natural product to be M+ ) 172. As a result, its
molecular formula proved to be either C10H20O2 (m/z 143 )
M-ethyl) or C9H16O3 (m/z 143 ) M-formyl), exhibiting either
one or two degrees of unsaturation, respectively. Because
of its relatively low Kovats index of 1156 on a polar GC
column (SupelcoWax-10),7 which indicated low polarity, the
latter atomic composition was regarded less likely. As a
consequence, the structure of the unknown was expected
either to be cyclic or to contain a carbonyl group or a CC
double bond. The latter case was ruled out because the
compound could not be catalytically hydrogenated.8 The
intense signal at m/z 143 indicated a rather stable fragment,
supposedly due to the formation of an oxonium ion.
Corresponding structures are typically formed upon R-cleav-
age from secondary and tertiary alcohols or ketones as well
as from ethers and acetals (including cyclic structures).9,10
As acetylation8 failed and because of the low Kovats index
of the compound, alcohol structures were considered less
likely.
Figure 2. Synthesis of racemic and optically active 2,2,4-triethyl-
5-methyl-1,3-dioxolanes.
the products were as expected. Upon gas chromatography,
the diastereomers were well resolved (R ) tr cis/tr trans )
1.10 on CP-Sil 5 and 1.02 on FFAP). While the mass spectra
of both isomers matched that of the natural product, the gas
chromatographic retention time of trans-2,2,4-triethyl-5-
methyl-1,3-dioxolane coincided with that of the target
Based on the analytical information obtained so far, the
natural product was hypothesized to be a cyclic acetal.
Because of the large amounts of 3-pentanone present in the
metasternal glands and the abundant signal at m/z 143 )
M+-ethyl in the mass spectrum of the target compound, the
(8) Attygalle, A. B. In Methods in Chemical Ecology 2; Millar, J. G.,
Haynes, K. E., Eds.; Kluwer: New York, 1998; pp 207-294.
(11) Friedel, R. A.; Sharkey, A. G., Jr. Anal. Chem. 1956, 28, 940.
(12) Blackett, B. N.; Coxon, J. M.; Hartshorn, M. P.; Lewis, A. J.
Tetrahedron 1970, 26, 1311.
(9) Francke, W.; Kitching, W. Curr. Org. Chem. 2001, 5, 233
.
(10) Marshall, J. T. B.; Williams, D. H. Tetrahedron 1967, 23, 321
.
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compound. However, a close inspection of our GC/MS data
revealed the presence of tiny amounts of the later eluting
(and higher boiling13) cis-isomer (see Supporting Informa-
tion).
As a final step, the enantiomeric composition of the
naturally occurring trans-2,2,4-triethyl-5-methyl-1,3-diox-
olane had to be determined by employing enantioselective
gas chromatography. For the syntheses of optically active
reference samples, (E)-2-pentene was used as the starting
material. A Sharpless bishydroxylation approach14 applying
AD-mix R or AD-mix ꢀ yielded (2S,3S)-2,3-pentanediol (S-
3) or its enantiomer, respectively (Figure 2). The NMR
spectra of the obtained diols were in accord with data
reported in the literature.15
Upon enantioselective gas chromatography using modified
cyclodextrins, the enantiomers of trans-2,2,4-triethyl-5-
methyl-1,3-dioxolane, prepared through an acid-catalyzed
reaction of 3-pentanone with optically active syn-2,3-
pentanediols, were baseline separated.
Figure 3. Chromatogram of an extract of metasternal glands of T.
brasiliensis using enantioselective GC/MS. TIC in black and ion
chromatogram for m/z 143 in gray. Tiny amounts of the later eluting
cis-isomer present in the glands did not produce a visible signal in
this GC (conditions: ref 7).
The synthetic trans-configured 1,3-dioxolanes showed an
enantiomeric excess (ee) of 92% for the (4S,5S)-stereoisomer
and 90% for its earlier eluting (4R,5R)-enantiomer. Com-
parison of mass spectra and retention times (coinjection) of
the synthetic reference compounds with corresponding data
of the natural product revealed the latter to be a mixture of
(4S,5S)- and (4R,5R)-2,2,4-triethyl-5-methyl-1,3-dioxolane
in a ratio of 4:1 (Figure 3). Due to the particularly small
amounts of cis-1 and the interference with other volatiles
present in the glands, it was impossible to determine the
enantiomeric composition of this isomer.
Investigations concerning behavior-mediating activities of
the new Triatoma compounds are underway.
Supporting Information Available: Experimental pro-
1
cedures, analytical data, and copies of H and 13C NMR
spectra for cis-1 and trans-1 and gas chromatograms of
natural extracts. This material is available free of charge via
the Internet at http://pubs.acs.org.
(13) van Risseghem, H. Bull. Soc. Chim. France 1960, 27, 1192.
(14) Sharpless, K. B.; Amberg, W.; Bennani, Y. L.; Crispino, G. A.;
Hartung, J.; Jeong, K.-S.; Kwong, H.-L.; Morikawa, K.; Wang, Z.-M.; Xu,
D.; Zhang, X.-L. J. Org. Chem. 1992, 57, 2768.
(15) Enders, D.; Nakai, S. Chem. Ber. 1991, 124, 219.
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