Published: April 12, 2011 Copyright r 2011 American Chemical Society and American Society of Pharmacognosy 690 dx.doi.org/10.1021/np100748r | J. Nat. Prod. 2011, 74, 690–694 ARTICLE pubs.acs.org/jnp Structure Elucidation and Synthesis of Dioxolanes Emitted by Two Triatoma Species (Hemiptera: Reduviidae) B. Bohman, †,# A. Tr€ oger, ‡ S. Franke, ‡,4 M. G. Lorenzo, § W. Francke, ‡ and C. R. Unelius* ,†,^ † School of Natural Sciences, Linnaeus University, SE-391 82 Kalmar, Sweden ‡ Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, D-20146 Hamburg, Germany § Laborat orio de Triatomíneos e Epidemiologia da Doenc -a de Chagas, Centro de Pesquisas Ren e Rachou/FIOCRUZ, 30.190-002, Belo Horizonte, Minas Gerais, Brazil b S Supporting Information I n rural areas of the Southern Cone of South America and Northeastern Brazil, Triatoma infestans and Triatoma brasilien- sis (Hemiptera: Reduviidae) are main vectors of Chagas disease, the principal health and socioeconomic burden caused by a parasitic infection in Latin America. 13 Triatomine bugs fre- quently invade human dwellings, where they develop colonies through blood-feeding on humans and domestic animals. In this context, the insects can transmit Trypanosoma cruzi, a parasite that acts as the etiological agent of Chagas disease. Since no vaccine is available for human immunization against T. cruzi and no effective treatment exists to cure chronic patients, the elimination of triatomine vectors is essential for Latin American national health programs. Volatile constituents of the metasternal glands (MGs) of T. infestans, Rhodnius prolixus, and T. brasiliensis have been sug- gested to be emitted during copulation and to play a role in sexual communication. 46 Manrique et al. identified five volatile com- pounds, predominantly 3-pentanone and short-chain alcohols, in the secretion produced by the MGs of T. infestans. 4 The second most abundant compound of this secretion was reported as unknown, although its mass spectrum was published. During studies on volatiles from MGs of T. brasiliensis, 6 3-pentanone was again identi fied as a major component, as well as (S)-2-methyl- 1-butanol, (R)-4-methyl-1-heptanol, and (R)-1-phenylethanol, together with the same unknown compound that was found in T. infestans. The ketone, chiral alcohols, and the unknown com- pound triggered electrophysiological responses, i.e., EAD deflections, in the antennae of male T. brasiliensis. 6 In a recent short communica- tion we reported the identification of the unknown as 2,2,4-triethyl-5- methyl-1,3-dioxolane (1), which in T. brasiliensis is produced as a mixture of (4S,5S)-1 and (4R,5R)-1 in a ratio of about 4:1. 7 Further investigations have now revealed that a number of additional acetals are produced in T. brasiliensis. Here we present the synthesis of highly pure stereoisomers of 1, as well as the structure elucidation and synthesis of four new naturally occurring alkylated dioxolanes (25) found in the MGs of these triatomines. Received: October 17, 2010 ABSTRACT: Volatiles from the metasternal glands of two species of true bugs of the Triatominae subfamily, Triatoma brasiliensis and Triatoma infestans, were analyzed by SPME-GC/ MS. Two sets of new natural products were found: (4S,5S)- and (4R,5R)-2,2,4-triethyl-5-methyl-1,3-dioxolane (1) (major com- ponent) and (4S*,5S*)-2,4-diethyl-2,5-dimethyl-1,3-dioxolane (2) (trace component), (2R/S,4S,5S)- as well as (2R/S,4R,5R)-4-ethyl-5-methyl-2-(1-methylethyl)-1,3-dioxolane (3) (minor component), (2R/S,4S*,5S*)-4-ethyl-5-methyl-2-(1-methylpropyl)-1,3-dioxolane (4) (trace component), and (2R/S,4S*,5S*)- 4-ethyl-5-methyl-2-(2-methylpropyl)-1,3-dioxolane (5) (trace component). Syntheses of optically active 1 and 3 were carried out by reacting pure enantiomers of 2,3-pentanediol with 3-pentanone or 2-methylpropanal. The preparation of pure stereoisomers of 2,3-pentanediol involved a novel key step for the synthesis of secondary alcohols: the reduction of a carboxylic ester by means of DIBAH and in situ alkylation of the intermediate by Grignard reaction at low temperature. Starting from the pure enantiomers of methyl lactate, all four stereoisomers of 2,3-pentanediol were synthesized and transformed to the corresponding isomers of 1 and 2. Relative configurations of the natural products and enantiomeric compositions of naturally occurring 1 and 2 were determined by comparison of their mass spectra and gas chromatographic retention times (co-injection) with those of authentic reference samples.