Lutzomyia longipalpis

Scheme 45 summarizes Mori s synthesis of the male-produced sex pheromone [(l ,3 ,7S)-3-methyl-a-himachalene (31)] of the sandfly (Lutzomyia longipalpis) in Jacobina, Brazil [70]. This sandfly is the vector of Leishmania chagasU the causative protozoan parasite of visceral leishmaniasis in South America. The key-steps of the synthesis of 31 were the asymmetric methylation of A to give C via B and the intramolecular Diels-Alder reaction of D to give E. 

The same sandfly Lutzomyia longipalpis in Lapinha, Brazil, produces (S)-9-methylgermacrene-B (32) as the male-produced sex pheromone, which was also synthesized by Mori as shown in Scheme 46 [71]. The key-step of this synthesis was the intramolecular cyclization of A to give B. 

IS, 3S, 7i )-3-methyl-a-himachalene, the sex pheromone of the Brazilian (from Jacobina, Brazil) male sandfly, Lutzomyia longipalpis, has been synthesized. The ring junction of this pheromone has the absolute configuration opposite to that of the known (IS, 3S, 7R)-3-methyl-a-himachalene (li , 7i )-a-himachalene of plant origin.The synthesis of the pheromone of the sandfly from Lapinha, Brazil has also been reported, the active pheromone compound being (S)-9-methylgermacrene-B. ... 

Hamilton, J. G. C Hooper, A. M., Ibbotson, H. C. el al. (1999b). 9-Methylgermacrene-B is confirmed as the sex pheromone of the sandfly Lutzomyia longipalpis from Lapinha, Brazil, and the absolute stereochemistry defined as S. Chemical Communications 2335-2336. 

In the psychodid sand fly, Lutzomyia longipalpis, the sex pheromone-producing glands occur on the 3rd and 4th abdominal segment of the male insects. The gland consists of large type III secretory cells with prominent end apparatus (Lane and de Souza Bemardes, 1990). 

Lane R. P. and de Souza Bemardes D. (1990) Histology and ultrastructure of pheromone secreting glands in males of the phlebotomine sandfly Lutzomyia longipalpis. Ann. Tropical Med. Parasitol. 84, 53-61. 

Hamilton, J.G., Ward, R.D., Dougherty, M. J., Maignon, R., Ponce, C., Ponce, E., Noyes, H. and Zeledon, R. (1996). Comparison of the sex-pheromone components of Lutzomyia longipalpis (Diptera Psychodidae) from areas of visceral and atypical cutaneous leishmaniasis in Honduras and Cost Rica. Ann. Prop. Med. Parasitol., 90, 533-541. 

America, both wild and domestic dogs enter the epidemiological chain and the vector is a common sandfly, Lutzomyia longipalpis, abundant in and around houses. The disease is more common in children in both Latin America and the Mediterranean area. 

The sandfly Lutzomyia longipalpis is the vector of the protozoan parasite Leishmania chagasi, the causative agent of visceral leishmaniasis in South and Central America. Population control of L. longipalpis is therefore of urgent importance to prevent the disease. In 1994, Hamilton and coworkers isolated the male-produced pheromone of L. longipalpis from Jacobina, Brazil, and proposed its structure as 3-methyl-a-himachalene (96, Figure 4.47) with unknown stereochemistry. We first synthesized ( R, 3R, 1 S )-( )-96.81 Enantiomer separation (optical resolution) of a synthetic intermediate enabled us to prepare both the enantiomers of 96, and their bioassay and GC comparisons with the natural pheromone showed the latter to be (lS,3S,lR)-96. 

In 1996 Hamilton et al. proposed 9-methylgermacrene-B (97, Figure 4.48) as the structure of the male-produced sex pheromone of Lutzomyia longipalpis from Lapinha, Brazil. We synthesized ( )-97 in 1999,84 and then both the enantiomers of 97 in 2000, as shown in Figure 4.48.85 The key step was the cyclization of A to give crystalline B after deprotection. The intramolecular cyclization reaction itself proceeded in 47-53% yield. The final isopropylidenation could not be achieved by the conventional Wittig reaction. The successful protocol was the use of samarium and chromium. 

Sano. S. 3-Methyl-ot-himachalene is confirmed, and the 20. relative stereochemistry defined, by synthesis as the sex pheromone of the sandfly Lutzomyia longipalpis from Jacobina. Brazil. Chem. Commun. 1999, 4. 355-356. 21. 

The sesquiterpene a-himachalene has been isolated from the New World sandfly Lutzomyia longipalpis, a carrier of a protozoan that is transmitted in the bite of the fly. The protozoan infection results in the disease leishmaniasis, one form of which can cause enlargement of the spleen and, if untreated, death. Scheme 11.58 presents a cartoon of a biosynthetic rationalization of its formation. 

M. D. Buescher et al.. Laboratory tests of repellents against Lutzomyia longipalpis (Diptera Psychodidae), J. Med. Entomol, 19, 176, 1982. 

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