Abstract
DFT calculations on the carbocation intermediates that connect the biosynthetic pathways leading to the sand fly pheromone sobralene and taxadiene have been made. Establishment of the conformation of the macrocyclic carbocation intermediate required to produce the (Z)-C8,C9 alkene bond in sobralene has identified new conformations of the verticillyl carbocation intermediates on the taxadiene biosynthetic pathway. These "sobralene-like" carbocation conformations provide an exothermic pathway to taxadiene and are validated by comparison to closely related structures (X-ray and NMR).
Highlights
Sobralene 1 is a recently discovered sex-aggregation pheromone produced by populations of the sand fly Lutzomyia longipalpis from Sobral, Brazil,[1] which is the main carrier of the Protist parasite Leishmania infantum, the causative agent of visceral leishmaniasis (VL)
Sobralene 1 is a newly discovered isomer of verticillene 2 and we propose that it has a biosynthetic connection to taxadiene 3 via the verticillyl carbocation intermediate D
The conformation sobD permits an energetically favourable transannulation reaction which leads to the sobralene-like conformer of the penultimate carbonium ion precursor E to taxadiene 3
Summary
Sobralene 1 is a recently discovered sex-aggregation pheromone produced by populations of the sand fly Lutzomyia longipalpis from Sobral, Brazil,[1] which is the main carrier of the Protist parasite Leishmania infantum, the causative agent of visceral leishmaniasis (VL). Ninety five percent of new VL cases (estimated at 200-400 thousand per year) occur in just ten countries (Bangladesh, Brazil, China, Ethiopia, India, Kenya, Nepal, Somalia, South Sudan and Sudan), and it is the second largest parasite killer in the world after malaria, resulting in 20,000-40,000 fatalities per year.[2,3] Sobralene 1 has the potential to be used in pheromone attractant traps as a vector control measure It has only been isolated in very small quantities from the sand flies, and methods need to be developed for its large scale production. This approach has been successfully employed for the production of closely related diterpenes such as taxadiene 34-10 and a collection of verticillenes[11,12] (e.g. verticillene 2), but the production of sobralene 1 has yet to be explored
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