Acid-Catalysed Rearrangement of the Sandfly Pheromone Sobralene to Verticillenes, Consolidating its Relationship inter alia to the Taxanes and Phomactins

Palframan, M. J.; Bandi, Krishna K.; Hamilton, James G. C.; Pattenden, Gerald

doi:10.1055/s-0039-1690131

Cited by 4 publications

(3 citation statements)

References 11 publications

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“…Recent experiments show that sobralene 1 isomerizes to verticillene 2 upon treatment with mild acid via cation D (i.e., 1 → sob D → 2 ), thus demonstrating that 2 is more thermodynamically stable than 1 . This finding is consistent with our calculations that show sob D is slightly higher (2.3 kcal/mol) in energy than vert D .…”

Section: Resultssupporting

confidence: 50%

“…Recent experiments show that sobralene 1 isomerizes to verticillene 2 upon treatment with mild acid via cation D (i.e., 1 → sob D → 2), 21 thus demonstrating that 2 is more thermodynamically stable than 1. This finding is consistent with our calculations that show sob D is slightly higher (2.3 kcal/mol) in energy than vert D. Without the structure of the sobralene synthase, we cannot assess if specific active site residues facilitate the desired deprotonation at C9 in the carbocation D to give sobralene 1, but it seems likely that the synthase is responsible for guiding carbocation D to adopt the sob D conformation during the deprotonation to form sobralene 1.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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The Impact of Macrocycle Conformation on the Taxadiene-Forming Carbocation Cascade: Insight Gained from Sobralene, a Recently Discovered Verticillene Isomer

2020

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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 cis-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, NMR).

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Section: Resultssupporting

confidence: 50%

Section: ■ Results and Discussionmentioning

confidence: 99%

The Impact of Macrocycle Conformation on the Taxadiene-Forming Carbocation Cascade: Insight Gained from Sobralene, a Recently Discovered Verticillene Isomer

2020

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“…share a biosynthetic origin the methylsesquiterpenes are derived from a 15-carbon precursor, farnesyl diphosphate and six of the seven enzymes of the mevalonate-pathway, plus enzymes involved in sesquiterpenoid biosynthesis, have been found in 9MGB-producing Lu. longipalpis [37] whereas the diterpenes are derived via a 20-carbon precursor, geranylgeranyl diphosphate [38].…”

Section: Introductionmentioning

confidence: 99%

Genomic analysis of two phlebotomine sand fly vectors of Leishmania from the New and Old World

et al. 2023

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Phlebotomine sand flies are of global significance as important vectors of human disease, transmitting bacterial, viral, and protozoan pathogens, including the kinetoplastid parasites of the genus Leishmania, the causative agents of devastating diseases collectively termed leishmaniasis. More than 40 pathogenic Leishmania species are transmitted to humans by approximately 35 sand fly species in 98 countries with hundreds of millions of people at risk around the world. No approved efficacious vaccine exists for leishmaniasis and available therapeutic drugs are either toxic and/or expensive, or the parasites are becoming resistant to the more recently developed drugs. Therefore, sand fly and/or reservoir control are currently the most effective strategies to break transmission. To better understand the biology of sand flies, including the mechanisms involved in their vectorial capacity, insecticide resistance, and population structures we sequenced the genomes of two geographically widespread and important sand fly vector species: Phlebotomus papatasi, a vector of Leishmania parasites that cause cutaneous leishmaniasis, (distributed in Europe, the Middle East and North Africa) and Lutzomyia longipalpis, a vector of Leishmania parasites that cause visceral leishmaniasis (distributed across Central and South America). We categorized and curated genes involved in processes important to their roles as disease vectors, including chemosensation, blood feeding, circadian rhythm, immunity, and detoxification, as well as mobile genetic elements. We also defined gene orthology and observed micro-synteny among the genomes. Finally, we present the genetic diversity and population structure of these species in their respective geographical areas. These genomes will be a foundation on which to base future efforts to prevent vector-borne transmission of Leishmania parasites.

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A diterpene synthase from the sandfly Lutzomyia longipalpis produces the pheromone sobralene

Ducker,

Baines,

Guy

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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The phlebotomine sandfly, Lutzomyia longipalpis , a major vector of the Leishmania parasite, uses terpene pheromones to attract conspecifics for mating. Examination of the L. longipalpis genome revealed a putative terpene synthase (TPS), which—upon heterologous expression in, and purification from, Escherichia coli —yielded a functional enzyme. The TPS, termed Ll TPS, converted geranyl diphosphate (GPP) into a mixture of monoterpenes with low efficiency, of which β-ocimene was the major product. ( E,E )-farnesyl diphosphate (FPP) principally produced small amounts of ( E )-β-farnesene, while ( Z,E )- and ( Z,Z )-FPP yielded a mixture of bisabolene isomers. None of these mono- and sesquiterpenes are known volatiles of L. longipalpis . Notably, however, when provided with ( E,E,E )-geranylgeranyl diphosphate (GGPP), Ll TPS gave sobralene as its major product. This diterpene pheromone is released by certain chemotypes of L. longipalpis , in particular those found in the Ceará state of Brazil. Minor diterpene components were also seen as products of the enzyme that matched those seen in a sandfly pheromone extract.

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Acid-Catalysed Rearrangement of the Sandfly Pheromone Sobralene to Verticillenes, Consolidating its Relationship inter alia to the Taxanes and Phomactins

Abstract: The sex-aggregation pheromone sobralene produced by the sandfly Lutzomyia longipalpis is isomerised to verticillenes in the presence of mild acid, thereby providing credence to the proposal that sobralene is a likely shunt metabolite of the taxadiene synthase cascade.

Cited by 4 publications

References 11 publications

The Impact of Macrocycle Conformation on the Taxadiene-Forming Carbocation Cascade: Insight Gained from Sobralene, a Recently Discovered Verticillene Isomer

The Impact of Macrocycle Conformation on the Taxadiene-Forming Carbocation Cascade: Insight Gained from Sobralene, a Recently Discovered Verticillene Isomer

Genomic analysis of two phlebotomine sand fly vectors of Leishmania from the New and Old World

A diterpene synthase from the sandfly Lutzomyia longipalpis produces the pheromone sobralene

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