Leptospermone

History

Leptospermone was first identified in 1927 and was extracted from a variety of plants in 1965, 1966 and 1968. It was first identified as a chemical in Callistemon citrinus in California in 1977. A biologist at the Western Research Centre of Stauffer Chemical Company noticed that very few plants grew under Callistemon citrinus bushes. After taking soil samples and creating an array of extracts, one was identified as an herbicide. While it did have herbicidal effects, the rate required for sufficient coverage was too high to be of practical use.

Leptospermone was optimized into thousands of compounds. Several were extremely effective but were too toxic, environmentally persistent or not selective enough. There are now several members of the triketone class of HPPD inhibitor herbicides on the market.

Synthesis

Leptospermone can be synthesized from phloroglucinol by a reaction with 3-methylbutanenitrile (isovaleronitrile) in the presence of a zinc chloride catalyst. Phloroisovalerone imine is produced which is then alkylated with iodomethane after initial treatment with sodium ethoxide and methanol to produce an intermediate which is treated with aqueous hydrochloric acid resulting in isovaleroylsyncarpic acid (leptospermone).

Biochemically, the plants take a different approach. Despite the fact that the biochemical synthesis has not been specifically investigated, it is clear that leptospermone is not an oxidized terpene (or specifically a sesquiterpene, ei. C15) as the cyclisation of farnesyl pyrophosphate cannot produce two dimethylate carbons that are separated by a single carbon nor would this be consistent with the natural occurrence of similar compounds with different keto-aryl side-chains in the members of the Myrtaceae (eg. flavesone, papuanone, isoleptospermone and grandiflorone and could be the intermediate, but other routes of biosynthesis may be possible, such as via isobutyryl-CoA, the result of the decarboxylative condensation of ketoisovalerate (ketone form of valine) (cf. polyketides).

Uses

Leptospermone was the blueprint for the compound mesotrione which has the trade name Callisto, a Syngenta herbicide.

References

References

1. (1999). "β-Triketones from Myrtaceae: Isoleptospermone from ''Leptospermum scoparium'' and Papuanone from ''Corymbia dallachiana''". J Nat Prod.
2. (2009). "Herbicidal 4-hydroxyphenylpyruvate dioxygenase inhibitors -- A review of the triketone chemistry story from a Syngenta perspective". Bioorg Med Chem.
3. van Almsick A. (2009). "New HPPD-Inhibitors - A Proven Mode of Action as a New Hope to Solve Current Weed Problems". Outlooks on Pest Management.
4. Cornes D. (2005). "Callisto: a very successful maize herbicide inspired by allelochemistry". The Regional Institute Ltd..
5. (2000). "Allelopathy in Ecological Agriculture and Forestry". Springer.
6. (2005). "Biosynthesis of Phloroglucinol". J Am Chem Soc.