Leptospermone
| Leptospermone | |
|---|---|
 | |
| IUPAC name 2,2,4,4-Tetramethyl-6-(3-methylbutanoyl)cyclohexane-1,3,5-trione | |
| Other names Isovaleroylsyncarpic acid; 6-Isovaleroyl-2,2,4,4-tetramethyl-1,3,5-cyclohexanetrione | |
| Identifiers | |
| CAS number | 567-75-9  |
| PubChem | 3083632 |
| ChemSpider | 2340805 |
| Jmol-3D images | Image 1 |
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| Properties | |
| Molecular formula | C15H22O4 |
| Molar mass | 266.33 g mol−1 |
(verify) (what is: / ?)Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa) | |
| Infobox references | |
Leptospermone is a chemical compound (a β-triketone) produced by some members of the myrtle family (Myrtaceae), such as Callistemon citrinus (Lemon Bottlebrush), a shrub native to Australia, and Leptospermum scoparium (Manuka), a New Zealand tree from which it gets its name.[1] Allelopathic studies have led to the commercialization of the analogous herbicidal compound mesotrione. Leptospermone is also studied as an antibacterial.
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. The final compound, mesotrione, is a triketone herbicide used as a selective herbicide for corn crops.[2]
Chemistry
Leptospermone can be synthesized from phloroglucinol by a reaction with 3-methylbutanenitrile (isovaleronitrile) in the presence of a zinc chloride catalyst. Phluroisovalerone 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).[3]
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[1]). Phloroglucinol is biosynthesized in a single step from malonyl-CoA[4] 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.[2] This herbicide was deemed “not likely to be carcinogenic to humans” by the EPA.[5] Mesotrione has been proven to be an effective preemergent herbicidal treatment for velvetleaf. This is beneficial because atrazine is effective on many broadleaf weed species but does not effectively control velvetleaf. Surprisingly, using atrazine and mesotrione together produced greater weed control than just the summed effect. These two chemicals had synergistic effect on common ragweed and common lambsquarters.[6] Atrazine has been considered by the EPA for stronger regulation, encouraging the development of replacement or additive herbicides. The cost of phasing out atrazine and replacing it with mesotione is estimated at $9.2 million.[7]
Leptospermone also has antibacterial potential. Studies have shown that it has strong inhibitive effects on Clostridium difficile and Clostridium perfringens.[8]
References
- ↑ 1.0 1.1 van Klink JW, Brophy JJ, Perry NB, Weavers RT (1999). "beta-triketones from myrtaceae: isoleptospermone from leptospermum scoparium and papuanone from corymbia dallachiana". J Nat Prod 62 (3): 487–489. PMID 10096865.
- ↑ 2.0 2.1 Derek Cornes (2005). "Callisto: a very successful maize herbicide inspired by allelochemistry". Fourth World Congress on Alleopathy. The Regional Institute Ltd. Retrieved May 26, 2011.
- ↑ Knudsen et al. (2000). Discovery of the triketone class of HPPD inhibiting herbicides and their relationship to naturally occurring β-triketones (Report). Zeneca Ag Products.
- ↑ Achkar J, Xian M, Zhao H, Frost JW (2005). "Biosynthesis of phloroglucinol". J Am Chem Soc 127 (15): 5332–5333. PMID 15826166.
- ↑ "Pesticide Fact Sheet (Mesotrione)". United States Environmental Protection Agency Office of Prevention, Pesticides, and Toxic Substances. June 4, 2001. Retrieved May 26, 2011.
- ↑ Scott L. Bollman, James J. Kells, and Donald Penner (2006). "Weed Response to Mesotrione and Atrazine Applied Alone and in Combination Preemergence". Weed Technology (Weed Science Society of America and Allen Press) 20 (4): 903–907. doi:10.1614/WT-04-304.1. JSTOR 4495772.
- ↑ Martin M. Williams II, Chris M. Boerboom, and Tom L. Rabaey (2010). "Significance of Atrazine in Sweet Corn Weed Management Systems". Weed Technology. Weed Science Society of Americva. Retrieved May 26, 2011.
- ↑ Jeong, Eun-Young; Jeon, Ju-Hyun; Kim, Hyung-Wook; Kim, Min-Gi; Lee, Hoi-Seon (2009). "Antimicrobial activity of leptospermone and its derivatives against human intestinal bacteria". Food Chemistry 115 (4): 1401. doi:10.1016/j.foodchem.2009.01.086.