Leptospermone is a
chemical compound
A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one ele ...
(a β-triketone) produced by some members of the myrtle family (''
Myrtaceae
Myrtaceae, the myrtle family, is a family of dicotyledonous plants placed within the order Myrtales. Myrtle, pōhutukawa, bay rum tree, clove, guava, acca (feijoa), allspice, and eucalyptus are some notable members of this group. All spe ...
''), such as ''
Callistemon citrinus'' (Lemon Bottlebrush), a shrub native to Australia, and ''
Leptospermum scoparium
''Leptospermum scoparium'', commonly called mānuka, () mānuka myrtle, New Zealand teatree, broom tea-tree, or just tea tree, is a species of flowering plant in the myrtle family Myrtaceae, native to New Zealand (including the Chatham Islan ...
'' (Manuka), a New Zealand tree from which it gets its name.
Modification of this
allelopathic chemical to produce
mesotrione
Mesotrione is the ISO common name for an organic compound that is used as a selective herbicide, especially in maize. A synthetic inspired by the natural substance leptospermone, it inhibits the enzyme 4-hydroxyphenylpyruvate dioxygenase (HP ...
led to the commercialization of derivative compounds as
HPPD inhibitor 4-Hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors (HPPD inhibitors) are a class of herbicides that prevent growth in plants by blocking 4-Hydroxyphenylpyruvate dioxygenase, an enzyme in plants that breaks down the amino acid tyrosine into molecu ...
herbicides
Herbicides (, ), also commonly known as weedkillers, are substances used to control undesired plants, also known as weeds.EPA. February 201Pesticides Industry. Sales and Usage 2006 and 2007: Market Estimates. Summary in press releasMain page fo ...
.
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 4-Hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors (HPPD inhibitors) are a class of herbicides that prevent growth in plants by blocking 4-Hydroxyphenylpyruvate dioxygenase, an enzyme in plants that breaks down the amino acid tyrosine into molecu ...
herbicides on the market.
Synthesis
Leptospermone can be synthesized from
phloroglucinol
Phloroglucinol is an organic compound with the formula C6H3(OH)3. It is a colorless solid. It is used in the synthesis of pharmaceuticals and explosives. Phloroglucinol is one of three isomeric benzenetriols. The other two isomers are hydroxyq ...
by a reaction with 3-methylbutanenitrile (isovaleronitrile) in the presence of a
zinc chloride
Zinc chloride is the name of inorganic chemical compounds with the formula ZnCl2 and its hydrates. Zinc chlorides, of which nine crystalline forms are known, are colorless or white, and are highly soluble in water. This salt is hygroscopic and e ...
catalyst. Phloroisovalerone imine is produced which is then
alkylated with
iodomethane after initial treatment with
sodium ethoxide
Sodium ethoxide, also referred to as sodium ethylate, is the ionic, organic compound with the formula , or NaOEt (Et = ethane). It is a white solid, although impure samples appear yellow or brown. It dissolves in polar solvents such as ethanol. ...
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
Terpenes () are a class of natural products consisting of compounds with the formula (C5H8)n for n > 1. Comprising more than 30,000 compounds, these unsaturated hydrocarbons are produced predominantly by plants, particularly conifers. Terpenes ar ...
(or specifically a
sesquiterpene
Sesquiterpenes are a class of terpenes that consist of three isoprene units and often have the molecular formula C15H24. Like monoterpenes, sesquiterpenes may be cyclic or contain rings, including many unique combinations. Biochemical modifica ...
, ''ei.'' C
15) as the cyclisation of
farnesyl pyrophosphate
Farnesyl pyrophosphate (FPP), also known as farnesyl diphosphate (FDP), is an intermediate in the biosynthesis of terpenes and terpenoids such as sterols and carotenoids. It is also used in the synthesis of CoQ (part of the electron transport ch ...
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
[). Phloroglucinol is biosynthesized in a single step from malonyl-CoA] 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
Valine (symbol Val or V) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated −NH3+ form under biological conditions), an α- carboxylic acid group (which is in the deprotona ...
) (cf. polyketide
Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynth ...
s).
Uses
Leptospermone was the blueprint for the compound mesotrione
Mesotrione is the ISO common name for an organic compound that is used as a selective herbicide, especially in maize. A synthetic inspired by the natural substance leptospermone, it inhibits the enzyme 4-hydroxyphenylpyruvate dioxygenase (HP ...
which has the trade name ''Callisto'', a Syngenta
Syngenta AG is a provider of agricultural science and technology, in particular seeds and pesticides with its management headquarters in Basel, Switzerland. It is owned by ChemChina, a Chinese state-owned enterprise.
Syngenta was founded ...
herbicide.[
]
References
{{Herbicides
Herbicides
Tetraones