Using a menthol-like compound to activate plant immune mechanisms

Certain chemicals can activate the innate defence mechanisms of plants, and researchers at the Tokyo University of Science are working on ways to use such chemicals as alternatives to harmful agricultural pesticides.

These researchers have found that a compound derived from menthol can boost the expression of defence-related genes in soybeans, corn, peas, and other crop species. This finding may pave the way to green agricultural technologies that shield crops from pests while minimizing damage to the environment.

Professor Gen-ichiro Arimura of the Tokyo University of Science, Japan, notes that “the development of agricultural technology to date has been largely reliant on the use of pesticides and chemical fertilizers, which has resulted in
environmental pollution and the destruction of ecosystems.”

As a greener alternative to pesticides, terpenoid signalling molecules may help farmers continue their production of vital foodstuffs while lessening the associated environmental costs.

In pursuit of this goal, Prof. Arimura and his colleagues chose to investigate the terpenoid compound menthol, which is derived from mint leaves and can activate plant immune
systems. The aim of this project, which the researchers describe in an article recently published in the journal Plant Molecular Biology, was to develop compounds that are structurally similar to menthol but improve upon menthol’s ability to activate
plant immune systems.

The researchers therefore experimented with chemically modifying menthol by attaching amino acids, which are a structurally diverse set of compounds that living cells use to construct proteins. In total, the researchers synthesized six different menthol derivatives with attached amino acids.

The researchers then tested the resulting menthol derivatives to see whether the modified compounds could outperform unmodified menthol at activating plant defense mechanisms. To do this, they treated soybean leaves with either menthol or one of the six menthol derivatives to see which of the derivatives, if any, could outclass menthol itself at boosting the expression levels of two defense-related soybean genes after 24 hours of exposure. The found that only one of the modified compounds bested menthol, and this compound
is called valine menthyl ester, or “ment-Val” for short.

The researchers found that spraying soybean leaves once with a ment-Val solution boosted expression of the defence-related genes for three days, and second spraying on the fourth day worked to boost the expression of those genes again.

These findings suggest that ment-Val could provide sustainable pest control for farmers growing soybeans. Further experiments showed that ment-Val also increased the expression of defence-related genes in other crops, including peas, tobacco, lettuce, and corn. Ment-Val also proved to be quite stable under various conditions, which suggests that farmers would probably not lose the compound to degradation during storage.

Overall, these results suggest that ment-Val could be extremely useful as an alternative to the chemical pesticides that so many farmers rely on. Prof. Arimura notes that spraying ment-Val may be an effective way “to reduce pest damage to soybeans and other crops.”

He has applied for a patent on ment-Val’s use as a crop protection agent, and he predicts that the commercialization of ment-Val “will generate billions of yen in economic benefits through its usage by companies operating in the fields of horticulture and agriculture.”

He also notes that ment-Val’s anti-inflammatory properties could make it useful for human medicine.

Asymmetric synthesis of Aziridine with a new catalyst can help develop novel medicines

Aziridine structures are an important component of several medicines and pharmaceutical drugs, due to which reactions yielding desirable aziridine structures with high purity have received much interest. In a new study, scientists from Japan have reported a high yield of aziridines with high purity from oxazolones using a novel catalyst and look into the underlying mechanism, paving the way for future development of novel drugs and medicines.

“Oxazolones are well-known for their versatility in affording biologically active compounds,” explains Professor Shuichi Nakamura from Nagoya Institute of Technology (NITech), Japan, who studies asymmetric reactions.

“However, the enantioselective reactions of 2H-azirines with oxazolones have not been very fruitful, despite being touted as one of the most efficient methods to synthesize aziridines.”

In a new study recently published in Organic Letters, Prof. Nakamura along with his colleagues from NITech and Osaka University, Japan, explored this issue and, in a significant breakthrough, managed to obtain aziridine-oxazolone compounds in high yields (99%) as well as high enantioselectivity or purity (98%). In addition, the team used an original catalyst they developed to catalyze the reactions they studied.

The team started off by heating α-azideacrylates at 150°C in an organic solvent tetrahydrofuran (THF) to prepare 2H-azirines and then reacted them with oxazolones in presence of various organocatalysts to produce different aziridine-oxazolone compounds.

In particular, the team examined the effect of the catalyst cinchonine and various heteroarenecarbonyl and heteroarenesulfonyl groups in organocatalysts derived from cinchona alkaloids and found that reactions using catalysts with either a 2-pyridinesulfonyl group or an 8-quinolinesulfonyl group gave both a high yield (81-99%) as well high enantiopurity (93-98%).

In addition, scientists observed that the reaction between a 2H-azirine containing an ethyl ester group and an oxazolone with a 3, 5-dimethoxyphenyl group in presence of the catalyst with 8-quinolinesulfonyl group also gave high yields (98-99%) as well as enantiopurity (97-98%).

The team then moved on to exploring the reaction between 2H-azirine with ethyl ester group and a wider variety of oxazolones in presence of the catalyst with 8-quinolinesulfonyl group.

In all of the reactions, they observed high yields (77-99%) and enantiopurities (94-99%) except one for the case of an oxazolone bearing a benzyl group and the catalyst with a 2-pyridylsulfonyl group that only produced a moderate yield (61%) and purity (86%). Moreover, they were able to convert the obtained aziridines into various other enantiomers without any loss of purity.

Finally, the team proposed a catalytic mechanism and a transition state for the reaction of 2H-azirines with oxazolones in which the catalyst activates both the oxazolone and the 2H-azirine, which then react to give an “addition product” that, in turn, yields the aziridine with the regeneration of the catalyst.

While the detailed mechanism is yet to be clarified, scientists are excited by their findings and look forward to the method’s application in medicine and pharmacology.

“It has the potential to provide people with new medicines and create new drugs as well as drug candidates that are currently difficult to synthesize. Moreover, the catalyst used in this study can be used for many other stereoselective synthetic reactions,” observes an
optimistic Prof. Nakamura.