} Flupyradifurone is a systemic

butenolide Butenolides are a class of lactones with a four-carbon heterocycle, heterocyclic ring structure.Joule JA, Mills K. (2000). Heterocyclic Chemistry 4th ed. Blackwell Science Publishing: Oxford, UK They are sometimes considered redox, oxidized deri ...

insecticide Insecticides are pesticides used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. The major use of insecticides is in agriculture, but they are also used in home and garden settings, i ...

developed by

Bayer CropScience Bayer AG (English: , commonly pronounced ; ) is a German multinational pharmaceutical and biotechnology company and is one of the largest pharmaceutical companies and biomedical companies in the world. Headquartered in Leverkusen, Bayer's a ...

under the name Sivanto. Flupyradifurone protects crops from sap-feeding pests such as aphids and is safer for non-target

organism An organism is any life, living thing that functions as an individual. Such a definition raises more problems than it solves, not least because the concept of an individual is also difficult. Many criteria, few of them widely accepted, have be ...

s compared to other insecticides. Sivanto was launched in 2014 since it obtained its first commercial registration in central America (

Guatemala Guatemala, officially the Republic of Guatemala, is a country in Central America. It is bordered to the north and west by Mexico, to the northeast by Belize, to the east by Honduras, and to the southeast by El Salvador. It is hydrologically b ...

and

Honduras Honduras, officially the Republic of Honduras, is a country in Central America. It is bordered to the west by Guatemala, to the southwest by El Salvador, to the southeast by Nicaragua, to the south by the Pacific Ocean at the Gulf of Fonseca, ...

Insecticide Resistance Action Committee The Insecticide Resistance Action Committee (IRAC) was formed in 1984 and works as a specialist technical group of the industry association CropLife to be able to provide a coordinated industry response to prevent or delay the development of insec ...

(IRAC) classified Flupyradifurone as 4D subset (

) and it is the first pesticide in the butenolide category. It was approved by

European Union The European Union (EU) is a supranational union, supranational political union, political and economic union of Member state of the European Union, member states that are Geography of the European Union, located primarily in Europe. The u ...

in 2015.

Characteristics

Sap-feeding insects have developed resistance to nearly all other kinds of insecticides but flupyradifurone is effective at controlling aphids and whitefly, thereby maintaining yields of crops such as

vegetable Vegetables are edible parts of plants that are consumed by humans or other animals as food. This original meaning is still commonly used, and is applied to plants collectively to refer to all edible plant matter, including edible flower, flo ...

fruit In botany, a fruit is the seed-bearing structure in flowering plants (angiosperms) that is formed from the ovary after flowering. Fruits are the means by which angiosperms disseminate their seeds. Edible fruits in particular have long propaga ...

cotton Cotton (), first recorded in ancient India, is a soft, fluffy staple fiber that grows in a boll, or protective case, around the seeds of the cotton plants of the genus '' Gossypium'' in the mallow family Malvaceae. The fiber is almost pure ...

, and

coffee Coffee is a beverage brewed from roasted, ground coffee beans. Darkly colored, bitter, and slightly acidic, coffee has a stimulating effect on humans, primarily due to its caffeine content, but decaffeinated coffee is also commercially a ...

. It also demonstrated positive

toxicological Toxicology is a scientific discipline (academia), discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnos ...

and ecotoxicological safety. According to a study by Bayer, who developed the compound, flupyradifurone has a high rate of uptake by

plant Plants are the eukaryotes that form the Kingdom (biology), kingdom Plantae; they are predominantly Photosynthesis, photosynthetic. This means that they obtain their energy from sunlight, using chloroplasts derived from endosymbiosis with c ...

s and crops. The authors used phosphor imaging analysis to monitor the uptake and translocation of yridinylmethyl-¹⁴Clabeled flupyradifurone by

tomato The tomato (, ), ''Solanum lycopersicum'', is a plant whose fruit is an edible Berry (botany), berry that is eaten as a vegetable. The tomato is a member of the nightshade family that includes tobacco, potato, and chili peppers. It originate ...

plants. The result revealed fast

root In vascular plants, the roots are the plant organ, organs of a plant that are modified to provide anchorage for the plant and take in water and nutrients into the plant body, which allows plants to grow taller and faster. They are most often bel ...

uptake and the even distribution of labeled flupyradifurone in the entire plant. Flupyradifurone is delivered via

xylem Xylem is one of the two types of transport tissue (biology), tissue in vascular plants, the other being phloem; both of these are part of the vascular bundle. The basic function of the xylem is to transport water upward from the roots to parts o ...

translocation in the plants. The concentration in the plants reached the highest point in 7 and 14 days. After 24 days of the application, a significant decline is observed. Flupyradifurone also featured excellent speed of action. The speed of action can be observed by the prohibition of honeydew excretion. After applying the flupyradifurone to the plant by spraying, the honeydew excretion is inhibited within 2 hours and all the

aphid Aphids are small sap-sucking insects in the Taxonomic rank, family Aphididae. Common names include greenfly and blackfly, although individuals within a species can vary widely in color. The group includes the fluffy white Eriosomatinae, woolly ...

s die after 48 hours. The result demonstrated that flupyradifurone has an exceptional speed of action compared to other insecticides. Flupyradifurone presented potent efficacy in controlling aphids and whiteflies. According to bioassays research, the flupyradifurone has lower LC₅₀ numbers of aphid and

whitefly Whiteflies are Hemipterans that typically feed on the undersides of plant leaves. They comprise the family Aleyrodidae, the only family in the superfamily Aleyrodoidea. More than 1550 species have been described. Description and taxonomy The A ...

compared to

imidacloprid Imidacloprid is a systemic insecticide belonging to a class of chemicals called the neonicotinoids which act on the central nervous system of insects. The chemical works by interfering with the transmission of stimuli in the insect nervous system. ...

. In the field trial, flupyradifurone controlled the lettuce aphid at a favorable rate via foliar applying. It had the highest efficiency (96%) of controlling lettuce aphid after 6–10 days of the application.

Mode of action

Flupyradifurone is an

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of insect

nicotinic acetylcholine receptor Nicotinic acetylcholine receptors, or nAChRs, are Receptor (biochemistry), receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the c ...

s, causing

depolarization In biology, depolarization or hypopolarization is a change within a cell (biology), cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolar ...

nerve cell A neuron (American English), neurone (British English), or nerve cell, is an excitable cell that fires electric signals called action potentials across a neural network in the nervous system. They are located in the nervous system and help to ...

s membranes. Insects cannot detoxify flupyradifurone according to the research of CYP6CM1-mediated

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

. Since flupyradifurone cannot be inactivated by

acetylcholinesterase Acetylcholinesterase (HUGO Gene Nomenclature Committee, HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme th ...

, it will lead to the failure of nerve system of insects and end up with the death of insects.

Synthesis

Flupyradifurone is structurally related to the natural insecticide, stemofoline which occurs in the plant species '' Stemona japonica''. Stemofoline has some advantageous features, such as being fast-acting and an effective antifeedant, but does not efficiently bind to insect nicotinic acetylcholine receptors. There are two ways to synthesis flupyradifurone. First, flupyradifurone can be synthesized from reacting tetronic acid with 2,2-difluoroethylamine to produce the intermediate, 4- 2-fluoroethyl)aminourane-2(5H)-one. Heating the reaction intermediate with 2-chloro-5-(chloromethyl)pyridine in THF under reflux yields flupyradifurone. In the second method, tetronic acid, 4-touluenesulfonic acid, and ''N''- 6-chloropyridin-3-yl)methyl2,2-difluoroethane-1-amine in toluene are heated under reflux for 2 hours to produce flupyradifurone.

Toxicological and ecotoxicological safety

Using the U.S. Environmental Protection Agency guidelines to classify

carcinogen A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruse ...

ic effects, flupyradifurone is categorized as "not likely to be carcinogenic to humans." It is not irritant to humans'

eye An eye is a sensory organ that allows an organism to perceive visual information. It detects light and converts it into electro-chemical impulses in neurons (neurones). It is part of an organism's visual system. In higher organisms, the ey ...

s and

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...

, and the EPA is not concerned about occupational exposure. Flupyradifurone is highly toxic to aquatic invertebrates. Flupyradifurone will bind to the nicotinic acetylcholine receptors of honey bees; however, it will only affect the taste and appetitive learning performance at the highest labeled concentration. The LD₅₀ of honey bee acute contact is >100 μg/bee and acute oral is 1200 ng/bee. For bumblebee, the acute contact LD₅₀ is >100 μg/bee.

References

{{Reflist Furanones Chloropyridines Difluoromethyl compounds Tertiary amines Neonicotinoids Disubstituted pyridines