Insect hormone mimics

Ketone (31) was used in a synthesis of juvabione (32) an insect hormone mimic produced by conifers. 

Stable in acidic, neutral and basic aqueous solutions Pale yellowish solid, faint characteristic odor Flash point 119°C (Pensky-Martens closed tester) Pyriproxyfen is an insect growth regulator which acts both as an ovacide and as an inhibitor of development (juvenile hormone mimic) against white flies, scale, and psylla. The specificity of pyriproxyfen, and its low mammalian toxicity, allow for some variation in application timing. For example, the lack of toxicity to bees allows pyriproxyfen to be applied during bloom on apple trees, and its low mammalian toxicity allows for a very short pre-harvest interval on citrus The residue definition is for pyriproxyfen alone... 

For Instance, many terpene derivatives mimic insect hormone actioa Juvabione (15) is the classical example of a juvenile hormone (JH) mimic that prevents egg maturation in Pyrrhocoris bugs. Aromatic terpene ethers (16), methylene dloxyphenyl terpene ethers (17), and other farnesyl derivatives also have JH activity and the latter ones (18) also cause sterility in Pyrrhocoris. For the most part JH active terpenes are among the sesquiterpenes but several monoterpenes also have insect sterilizing effects (19. 20). The acyclic monoterpene cltral reduces the fertility of rats by causing follicular degeneration (21). 

Retinoic Acid Receptor. Most of the biological effects of retinoids are mediated through the retinoic acid receptor (RAR) and the retinoid X receptor (RXR). Both all-/ran.s-retinoic acid and 9-d.v-rctinoic acid serve as agonists of RAR, while only 9-d.v-rctinoic acid functions as an agonist of RXR. The functional RAR exists as a heterodimer with RXR, while functional RXR exists as a homodimer. Methoprene is a juvenile hormone III analogue that mimics the activity of this insect hormone. 

The pest mosquito Aedes nigromacul Ls of the vast San Joaquin valley of California went resistant to organochlorines by 1951, to parathion by 1960, to fenthion by 1965, and to chlorpyrifos (Dursban) by 1970. At present reliance is placed on larvicidal oils, the juvenile-hormone mimic methoprene (Altosid) and the insect growth regulator diflubenzuron (Dimilin), — and on better management of surplus irrigation water. Residual sprays for housefly control, at first so spectacular with the organochlorines, had to move into the OP compounds, which were then knocked out in... 

The multiresistant strains now extant also show a certain cross-tolerance, but not resistance, to the third-generation insecticides such as the juvenile-hormone mimics and other so-called insect growth regulators, as was found in strains of the housefly, flour beetle and tobacco budworm. Resistance to the JH mimic methoprene and Monsanto-585 has been induced by laboratory selection of Culex taxsalis (28) and Culex pipiens (29), and to Monsanto-585 in Culex quinquefasstatus (30). Whatever insect or IGR is chosen, the result of exposure to selective doses in successive generations is usually the development of resistance, repeating our previous experience with chemosterilants, and the... 

An example of increasing the efficiency by decreasing the flow rate is shown on a pellicular silica gel column in Figure 6-5a. (This figure was shown previously as Fig. 4-15.) This is the separation of a cis and trans isomer of synthetically prepared juvenile hormone mimics which are separated in the normal-phase mode. (Juvenile hormone mimics are used to stop or retard the maturation process of insects and, hopefully, control the insect population.) The presence of benzene is probably residue from the reaction solvent. At 2 mL/min the first peak corresponds to 5000 plates and the last peak corresponds to 2300 plates. By lowering the flow rate to 0.5 mL/min, there is a corresponding increase in efficiency in the separation. With the additional efficiency at the slower flow rate, it is possible to observe a small, additional shoulder (peak) under the first peak. However this was done at the expense of increased time (a factor of 4). 

The existence of a cytosolic epoxide hydrolase was first indicated by its ability to hydrolyze analogs of insect juvenile hormone not readily hydrolyzed by microsomal epoxide hydrolase. Subsequent studies demonstrated a unique cytosolic enzyme catalytically and structurally distinct from the microsomal enzyme. It appears probable that the cytosolic enzyme is peroxisomal in origin. Both enzymes are broadly nonspecific and have many substrates in common. It is clear, however, that many substrates hydrolyzed well by cytosolic epoxide hydrolase are hydrolyzed poorly by microsomal epoxide hydrolase and vice versa. For example, l-(4 -ethylphenoxy)-3,7-dimethy I -6,7-epoxy-//7//i,v-2-octene, a substituted geranyl epoxide insect juvenile hormone mimic, is hydrolyzed 10 times more rapidly by the cytosolic enzyme than by the microsomal one. In any series, such as the substituted styrene oxides, the trans configuration is hydrolyzed more rapidly by the cytosolic epoxide hydrolase than is the cis isomer. At the same time, it should remembered that in this and other series,... 

Although juvenile hormone itself is too unstable in light and too expensive to synthesize for use in controlling insect populations, related compounds, called juvenile hormone mimics, have been used effectively. The best known example is called methoprene, sold under such trade... 

Juvenile hormone agonists as pesticides Methoprene is a juvenile hormone mimic preventing metamorphosis and is used to control a wide variety of insects, especially Diptera and Pharaoh s... 

Ethyl-4-[2-(t-butylcarbonyloxy)butoxy] benzoate (ETB, ZR-2646, 71) occupies an intermediate position between the juvenile hormone mimics and the antijuvenile hormones to be discussed later. It acts as an anti-JH at low doses and as a JH mimic at high doses. The nature of this JH agonist/antagonist action is not understood, yet its interference with the induction of juvenile hormone esterase seems to elucidate at least partly its action on insects (Staal, 1977 Sparks et al., 1979). 

Insect Juvenile Hormones and Plant Juvenile Hormone Mimics... 

Another example of a sesquiterpene-derived insect juvenile hormone is that of the giant silkworm moth, Hyalophora cecropia (Fig. 21.18). Several juvenile hormone mimics have been found in plants (Bowers, 1985,1991,1992 Fraga, 1991 Menn and Beroza, 1972). 

Fig. 21.18. Insect juvenile hormones and juvenile hormone mimics (modified from Jennings et al., 1975 modified and used with permission of the copyright owner, the Royal Society of Chemistry, Cambridge).

A number of plants synthesize ecdysteroids and sequester them in much greater concentrations than do insects (Fig. 23.19). It is probable that these compounds serve as defensive systems in the plant much in the same way as juvenile hormone mimics. For activity, a cw-A,B-ring fusion, a 6-keto-7-ene group, a full sterol side chain with a 22/ -oxygen function, an oxygen function at C-3, and oxygen groups at C-14 and 2p are necessary. However, not all insects may respond in an identical manner (Camps, 1991). 

Methoprene (marketed as Precor), an insect juvenile hormone mimic used in flea control products for pets, works by preventing the development of flea eggs and larvae. The effective form of methoprene, shown here, is optically active. Locate the stereogenic center and determine its configuration (R,S). 

Jacobson M, Redfern RE, Mills GDjr (1975) Naturally occurring insect growth regulators. - III. Echinolone, a highly active juvenile hormone mimic from Echinacea angustifolia roots. Lloydia 38 473-476... 

The use of juvenile hormone mimics to control certain insect populations the use of organometallic reagents to synthesize the Cjg juvenile hormone (Opener, Section 20.10C)... 

Insect defensive compounds are usually eflFective at short distance and their toxicity or repellency is not sufficient for them to have found any industrial application. Venoms can be powerful, but usually require injection. Of the insect hormones, ecdysteroids (Chapter 7) have not yet found practical appUcation, but there are several examples, in special circumstances, of very effective use of juvenile hormone mimics. 

A. Nakayama and W. G. Richards, A quantum chemical study of insect juvenile hormone mimics The active conformation and the electrostatic similarities. Quantitative Structure-Activity Relationships, 6, 153, 1987. 

Caterpillars and other moulting insects excrete the hormone a-ecdysone which at moulting time becomes hydroxylated to 20-hydroxyecdysone (20-E), which in turn triggers the moulting process enabling the insect to shed its exoskeleton and resume feeding. Rohm and Hass have developed a novel insecticide, tebufenozide (Formula 9.5) which mimics 20-E, binding to the same site. The consequence of this is that the insect stops... 

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