Insect hormones ecdysone

Tebufenozide acts by mimicking the effects of the insect hormone ecdysone, which along with juvenile hormone, controls the initiation of a molt. Exposure to tebufenozide induces a premature molt that traps the insect in its old cuticle. This compound is especially effective against caterpillars. 

Nuclear receptors for the steroid hormone ecdysone in Drosophila deserve special consideration, for several reasons. First, the insect hormone ecdysone (Fig. 11.2) was the first steroid hormone shown to act at the level of the gene, because it induced puffs in the giant chromosomes of the fruitfly. Secondly, ecdysone activates the developmental programme of Drosophila, and, finally, the sequences of the DNA-binding domain (DBD) of the Drosophila nuclear ecdysone receptor and of receptor homologues (for example, the COUP-TFs chicken ovalbumin upstream promoter transcription factors) are highly conserved and nearly identical in vertebrates and humans. 

A key step in the partial synthesis of the steroidal insect hormone ecdysone is introduction of a 14a-hydroxyl group. Three groups [Schering (Berlin)-Hoffmann La Roche (Basel)18d and Syntex18 ] achieved this end by allylic oxidation of A7-6-keto-stcroids, both 5a and 5/3, by selenium dioxide in dioxane. Yields are high. 

Several authors have reported the analysis and purification by TLC, of substances which had been tritiated according to the Wilzbach procedure. Thus glycerol ethers [262], the insect hormone ecdysone [338], vitamin Dg [501] and other steroids [501, 513, 617] (see Fig. 93, p. 170) and cardiac glycosides [551] have been purified on silica gel G layers. Unsaturated fatty acids have been isolated by TLC on silver nitrate-impregnated silica gel layers [425, 628]. 

XLIII Tebufenozid I Antagonist of the insect hormone ecdyson >5000(R)... 

Most of the more recently described allenic steroids bear an allene group at the 17-position, which was usually formed by an SN2 substitution [106] or reduction [86d] process of a suitable propargylic electrophile. Thus, reduction of the pro-pargylic ether 109 with lithium aluminum hydride followed by deprotection of the silyl ether resulted in the formation of the allenic steroid 110, which irreversibly inhibits the biosynthesis of the insect moulting hormone ecdysone (Scheme 18.35) [107]. 

Juvenile hormone plays a critical role in maintaining the juvenile or larval stage of insects, and if its secretion is not controlled, normal development to the adult stage is prevented. Use of hormones or substances with hormonelike activity to control insect populations is an area of intense research interest and activity.2 The secretion of juvenile hormone is controlled by other hormones originating in the brain (brain hormone) and the phthoracic gland (moulting hormone, ecdysone see Table 30-2). 

Figure 2 Principal reaction paths of metabolism of ecdysone. The larger the print, the more common the reaction in known examples. Modified from R. Lafont C. Dauphin-Villemant J. T. Warren H. H. Rees, Insect Hormones. In Comprehensive Molecular Insect Science-, Elsevier Oxford, 2005 Vol. 3, pp 125-195, Fig. 15, Copyright Elsevier, 2004, in turn Modified from R. Lafont J.-L. Connat, Pathways to Ecdysone Metabolism. In Ecdysone From Chemistry to Mode of Action-, J. Koolman, Ed. Georg Thieme Stuttgart, 1989 Chapter 14, Fig. 14.1.

Neurohormones are, however, implicated in the control of color changes in insects. The somewhat slow, morphological color changes resulting from qualitative or quantitative alterations in pigmentation are regulated by multiple hormones--juvenile hormone, ecdysone, and neurohormones--the interplay of which seems to vary with the insect species (6). 

The cDNAs for the glucocorticoid and the oestrogen receptors were isolated more than 15 years ago. They were among the first genes, coding for transcriptional gene activators, to be identified. The family of nuclear receptors is the largest family of transcription factors. Until now, more than 150 different members of the superfamily of nuclear receptors, from worms to insects to humans, have been described. The discovery of an insect receptor for a steroid hormone, ecdysone, indicated that this kind of receptor must have evolved prior to the separation of vertebrates and invertebrates. 

Polarimeters for measuring optical rotation are so sensitive that they can measure rotations to 0.001°, an important fact when only small amounts of sample are available. Ecdysone, for example, is an insect hormone that controls molting in the silk- j worm moth. When 7.00 mg ecdysone was dissolved in 1.00 mL chloroform and the solution was placed in a cel with a 2.00 cm pathlength, an observed rotation dT -I-0.087° was found. Calculate [a]n for ecdysone. 

Sterols. A considerable amount of work was devoted to the study of backbone rearrangements. - While partial syntheses of an insect moulting hormone, ecdysone, were announced by several groups, evidence is accumulating on the widespread occurrence in natxire of its hydroxylated derivatives. This year saw the isolation of 20-hydroxy-ecdysone - - from silkworm (ecdysterone), crayfish - (crustecdysone), oak-silk moth, tobacco hornworm, and from plants such as Podocarpus nakaii, Podocarpus elatus, and Achyranthis. The ready isolation of insect-moulting hormones from plants in contrast to -the extremely poor... 

Our laboratory is concerned with targeting potential insecticides that disrupt normal development and metamorphosis in insects. Juvenile hormones (JHs), acting in concert with the steroid hormone ecdysone, are believed to control the timing of the larval-larval molts, larval-pupal and pupal-adult transformations of the insects. It has been demonstrated that the events leading to pupation are initiated by reduction of the JH titer in the hemolymph. In addition to a cessation of biosynthesis, this reduction in JH titer is controlled by degradative metabolism (16,17). Hydrolysis of the epoxide and ester functionalities present in active JH are two routes of degradation and subsequent inactivation of JH (18). The primary route of JH metabolism in the hemolymph of last stadium lepidopterous larvae is ester hydrolysis, and it is catalyzed by the enzyme juvenile hormone esterase (JHE). JHE has been shown to... 

The important insect hormone a-ecdysone (121) and related steroids are also present in plants (Section 9). Their biosynthesis from cholesterol probably proceeds via the A -diene to the triolone (119). The side chain is then hydroxylated to the (22/ )-hydroxy steroid (120), a-ecdysone (121), and ) -ecdysone (122) (crustecdysone). Finally, breakdown of )8-ecdysone gave... 

The biosynthesis and metabolism of the insect moulting hormone, ecdysone have been the subject of recent reviews [184-186]. Ecdysone (107) was first isolated in a crystalline form from the silkworm, Bombyx mori, by Butenandt and Karlson in 1954, and the structure was determined in 1965. Soon after, the second moulting hormone was isolated and the structure was elucidated as 20-hydroxyecdysone (108). Ibe same hormone was also isolated from the sea-water crayfish, Jasus lalandei by Horn in 1966. Many ecdysone analogues were isolated from arthropods and certain... 

The sterol requirements of invertebrates are frequently satisfied by modification of dietary steroids. Thus, cholesterol is formed from 24-alkylated steroids, such as ergosterol and /5-sitosterol, by Crustaceans and insects. The mechanism of this process seems to be the reverse of their mode of formation. The 24-ethyl group of -sitosterol is converted into a 24-ethylidene group with fucosterol, and cholesta-5,24-dienol is formed on loss of the alkyl group. Cholesterol is required in insects for metabolism to the hormone ecdysone (84). However, plants also produce ecdysone and both organisms metabolize cholesterol to ecdysone. which is then further metabolized to ecdysterone (85)." ... 

It is of interest that the structure of brassinolide resembles that of the insect molting hormone, ecdysone, which also is of plant origin. The structure of ecdysone is shown in Figure 1 and differs from the structure of brassinolide in that the orientation of the vicinal hydroxyl group at C-2 and C-3 is beta, the A/B junction is cis rather than trans as in the brassinolide structure and that ecdysone lacks the lactone oxygen in the B-ring. 

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