Steroids ecdysone

Structure-activity relationship for the activity of non-steroidal ecdysone agonists and the prediction of the ligand binding to the Bombyx mori ecdysone receptors (Y. Nakagawa, Kyoto Univ., Japan)... 

This chapter reviews the structures and biology (physiological, biochemical and molecular basis of mode of action, insect activity spectrum, and eco-toxicological safety) of the commercialized BAH non-steroidal ecdysone agonist insecticides (refer to former reviews on this topic [4—6, 12]). 

Several years after the first insecticidal bisacylhydrazine (Fig. 25.1.1 2) was seren-dipitously discovered at the Rohm and Haas Company [9] the first prototype of a bona fide non-steroidal ecdysone agonist bisacylhydrazine, RH-5849 (Fig. 25.1.1 ... 

Fig. 25.1.2. Chemical structure of the first non-steroidal ecdysone agonist compound (RH-5849) with insecticidal activity. Different substitutions on this molecule led to the discovery of the four bisacylhydrazine commercial insecticides. The letters and the numbers refer to substitutions shown in the boxes around the structure.

Elucidation of the crystal stmcture of HvEcR/HvUSP heterodimeric LBDs in the absence or presence of steroidal or non-steroidal ligands [21] conclusively demonstrated the binding of BAH in the EcR LBD. These results also made it possible to verify the pharmacophore stmctural requirements for both an ecdyste-roid (ponasterone A) and a non-steroidal ecdysone agonist BAH (BY106830) interaction with residues specifically in a lepidopteran EcR LBD (Fig. 25.1.3A and 3B,... 

Measurement of Receptor-Binding Activity of Non-Steroidal Ecdysone Agonists Using in vitro Expressed Receptor Proteins (EcR/USP Complex) of Chilo suppressalis and Drosophila melanogaster... 

Figure 1. Structures of ecdysteroids (I) and non-steroidal ecdysone agonists (II, HI).

Figure 4. Relationship of receptor-binding activities (pICso) between C. suppressalis and D. melanogaster. Solid circles, ecdysteroids. Open circles, non-steroidal ecdysone agonists.

The stereocontroUed syntheses of steroid side chains for ecdysone, cmstecdysone, brassinoHde, withanoHde, and vitamin D have been reviewed (185). Also, other manuscripts, including reviews on the partial synthesis of steroids (186), steroid dmgs (187—189), biologically active steroids (190), heterocychc steroids (191), vitamin D (192), novel oxidations of steroids (193), and template-directed functionali2ation of steroids (194), have been pubhshed. 

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]. 

Insect steroid metabolism has two biochemically distinctive components dealkylation of phytosterols to cholesterol and polyhydroxylation of cholesterol to ecdysone. We will focus on the first of these. Lacking the ability to synthesize sterols de novo, insects instead have evolved a dealkylation pathway to convert plant sterols to cholesterol(7-10). The dealkylation pathways are apparently absent in most other higher and lower organisms, which can convert mevalonate to squalene and thence into sterols( ). Specific insecticides are possible based on these biochemical differences. 

Ecdysone is the steroid hormone of the arthropods. It can be regarded as an early form of the steroid hormones. Steroid hormones with signaling functions also occur in plants. 

The most important steroid hormones in vertebrates are listed on p. 57. Calcitriol (vitamin D hormone) is also included in this group, although it has a modified steroid structure. The most important steroid hormone in invertebrates is ecdysone. 

Ecdysone, a highly hydroxylated steroid (Fig. 22-12), is a molting hormone for insects.331,332 Several molecules with ecdysone activity are known, and some of these are produced by certain plants. Although ecdysones are needed by insects for larval molting, they are toxic in excess. Perhaps plants protect themselves from insects by synthesizing these substances. 

Ecdysone stimulates the synthesis of RNA in tissues. Visual demonstration of the effect is provided by its action on polytene chromosomes of fly larvae (Fig. 26-14).361 Fifteen minutes after the application of ecdysone, a puff is induced on one band of the chromosome a second puff forms at a later time while a preexisting puff diminishes. Thus, like steroid hormones in mammals, ecdysone appears to have a direct controlling effect on transcription. The cuticle-shedding process (ecdysis) is initiated by the brain peptide eclosian. However, the brain may be responding to the ecdysis-triggeiing hormone, a peptide that is secreted by a series of epitracheal glands located in various segments of the body.362... 

Eukaryote organisms primarily respond to external signals by an initial signal perception by receptors. In general, such receptors can be either cytosolic or located on the plasma membrane [13-15]. The former mechanism applies to thyroid hormones (triiodothyronine and tetraiodothyronine or thyroxine), retinoids (e.g. retinoic acid), the insect developmental hormones such as ecdysone, steroid hormones (such as... 

Generally useful reagent with a high silyl donor ability will not react with amino groups will not cause formation of enol-ether on unprotected ketone groups especially useful for ecdysones, norepinephrine, dopamine, steroids, sugars, sugar phosphates, and ketose isomers... 

As reviewed by Williams (43), ecdysone has been isolated from more than 10 species of conifers, 20 ferns, and 30 flowering plants (out of 1000 species surveyed). A total of 28 different plant ecdysones are known, the most ubiquitous being /3-ecdysone. The ecological significance of /3-ecdysone in plants is unclear. It is not toxic when orally ingested (as feeding larvae would obtain it from a food plant), but there is some evidence that it could be a feeding deterrent in concentrations as low as 1 ppb. Perhaps it serves as a steroid base for other compounds once it is in an insect s metabolic system. 

The term ecdysteroid was originally defined as "all compounds structurally related to ecdysone" [4], However, Lafont and Horn [5] differentiated between true ecdysteroids and ecdysteroid-related compounds. True ecdysteroids possess a steroid nucleus with an A/B-cis-ring junction and a 14a-hydroxy-7-en-6-one chromophore, irrespective of their biological activity, while ecdysteroid-related compounds do not fulfil all these criteria. 

Fluorocarbonsilyl ethers were studied by Morgan and Poole [341] with steroids of the ecdysone group. Perfluorinated alkyldimethylsilyl ethers are thermally unstable and decompose at the temperatures required for the GC of sterols (Scheme 5.32). Derivatives... 

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