Ecdysone synthesis

The similarities between ecdysone synthesis in the insect prothoracic gland and the ovary are obvious and in each case synthesis is initiated in response to a hormone originating in the brain. Both bear a striking resemblance to the mammalian system where steroid hormone synthesis in the various endocrine tissues is initiated in response to the release of appropriate hormones from the anterior pituitary. 

Since the elucidation of the structure of ecdysone, a number of synthetic cholesterol derivatives have been demonstrated as possible intermediates in the conversion of cholesterol into ecdysone. However, few attempts have been made to isolate the intermediates of ecdysone synthesis in the PG. Only 3j8-hydroxy-5a-cholestan-6-one (111) was isolated from the organ culture medium of the silkworm PG as a possible intermediate [193]. The PG possesses a comparatively large percentage of 7-dehydro-cholesterol (110) in several insects. Thus, 7-dehydrocholesterol may also be a possible early intermediate in the transformation of cholesterol into ecdysone [194]. 

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. 

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... 

Another common mechanism for modulating hormonal response involves two (or more) hormonal inputs with both positive and negative effects (see fig. 24.21). The hypothalamic peptides, somatostatin and GRF, have opposite effects on GH synthesis and secretion. Similarly, glucagon and insulin have opposite effects on gluconeogenesis in the liver (see the discussion earlier in this chapter), and some of the effects of ecdysone on gene expression in insects are blocked by juvenile hormone (a terpene derivative fig. 24.22). 

In this context the comparison of the insecticide diflubenzuron with the fungicide polyoxin D is interesting in more than one respect. It not only closes the circle in our paper, so to speak, but it can also furnish strong circumstantial evidence to support our hypothesis of the mode of action of diflubenzuron. Marks and Sowa were the first to compare diflubenzuron and polyoxin D in their effects on the A ecdyson-dependent in-vitro synthesis of chitin by the cockroach (Leucophaea maderae) leg regenerates (4, ) These authors found that both compounds almost completely inhibited the incorporation of C-labeled D-glucosamine into the chitin fraction. In a later study with 1 C-labeled N-acetyl-D-glucosamine similar results were obtained, and the I50 value of inhibition of chitin synthesis was found to be 6.1 1 x 10 -10m for diflubenzuron and 7.53 x 10"7 M for polyoxin D (4 8) The difference in intrinsic activity can partly be explained by the roughly hundredfold accumulation of dif lubenzuron in the insect tissue. 

The partial synthesis from solasodine of nitrogen-containing analogues of ecdysone has been explored.22 In the successful route, 7V,0-diacetylsolasodine (16b) was treated with TV-bromo acetamide and HCI04. The bromohydrin (26a) that was formed was reductively debrominated with chromous acetate and butanethiol to... 

Mu X, LeBlanc GA. 2004. Synergistic interaction of endocrine-disrupting chemicals model development using an ecdysone receptor antagonist and a hormone synthesis inhibitor. Environ Toxicol Chem 23 1085-1091. 

The synthesis of ecdysone, the only ecdysteroid formed by the prothoracic glands, is under the control of the prothoracicotropic... 

Where functional groups are present which are more readily oxidized than the ether group, multiple reactions can occur. For example, in their total synthesis of (-i-)-tutin and (-i-)-asteromurin A, Yamada et al. observed concomitant oxidation of a secondary alcohol function in the oxidation of the ether (30) with ruthenium tetroxide (equation 24). The same group successfully achieved the simultaneous oxidation of both ether functions of the intermediate (31) in their related stereocontrolled syntheses of (-)-picrotox-inin and (-i-)-coriomyrtin (equation 25). Treatment of karahana ether (32) with excess ruthenium tetroxide resulted in the formation of the ketonic lactone (33) via oxidation of both the methylene group adjacent to the ether function and the exocyclic alkenic group (equation 26). In contrast, ruthenium tetroxide oxidation of the steroidal tetral drofuran (34) gave as a major product the lactone (35) in which the alkenic bond had been epoxidized. A small amount of the 5,6-deoxylactone (17%) was also isolated (equation 27). This transformation formed the basis of a facile introduction of the ecdysone side chain into C-20 keto steroids. 

Other steroid systems have also been investigated. Methyl groups at the bridgehead position always shield the /3-side and thus promote exclusive a-attack. Additionally, for the triacetoxy derivative 1268, an intermediate in the synthesis of a-ecdysone, and for 3j6-acetoxy-8(14)-cholesten-6-one (14)69, the regioselectivity of the ene reaction with singlet oxygen is high. In both cases only the y-hydroperoxy-a,/J-unsaturated ketone is formed. 

Several accounts have also been devoted to the synthesis of ecdysones and related substances. The analogues (410) of a-ecdysone (411) were prepared by a reaction sequence (Scheme 28) which involved bromination at position 5 of... 

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. 

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