A-Ecdyson

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... 

Solv. Ref. C- Cholestan-3-one Dioxane/CHClj [65 a] Cholesta-3,5- dien-7-one Dioxane/CHCl3 [65 a] Cholest-5-en-7-on-3/J-yl acetate Dioxane/CHCl3 [65 a] 2/ ,3/ ,14oc- Trihydroxy- 5/i-cholest- 7-en-6-one Pyridine-d5 [588] a-Ecdysone Pyridine-d3 [588] a-Ecdysone triacetate Pyridine-d5 [588]... 

To date, the definitive conversion of cholesterol to a-ecdysone by these glands in vitro has not yet been reported, and without such evidence neither the detailed study of ecdysone biosynthesis nor its inhibition by chemicals as potential pesticides can be expected to progress rapidly. 

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. 

Because compounds (345)—(348) show the same biological activity it was argued185 that compound (349) (2,25-dideoxy-a-ecdysone) should also exhibit maximum... 

Ecdysone (= a-Ecdysone) Lychnisfulgens (Caryophyllaceae), ECDY-R agonist [bracken fern... 

Figure 4. Possible biosynthetic pathway from dietary steroids to a-ecdysone.

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. 

A detailed survey of the isolation and chemistry of the ecdysones has appeared. The isolation of deoxycrustecdysone (402a), deoxyecdysone (402b), and a-ecdysone (402c) has been reported. The structures of stachysterone A... 

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... 

Diosgenin has been converted into a-ecdysone by a multistage sequence which made use of the stereochemical features of the spiro-acetal system to attain the required configurations at C-20 and C-22 in the product. Most of the steps were already known in principle, but the reduction of the 16,22-epoxy-7,14-dien-6-one... 

The ability of insect sulfotransferases to catalyze the sulfation of plant and insect steroids may simply reflect the broad substrate specificity of the enzymes. On the other hand, it may be indicative of a more important physiological function of the enzymes. Sulfate esters of cholesterol, campesterol and e-sitosterol have been identified in the meconium of tobacco hornworm (M. sexta) pupae ( ), and these steroids are known precursors of a-and e-ecdysone and other molting hormones in this species ( ). Further, there is evidence that houseflies (M. domestica) and diapausing pupae of M. sexta convert 22,25 bisdeoxyecdysone, a-ecdysone and 20-hydroxyecdysone into sulfate and glucoside conjugates ( ). 

Cholesterol or other sterols available from the diet or gut microflora are converted to the active hormone 20-hydroxyecdysone ([3-ecdysone or ecdys-terone) through several oxidative steps involving CYP enzymes. The last step is oxidation of a-ecdysone to (J-ecdysone, which can occur in many tissues, such as in the organ called the fat body. 

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... 

Subsequent hydroxylation of a-ecdysone yields )8-ecdysone (Fig. 19), the most oxidized ecdysone normally encountered in plants. 

Butenandt and Karlson (1954) isolated the moulting hormone and called it a-ecdysone (80). The elucidation of its structure is associated with the name of Karlson et al. (Karlson et al., 1963 Huber and Hoppe, 1965 Hoppe and Huber, 1965). 

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