Stereoselective synthesis and moulting activity of 2,3-diepi-20-hydroxyecdysone and 2,3-diepi-5α-20-hydroxyecdysone (original) (raw)
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Stereoselective synthesis and moulting activity of 2,3-diepi-20-hydroxyecdysone
2003
The ecdysteroid analogues 2,3-diepi-20-hydroxyecdysone and 2,3-diepi-5a-20-hydroxyecdysone have been synthesized from the readily available ecdysteroid, 20-hydroxyecdysone, and moulting activity has been determined using the Musca bioassay. As expected, the 2,3-diepi-analogue was less active than the parent ecdysteroid, 20-hydroxyecdysone. However, the 2,3-diepi-5a-analogue, which was expected to be inactive in the assay, exhibited moulting activity though it was approximately 1.5-fold less active than its 5b-analogue. The activity of the 5a-analogue could possibly result from the ability of this compound to bind to the ecdysteroid receptor. Alternatively, a possible in vivo C-5 epimerization of the 2,3-diepi-5a-analogue to the corresponding 5b-analogue could account for its activity.
Insect Biochemistry and Molecular Biology, 2002
The biological activities of selected specific ecdysteroids obtained by photochemical or chemical transformation are compared in the BII bioassay, in which the potency reflects the affinity of binding to the ligand-binding site of the Drosophila melanogaster ecdysteroid receptor. The compounds tested represent 14-deoxy, 14-dehydroxy, 14-hydroperoxy and 14-epi derivatives of 20-hydroxyecdysone and were selected on the basis of their close structural relationship to elucidate the contribution of the 14-hydroxy group and the stereochemical configuration at C-14 to ecdysteroid agonist activity. The structure–activity relationship shows that a 14-hydroxy group is not required for activity. However, the α-configuration of –H, –OH or –OOH at C-14, which determines the C/D rings trans-annelation, is very significant for activity; it is as important for activity as the well studied A/B rings cis-annelation. Compounds containing a double bond involving C-14 showed low activity with the exception of the specific, and so far unique, ecdysteroid dimer 7,7′-bis-[14-deoxy-8(14)-ene-20-hydroxyecdysone], which was obtained as the main product of the photochemical transformation of 20-hydroxyecdysone. The relatively high biological activity of this dimeric compound is discussed.
Biological activity of natural and synthetic ecdysteroids in the B11 bioassay
Archives of Insect Biochemistry and Physiology, 1997
The potencies of 19 ecdysteroids are compared in the B II bioassay, which reflects the affinity of binding to the ligand binding site of the Drosophila melanogaster ecdysteroid receptor. The compounds tested represent either natural products isolated from plants (phytoecdysteroids) or fungi (mycoecdysteroids) or synthetic analogues based on insect metabolites (zooecdysteroids). None of the tested compounds showed any antagonistic activity, but all possessed quantifiable agonistic activity. All the mycoecdysteroids were less potent than the major insect ecdysteroid, 20-hydroxyecdysone (20E). Also, conjugation of 20E with a glucose moiety results, as expected, in considerable reduction in biological activity, but the remaining activity is dependent on the position of conjugation. The implications of these findings for the structure/activity relationship of ecdysteroids are discussed. Arch. Insect Biochem. Physiol. 35:219-225, 1997.
Insect Biochemistry and Molecular Biology, 2002
A number of 22-O-alkyl ether and acyl ester derivatives have been prepared and their moulting activity determined, using the Musca assay. It was found that a free 22-hydroxyl group is not an essential structural requirement for an ecdysteroid to exhibit high moulting activity. The activity of a 22-O-substituted ecdysteroid may even be higher than that of the parent compound, providing that the substituent constitutes a functional group that can enhance biological activity. The moulting activity is not sensitive to steric factors at the 22-position. Ecdysteroid without a 22-hydroxyl group may exhibit high moulting activity if a functional group that can enhance activity is present at an appropriate position.
Steroids, 2002
Structural modification of 20-hydroxyecdysone (20E) based on photochemical transformation yielded dimeric ecdysteroid 7αH,7′αH-bis-[(20R,22R)-2β,3β,20,22,25-pentahydroxy-5β-cholest-8(14)-en-6-one-7-yl] as a main product. Its structure was determined by detailed NMR analysis. Furthermore, two new monomeric analogues: 14-epi-20-hydroxyecdysone and 14-deoxy-14,18-cyclo-20-hydroxyecdysone were identified in addition to the earlier described 14-deoxy and 14-hydroperoxy derivatives of 20E. Formation of the specific and so far unique ecdysteroid dimer has not been observed in earlier photo-transformation studies. The transformed dimeric analogue of 20-hydroxyecdysone retained the high agonistic activity on the ecdysone receptor in the BII-bioassay compared with the original 20E.
Dimeric Ecdysteroid Analogues and Their Interaction with the Drosophila Ecdysteroid Receptor
Collection of Czechoslovak Chemical Communications, 2006
Three structurally related specific ecdysteroid derivatives, 7,7′-dimers of 14-deoxy-8(14)-ene transformed 20-hydroxyecdysone, ponasterone A and ajugasterone C, were obtained by photochemical transformation. The structures of the dimeric ecdysteroids were identified mainly by NMR spectroscopy supported by MS and IR spectroscopy. Yields of the dimerisation products were dependent on the reactant concentrations and photoreaction conditions. Inert gas atmosphere supported high yields, whereas oxygen atmosphere fully prevented the dimer formation. All the three dimers retained a rather high agonistic activity at the ecdysteroid receptor in the Drosophila B II bioassay when compared with the relevant original ecdysteroids.