C-25 epimeric 26-haloponasterone A: synthesis, absolute configuration and moulting activity.
A convenient synthesis of inokosterone has been accomplished. Inokosterone exists as two C-25 epimers, which could be separated from each other through their diacetonide derivatives. The absolute configuration of these compounds was determined. Two C-25 epimers of 26-chloroponasterone A were synthesized from the respective C-25 epimeric inokosterone. Two epimeric 26-bromo and 26-iodoponasterone A compounds were also synthesized. Moulting activity of these compounds was evaluated using the Musca bioassay, and it was found that the (25S)-26-halo analogues were more active than the corresponding (25R)-26-halo analogues. Among the 25S series, an increase in activity with an increase in size of the halogen atom was observed, indicating that the steric factor was more important than the electronic factor in binding of these ecdysteroid analogues to the receptor. On the other hand, a decrease in activity with an increase in size of the halogen atom was noted in the 25R series, suggesting that the steric factor was less important than the electronic factor. The results indicated that the configuration at C-25 and the substituent at C-26 have significant influences on the interaction of ecdysteroids with their receptor.
Yingyongnarongkul
Boon-Ek
BE
Department of Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand. boonek@ram.1.ru.ac.th
Kumpun
Saowanee
S
Chimnoi
Nitirat
N
D000818:Animals; D001966:Bromine / Q000737:chemistry; D002713:Chlorine / Q000737:chemistry; D002782:Cholestenes / Q000138:chemical synthesis* / Q000737:chemistry; D026461:Ecdysteroids / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004441:Ecdysterone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry; D006793:Houseflies / Q000187:drug effects; D006846:Hydrocarbons, Halogenated / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007814:Larva / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008968:Molecular Conformation; D015394:Molecular Structure; D018978:Molting / Q000187:drug effects*; D013237:Stereoisomerism
D002782:Cholestenes; D026461:Ecdysteroids; D006846:Hydrocarbons, Halogenated; C100084:inokosterone; D005461:Fluorine; D002713:Chlorine; D004441:Ecdysterone; C008999:ponasterone A; D001966:Bromine