Ergosteroids III. Syntheses and biological activity of seco-steroids related to dehydroepiandrosterone.
The unusual activity of some D-ring-seco estrogens led us to prepare several seco steroids related to dehydroepiandrosterone (DHEA) and to test for their ability to mimic thyroid hormone and 7-oxo-DHEA (1) as inducers of thermogenic enzymes in rats' livers. Only one, 3 beta-acetoxy-17a-oxa-androst-5-ene-7,17-dione (17), was capable of inducing both mitochondrial glycerophosphate dehydrogenase and malic enzyme. The closely related 3 beta-hydroxy-17a-oxa-androsta-5,15-diene-7,17-diones (both 14 alpha and 14 beta, 14 and 15) induce the formation of malic enzyme but not of glycerophosphate dehydrogenase. The 3 beta-propionyl ester of the above 14 alpha steroid was not active, presumably because it was not deacylated in vivo. The 16,17 dicarboxylic acid (9) produced by opening the D-ring also induced the formation of malic enzyme but not of glycerophosphate dehydrogenase. 3 beta-Acetoxyandrost-5-ene-7,16,17-trione, an intermediate in the synthesis of D-ring seco compounds enhanced the formation of both enzymes. Twelve other D-ring seco compounds were not active. Seco androstanes oxygenated at position 7 and with expanded A or B rings were not active.
Reich
I L
IL
Institute for Enzyme Research, University of Wisconsin-Madison 53705, USA.
Lardy
H
H
Wei
Y
Y
Marwah
P
P
Kneer
N
N
Powell
D R
DR
Reich
H J
HJ
D000818:Animals; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D051381:Rats
D003687:Dehydroepiandrosterone