Synthesis and biochemical evaluation of the novel steroid androsta-4,6,8(9)-triene-3,17-dione

J Enzyme Inhib. 1990;4(2):121-9. doi: 10.3109/14756369009040733.

Abstract

According to a proposed aromatisation mechanism by which estrogens are biosynthesized from androgens, the novel steroid androsta-4,6,8(9)-triene-3,17-dione (FCE 24918) should behave as a suicide substrate for aromatase. The synthesis of this triene steroid has been accomplished starting from androsta-4,7-diene-3,17-dione (4) by the acid-catalysed cleavage of the corresponding 7,8 alpha-epoxide, 5, and it was obtained together with androsta-4,6,8(14)-triene-3,17-dione (FCE 24917) as a side product. The time-dependent inactivation of placental aromatase by the two isomers was studied comparatively and showed that the 4,6,8(9)-triene moiety acts as a latent alkylating group.

Publication types

  • Comparative Study

MeSH terms

  • Androstatrienes / chemical synthesis
  • Androstatrienes / chemistry
  • Androstatrienes / pharmacology*
  • Aromatase Inhibitors*
  • Female
  • Humans
  • Microsomes / enzymology
  • Placenta / enzymology
  • Pregnancy
  • Structure-Activity Relationship

Substances

  • Androstatrienes
  • Aromatase Inhibitors
  • androsta-4,6,8(9)-triene-3,17-dione