Synthesis of 6α,7α- and 6β,7β-aziridinoandrost-4-ene-3,17-diones and related compounds: potential aromatase inhibitors

Abstract

The stereospecific synthesis of the novel 6β,7β- and 6α, 7α-aziridinoandrost-4-ene-3,17-dione 21 and 23 has been accomplished by treatment of vicinal azidohydrins 19 and 20 respectively with triphenylphosphane. Several related compounds (fused steroidal oxiranes, azidohydrins and an azide) were also synthesized. Reaction of (E)-6-hydroxyiminoandrost-4-ene-3β,17β-diol 2 with lithium aluminium hydride (LAH) gave, respectively, 5β,6β- and 5α,6α-aziridinoandrostane-3β,17β-diol 5 and 6. Although the 6,7-aziridines and their N-derivatives are poor inhibitors of human placental microsomal aromatase, most of the other compounds are modest inhibitors, while 7α-acetoxy-6β-azidoandrost-4-ene-3,17-dione 24 is a potent inhibitor of the enzyme (IC₅₀-value = 0.40 µ mol dm^–3).