SYNTHESIS OF 6-ALPHA,7-ALPHA-AZIRIDINOANDROST-4-ENE-3,17-DIONES AND 6-BETA,7-BETA-AZIRIDINOANDROST-4-ENE-3,17-DIONES AND RELATED-COMPOUNDS - POTENTIAL AROMATASE INHIBITORS

The stereospecific synthesis of the novel 6 beta,7 beta- and 6 alpha, 7 alpha-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-3 beta,17 beta-diol 2 with lithium aluminium hydride (LAH) gave, respectively, 5 beta,6 beta- and 5 alpha,6 alpha-aziridinoandrostane-3 beta,17 beta-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 7 alpha-acetoxy-6 beta-azidoandrost-4-ene-3,17-dione 24 is a potent inhibitor of the enzyme (IC50-value = 0.40 mu mol dm(-3)).