Novel time-dependent inhibitors of human placental aromatase

Aromatase is a cytochrome P sub(450) enzyme system that converts androgens to estrogens by oxidative dealkylation of the angular C-19 methyl group and aromatization of the steroidal A ring. The initial hydroxylations produce the 19-hydroxy and 19-oxo androgen derivatives, whereas the site of the third hydroxylation has not yet been determined. The C-10, C-2 hydroxyethyl bridged species could be viewed as stable, carbon analogues of lactol. This communication describes their synthesis, their affinities for human placental aromatase, and the synthesis of related compounds (halohydrins) that are potent, time-dependent inhibitors of aromatase.