REACTION OF THIOL NUCLEOPHILES WITH 1,2-EPOXY-ESTRENE-3-ONE-17-BETA-OLS AND 4,5-EPOXY-ESTRENE-3-ONE-17-BETA-OLS

Four ring A steroidal epoxyenones as probable intermediate in the formation of catechol estrogens were synthesized. The isomeric 1-alpha,2-alpha-epoxy-17-beta-hydroxyestr-4-en-3-one (9) and 1-beta,2-beta-epoxy-17-beta-hydroxyestr-4-en-3-one (8) were synthesized from 17-beta-hydroxy-5-alpha-estra-3-one. The isomeric 4-alpha,5-alpha-epoxy-17-beta-hydroxyestr-1-en-3-one (11) and 4-beta,5-beta-epoxy-17-beta-hydroxyestr-1-en-3-one (10) were prepared from 19-nortestosterone. The reaction of 9 and 10 with sodium/ethanethiol resulted in the formation of three types of reactions leading to multiple products: 1,4-addition, opening of epoxide, and epoxide opening followed by dehydration. Reaction of 8 with ethanethiol gave only one compound identified as 2-ethanethio-1,4-estradien-17-beta-ol-3-one, while reaction of 9 with ethanethiol gave an unusual product identified as 4-estren-1-alpha, 17-beta-diol-3-one. Unlike reaction of ethanethiol with 9 and 10, reaction with N-acetylecysteine or glutathione results in epoxide opening followed by dehydration leading to the formation of estradiol-4-thioethers.