title: Reaction of thiol nucleophiles with 1,2-epoxy- and 4,5-epoxy-estrene-3-one-17 beta-ols.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis 55455.
authors.forename: M A
authors.initials: MA
authors.lastname: Ghaffari
authors.forename: Y J
authors.initials: YJ
authors.lastname: Abul-Hajj
mesh_terms: D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D045166:Estradiol Congeners / Q000138:chemical synthesis / Q000737:chemistry*; D002393:Estrogens, Catechol / Q000138:chemical synthesis; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet
chemical_list: D004852:Epoxy Compounds; D045166:Estradiol Congeners; D002393:Estrogens, Catechol; D007202:Indicators and Reagents; C047127:1,2-epoxyestrenolone; D009277:Nandrolone; C066814:4,5-epoxyestrene-3-one-17-ol