title: BC-spiro-estradiols. Synthesis and estrogen receptor binding affinity of four new estradiol isomers.
abstract: The synthesis of four new isomers of estradiol in which the ring A to ring C planes are perpendicular to each other as a result of a spiro BC ring junction is described. Heterocyclic analogs and carbocyclic homologs of these compounds are also reported. Estrogen receptor binding studies show that the spiro compounds with the natural stereochemistry at C9 bind almost as strongly as estradiol but with greater β to α selectivity. These studies show that the estrogen receptors can readily accommodate isomers of estrogen with substantially different fixed shapes than the native ligand.
authors.affiliation: Department of Chemistry, University of Ottawa, Ottawa, Canada.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Asim
authors.forename: Daria
authors.initials: D
authors.lastname: Klonowska
authors.forename: Christine
authors.initials: C
authors.lastname: Choueiri
authors.forename: Ilia
authors.initials: I
authors.lastname: Korobkov
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Carlson
authors.forename: John A
authors.initials: JA
authors.lastname: Katzenellenbogen
authors.forename: Tony
authors.initials: T
authors.lastname: Durst
mesh_terms: D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D006571:Heterocyclic Compounds / Q000737:chemistry; D007536:Isomerism; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000737:chemistry* / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry*
chemical_list: D006571:Heterocyclic Compounds; D011960:Receptors, Estrogen; D013141:Spiro Compounds; D004958:Estradiol