title: Stereoselective construction of the 5-hydroxy diazabicyclo[4.3.1]decane-2-one scaffold, a privileged motif for FK506-binding proteins.
abstract: A stereoselective synthesis of a derivatized bicyclic [4.3.1]decane scaffold based on an acyclic precursor is described. The key steps involve a Pd-catalyzed sp(3)-sp(2) Negishi-coupling, an asymmetric Shi epoxidation, and an intramolecular epoxide opening. Representative derivatives of this novel scaffold were synthesized and found to be potent inhibitors of the psychiatric risk factor FKBP51, which bound to FKBP51 with the intended molecular binding mode.
authors.affiliation: Max Planck Institute of Psychiatry , Kraepelinstr. 2, 80804 München, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bischoff
authors.forename: Claudia
authors.initials: C
authors.lastname: Sippel
authors.forename: Andreas
authors.initials: A
authors.lastname: Bracher
authors.forename: Felix
authors.initials: F
authors.lastname: Hausch
mesh_terms: D000473:Alkanes; D053961:Azabicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D004852:Epoxy Compounds / Q000737:chemistry; D015394:Molecular Structure; D017434:Protein Structure, Tertiary; D013237:Stereoisomerism; D022021:Tacrolimus Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D000099159:Tacrolimus Binding Protein 5
chemical_list: D000473:Alkanes; D053961:Azabicyclo Compounds; D004852:Epoxy Compounds; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C000599316:5-hydroxy diazabicyclo(4.3.1)decane-2-one; C012867:decane