Stereoselective construction of the 5-hydroxy diazabicyclo[4.3.1]decane-2-one scaffold, a privileged motif for FK506-binding proteins

Matthias Bischoff; Claudia Sippel; Andreas Bracher; Felix Hausch

doi:10.1021/ol5023195

Stereoselective construction of the 5-hydroxy diazabicyclo[4.3.1]decane-2-one scaffold, a privileged motif for FK506-binding proteins

Org Lett. 2014 Oct 17;16(20):5254-7. doi: 10.1021/ol5023195. Epub 2014 Oct 6.

Authors

Matthias Bischoff¹, Claudia Sippel, Andreas Bracher, Felix Hausch

Affiliation

¹ Max Planck Institute of Psychiatry , Kraepelinstr. 2, 80804 München, Germany.

PMID: 25286062
DOI: 10.1021/ol5023195

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkanes
Azabicyclo Compounds / chemical synthesis*
Azabicyclo Compounds / chemistry
Catalysis
Epoxy Compounds / chemistry
Molecular Structure
Protein Structure, Tertiary
Stereoisomerism
Tacrolimus Binding Proteins / chemistry*
Tacrolimus Binding Proteins / metabolism

Substances

5-hydroxy diazabicyclo(4.3.1)decane-2-one
Alkanes
Azabicyclo Compounds
Epoxy Compounds
Tacrolimus Binding Proteins
tacrolimus binding protein 5
decane