Stereoselective synthesis of (3-aminodecahydro-1,4-methanonaphthalen-2-yl)methanols targeted to the C1 domain of protein kinase C

Abstract

Protein kinase C (PKC) is a widely studied molecular target for the treatment of cancer and other diseases. We have approached the issue of modifying PKC function by targeting the C1 domain in the regulatory region of the enzyme. By using the X-ray crystal structure of the PKCδ C1b domain combined with molecular modeling, we discovered (3-aminodecahydro-1,4-methanonaphthalen-2-yl)methanol as a novel C1 domain ligand. The stereoselective synthesis of this tricyclic γ-amino alcohol was based on two successive Diels–Alder reactions to construct the six continuous stereocenters of the key intermediate.