Synthesis of dihydrofuran-fused perhydrophenanthrenes having a phenolic hydroxyl group as a novel anti-Alzheimer’s disease agent

Abstract As a part of our research program on developing novel anti-Alzheimer’s disease medicines, several dihydrofuran-fused perhydrophenanthrenes ( DFs ) possessing a phenolic hydroxyl group were found to exhibit potent dendritic and axonal regeneration activities. Introduction of a methoxy group into the perhydrophenanthrene skeleton was successfully achieved via a PhI(OAc) 2 -mediated phenolic oxidation of a benzocyclobutene nucleus and subsequent tandem intramolecular electrocyclic reactions based on o -quinodimethane chemistry. We could reveal that a new methoxy derivative having a phenolic hydroxyl group exerted the most significant effects on the dendritic and axonal extensions in the damaged neurons, among DFs examined in this study.