Total synthesis of (±)-plumbazeylanone, a naphthoquinone trimer from Plumbago zeylanica

Abstract

We have investigated the total synthesis of (±)-plumbazeylanone (1), a naphthoquinone trimer based on two different pathways (I) and (II). The synthetic approach based on pathway (I) was not successful. However, the first synthesis of 1 from plumbagin (2a) was achieved by utilizing an unsymmetrical methylene-bridged dimer (20b), with a naphthoquinone unit and a naphthalene unit as a key intermediate, based on pathway (II), in 11 steps with an overall yield of 5.9%. This synthesis features regioselective nucleophilic 1,2-addition of the naphthyllithium reagent 4a to the C-1 position of naphthoquinone 20b, and the regio- and stereoselective dienonephenol-type rearrangement of the 1,2-adduct 21b (1,2-migration of the naphthyl group to the C3-position on 21b) with 2 N-NaOH.