Study on Integrated Synthesis of Dimeric Pyranonaphthoquinones: Preparation of Versatile Synthetic Intermediate and Conversion into ent-Hemi-actinorhodin and ent-Hemi-γ-actinorhodin

Abstract

AbstractFor developing general synthetic access toward dimeric pyranonaphthoquinones including β-naphthocyclinone, actinorhodin, and γ-actinorhodin, we report stereodefined 6,9,10-trioxypyranonaphthalene as a versatile intermediate. Its robust preparation started from ethyl (S)-4-chloro-3-hydroxybutyrate. The pyranonaphthalene core was constructed by a Michael–Dieckmann sequence, and methylation using Me3Al and BF3·OEt2 established the required trans structure in a scalable manner. Conversion of this intermediate into ent-hemi-actinorhodin and into ent-hemi-γ-actinorhodin are also reported, in which the conditions for the oxidative lactonization were optimized.