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

Abstract

For developing general synthetic access toward dimeric pyrano-naphthoquinones including β-naphthocyclinone, actinorhodin and γ-actinorhodin, we report stereo-defined 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 to ent-hemi-actinorhodin and to ent-hemi-γ-actinorhodin are also reported, in which the conditions for the oxidative lactonization were optimized.