Total Synthesis of Two Naphthoquinone Antibiotics, Psychorubrin and Pentalongin, and Their C(1)-Substituted Alkyl and Aryl Derivatives

Abstract

The synthesis of 1-alkyl- and 1-aryl-1H-naphtho[2,3-c]pyran-5,10-diones, bearing a C(3)−C(4) double bond, was performed by two alternative cyclization strategies of 2,3-disubstituted 1,4-naphthoquinones. Lemieux−Johnson oxidation of 2-allyl-3-hydroxymethyl-1,4-dimethoxynaphthalenes and subsequent oxidative demethylation of the intermediate 3,4-dihydro-5,10-dimethoxy-1H-naphtho[2,3-c]pyran-3-oles to the corresponding 3,4-dihydro-3-hydroxy-1H-naphtho[2,3-c]pyran-5,10-diones gave, after acid-catalyzed dehydration, the desired 1H-naphtho[2,3-c]pyran-5,10-diones. Alternatively, the pyranonaphthoquinone ring system was constructed by intramolecular acid-catalyzed condensation of (3-hydroxymethyl-1,4-naphthoquinone-2-yl)acetaldehyde acetals. Using this synthetic approach, the synthesis of two naturally occurring naphthoquinone antibiotics, pentalongin and psychorubrin, is reported.