Total synthesis of two naphthoquinone antibiotics, psychorubrin and pentalongin, and their C(1)-substituted alkyl and aryl derivatives

The synthesis of 1-alkyl- and 1-aryl-1H-naphtho[2,3-c]pyran-5,10-dione bear ing a C(3)-C(4) double bond, was performed by two alternative cyclization s trategies of 2,3-disubstituted 1,4-naphthoquinones. Lemieux-Johnson oxidati on of 2-allyl-3-hydroxymethyl-1,4-dimethoxynaphthalenes and subsequent oxid ative demethylation of the intermediate 3,4-dihydro-5,10-dimethoxy-1H-napht ho[2,3 -c]pyran-3-oles to the corresponding 3,4-dihydro-3-hydroxy-1H-naphth o[2,3-c]pyran-5, 10-diones gave, after acid-catalyzed dehydration, the de s hed 1H-naphtho[2,3-c]pyran-5,10-diones. Alternatively, the pyranonaphthoqui none ring system was constructed by intramolecular acid-catalyzed condensat ion of(3-hydroxymethyl-1,4-naphthoquinone-2-yl)acetaldehyde acetals. Using this synthetic approach, the synthesis of two naturally occurring naphthoqu inone antibiotics, pentalongin and psychorubrin, is reported.