Efficient Synthesis of (+)-Kalafungin and (-)-Nanaomycin D by Asymmetric Dihydroxylation, Oxa-Pictet-Spengler Cyclization, and H2SO4-Mediated Isomerization

The pyranonaphthoquinone antibiotics and antitumor agents (+)-kalafungin (1) and (-)-nanaomycin D (3 = ent-1) were synthesized from 1,5napthalenediol (13) in 11 steps. Stereocontrol was high: 99.5 ee/93% diastereoselectivity for 1, 98.5% ee/94% diastereoselectivity for 3. Enantiocontrol was achieved by the asymmetric dihydroxylation of the (beta),(gamma)unsaturated ester 9. Diastereocontrol was realized in the final step by an almost complete epimerization in H2SO4.