The first, enantiospecific total syntheses of pyranonaphthoquinone antibiotics, (-)-nanaomycins (1 and 5) and their enantiomers, (+)-kalafungins (2 and 5') are described in overall yields of approximately 18% and 13%, respectively, by an "enantiodivergent" strategy from a common optically active intermediate 7, which has been derived from L-rhamnose (11) via condensation of the α,β-unsaturated ketone 10 and the phthalidylsulfone 9. The Wittig reaction of the key intermediate 7 with ethoxycarbonylmethylene-triphenylphosphorane gave the C-3 epimers 21 and 22, the former of which was converted into (-)-nanaomycins (1 and 5). The latter 22 was led to (+)-kalafungins (2 and 5') through the fascinating epimerization at C-1 and C-4 positions of 24 by sulfuric acid.
