Enantioselective synthesis of a cyclopentannulated kalafungin analogue

Abstract

The enantioselective synthesis of a cyclopentannulated analogue 8 of the pyranonaphthoquinone antibiotic kalafungin 1 is described. Addition of cyclopentadiene to naphthoquinone 2 which bears a pantalactone chiral auxiliary at C-2, afforded cyclopentannulated naphthofuran 4 after tin(IV) chloride induced fragmentation of the initial Diels-Alder adduct 3. The pantolactone auxiliary was then removed using lithium borohydride and the resultant aldehyde 5 converted to a methyl ketone 6 by treatment with methyl lithium followed by oxidation with manganese dioxide. The enantiomeric excess of methyl ketone 6 obtained in this manner was established to be 96% by chiral HPLC. Oxidative rearrangement of methyl ketone 6 using silver(II) oxide and nitric acid afforded lactol 7 which was reduced to cyclopentannulated pyranonaphthoquinone 8 using triethylsilane and trifluoroacetic acid.