Synthesis of 5-epi-7-deoxykalafungin and 5-epi-7-O-methylkalafungin

Abstract

The syntheses of 5-epi-7-deoxykalafungin (12a) and 5-epi-7-o-methylkalafungin (12b), compounds closely related to the pyranonaphthoquinone antibiotic kalafungin (1), have been completed making use of the transformation of one tricyclic ring system into another. The uncatalysed 1,4-addition of 2-trimethylsilyloxyfuran (4) to the 2-acetyl-1,4-naphthoquinones (8) gave the furo[3,2-b]naphtho[2,1 -d]furans (9) which underwent facile oxidative rearrangement in 72–76% yield using cerium(IV) ammonium nitrate, to the furo[3,2-b]naphtho[2,3-d]pyrans (11) which contain the same ring system as the natural product kalafungin (1). Reduction of the hemiacetals (11) to the cyclic ethers (12) was effected using triethylsilane in trifluoroacetic acid. The analogous rearrangement of the furo[3,2-b]benzofuran (5a) to the furo[3,2-b][2]benzopyran (6) proceeded in only 27% yield. Further insight into the mechanism of the initial 1,4-addition reaction was gained by isolation of the intermediate (13) in the reaction of 2-trimethylsilyloxyfuran (4) with the naphthoquinone (8a).