Synthesis of 8-bromokalafungin as an intermediate for the preparation of C-glycoside derivatives

The preparation of 8-bromokalafungin (20) which is a key intermediate for the synthesis of C-glycoside containing pyranonaphthoquinone antibiotics related to medermycin (6) is described. Although attempts to selectively monobrominate kalafungin (1) at C8 were unsuccessful, 8,10-dibromokalafungin (21) was prepared by using excess N-bromosuccinimide in chloroform. Selective bromination at C6 on a naphthalene ring was achieved upon treatment of naphthol (9) with N-bromosuccinimide (1 equiv.). Conversion of naphthol (9) into naphthoquinone (15) was effected by methylation, Baeyer-Villiger oxidation, acetylation via a Fries rearrangement and oxidation with eerie ammonium nitrate. Conversion of the 7-bromo quinone (15) into 8-bromokalafungin (20) proceeded through subsequent addition of 2-trimethylsilyloxyfuran (16) followed by oxidative rearrangement of the resultant furonaphthofuran (17) to furonaphthopyran (18). After reduction of the lactol (18) to cis ether (19), demethylation and epimerization at C5 with boron tribromide afforded 8-bromokalafungin (20). 8-Bromokalafungin (20) failed to undergo Pd(0)-mediated cross-coupling reactions with the stannyl glucal (22).