SYNTHESIS OF 8-BROMOKALAFUNGIN AS AN INTERMEDIATE FOR THE PREPARATIONOF C-GLYCOSIDE DERIVATIVES

The preparation of 8-bromokalafungin (20) which is a key intermediate for the synthesis of C-glycoside containing pyranonaphthoquinone antib iotics related to medermycin (6) is described. Although attempts to se lectively monobrominate kalafungin (1) at C8 were unsuccessful, 8,10-d ibromokalafungin (21) was prepared by using excess N-bromosuccinimide in chloroform. Selective bromination at C6 on a naphthalene ring was a chieved upon treatment of naphthol (9) with N-bromosuccinimide (1 equi v.). Conversion of naphthol (9) into naphthoquinone (15) was effected by methylation, Baeyer-Villiger oxidation, acetylation via a Fries rea rrangement and oxidation with eerie ammonium nitrate. Conversion of th e 7-bromo quinone (15) into 8-bromokalafungin (20) proceeded through s ubsequent addition of 2-trimethylsilyloxyfuran (16) followed by oxidat ive rearrangement of the resultant furonaphthofuran (17) to furonaphth opyran (18). After reduction of the lactol (18) to cis ether (19), dem ethylation and epimerization at C5 with boron tribromide afforded 8-br omokalafungin (20). 8-Bromokalafungin (20) failed to undergo Pd(0)-med iated cross-coupling reactions with the stannyl glucal (22).