8-ETHENYL-1-HYDROXY-4-BETA-D-RIBOFURANOSYLBENZO[D]NAPHTHO[1,2-B]PYRAN-6-ONE AND 8-ETHENYL-1-HYDROXY-4-(2'-DEOXY-BETA-D-RIBOFURANOSYL)BENZO[D]NAPHTHO[1,2-B]PYRAN-6-ONE - SYNTHETIC C-GLYCOSIDES RELATED TO THE GILVOCARCIN, RAVIDOMYCIN, AND CHRYSOMYCIN ANTIBIOTICS

Syntheses of 8-ethenyl-1-hydroxy-4-beta-D-ribofuranosylbenzo[d]naphtho[1,2-b]pyran-6-one (1) and 8-ethenyl-1-hydroxy-4-(2'-deoxy-beta-D-ribofuranosyl)benzo[d]naphtho[1,2-b]pyran-6-one (2) have been accomplished. These two compounds are the first synthetic C-glycosides structurally related to the gilvocarcin, ravidomycin, and chrysomycin antibiotic class which possess the aglycon substituents (hydroxyl at C-1 and ethenyl at C-8) considered critical for the photolytic nicking of DNA. Anthracycline C-glycoside 1 was prepared by a route involving Lewis acid-catalyzed C-glycosyl bond formation between the tetracyclic aglycon and 1,2,3,5-tetra-O-acetyl-D-ribose followed by construction of the aglycon 8-ethenyl substituent from the corresponding ethyl group by radical bromination-dehydrobromination. Synthesis of C-glycoside 2 utilized a different, complementary procedure for C-glycosyl bond formation by palladium-mediated coupling of an iodoaglycon derivative with 1,4-anhydro-2-deoxy-3-O-(tert-butyldiphenylsilyl)-D-erythro-pent-1-enitol, a furanoid glycal designed to form only beta-C-glycosyl bonds in this reaction. In the synthesis of 2, the 8-ethenyl substituent of the aglycon was installed prior to C-glycosyl bond formation since, in this case, attempted ethyl group bromination led instead to conversion of the carbohydrate moiety to a furan.