Solid-phase synthesis of deglycobleomycin and bleomycin

The bleomycins are a group of structurally related glycopeptide antibiotics originally isolated from Streptomyces verticillus in the 1960s. They are used for the treatment of cancers including Hodgkin's lymphomas, carcinomas of the skin, head and neck, and testicular tumors. Whereas analogs of bleomycin have been synthesized to facilitate an understanding of its biochemical properties, the complexity of the molecule has severely limited the total number of analogs synthesized. The solid-phase synthesis of fully functional and active deglycobleomycin and bleomycin analogs is described. This approach has resulted in the synthesis of over 160 unique deglycobleomycin and bleomycin analogs in the past two years, an accomplishment that would not have been possible without the solid-phase methodology.