Analogues of bleomycin: Synthesis of conformationally rigid methylvalerates

[GRAPHICS] Several conformationally rigid analogues of the methylvalerate subunit cont ained within the linker domain of the antitumor antibiotic bleomycin have b een prepared. These compounds have been protected in a fashion suitable for the solid-phase synthesis of bleomycin. Bleomycin congeners containing the se analogues should facilitate a more detailed understanding of the nature of the conformational bend that the methylvalerate moiety is thought to imp art to the natural product.