Synthesis and NMR characterization of selectively 15N-labelled trans- and cis-butenediamido-linked bis-netropsins

The synthesis of specifically 15N labelled trans- and cis-isomers of bis-netropsins derived from 2-butene-1,4-dicarboxylate as the central linker, namely the (E)-and (Z)-forms of N-[2-[2-[(3-amino-3-iminopropyl)(15N)aminocarbonyl]-1-methylpyrr ole-4-amino-carbonyl]-1-methylpyrrol-4-yl], N'-[2-[2-[(3-amino-3-iminopropyl) aminocarbonyl]-1-methylpyrrole-4-aminocarbonyl]-1-methylpyrrol-4-y l]-2-butenediamide are described. A highly convergent synthetic route was adopted for the preparation of the trans-derivative starting from N-methyl-4-nitro-2-trichloroacetylpyrrole and fumaroyl chloride. The most efficient methods of coupling aminopyrrole intermediates with activated carboxylic acid derivatives were utilized and the 15N-labelled moieties were incorporated in the later stages of the synthesis. The preparation of the cis-derivative, starting with maleic anhydride, required a modification of the above strategy due to the nature of products formed upon initial coupling with aminopyrrole derivatives. (Author)