Use of the Wolff rearrangement of diazo ketones from amino acids as a synthetic method for the formation of oligonucleo-peptides: A novel approach to chimeric biomolecules

Photolysis and Ag-benzoate-catalyzed decomposition of the diazo ketones 2 and 4 derived from Z-Ala-OH and Z-Ala-Ala-OH in the presence of oligonucleotide derivatives bearing at the 5'-terminus an NH2 instead of the OH group, or an aminohexyl phosphate group lead to Z-protected 3-aminobutanoyl and to Z-Ala-beta-HAla derivatives, respectively (conjugates 12, 13, and 17-23, Schemes 3-5). In solution, this amide-forming acylation reaction could be realized only with oligomers containing up to 8 unprotected nucleotide building blocks (Schemes 3 and 4). With the analogous polymer-bound and protected oligonucleotide derivatives as amino nucleophiles, excellent yields were obtained with all chain lengths tested (up to 15mer, Scheme 5). The products were purified by reversed-phase HPLC and characterized by MALDI-TOF mass spectrometry (Figs. 2-4, Table 2) and by capillary gel electrophoresis (Fig. 2).