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 NH 2 instead of the OH group, or an aminohexyl phosphate group lead to Z‐protected 3‐aminobutanoyl and to Z‐Ala‐β‐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 ).