USE OF THE WOLFF REARRANGEMENT OF DIAZO KETONES FROM AMINO-ACIDS AS ASYNTHETIC METHOD FOR THE FORMATION OF OLIGONUCLEO-PEPTIDES - A NOVEL-APPROACH TO CHIMERIC BIOMOLECULES

Photolysis and Ag-benzoate-catalyzed decomposition of the diazo ketone s 2 and 4 derived from Z-Ala-OH and Z-Ala-Ala-OH in the presence of ol igonucleotide 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 (conjug ates 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 t he analogous polymer-bound and protected oligonucleotide derivatives a s amino nucleophiles, excellent yields were obtained with all chain le ngths tested (up to 15mer, Scheme 5). The products were purified by re versed-phase HPLC and characterized by MALDI-TOF mass spectrometry (Fi gs. 2-4, Table 2) and by capillary gel electrophoresis (Fig. 2).