Synthesis of functionalized, 13-alkyl-substituted coralyne derivatives and investigation of their interactions with
Laurin Beckmann1, Jason Lennard Kunze1, Hannah Karola Strunk1
1Department of Chemistry-Biology, and Research Center of Micro- and Nanochemistry and (Bio-)Technology (Cμ), University of Siegen, Adolf-Reichwein-Str. 2, 57068 Siegen, Germany.
Abstract:
With the goal to develop coralyne-based ligands for abasic site-containing DNA (AP-DNA), different synthetic routes towards the functionalization of coralyne were tested. In particular, the alkylation of the benzylic position in papaverine and subsequent cyclization by treatment with acetic anhydride in sulfuric acid led to the synthesis of a coralyne derivative with an alkoxyamine-functionalized linker attached at position C13. Firstly, it was demonstrated with a resembling model compound that the alkylation of the coralyne scaffold does not influence the DNA-binding properties. Furthermore, it was shown that the alkoxyamine function can be readily released from a Boc-protected precursor and that the corresponding coralyne-alkoxyamine conjugate can operate as a ligand for AP-DNA and as inhibitor of enzymatic repair of abasic sites.
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