Synthesis of 9-arylalkynyl- and 9-aryl-substituted benzo[b]quinolizinium derivatives by Palladium-mediated cross-coupling reactions.

Siva Sankar Murthy Bandaru,Carola Schulzke,Heiko Ihmels,Mohebodin Karbasiyoun,Darinka Dzubiel,Mohamed M A Mahmoud

doi:10.3762/bjoc.14.161

Abstract

9-Arylbenzo[b]quinolizinium derivatives were prepared with base-free Suzuki–Miyaura coupling reactions between benzo[b]quinolizinium-9-trifluoroborate and selected benzenediazonium salts. In addition, the Sonogashira coupling reaction between 9-iodobenzo[b]quinolizinium and the arylalkyne derivatives yielded four novel 9-(arylethynyl)benzo[b]quinolizinium derivatives under relatively mild reaction conditions. The 9-(N,N-dimethylaminophenylethynyl)benzo[b]quinolizinium is only very weakly emitting, but the emission intensity increases by a factor >200 upon protonation, so that this derivative may operate as pH-sensitive light-up probe. Photometric and fluorimetric titrations of duplex and quadruplex DNA to 9-(arylethynyl)benzo[b]quinolizinium derivatives revealed a significant binding affinity of these compounds towards both DNA forms with binding constants of Kb = 0.2–2.2 × 105 M−1.

Highlights

Polycyclic cationic hetarenes are a paradigm of DNA-binding ligands whose association with the nucleic acid may affect the biological activities of the DNA [1,2,3,4]
Synthesis of 9-aryl-substituted benzo[b]quinolizinium derivatives 1a–d The 9-aryl-substituted benzo[b]quinolizinium derivatives 1a–d were prepared under base-free conditions by the Pd-catalyzed Suzuki–Miyaura reaction of the aryldiazonium salts 4a–d with benzo[b]quinolizinium-9-trifluoroborate (3b)
To identify appropriate reaction conditions for the base-free synthesis of derivatives 1a–d, different catalysts and solvents were tested for the cross-coupling reaction of benzo[b]quinolizinium-9-trifluoroborate (3b) and benzenediazonium salt 4a (Scheme 1, Table 1)

Summary

Introduction

Polycyclic cationic hetarenes are a paradigm of DNA-binding ligands whose association with the nucleic acid may affect the biological activities of the DNA [1,2,3,4]. A DNAbound heterocyclic ligand may interfere with DNA–enzyme recognition events, which are essential for DNA-based cellular processes, e.g., gene replication or transcription [1]. To this end, it was shown that DNA-binding ligands may operate as chemotherapeutic anticancer, antiviral or antibacterial drugs, for example as topoisomerase inhibitors [5]. Based on the principles and requirements of ligands that bind to duplex DNA, nu-.

Results

Discussion

Conclusion