Studies Toward Diverse Tricyclic Heterocycles Through Lewis Acid-Promoted Aza-Nazarov Cyclization
VRB-210
Heather Blaser
508-999-8587
hblaser@umassd.edu
Title: Studies Toward Diverse Tricyclic Heterocycles Through Lewis Acid-Promoted Aza-Nazarov Cyclization by thamanna Begum
Advisor: Dr. Sivappa Rasapalli, Chemistry & Biochemistry Dept.
Committee Members:
Dr. Shuowei Cai, Chemistry & Biochemistry Dept.
Dr. Wei-Shun Chang, Chemistry & Biochemistry Dept.
Abstract:
Polycyclic alkaloids are valued structures which are sought after in drug discovery for their bulky, rigid nature and their wide range of pharmaceutical applications. Already found in nature, these compounds exhibit antimicrobial, antifungal, and antitumor properties, which attract interest due to their potential in medicinal chemistry. Being able to synthesize and redesign these molecules is an advantage to optimize selectivity and precise binding to specific biological substrates. However, conventional approaches to these architecturally complex frameworks demand extensive experimental steps with low yields, limiting access to structural diversity. This research employs the Aza-Nazarov cyclization reaction to fold varying alkaloid precursors into tricyclic heterocycles with great diversity in a single acid-catalyzed step. Precursors containing indole, benzimidazole, and imidazo[1,2- α]pyrimidine cores with different substituents were synthesized, featuring either typical Nazarov conjugated systems or α-ketoamides that serve as double-bond equivalents. These were then subjected to a variety of Lewis acids in different conditions, including solvent systems, temperatures, and addition of catalysts, to promote ring closure with NMR and X-ray crystallography for structure determination. Optimizations of reaction conditions for improved purity and higher yield are ongoing. This thesis serves a purpose to extend the synthetic scope of Aza-Nazarov cyclization across multiple alkaloid frameworks, enabling easier access to bioactive compounds with pharmacological prospectives.