Date of Award


Document Type


Degree Name

Master of Science (MS)


College of Science and Mathematics


Chemistry and Biochemistry

Thesis Sponsor/Dissertation Chair/Project Chair

David P. Rotella

Committee Member

David W. Konas

Committee Member

Saliya A. de Silva


Bicyclic compounds--Synthesis, Pharmaceutical chemistry, Ligands (Biochemistry)


Conformationally restricted bicyclic amines have been found to be very useful scaffolds in medicinal chemistry. Examples can be found in the chemical literature for the application of conformationally restricted diamines. These molecules can be used as enzyme inhibitors or GPCR ligands. Conformational restriction can improve affinity and selectivity toward receptors. The stereochemical diversity-oriented approach is a method that explores stereochemical effects in small molecule ligands for proteins. It is an effective strategy when the bioactive conformation of a ligand and the pharmacophore of the binding site are unknown. These concepts are applied in the design the target [4.2.1]di-azabicyclic compounds. The nitrogen atoms can be functionalized differently if they are protected appropriately to provide increased structural diversity. The shift of the nitrogen atom along the four-atom bridge provides the opportunity to scan a broad region of space. The modified approach of the synthesis toward these targets utilizes selective oxidation/reduction and stereochemically well-defined reactions to modify the functional groups and stereochemistry in the compound. This paper describes the research done so far to obtain these conformationally restricted diamine targets and the characterization of the novel intermediates.

File Format


Included in

Chemistry Commons