| Abstract | A revival of attention paid to large drugs, such as cyclic macrocycles, has been fueled by the idea that there may be therapeutic targets available to them that are unavailable to smaller molecules. The pharmaceutical space that includes large, cyclic molecules has long been ignored by drug developers. This phenomenon is because, based on Lipinski's Rule of 5, orally absorptive drugs shouldn't exist there. Additionally, the chemistry of synthesizing such large molecules is complex, time intensive, and unpredictable. The Simanek group aims to establish a novel and straightforward synthesis. Establishing this approach allows for investigation into why large drugs, like the immunosuppressant cyclosporin, are so successful. Additionally, this research creates opportunities to design large cyclic drugs with intentionality and flexibility. This intentional design includes the addition of specific functional groups and amino acids. The long-term goal of this project is the synthesis of the complete macrocycle. The short-term accomplishment of this experiment is the synthesis of the trisubstituted triazine ring, called Intermediate 3 or I-3 . To create the target molecule, I-3, three groups were substituted onto a triazine ring. The target molecule has a triazine with a BOC-protected hydrazine group, a morpholine, and phenylalanine. This synthesis occurred in a stepwise substitution process. The product was purified through silica column chromatography. Upon examination by 13C and 1H NMR, the spectra reveal resonances that are diagnostic for macrocycle formation. Thus, it was determined that the trisubstituted molecule was successfully synthesized. |
