Macrocylic polyamines serve as ligands to coordinate with metal ions and are commonly used to mimic the active sites of enzymes. Our goal was to synthesize a polyamine, namely, 1,4,8-Triazacycloundecane (TACU). It is an intermediate reagent that will be used as a scaffold to mimic the active sites of physiologically significant enzymes such as carboxypeptidase and thermolysin. In the first step, Hexahydropyrimidopyrimidine underwent a bimolecular nucleophilic substitution reaction (SN2) with the ditosylate 1,2-bis(tosyloxy)ethane by stirring at room temperature for 48 hours resulting in a tricyclic salt of a carbocation intermediate at the most centered carbon in the molecule. This intermediate was reduced by addition of a mild reducing agent (sodium borohydride) and stirring for another 24 hours to form an orthoamide. In the second step, the orthoamide was acid-hydrolyzed to form TACU. The product was confirmed using nuclear magnetic resonance spectroscopy (1H NMR and 13C NMR) and gas chromatography-mass spectrometry (GC-MS). With modifications to the procedure such as adding Hexahydropyrimidopyrimidine, 1,2-bis(tosyloxy)ethane, and sodium borohydride all at once then stirring for 48 hours, along with purification methods. We were able to decrease the overall time the reaction takes and also increase the yield of pure product for both the Orthoamide step and TACU step, which significantly increased the overall yield. Such an unsymmetrical polyamine will help in understanding its role in the synthesis, structure and function of an enzyme mimic.

Synthesis of an unsymmetrical polyamine

ACS Spring 2022

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