Synthesis of an unsymmetrical polyamine

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 the intermediate of one such polyamine, namely, 1,4,8-Triazacycloundecane (TACU), in hopes of obtaining greater understanding of the low yield of TACU. TACU 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. The synthesis of the desired guanidinium intermediate was performed in one step. In that 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. Such an unsymmetrical polyamine will help in understanding its role in the synthesis, structure and function of an enzyme mimic.
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 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).
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Abstract/Description: 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 the intermediate of one such polyamine, namely, 1,4,8-Triazacycloundecane (TACU), in hopes of obtaining greater understanding of the low yield of TACU. TACU 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. The synthesis of the desired guanidinium intermediate was performed in one step. In that 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. Such an unsymmetrical polyamine will help in understanding its role in the synthesis, structure and function of an enzyme mimic. 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 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).
Subject(s): Undergraduate Research
Date Issued: 2021