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Synthesis, characterization, and biological assessment of a macrocycle containing lysine

Jelinek, Trevon
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Date
2022
Additional date(s)
5/19/2022
Abstract
The synthesis of the lysine macrocycle begins with the step-wise substitution of cyanuric chloride with nitrogenous nucleophiles. The three chlorine atoms are replaced with BOC-hydrazine followed by protected D-lysine and finally an auxillary amine such as morpholine or dimethlyamine. The protecting groups explored were a butyl (BOC) or benzyl (Z) carbamate. To arrive at this first intermediate, a carboxylic acid, the temperatures were varied to control reaction kinetics in order to deliberately mono substitute and obtain desired compound (6.8% yield). After purification and characterization, this acid undergoes a coupling reaction with an amino acetal to provide the monomer for macrocyclization in 10% yield. Treating the monomer with acid leads to dimerization. The desired macrocycle is obtained in quantitative yield and used without purification. Throughout the synthesis, one- and two-dimensional 1H spectroscopy is used to establish structure. The antibacterial activity of this macrocycle (and others) relied on evaluating the minimum inhibitory concentration (MIC) against both Gram-positive (Escherichia coli) and Gram-negative (Staphylococcus aureus) bacteria. The macrocycle did not affect bacterial growth: no MIC could be measured at the maximum concentration of 500 ug/mL.
Contents
Subject
Macrocycle
antibiotic
lysine
MIC assay
synthesis
amino acid
amino acid macrocycle
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Research Projects
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Department
Chemistry and Biochemistry