By Emma Ostrander, Caroline Pitches
Faculty mentor: Dr. Davis Oldham
In order to treat tuberculosis, specific KasA enzyme competitive inhibitors must be synthesized. This was done by doing a Grignard reaction, chlorination of an alcohol, and alkylation. For the Grignard reaction, bromobenzene was mixed with magnesium and then mixed with 1-benzylpiperidin-4-one. Ammonium chloride was then added. For the chlorination reaction, 1-naphthalenemethanol was dissolved in dichloromethane, added to pyridine, and then added to thionyl chloride. The solution was filtered using a separatory funnel. The solution was
then concentrated using a rotary evaporator. The resulting compound was
1-(chloromethyl)naphthalene. For the alkylation reaction, 4-phenylpiperidin-4-ol, sodium carbonate, acetonitrile, and 1-(chloromethyl)naphthalene were combined. This solution was refluxed and then concentrated using a rotary evaporator. Column chromatography was then conducted to purify the final product, 1-(naphthalen-2-ylmethyl)-4-phenylpiperidin-4-ol. For the chlorination reaction, GC-MS data was collected as well as NMR and IR spectra. NMR and IR
spectra were obtained from the alkylation reaction. For chlorination, when comparing the carbon NMR of the reactant and product, some differences in the peaks were observed. When looking at the GC data, the M+ peak was 176. The IR spectrum included a peak for an alkyl halide C-Cl stretch at the wavenumber 777.02 cm-1. From the alkylation data, the NMR had 17 peaks and
the IR did not show peaks for the amine functional group. The reactions were successful and went to completion. This is because differences in the chlorination NMR suggest product was formed, the M+ peak was at the expected molecular weight of the chlorination product, the chlorination IR contained peaks expected from the product, the alkylation NMR had the expected number of peaks, and the alkylation IR did not include the amine group. The final product had a tertiary amine group which cannot be visualized on IR spectra. From the three
reactions conducted, a KasA inhibitor was synthesized.
