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First NMR Data for Barker College 2019 - Daraprim Analogue Project #1

Open alintheopen opened 5 years ago

alintheopen commented 5 years ago

BC 1-2 1HNMR

BC-1-2 13C

katieterrett commented 4 years ago

Update on progress at Barker College:

I have had one student working on this synthesis as part of his Science Extension research project. We were tasked with synthesising the iodo-analogue of Daraprim in order to compare the biological activity of this analogue with Daraprim.

We have attempted the synthesis of the first intermediate, 3-oxo-2-(4-iodo) phenyl pentanenitrile from 4-iodophenylacetonitrile following the procedure that Sydney Grammar used for the synthesis of the the related chloro-derivative.

image

Details of our synthetic procedure are here: https://malaria.ourexperiment.org/barker_college/16346/Attempted_synthesis_of_3oxo24iodo_phenyl_pentanenitrile.html

We obtained a mixture of products, seemingly two major products. Our initial thinking is that we have isolated both the keto and enol tautomers as several distinctive peaks can be seen in the NMR spectra. Alternatively a second product may be explained by a by-product arising from the reaction with oxygen which has been observed before for related small scale syntheses carried out by Sydney Grammar.

My student prepared a great research report which outlines the project nicely. I am not confident with our analysis of the products from this reaction as I am a bit rusty in this area, and we didn't obtain other analytical data in time. I'd be interested to see what others think about the identity of these two products and where to go from here.

Future directions: If we continue to pursue the synthesis of this analogue we will need to scale up the reaction so we can isolate and purify the products. This will be difficult as TLC analysis reveals only one spot on the crude TLC plate. Investigations will be required in this area. Additionally, the starting material 4-iodophenylacetonitrile is expensive and has prevented us from undertaking this reaction on a larger scale thus far. We may need to investigate the synthesis of this starting material to remedy this if we continue to pursue this analogue of Daraprim.

Science Extension Final Report-Lucas-KMT-v2[1].docx