All Notebooks | Help | Support | About
28th August 2015 @ 13:25

In the past two months, I was doing Open Source Malaria project in lab with Alice Williamson. My project came to an end as the end of my exchange was approaching. The aim of my project was evaluating the possibility of using NBS bromination and cross-coupling reaction to synthesize Series 4 Triazolopyrazine Series Compounds. The importance of this exploration is that it enables the more late-stage diversification of the triazolopyrazine core structure, which is more promising than the current approach. (Picture below shows current approach(top) and new approach(bottom))

Here is a summary of what I’ve done and accomplished during my stay.

With the preliminary results of this area in hand, we firstly repeated the known reactions to make the triazolopyrazine. H NMR confirmed the right structure. We started the NBS bromination reaction straight after that. According to H NMR, we’ve known that the desired mono-brominated product was successfully obtained. The remaining problem was that the product was hard to be purified and isolated. We’ve tried recrystallization and chromatography to get the relatively pure product with a bad yield. The reasons for this problem would probably be a) generation of multi-brominated byproducts b) remaining staring materials which was not brominated by NBS c) residue of NBS and its byproducts d) similar polarity between the products with bromine in different positions. To optimize the reaction, we used acetic acid as catalyst to facilitate the reaction. Comparison of H NMR revealed a possibility of switched selectivity due to the presence of acetic acid which was exciting, although there was no positive sign showing that the reaction was facilitated. 

Suzuki coupling reaction was another focus of my project. With the relative pure products obtained in bromination reaction, we started the Suzuki reaction with different conditions and obtained the arylated products according to H NMR results. What surprised us was there might be a switch of arylation selectivity in the reaction, which was interesting. Although we did not optimize the reaction systematically, we still got some valuable clues in these attempts which enabled a broader exploration on reaction conditions.

Another part of my work was to develop new method to synthesize triazolopyrazine structure. We found an alternative way to make the compound where no further purification was required. But the yield was not satisfactory. 

Apart from the research work in the project, I also enjoyed the process where I was able to improve my ability to search literature and write project description. More information about bromination reaction was included in the description paper. Also, I want to thank the group for giving me an opportunity to elaborate my project in front of all members. It was an enjoyable thing which improved my ability to explain academic topic to others clearly and systematically.

I really enjoyed the past eight weeks I spent with Mat, Alice and other group members, had great research and life experience. It was a great honor for me to work with so many nice and excellent people who helped me out during my stay. I would recommend this project to other students in Nanjing University who are interested in this exchange program, spread the open science idea to others and encourage more people to contribute to this project. I would like to thank Prof. Mat Todd for providing me with this stage to do some research and his instructions, thank Alice Williamson for all the care and instructions not only in academic work but also in daily life. Thanks again for the good memory you gave me.

 

All the best,

Tianyi Zheng (exchange student from Nanjing University)

Attached Files
15th July 2015 @ 11:54

Hi,

I’m Tianyi, currently an exchange student from Nanjing University. I’ll be in Mat’s group for two months and now I am doing some chemistry on the Open Source Malaria project with Alice in lab.

My work mainly focuses on the construction of the MMV669846, which has one less nitrogen in its core structure compared to other molecules. This molecule is promising because it’s biological active against malaria and has improved metabolism. The construction and modification of its core structure is the key to the whole synthesis of this kind of compound.

The first task is to develop new methods for core synthesis.

For modification of the core structure, that is to substitute the hydrogen on 3-position, we’ll develop new methods on bromination chemistry so that we can functionalise the core structure further. We’ll start with 5-chloro-[1,2,4]triazolo[4,3-a]pyrazine as a model.

Our third task is to replace the hydrogen connected to 2-position carbon with groups like methyl etc. We do this in order to improve metabolism of the compound on one hand and to use the substituent group as a handle to attach the compound to the surface of solid on the other hand. We'll start with 5-chloroimidazo[1,2-a]pyrazine.

 

Finally, we’ll see if we can synthesise a functionalised core in only one step.

Attached Files