My Summer as an Organic Chemist

My research this summer has focused on finding novel routes to synthesize natural products. Natural products are chemical compounds that are produced by living organisms and are found to occur in nature. Typically, when extracted from their natural source, it is only possible to isolate small amounts of these natural products. This is why organic chemists seek to find methods to synthesize these compounds in the lab in larger quantities.

I have spent the last six weeks (and last spring semester) working with quinones. As I described in my abstract, these are oxidation products of aromatic compounds. I began this research with a target natural product (natural product 1) in mind, two starting materials, and a rough idea of a useful and efficient route through which I could synthesize the molecule. This route was devised by Dr. Lashley and our collaborator in Germany, Dr. Hamid Nasiri, who has helped us along the way and who will be doing the actual biochemical testing on these molecules, once I have synthesized enough for him to actually work with.

The research has proved to be slow and at times a little frustrating, but apparently that’s the nature of scientific research. There have been a few occurrences where I have hit a wall with my current path, and had to take an entirely different one. The first few weeks this summer I spent searching for a way to perform a decarboxylation reaction to attach a vinylic substituent to a quinone ring. After much experimentation and further literature research, it appears that any attempt so far to adhere a vinylic substituent to a quinone ring has been unsuccessful. At this point I had to scrap the idea, and look for a new natural product that was more likely to yield successful results.

We then moved into trying to react the starting quinones with carboxylic acids to attach alkyl chains to the rings. This has so far proved much more successful. A few of the products to which I have attached alkyl chains will be sent for biochemical testing. The issue that has arisen here is that the starting material has many spots on the ring to which the alkyl group is able to attach. As such, multi-substituted products have been produced as well as mono-substituted products. These prove difficult to separate, and that is something that I am working on this last week.

After working with the decarboxylation reaction for a while, we decided to try a different path, using a bromide reagent. The goal was to synthesize the two natural products depicted below (Natural Product 2 and Natural Product 3). This so far has proved a very successful method of synthesis, and has also led to the production of multi-substituted products. These were easier to separate than those of the decarboxylation reaction, and that is what I did last week. So far I believe that I have synthesized the two mono-substituted natural products, but I am awaiting further NMR and mass spectroscopy identification to be sure of it.

I am currently in my last of the seven weeks of research. At the end of this week, when I have all the products that I will be sending to Germany for testing in sufficient quantities, I will post the second of my updates to conclude how the organic synthesis part of this project went. During the month of July and possibly into August, the products will undergo biological testing at the University of Frankfurt and other institutions with which Dr. Nasiri has connection. I will post my third blog update after speaking with him at the conclusion of the testing, to see if any of the molecules have any biological (or hopefully clinical) usefulness or significance.

My work has made use of organic laboratory techniques not taught in introductory labs, such as lots of column chromatography, operating proton and carbon NMR, and eventual mass spectroscopy, once I have purified everything. Attached are some pictures of some of the laboratory techniques I have made use of this summer. The first is a rotary evaporator. The second is an example of column chromatography on a sample. The third is a reaction carried out in order to synthesize a desired carboxylic acid, making use of a piece of glassware called a Dean-Stark apparatus, which I had never heard of. The final picture is of a thin-layer chromatography plate.

My experience so far this summer has been incredibly enjoyable. I have thoroughly enjoyed learning all that I have about drug design and the processes behind it. I have also enjoyed working with Dr. Lashley and the other lab members. I look forward to hearing the results of the biochemical testing and hope that the molecules that I have synthesized may have some biological use.

Reference Gallery:

Natural Product 1

Natural Product 1

Natural Product 2

Natural Product 2

Natural Product 3

Natural Product 3

Picture 1

Rotary Evaporator

Picture 2

Column Chromatography

Picture 3

Reaction Using Dean-Stark Apparatus

Picture 4

TLC Plate

Comments

  1. Hi Andrew, my knowledge of chemistry is rather limited, so I found your post a little hard to read with all of the jargon, but I imagine that those with experience in the field were able to form a better picture of what you actually did. I am very impressed by the amount of individual thought and original work that you had to do for a professor’s research. You seem extremely knowledgable of and invested in the subject, and I am excited to hear about your results at the Symposium. What will the compound that you are trying to synthesize actually do? Is it a model for another similar structure or will the novel route you are looking for be the final result? Thank you for such a detailed post!

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