What? I spent this summer working on a research project in a natural products lab in The Ohio State College of Pharmacy. I spent the summer working on the synthesis of several pyrrole alkaloids found in Goji Berries. Some Goji berry extracts have shown potential cancer chemopreventive activity when tested in vitro. While these compounds have varying activity profiles, it is unclear what causes one compound to be more or less active than others. Several pyrrole alkaloids isolated from Goji berries have never been stereochemically described
The primary goal of my STEP Undergraduate Research Project was to synthesize several pyrrole alkaloids in order to stereochemically interrogate each compound. In addition, the second aim was to develop a method for synthesizing analogues of these pyrrole alkaloids in order to study the relationship between structure and quinone reductase induction activity when tested in vitro.
In order to synthesize the desired pyrrole alkaloid, I used 5-(hydroxymethyl)furfural as the starting material. The starting material was first protected with tetrahydropyran (THP). The aldehyde was reduced to a primary alcohol and protected with tert-butyldiphenylsilane (TBDPS). The di-protected furan was oxidized to a 2,3-unsaturated 1,4-diketone compound with MCPBA, and then converted to a saturated 1,4-diketone compound via a zinc reduction. Two methods for Paal-Knorr pyrrole synthesis were used, separately, to couple methyl-protected d-alanine with. The first method involved the use of catalytic amounts of iodine, and the second involved reflux conditions with acetic acid. NMR data collected suggested that both attempts were unsuccessful.
I now believe that the synthesis of the desired pyrrole compound is being prevented by steric issues. The TBDPS protecting group was chosen because of its UV activity; however, it is a bulky protecting group and is likely preventing the diketone compound from cyclizing to a pyrrole. Triethylsilane (TES) is another silyl ether protecting group that, though more labile than TBDPS, is much less bulky. The use of TES instead of TBDPS may eliminate the steric issues that are theoretically preventing the formation of the pyrrole.
The long term impact of this work is to potentially lead to the development of new drugs or dietary supplements that prevent or treat various types of cancer. Upon successful synthesis of the desired pyrrole alkaloid following typical removal of protecting groups and one oxidation step, the biological activity and optical rotation of the compound will be compared with the previously isolated compound. Additionally, the same method will be used for the synthesis of other pyrrole alkaloids isolated from Goji berry extracts, and analogues of these compounds, in order to study their configuration and structure-activity relationships.
So What? I learned a great deal from my STEP experience. Each day I came into lab in the morning and worked until dinner. At the beginning of the summer it was very overwhelming to come into my lab and have 8 hours of work to complete. It was a big adjustment to being working independently on a project because I had previously been working on a different project with one of the graduate students in my lab.
During the summer, there were several weeks where some of the graduate students were away at conferences. This made it harder to ask questions about things that may have gone wrong with my project or about what to do next. Because of this, I became more independent at solving problems. I familiarized myself with the resources necessary to answer many of my questions by myself.
Now What? The experience I had with my STEP Undergraduate Research project has and will continue to affect many aspects of my life. Academically, I have a much better understanding of the chemistry. This summer I learned many things that I would not have had the opportunity to learn in a classroom. I also put to practice many of the concepts I had learned in classes. In general, this experience gave meaning to many of the things I had learned and will learn in my chemistry classes.
This experience affected some of my personal goals as well. One goal that I had set for myself was to present my research at a poster forum. Because of the work I completed during the summer, I was able to present my research at the Fall Undergraduate Research Forum and I plan on presenting at the Denman Forum as well. Another goal I have set for myself is to publish my work in a journal. As I continue to do further research on my project, I will hopefully be able to publish my findings in one (or several) journals.