Maryanoff

This page is about my experience in the UsefulChem project and what I have so far learned.

My name is Lin Cheng and I am sophomore biology major at Drexel University. During the summer of 2006, I received a Maryanoff scholarship to participate in research in the field of chemistry. I joined the UsefulChem Project under the guidance of Dr. Bradley. Two other students that I work closely with are Khalid Mirza and James Giammarco. When I first came to the Useful Chem Project, my experience in chemistry and laboratory techniques was limited to what I learned in my freshman general chemistry courses. The research I do in the lab encompasses a wide range of aspects that includes synthesis of reagents to be used in the synthesis of the target diketopiperazines that are believed to be anti-malaria compounds.
 * Introduction**

The UsefulChem Project is an open source science project where are the data collected are posted online on the wiki (current experiments and other useful information) and blogs ([|main blog], [|molecules], [|past experiements]) in real time. At the moment, Dr. Bradley and the UsefulChem group are focusing on identifying, synthesizing, and testing anti-malaria compounds. The target diketopiperazines that are thought to be anti-malaria compounds were complied by Find-A-Drug. A collaborator, Bill Bergman, from the Drexel Queen Lane campus was found and is willing to do vitro testing is a molecule is successfully synthesized. The chemistry of the project initially started with a [|solid support synthesis] to make the diketopiperazines but eventually changed to the one pot [|Ugi Synthesis]. Right now, the goal is make successfully synthesize a diketopiperazine using the Ugi synthesis that is similar to the target anti-malaria compounds identified by Find-A-Drug.
 * What is the UsefulChem Project?**

When I first joined, James was perfecting the synthesis reaction of DOPAL, since previous reactions had failed. My first experiment as a part of the UsefulChem group was to help James synthesize DOPAL (EXP016). James walked me through the procedure and taught me several laboratory techniques. It was during this reaction that I learned how to run my first [|TLCs] and do an ether extraction. The reaction was a success in that a crude product was formed. I went on to perform another successful synthesis with Khalid that resulted in a pure product, without chromatography (EXP025). However, when I attempted a DOPAL synthesis by myself the reaction failed even though the procedure was based on the successful attempts (EXP024).
 * Synthesis of DOPAL**

Later on, I did my first distillation with the help of Khalid (EXP039). My objective was to purify crude phenylacetaldehyde by vacuum distillation. At first, the product was not coming off at the temperature calculated based on the pressure, but product eventually came off at around 20 degrees higher than expected. However, 4 mL of pure phenylacetaldehyde was collected from 10 mL of the original crude product. The pure product was used later on in the formation of an imine in the first step of a Ugi synthesis (EXP042).
 * Distillation**

I made several attempts to synthesize a diketopiperazine, but none of them resulted in a successful synthesis. My first attempt was with James and we used the three components piperonal, 5-methylfurfurylamine, and N-(tert) butoxycarbonyl) L-methionine (EXP017). Although the reaction was not successful, I learned how to reflux as well as use the rotovap and the high vac. In the next attempt, it was decided that the Boc-Met-OH would be replaced by Boc-Gly-OH because of its simplicity (EXP019). After cyclization, I used a chromatotron to perform multi-separations. However, NMRs showed that the separations were unsuccessful because they contained too many impurities. Based on TLCs and NMRs, the diketopiperazine appears to be slow moving, and not fast moving, as previously thought. My third attempt at the Ugi synthesis used the same reagents as EXP019, but the reaction occurred over a period of one month with no cyclization (EXP026). Based on the NMRs, most of the piperonal has reacted. Compared to EXP019, more piperonal reacted, possibly indicating that piperonal is an aldehyde that is slow to react because 1 month was taken to complete this reaction, instead of the 20 hours taken in EXP019. I then performed flash chromatography to separation the Ugi product (cyclization has still not occurred) from any impurities. While it seemed that I had better success in separation by [|column] instead of by chromatotron, the NMRs still showed traces of impurities. In order to pinpoint where the reaction went wrong, the conclusion was to break up the Ugi reaction into steps. The latest attempt was to do the first step of the Ugi reaction (formation of an imine) using t-butylamine and the pure phenylacetaldehyde distilled from EXP039 in CDCl3 (EXP042). The entire reaction was done in an NMR tube and monitored by H-NMR and C13-NMR at certain time intervals after mixing.
 * Ugi Synthesis**

One thing that I have learned while working in a research lab is that patience is very important. More time is spent doing outside research, setting up the experiment, and analyzing the results then actually doing the reaction. I’ve learned many laboratory techniques during my times at the UsefulChem Project that I would not have learned until I had taken an organic chemistry lab course. These techniques, while seemingly simple, are not always successful. Following published procedures is not always 100% successful because the conditions could be irreproducible or a factor could be unaccounted for. Chemistry is like cooking, just because you follow the recipe it does not mean that the food will turn out perfect. Only if the steps are patiently followed correctly and the perfect conditions are achieved, can you obtain the results that you were hoping to get.
 * What I Learned**

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