This summer I’m working closely with Brett Hemric, my graduate student mentor, on a synthetic method that he’s been developing in Dr. Wang’s lab. The project aims to demonstrate an efficient synthesis of the 1,2-oxyamino functionality and to understand the mechanism behind it, with an ultimate goal of developing both novel pharmaceuticals and derivatives of currently existing ones.
Fitting into the lab’s general focus on olefin difunctionalization, Brett’s method features a one-step olefin oxyamination using an electrophilic nitrogen source – a novel contrast to traditional methods involving multiple steps and limited substrate scope.
My work in lab so far has largely consisted of starting material syntheses and methodology reactions. Most of my products have been various O-benzoylhydroxylamine derivatives, the electrophilic nitrogen source utilized in Brett’s chemistry. The relatively simple process of synthesizing these compounds served as a great introduction to lab techniques and instruments, which I’ve found really quite interesting. Exciting highlights include (eventually) becoming competent and trained in using the NMR, being able to synthesize a couple of substrates more or less on my own, and setting up my own hood!
More difficult endeavors have been troubleshooting when techniques fail unexpectedly, as well as convincing myself that the rotovapor pulling a maximum vacuum will not in fact cause glassware to implode and become a black hole.
In addition, my hydroxylamine syntheses are useful to the project (not actually just busywork!) as starting materials for methodology reactions – running the same reaction several times while manipulating one variable at a time (e.g. temperature, concentration, etc.) to test for optimal conditions. I ran a couple of methodology reactions testing whether a particular temperature or catalyst would minimize the side-products that Brett and I were seeing in some of the oxyamination. Although we have yet to fully optimize this, it’s a goal we’re continuing to work on.
Lastly, I’m synthesizing particular starting materials that, when used in Brett’s oxyamination reaction, will provide insight into whether or not the reaction mechanism involves a radical. These substrates are certainly trickier to produce than our friendly neighborhood hydroxylamines, but at least I have my work cut out for me. Furthermore, I’m also working on using Brett’s reaction to synthesize novel GPCR ligands, thus relating abstract organic reactions to a more relevant biomedical application. There’s always something to do in lab, and I wouldn’t have it any other way.
Your lab work sounds really interesting! What kind of pharmaceuticals could be developed if your project succeeds? Also, how do you typically troubleshoot when something goes wrong?