Grace Geiger, “Synthesis of Diketopiperazines for the Synthesis of Novel Tryprostatin-Based Microtubule Inhibitors”
Mentor: M Mahmun Hossain, Chemistry & Biochemistry
Poster #65

Trypotstatin A (TPS A) is a microtubule inhibitor that exhibits anticancer properties. Microtubules are integral to cell division as they ensure chromosomes are correctly separated and distributed to daughter cells. Cancer cells divide uncontrollably, which makes microtubules a potential drug target when developing cancer therapies. TPS A was originally isolated from a sea sediment sample collected from the Mouth of Oi river in Sizuoka prefecture, Japan, and is naturally produced by Aspergillus fumigatus. Unfortunately, TPS A is difficult to isolate in large quantities, and has lower activity than other microtubule inhibitors on the market. However, studies have shown that some analogs of TPS A have higher activity than the natural product. Our goal is to synthesis new analogs with even higher activity and shorter synthetic pathways while reducing the hazardous chemicals previously used to synthesize TPS A. An important step in our synthesis of TPS A analogs is the creation of a diketopiperazine. This diketopiperazine can be modified in several ways, making it useful for producing new analogs. My work involves the creation of several diketopiperazine compounds that will be incorporated into the synthesis of TPS A analogs. Methods used to create these diketopiperazines include amide coupling, catalytic hydrogenation, thermocyclization, and column chromatography. Additionally, Thin layer chromatography was used to verify reaction completion and Mass spectroscopy and Nuclear Magnetic Resonance were used to verify identification and purity. If successful, we will create a highly selective and active microtubule inhibitor that can later be used as a cancer treatment.