Synthesis of Diketopiperazines, Possible Malaria Enoyl Reducatase Inhibitors Using Open Source Science
Alicia Holsey Research Advisor: Jean-Claude Bradley

Open source science is a collaborative method in which the scientific community is able to contribute to the project by posting comments on blogs and wikis. Open source science is well suited to solve problems endemic to third world nations including infectious diseases such as malaria. The synthesis of diketopiperazines (DKPs) is investigated as possible inhibitors to enoyl reductase, a protein that malaria uses to synthesize critical fatty acids.

Diketopiperazines can be synthesized via a Ugi/de-BOC/Cyclize (UDC) method. The first part of the synthetic pathway involves a Ugi synthesis where an isocyanide, an amine, a boc-protected carboxylic acid, and an aldehyde are added together in equimolar concentrations in methanol. These components are allowed to sit at room temperature for approximately 24 hours. Crystals of the Ugi product are formed and removed from the solution. Structure of the Ugi product is confirmed via proton nuclear magnetic resonance spectroscopy (HNMR). Cyclization of the diketopiperazines has yet to be fully achieved, however investigation is ongoing.