Essay --

The original synthesis did not go to completion; starting materials remained unreacted. This was confirmed when the purified product was isolated and determined to not be pure (Figure 7). Increasing the amount of solvent (DMF), obtaining a crude HNMR spectrum after 3 hours of the reaction to monitor reaction progress, increasing the reaction length with respect to the findings of the crude HNMR spectrum, obtaining a pH of 2-3 during the acidification (in order to obtain only the carboxylic acid product instead of a mixture with the carboxylate salt) and refining the recrystallization method, are all some of the adjustments to the experimental parameters. When the reaction parameters were changed to 6 hours and the acidified product had a pH of 2-3, a 20% yield of a white, flaky solid of the 4-4 coupling product was obtained. When the reaction parameters were changed to 18 hours, a 32% yield was obtained. However, a significant amount of decarboxylated byproduct was formed. A re crystallization procedure was developed to isolate the pure 4-4 coupled product (See Methods). An alternate synthetic pathway was developed due to the low percent yield and high levels of undesired side products of the reaction. Such characteristics are not ideal for a key starting material in a long synthetic series.Botulinum neurotoxins (BoNTs) are poisons that infect humans and are known to cause the human disease botulism 1,2,3,4,5. Having an LD50 of 1.0ng/kg body weight for humans, this makes the botulinum neurotoxin one of the most toxic known poisons still active today. BoNTs are listed as a category A bio threat agent by the United States Centers for Disease Control and Prevention 1,2,3,4,5. Currently, there is no cure or effective treatme... ... be the most advantageous line of study 1,2,3,4,5. Unlike vaccines, chemically stable small molecules would remain viable for many years due to the dramatically larger half-lives. A large number of peptide-based inhibitors have been explored, but due to their short in vivo lifetimes, they make a poor candidate for new drugs 2. Broad spectrum BoNT inhibitors have been largely attempted to develop, but have rarely been met with success. Therefore, shifting the focus to develop serotype specific inhibitors have been the new focus in combatting botulinum neurotoxins. The overall goal has been modified to develop small, cell-permeable, low molecular weight, non peptidic drug like molecules capable of inhibiting BoNT/A, the deadliest of the seven serotypes. In order to achieve this, small molecule drug development is aimed at inhibiting the LC activity of BoNT/A 5.