| Scope and Method of Study: The drug RAB1, which was previously prepared in our laboratory, has sparked our interest in the chemical potential of phthalazine derivatives. Phthalazine is a substructure of RAB1, which has shown activity against Bacillus anthracis, the bacterium that causes anthrax. With the goal of improving the activity of RAB1, we have developed an efficient synthesis of selected phthalazine derivatives. Our strategy began with a substituted benzaldehyde which was converted to a phthalaldehyde in a four step process. The key synthetic step in our procedure was a lithiation step, which allowed for the addition of a second aldehyde, giving the desired substituted phthalaldehyde. This product was then cyclized by the addition of hydrazine to afford the aromatically-stabilized, substituted phthalazine product. The thesis will discuss our strategy, reaction optimization, etc.;Findings and Conclusions: An efficient procedure was developed for the preparation of substituted phthalazine derivatives. In a four step synthetic procedure an average overall yield of 50% was obtained. A diverse library was readily obtained based on the availability of starting material. Furthermore, specific substitution was achievable by utilizing the different methods of lithiation. |
