| Abstract | The non-mevalonate biosynthetic pathway has only recently been mapped and identified as a potential target for the development of novel antibiotics. With the current problems in regard to antibiotic resistance, the discovery of new compounds that are active medicinally against bacterial infections like malaria and tuberculosis, that cause the death of approximately two million people worldwide yearly, is imperative. The goal of this project was aimed at the synthesis and evaluation of methylerythritol cyclodiphosphate (MEcPP) and 4-hydroxy-3-methyl-2-(E)-butenyl-4- diphosphate (HMBPP) analogs as potential therapeutic agents against bacterial infections such as malaria, tuberculosis, and related infections. In bacteria and plants, the non-mevalonate biosynthetic pathway is utilized to produce crucial isoprenoid building blocks. This pathway is appealing as a target for the development of new antibiotics because it is absent in humans, likely resulting in reduced toxicity and side effects. Particularly, MEcPP analogs may be especially selective due to the unique 8-membered cyclic pyrophosphate moiety in MEcPP. An MEcPP analog has never been synthesized before, and this project intended to prepare and evaluate both cyclic and acyclic MEcPP and HMBPP mimics. The goal of this project was to take steps toward filling the gaps in current knowledge that may allow for the production of antibiotics, specifically those of medicinal relevance with activity on resistant bacterial strains. |
