Sialic acids derivatised at C-4 as ligands for bacterial SSS transport proteins

This master thesis project focuses on establishing a synthetic method with the prospect of developing new antibacterial agents. Due to the increment of resistant strains of bacteria throughout the world, this area of research is well motivated. The nine-carbon sugar - sialic acid - is a highly prevalent communication molecule on human cell surfaces. It signals that the cells are endogenous and not harmful. This signalling mechanism is mimicked by exogenous cells - bacteria -, masking them as human cells and thus resisting the host’s innate immune response. As a result the bacterial strain can grow uncontrolled leading to an infection in the human body. Therefore, it seems that a disruption of their protective mechanism, with means of sialic acid, poses an excellent antibacterial target. This work has focused on finding a pathway to be able to modify position C-4 of sialic acid. A couple of different approaches have been tried out leading to one successful way to conduct the desired modification. It was concluded that a complete protective strategy was required where all hydroxyl groups were protected except for OH-4. Eventually, a sialic acid derivative with a substituent at C-4, consisting of a triazole ring and a para-substituted fluorophenol, was identified by MS.Since the discovery of penicillin in the 1940’s, mankind have been spared deaths caused by bacterial infections. Up until today we rely on the curing benefits of antibiotics. This is a security we will lose within a short period of time, as in the recent years, more and more resistant bacteria have been detected. The development of resistant bacterial strains is on one hand a result of evolutionary adaption but foremost a result of overuse of antibiotics. Before us stands an unpleasant picture of a healthcare with no weapons in the fight against bacterial diseases. To change this picture, we need to change the way we use antibiotics and we need to find novel antibiotics. The work of this thesis focuses on the latter