In modern medicine, a variety of antibiotics are used to treat diseases. As a result, bacteria develop resistance against antibiotics faster than before, and several antibiotics lose their effectiveness, in some cases even completely. For this reason, there is an ambitious search for new antibiotics that work effectively against bacteria.

A new potential class of antibiotics inhibits the enzyme LpxC, which plays a role in the biosynthesis of lipid A, being part of the outer membrane of Gram-negative bacteria. LPC-233 is among them and is of particular interest due to its minor side effects compared to other antibiotics of this class. Therefore, a synthetic route with high yields and purity is of great interest, also regarding possible future applications in medicine.

In this work, a synthetic route is described, in which (2S,3S)-methyl-2-amino-4,4-difluoro-3-hydroxy-3-methylbutanoate (-)-CSA and 4-(cyclopropylbuta-1,3-diyn-1-yl)benzoic acid are synthesized as precursors. Then they are coupled with HATU and finally transformed into LPC-233. The synthesis was successful, however, with a total yield of 0.2 % for a mixture of enantiomers, which is less than already reported. The reasons for the partially large differences in yield compared to the previously published yields for the individual reaction steps are explained. Nevertheless, the MS spectrum does not indicate any impurities. As the color of the product differs from the one reported, it must be assumed that the synthesis carried out in this work gave higher purities, besides the fact that the product was not enantiomerically pure. Furthermore, this work depicts the reaction mechanisms for a greater understanding of the single reaction steps.

Additionally, two byproducts that arose during a Sonogashira coupling were investigated by mass spectrometry and characterized based on the fragmentation patterns as 1,4-dicyclopropylbuta-1,3-diyne and methyl-4-(1,2,2-tribromovinyl)benzoate, respectively. Potential mechanisms leading to these byproducts were proposed based on theoretical considerations alone, which can serve as a foundation for further, including practical, investigations to improve the frequently used Sonogashira coupling with regard to the reduction of byproducts.