Nowadays, the Gram-negative bacteria research re-gained its interest due to the growing concern of the lack of treatment against drug-resistant bacteria. The mutations in outer membrane and porin channel are the main causes of this resistance, prohibiting the drug from penetrating into bacteria. To overcome these resistance, many research groups have mimicked “siderophore”, high-affinity iron-chealating compound that bacteria produces to transport iron ion across cell membrane for its essential ingredient. Thus, siderophore was incorporated into the antibiotic via a specific linker to penetrate cell wall of bacteria, then its active ingredient would show antibacterial activity in the cell.
LCB10-0200, was patented by LegoChemBioscience (US2012/264727) which represnts a typical example of this strategy in which cepha unit was connected to the dihydroxypyridinone siderophore via disubstituted pyrimidine linker.
Here in this poster, we will show the total synthesis of LCB10-0200 in the original medicinal chemistry (mg scale) as well as the synthesis in view of process chemistry for larger scale (kg scale), specifically focused on the linker-siderophore unit.