Synthesis of Fused Benzene Amphiphiles

Abstract

The discovery of antibiotics have made some major advances in treatment of infectious diseases, other medical treatments and surgery. For the past few decades, overuse, inappropriate prescribing and extensive use of antibiotics in agriculture has lead to a proliferation of resistant bacteria. In order to deal with this evolution, new types of antibiotics, as well as a downscaling of the current overuse of existing antibiotics is essential. Antimicrobial peptides are a novel class of antibiotic agents that are promising towards the emerging resistance crisis. They selectively coordinate to the net negatively charged membrane of bacteria and causes membrane disruption through displacement of lipids and alteration of the membrane structure. In order for the microbes to develop resistance they need to change the structural composition of their membranes, which is improbable. The structure of the synthesized target molecules 1a-b, 15a-c and 19c has an amphipathic structure with a hydrophobic part that is connected to a cationic head group by an indene scaffold. A key reaction in the synthetic route of these compounds is the [2+2+2] cycloaddition of 4 and different alkynes 10a-c. The route involves preparation of 10a-c and further functionalization of the diethylester 11 after the [2+2+2] cycloaddition.