Projects ToSiAn

Antimicrobial resistance represents a significant challenge in the global healthcare system. One potential solution is the development of new synthetic analogs of existing antibiotic classes. However, bacteria can more easily modify their resistance mechanisms against such compounds. A more sustainable solution to this problem lies in the development of new classes of antimicrobial compounds.

As part of this project, representatives of three classes of compounds will be synthesized for the first time. These compounds have previously been isolated from natural sources, structurally characterized, and shown to exhibit significant in vitro antimicrobial activity, particularly against some resistant bacterial strains. Antimicrobial testing will be conducted on the synthesized compounds to confirm their activity across a broader bacterial panel. The three recently discovered classes of compounds that will be addressed in this project are:

a) Penicyclones
b) Spiromastols and spiromastixones
c) Dispirolopyridines

During the development of synthetic approaches for these compound classes, new synthetic methodologies for specific structural motifs of each class will also be developed to establish a robust approach to challenging structural fragments. Some of the methodologies to be developed include the double Grignard reaction and nickel-catalyzed synthesis of diaryl ethers. Additionally, the synthesis of structural analogs within each of these classes is planned to facilitate SAR (Structure-Activity Relationship) studies of the respective compound classes.