Evolution of Novel 16-Membered Ketolide Antibiotics:Convergent Synthesis and Biological Evaluation of Tylosin Derivatives

• Applicant: Dr. Daniel Tobias Hog
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2014 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 251194615

Evolution of Novel 16-Membered Ketolide Antibiotics:Convergent Synthesis and Biological Evaluation of Tylosin DerivativesWithin the last 60 years, macrolide antibiotics have emerged as highly important therapeutics in medicine. Due to the clinical overuse of these drugs, however, pathogenic microorganisms have developed multiple drug resistance over the past decades. Hence, the treatment of certain infections has become a great challenge and consequently, the development of new antibacterial agents is in great demand. Beside semi-synthetic strategies, convergent syntheses of novel scaffolds provide a platform to discover new antibiotics. This research proposal aims at realizing a robust and scalable route toward a library of novel 16-membered macrocyclic tylosin analogues by a late stage diversification of a common intermediate. The proposed structures were deduced from the increasing understanding of the molecular binding of macrolide antibiotics to the bacterial ribosome and should be enantioselectively accessed by a convergent approach from two fragments of similar complexity. Subsequently, we plan to determine the antibiotic properties of the synthesized analogues against a panel of resistant bacterial strains. Thus, the proposed studies combine the challenges of stereoselective synthesis in an acyclic setting with the prospects of exploring new potentially anti-infectious compounds to advance the field of antibiotics.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Andrew G. Myers, Ph.D.