Synthesis of Bioactive Natural Products
Natural products have served as potent therapeutics against pathogenic bacteria since the golden age of antibiotics of the mid-20th century. However, continuous resistance of pathogens to antibiotics remains one of the most severe challenges for modern medicine, posing the need to develop new, more effective antibiotic drugs. Among them, abyssomicin C was the first member that caught the eye of the scientific community. Their activity against methicillin-resistant Staphylococcus aureus mycobacteria and Gram-positive bacteria and their involvement in the inhibition of pABA biosynthesis brought the abyssomicin pharmacophore to the attention of researchers for the development of novel antifolates. Although many researchers have been involved in the development of unique approaches towards this compound, no scalable synthesis has been achieved. The current project aims at the development of an efficient and concise synthetic methodology that will allow the preparation of abyssomicin C and related spirotetronate polyketides and analogues in a scalable, facile and uncomplicated manner. Different approaches based on the transformations followed in biosynthesis are studied, and the best conditions for their implementation are investigated.
This research project is funded by an IKY scholarship awarded to the PhD candidate of the Agricultural University of Athens, Aleksander Canko, for its implementation in our laboratory under the supervision of Dr Vidali.