Biooxidative Approach to Novel C- Nucleosides

From the scientific point of view the introduction of enzymes as catalysts into synthetic organic chemistry makes possible many new highly enantioselective transformations. From the technological point of view, biocatalysis is a cost-efficient environmental friendly process useful for the preparation of fine chemicals. Moreover, the biocatalytic elaboration of novel and powerful pharmaceutical products represent new tools for the treatment of several illnesses, and the use of green processes allow high reduction of waste and environmental contaminantion. Therefore, the development in this field will undoubtedly have beneficial and possitive effects on the improvement of the health and quality of life the society. Especially, the field of enantioselective Baeyer-Villiger oxidations is a domain for biocatalytic methods and involves monooxygenases (BVMOs) offering an appealing "green chemistry" alternative approach to chiral lactones. The major goal of this postdoctoral project is to establish a novel biooxidative approach to chiral carbo- and heterocyclic lactones as an efficient entry to new and novel chiral modified nucleosides. This project involves the initial screening for suitable expression systems of BVMOs to generate chiral lactones which will be carried out on mg scale. After the identification of appropriate strains, the optimization of fermentation conditions and biotransformation scale-up will be accomplished to deliver gram quantities of lactones with appropriate optical purity. This is a prerequisite for the subsequent stage of chemical transformation of the lactone to the precursors for the modified nucleosides. Modified nucleosides are highly active pharmaceutical products for the treatment of important and socially costly illnesses such as viral infections (herpes or HIV) and potential oncolytic agents (Tiazofurin), among others. The final step of this project will involve the formal total syntheses of enantiomerically pure examples of novel and useful chiral modified nucleosides.