CBC Colloquium Series: "Chemical and Biocatalytic Synthesis of Natural Products" by Dr. Chi Ting

In this presentation, the chemical and biocatalytic synthesis of amino acid-derived natural products will be discussed.  Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a growing class of natural products, many of which possess antimicrobial activity. Sactipeptides are one subclass of RiPPs that are defined by thioaminoketal functional groups. In this presentation, thioaminoketals are assembled through the Markovnikov hydrothiolation of dehydroamino acids using a dithiophosphoric acid catalyst. This method enabled the total synthesis of enteropeptin A and the stereochemical assignment of the natural product. In the synthesis, the Markovnikov hydrothiolation reaction was applied in a stereoselective cyclization to form the thiomorpholine ring. These results form a foundation and potential guidelines for the development of stereoselective peptide cyclization. 

In the second part of the presentation, a chemoenzymatic synthesis of 13-oxoverruculogen, an endoperoxide, is achieved using enzymatic C-H peroxidation and transition metal catalyzed C-C bond activation reactions. Biocatalysis is an emerging area of research which incorporates the use of enzymatic reactions to streamline complex molecule synthesis. Central to the synthesis involves the use of a non-heme iron alpha-ketoglutarate dependent enzyme for C-H oxidation and eight-membered endoperoxide formation.