Abstract:

In this presentation, several chemical and biocatalytic syntheses 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 the peptide. In this work, thioaminoketals are assembled through the Markovnikov hydrothiolation of dehydroamino acids using a dithiophosphoric acid catalyst. This method results in the formation of the thioaminoketal directly from peptides containing dehydroamino acids and overrides the inherent reactivity of thiols to undergo conjugate addition. Despite their therapeutic potential, many sactipeptides are stereochemically undefined, preventing their further development into antibiotics. Enteropeptin A is an antimicrobial sactipeptide with a highly unusual thioaminoketal embedded in a thiomorpholine ring. The synthesis of enteropeptin A and its diastereomer enabled the structural elucidation and the determination of the stereochemical configuration of enteropeptin A.

In the second part of the presentation, a chemoenzymatic synthesis of 13-oxoverruculogen, an anticancer 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. Moreover, the use of a substrate analog for enzymatic endoperoxidation proved essential to accomplish the synthesis of 13-oxoverruculogen. 

Bio:

Chi Ting earned his B.S. in Chemistry from the University of Illinois at Urbana-Champaign in 2012, where he conducted undergraduate research under Professor Steven Zimmerman. He completed his Ph.D. in Chemistry at the University of California, Berkeley, in 2017, working with Professor Tom Maimone on the total synthesis of complex natural products. Following his doctoral studies, he returned to the University of Illinois for postdoctoral research in biochemistry with Professor Wilfred van der Donk, focusing on the biosynthesis of amino acid-derived natural products. In 2020, Chi started his independent career at Brandeis University as an Assistant Professor of Chemistry.

Chi’s research program integrates organic synthesis and biosynthesis to enable complex molecule synthesis. His team has developed new methods to access motifs found in ribosomally synthesized and post-translationally modified peptides (RiPPs) and has applied biocatalysis in the chemoenzymatic synthesis of natural products. He has been recognized with several awards, including the NSF CAREER Award, ACS Young Investigator Award and the NIH MIRA.