Details

Title of the project: Total Synthesis of Cicutoxin and FR252921 via a Unified Pericyclic Approach

Finishing date: 01/2019

Research topic of the student: The Thesis project was divided in three main axes. On the one hand, a collaborative effort with the Janovjak and Weinzinger groups saw the preperation of photoswitchable variants of a hERG modulator, as well as several derivatives aimed at gaining SAR data. A second topic dealt with the total synthesis of polyene toxins from the Cicuta genus by an innovative domino cuprate addition/electrocyclic ring opening. The GABA_A channel modulation properties of these toxins and synthetic, non-natural analogues were investigated in collaboration with the Ernst group. The third focus was on the development of a novel and concise total synthesis of immunosupressive natural products, which was achieved in a very short number of steps and in high efficiency. The targets, the so-called FR molecules, offered an opportunity to do extensive SAR, to achieve the preperation of gram-amounts of these complex secondary metabolites (featuring a 19-membered ring macrocycle, several unsaturations and stereogenic centers) and to design non-natural analogues which are currently under further study to help determine the nature of their biological target.

Publications with Supervisor: https://www.ncbi.nlm.nih.gov/pubmed/

Research stays abroad: 20.03.2018 – 17.06.2018: Host: Christian Hackenberger, Chemical Biology Research Group, Leibniz-Institut für Molekulare Pharmakologie, Berlin, Germany; Topic: „Tau protein synthesis and modification”.

Lab rotation (2 weeks): Host: Marko Mihovilovic, Topic: Biotin tagged FR252921 for target deconvolution; 07/2018

Place after graduation: Since 02/2019: Postdoctoral Researcher at Ecole Polytechnique Fédérale de Lausanne, Laboratory of electrophiles and genome operation; Switzerland;

In 07/2020 Yong Chen received a 3 year BOF Postdoc Fellowship at the Univsity of Ghent, Belgium, Lab for Biopharmaceutical Sciences, PI: Prof. Bruno De Geest.