Achieving molecular complexity via metal-free domino reactions

Svetlana B. Tsogoeva / Friedrich-Alexander-Universität Erlangen-Nürnberg

January 18, 2023, 3 - 4 pm CET

Online live talk

Introduction

A domino process is a powerful tool to economically and sustainably build up complex molecular architectures which drastically reduces the number of work-up and purification steps. Recently, we developed new metal-free multi-step domino reactions and one-pot processes for the waste-reducing and cost-effective preparation of versatile frameworks, which otherwise are difficult to access via traditional methods. The developed new methods engage simple and readily available compounds in a wide range of domino reactions to construct e.g., azabicycles, quinazolines, quinazoline-thiohydantoins, 2,6-dicyanoanilines, o‐terphenyls and hexaarylbenzenes of interest for medicinal chemistry and materials science. Very recently, we disclosed a versatile autocatalytic transamination metathesis reaction, which is a multi-step domino process. This novel methodology gives rapid and atom-economical access to N-substituted 1,4-dihydropyridines, which are privileged structures in bioactive compounds and pharmaceuticals.

The in vitro tests against multidrug‐resistant P. falciparum strains (Dd2 and K1), human cytomegalovirus (HCMV), and multidrug-resistant P glycoprotein-overexpressing CEM/ADR5000 leukemia cells revealed the selected domino products and some corresponding artemisinin-containing hybrid compounds as highly active agents, outperforming the clinical reference drugs. These recent results will be discussed in the talk.

 

Selected references

[1] F. E. Held, A. A. Guryev, T. Fröhlich, F. Hampel, A. Kahnt, C. Hutterer, M. Steingruber, A. Nesterov-Mueller, M. Marschall, S. B. Tsogoeva, Nature Commun., 2017, 8:15071.

[2] A. Çapcı, M. M. Lorion, H. Wang, N. Simon, M. Leidenberger, M. C. Borges Silva, D. R. M. Moreira, O. Friedrich, B. Kappes, J. Wang, L. Ackermann, S. B. Tsogoeva, Angew. Chem. Int. Ed., 2019, 58:13066.

[3] B. W. Grau, M. Dill, F. Hampel, A. Kahnt, N. Jux, S. B. Tsogoeva. Angew. Chem. Int. Ed., 2021, 60:22307.

[4] V. Klein, F. Schuster, S. B. Tsogoeva. Preprint: ChemRxiv. 2022, https://doi.org/10.26434/chemrxiv-2022-m6k1v.

 

Svetlana B. Tsogoeva 

graduated with distinction in 1995 from St. Petersburg State University, where she completed her doctoral thesis in 1998 on the “Synthesis of Modified Analogues of Steroid Estrogens” supported by Procter & Gamble. Then, she moved to Johann Wolfgang Goethe University, Frankfurt am Main, Germany, for postdoctoral research. In July 2000 she joined the Degussa AG Fine Chemicals Division as a research scientist. In January 2002 she was appointed the first Junior Professor in Germany at the Georg-August-University of Göttingen. Since February 2007, she has been a professor of Organic Chemistry at the Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Germany. She has published over 140 papers in international peer-reviewed journals. Her awards and distinctions include a Thieme Chemistry Journal Award (2007), an Otto-Röhm Research Award (2012), Research Grant Awards from the Wilhelm Sander-Stiftung (2020) and the Volkswagen Foundation (2022). Her research is currently focused on multi-step domino reactions & one-pot processes, organocatalysis, and medicinal chemistry.