Lecture – Burkhard König

Cross-coupling reactions are essential tools for the modification of bioactive molecules and drugs. However, many structures of interest for modification are very polar and, without protection, soluble only in water, while typical cross-coupling protocols require dipolar aprotic organic solvents.

We have developed photochemical cross-coupling protocols that work at the oil-water interface¹ or in aqueous media,² allowing the conversion of charged or very polar compounds without prior protection.^3,4

Light also allows for a reversible and remote control of the pharmacological activity of molecules by photoisomerization. We briefly discuss examples of photochromic GPCR-ligands^5,6 and cyclic nucleotides, and their reversible modulation in vitro and in label-free impedance whole cell assays.⁷

References:

1. Y.- M. Tian, W. Silva, R. M. Gschwind, B. König, Science 2024, 383, 750-756.
2. Y.-M. Tian, E. Hofmann, W. Silva, X. Pu, D. Touraud, R. M. Gschwind, W. Kunz, B. König, Angew. Chem. Int. Ed. 2023, 62,e202218775.
3. I. Ghosh, N. Shlapakov, T. A. Karl, J. Düker, M. Nikitin, J. V. Burykina, V. P. Ananikov, B. Koenig, Nature 2023, 619, 87 and unpublished results.
4. J. A. C. Delgado, Y.-M. Tian, M. Marcon, B. König, M. W. Paixão, J. Am. Chem. Soc. 2023, 145, 26452.
5. U. Wirth, K. Raabe, P. Kalaba, E. Keimpema, M. Muttenthaler, B. König, J. Med. Chem. 2023, 66, 14853.
6. U. Wirth, J. Erl, S. Azzam, C. Hoering, M. Skiba, R. Singh, K. Hochmuth, M. Keller, J. Wegener, B. König, Angew. Chem. Int. Ed. 2023, e202215547.
7. C. Haag, J. Erl., K. Helbig, J. Wegener, B. König, ChemRxiv, 2024, 10.26434/chemrxiv-2024-cq5rz.