Directed evolution for abiological radical-relay C(sp3)−H azidation. First Science publication of our group!

/0 Comments/in , , /by

In this work, we show that it is possible to perform directed evolution guided by computational results (performed in our group) to reprogram nonheme iron enzymes to catalyze an abiological C(sp3)‒H azidation reaction through iron-catalyzed radical relay. This biocatalytic transformation uses amidyl radicals as hydrogen atom abstractors and Fe(III)‒N3 intermediates as radical trapping agents. We established a high-throughput screening platform based on click chemistry for rapid evolution of the catalytic performance of identified enzymes. The final optimized variants deliver a range of azidation products with up to 10,600 total turnovers and 93% enantiomeric excess. Given the prevalence of radical relay reactions in organic synthesis and the diversity of nonheme iron enzymes, we envision that this discovery will stimulate future development of metalloenzyme catalysts for synthetically useful transformations unexplored by natural evolution.

This work was carried out by J. Rui, Q. Zhao, A. J. Huls, Z. Chen, V. Reshetnikov and Prof. X. Huang from the Department of Chemistry of the Johns Hopkins University, J. C. Paris and Prof. Y. Guo from the Department of Chemistry of Carnegie University and J. Soler and Dr. M. Garcia-Borràs from the DiMoCat group of the Institute of Computational Chemistry and Catalysis of the University of Girona.

We are very proud of the work by Marc Garcia-Borràs and Jordi Soler! Congratulations!!!

 

Jinyan Rui, Qun Zhao, Anthony J. Huls, Jordi Soler, Jared C. Paris, Zhenhong Chen, Viktor Reshetnikov, Yunfang Yang, Yisong Guo*, Marc Garcia-Borràs* and Xiongyi Huang*. Directed evolution of nonheme iron enzymes to access abiological radical-relay C(sp3)-H azidation. Science, 2022, 376, 6595. DOI: 10.1126/science.abj2830.

 

News @ Views article in Nature Synthesis

/0 Comments/in , /by

A paper in the News & Views section of Nature Synthesis reporting the significance of Rh-catalyzed cycloaddition reactions done by Uchiyama, Tanaka and co-workers has been written by Anna Roglans and Anna Pla-Quintana.

Dr. Roglans and Dr. Pla-Quintana take advantage of their expertise in transition-metal catalysed [2+2+2] cycloaddition reactions of unsaturated substrates to summarise and highlight the work done by this Japanese research group. We note that this process is a powerful tool to synthesize a wide range of six-membered rings with high levels of diversity and complexity in a single reaction step with perfect atom economy.

Pla-Quintana, A., Roglans, A. Cyclotrimerization takes orders from rhodium. Nat. Synth (2022). https://doi.org/10.1038/s44160-022-00059-8.

 

3-D aromaticity is not as usual as it may seem

/0 Comments/in , , /by

The aromaticity of 3-D closo boranes, zintl ions, and charged fullerenes is widely accepted. On the other hand, several fully p-conjugated macrocycles with puckered or cage-type structures were recently found to exhibit aromatic character according to both experiments and computations. We examine their electronic structures and put them in relation to 3D-aromatic molecules (e.g., closo-boranes) and to 2D-aromatic polycyclic aromatic hydrocarbons. Using qualitative theory combined with quantum chemical calculations, we find that the macrocycles explored hitherto should be described as 2D-aromatic with three-dimensional molecular structures (abbr. 2D-aromatic-in-3D) and not as truly 3D-aromatic. We establish the conditions that have to be fulfilled to classify a compound as 3D-aromatic. Indeed, we show that it is not easy to design new 3D-aromatic compounds. This work was carried out by Dr. Ouissam El Bakouri, Dr. Kjell Jorner, Dr. Rabia Ayub and Prof. Henrik Ottosson from the Ångström Laboratory of the Uppsala University, Prof. Patrick Bultinck from the Department of Chemistry of Chent University and Dr. Dariusz W. Szczepanik and Prof. Miquel Solà from the DiMoCat group of the Institute of Computational Chemistry and Catalysis of the University of Girona

El Bakouri, D. W. Szczepanik, K. Jorner, R. Ayub, P. Bultinck, M. Solà* and H Ottosson*. Three-Dimensional Fully p-Conjugated Macrocycles: When 3D-Aromatic and when 2D-Aromatic-in-3D? J. Am. Chem. Soc., 2022, DOI: 10.1021/jacs.1c13478.

The article has been highlighted and discussed in the following entry of Chemistry World:

Many molecules mislabelled as 3D aromatic